text:
Cost and Quality-of-Care Website Utilization by the Orthopaedic New Patient Population
Alexander M. Crawford, MD, William Ciurylo, DO, MA, Jeremy T. Smith, MD, Eric M. Bluman, MD, PhD, Brandon E. Earp, MD, Christopher P. Chiodo, MD
©2021 by The Orthopaedic Journal at Harvard Medical School
BACKGROUND Efforts to increase transparency of healthcare quality and cost reporting has resulted in the proliferation of cost and quality-of-care websites (CQCWs). Little is known, however, about the rate of public utilization of these websites. The purpose of this study is to investigate the prevalence of use and perceived value of CQCWs by patients seeing an orthopaedic provider for the first time.
METHODS Three hundred adult orthopaedic outpatients were surveyed prior to their first ambulatory orthopaedic encounter. Participants were asked if they had accessed specific CQCWs prior to selecting their orthopaedic surgeon. Participants were also surveyed about their perceptions regarding the utility of CQCWs compared to other factors when selecting their surgeon.
RESULTS Overall, 167 of 300 patients (55.7%) reported knowing of at least one CQCW. However, only 83 patients (27.7%) actually consulted a CQCW prior to choosing their orthopaedic surgeon. Though Blue Cross Blue Shield’s Cost and Quality Tools was the most popular website investigated, it was used by only 9% of our patient population. Patients insured by Medicare were significantly less likely to use CQCWs, as were patients older than 70 years of age. Those who used CQCWs valued other information (such as surgeon reputation and insurance coverage) more than information found on CQCWs.
CONCLUSIONS A slight majority of orthopaedic outpatients reported being aware of CQCWs. However, relatively few patients found utility in consulting these websites. These results highlight a potential opportunity for improvement within the domain of cost and quality-of-care reporting.
LEVEL OF EVIDENCE Level V Cross-Sectional Analysis
KEYWORDS Cost and quality-of-care website; physician-rating-website, orthopaedic surgery
Cost effectiveness and quality of care are integral to healthcare reform strategies. In attempts to improve value, private business ventures, government agencies, and commercial insurance companies have begun to report cost and quality metrics. Private businesses have created what are known as physician-rating websites (PRWs) such as RateMDs, HealthGrades, and Yelp. Meanwhile, government agencies such as the Centers for Medicare and Medicaid Services (CMS) and commercial insurance companies have created what our group calls cost and quality-of-care websites (CQCWs). Examples of CQCWs include Hospital Compare, Physician Compare, Blue Cross Blue Shield’s Cost and Quality Tools, and Aetna’s Member Payment Estimator.
PRWs have been an intense focus of recent literature. These websites allow anonymous users to comment on and rate physicians.1,2 The prevalence of PRW use in the general population has been found to range from 23% to 28%.3-7 It has been reported that between 3% and 32% of physicians are rated on any individual PRW and that the vast majority of ratings are positive.8-14 While PRWs do provide increased transparency in the healthcare system, this transparency comes with several shortcomings. Ratings may not come from verified patients,1,2 may be based on a low number of reviews,9-11 and have not been associated with better outcomes.15,16
In contrast, little has been written about CQCWs. CQCWs, simply stated, are governmental or commercial insurance websites that attempt to provide information regarding cost and/or quality-of-care metrics from verified patient encounters.17,18 For example, Physician Compare displays performance data from the Physician Quality Rating System, which tracks over 200 quality of care metrics as well as biographic information about physicians who participate in Medicare.18
The focus of this study was to evaluate the use of CQCWs within the orthopaedic new patient population, and to examine patients’ perceptions regarding the utility of these websites. Specifically, we examined the frequency with which new orthopaedic surgery patients use CQCWs, which websites were utilized, and whether patient demographics affected website use. Additionally, we evaluated patients’ perceptions about the utility of information reported on these websites with regard to their selection of the orthopaedic surgeon they saw.
Following approval from the hospital’s Institutional Review Board, 300 adult orthopaedic outpatients were prospectively recruited at a tertiary academic medical center. All patients were seeing their provider for the first time. Patients were excluded only if they were younger than 18 or did not speak English. All participants gave informed consent before participating. Enrollment occurred during June and July of 2015 and compensation was a $5 gift card.
The CQCWs eligible for inclusion were determined a priori. Websites were included in analysis if:
- a publicized cost or quality-of-care website affiliated with governmental agencies, or
- a cost or quality-of-care website offered through the most common commercial insurers within our patient population
Generally, websites affiliated with commercial insurers required users to create a profile and were restricted to only those patients of the same insurance type. The final list of websites included was agreed upon by a consensus among the authors and is shown in Table 1. These websites contain a variety of information that is either factual (e.g. reports from the most recent Joint Commission visit in the case of Joint Commission Quality Check) or subjective but based on verified patient encounters (e.g. physician ratings within one of the commercial insurance websites).
Participants were asked to complete a 19-question written survey (Appendix 1*). This survey included questions about patient awareness of and use of individual CQCWs, as well as their perception regarding the importance of information provided by such websites when selecting an orthopaedic surgeon. The survey also included questions about other factors that may have influenced their choice of provider (e.g. provider’s reputation, physician referral, location, and friend/family recommendation). Use of CQCWs was determined both for CQCWs as a whole and for each individual website. Demographic cohorts were compared on the basis of those who used one or more CQCWs versus those who used none. Perceived importance results were stratified using a 5-point Likert scale, anchored with Unimportant and Very Important. Responses of Important or Very Important were grouped together as top-box responses and used to determine relative importance of these factors. Responses to perceived importance questions were considered only from participants who had used one or more CQCWs.
Two-tailed Fisher’s Exact Tests were used to determine whether use of CQCWs differed by patient demographic factors. 95% confidence intervals were calculated for comparative importance of factors in selecting a new orthopaedic surgeon. Results with P<0.05 were considered statistically significant.
Three hundred of the 344 new orthopaedic surgery patients approached agreed to participate in the study (87.2% response rate). The study cohort was comprised of 93 males and 207 females with an average age of 55 years (Table 2). Seventy-two patients (24.0%) were insured by Medicare. Five (1.7%) were insured by Medicaid.
Overall, 167 patients (55.7%) reported being aware of at least one CQCW while 133 (44.3%) had never heard of any. Eighty-three patients (27.7%) reported using at least one CQCW in selecting their new orthopaedic surgeon.
Individual website use by the total cohort ranged from 1 to 9%, with Blue Cross Blue Shield’s Cost and Quality Tools being the most frequently used (Table 1). The most frequently used government sponsored CQCW was the Commonwealth of Massachusetts Board of Registration in Medicine, although this was only used by 4.3% of our patients (Table 1).
Use of CQCWs by demographic is reported in Table 3. Those insured by Medicare, those older than 70, and females were significantly less likely to use CQCWs than their respective comparative cohorts (P=0.011, 0.019, 0.026 respectively (Table 3). Race, orthopaedic subspecialty, and income were not significantly associated with CQCW use.
Factors that influenced a patient’s decision to select a new orthopaedic surgeon are listed in Figure 1. Overall, 83 patients used at least one CQCW and were therefore selected for this analysis. Reputation of a surgeon, insurance coverage, physician ratings (such as those found on PRWs) and referral from another provider were considered the most important factors in selecting a new orthopaedic surgeon. Quality-of-care information provided by commercial and government websites was deemed important by patients, with 73% and 68% of patients indicating that these factors were important or very important, respectively. Fewer patients reported that cost-of-care information was important. Cost to insurance company was deemed important by the fewest number of patients.
While much has been written about physician rating websites (PRWs), less is known about cost and quality-of-care websites (CQCWs). This distinction is important because recent literature has suggested that the ratings found on PRWs may not come from verified patients,1,2 may be based on a low number of reviews,9-11 and have not been associated with better outcomes.15,16 By contrast, CQCWs offer the potential to convey either factual information (such as in the case of CMS Provider Charge Data) or subjective data that is based on confirmed patient encounters (such as in the physician rating portions of commercial insurance websites). As such, CQCWs may deliver meaningfully different information to patients than they would receive on PRWs. Within this context, we sought to characterize the use and perceived value of CQCWs as defined by patients seeing an orthopaedic provider for the first time.
In the population we studied, 55.7% of patients were aware of and 27.7% had actually used a CQCW. To our knowledge, the rates of awareness and use of these websites among orthopaedic patients has not been previously investigated. Meanwhile, it has been documented that approximately 65-74% of patients have heard of and 23-28% of patients have used PRWs when selecting a physician.3-7 Thus, while slightly more patients have heard of PRWs than CQCWs, the prevalence of use of both are roughly equivalent at least based on historical standards.
Individual CQCW use was fairly infrequent across our patient population. With the exception of BCBS’s Cost and Quality Tools, no individual website was used by more than 13 (4.3%) of our patients. Although BCBS’s Cost and Quality Tools website was used by 27 (9.0%) of our patients, BCBS did insure a plurality (30.3%) of our patient population. This is important context because most commercial insurance websites are only offered to those patients with that specific insurance. Subgroup analysis amongst commercial insurers revealed wide heterogeneity in the utilization of their websites by their respective patient populations. For example, Cigna’s Find Doctors and Services website performed comparatively well as it was used by 100% of Cigna patients, whereas Harvard Pilgrim’s Now iKnow website performed relatively poorly as it was used by only 25.6% of those insured by Harvard Pilgrim. (Table 1). We suspect this heterogeneity may be due to a combination of websites being marketed differently by individual insurers, website quality dissimilarities, different market dynamics (i.e. co-pays) amongst insurers, and disparate plans (i.e. health maintenance organizations versus preferred provider organizations) utilized by differently insured subgroups.
However, even amongst the open access CQCWs (e.g. Physician Compare) utilization remained quite low (ranging from 1 to 4.3% of our patient population). We believe this could be due to lack of advertising of open access CQCWs, though the evidence of this is currently lacking. We also suspect that the substantial number of different open access CQCWs makes it difficult for patients to keep up with all of the available information, which is often unique on each website. The implication of this finding is that patients who search for cost and quality-of-care information online are likely accessing different information based on the website they visit. We believe the large number of unique CQCWs may be exhaustive to patients. Perhaps one centralized open access CQCW with all appropriate information would achieve more traction.
We found that patients insured by Medicare accessed CQCWs at a significantly lower rate than did all of our other patients (P=0.011). One possible explanation for this is that the Medicare patient population skews older. Prior literature has demonstrated that elderly patients are less Internet proficient19 and that they use PRWs at a lower rate5,6 than younger patients. Indeed, we found this to be the case amongst our patient population; those who were 70 years old or older used these websites significantly less frequently than the rest of the patient population (P=0.019). Therefore, some of the difference between CQCW use by Medicare patients versus the rest of our patient population might be explained by age. Additionally, although no Medicaid patients used CQCWs, too few were surveyed to determine the significance of this finding (P=0.327).
We additionally found men to use CQCWs significantly more than women (P=0.026). This finding is not well documented in the existing literature. In fact, studies have found that women access PRWs6 and general health websites at significantly higher rates than men.20 None of these studies, however, investigated how gender influenced website use amongst the orthopaedic new patient population.
Among those who accessed the websites investigated, factors other than CQCWs were reported by many patients to be more important than CQCWs. These factors included surgeon’s reputation, insurance coverage, physician ratings, and referral. Physician ratings, which can be found on some hospitals’ websites but are mostly found on PRWs, were still considered important or very important by the majority (80.3%) of our patients who used CQCWs1,21 (Figure 1). This is concerning because it has been documented that ratings on PRWs are determined by very few reviews, are not from verified patients, and are not associated with better outcome measures.1,2,9-11,15,16 Though aspects of CQCWs have been called into question, they do provide mostly objective measures from verified patient encounters and may provide a better alternative to PRWs.17,22-24 Further investigation into the public’s perception of PRWs versus CQCWs is recommended.
Our study was limited to new patients visiting an academic tertiary care facility. No attempts were made to normalize our study population or to weight results based on representative demographic. Moreover, some of the websites investigated are relevant only to the Massachusetts market. Therefore, the generalizability of our findings is not known. Nevertheless, we believe the data presented here highlight the need for more, and larger studies to be performed across the country regarding patient behavior as it relates to cost and quality-of-care information.
In summary, most orthopaedic new patients have heard of CQCWs but a majority-particularly those insured by Medicare, those older than 70, and females-do not use them. Even amongst those who actively seek out CQCWs before selecting a new orthopaedic surgeon, other factors are considered more important than much of the information found on CQCWs. Improving quality and minimizing cost are desirable goals for healthcare reform. However, patient behavior as it relates to cost and quality-of-care information should be considered prior to designing further reform initiatives.

domain: medical


text:
Thanks so much for the fantastic job the two of you did grooming my two samoyeds. Especially their baths. I simply can't manage them on my own. Not only that, they looked and felt and smelt lovely, and that is still the case, even after a week of walks and swims.
All 3 of us are truly grateful.
Jacqui has been grooming our cocker spaniel, Jock, for years. The mobile grooming is so convenient and takes the hassle out of dog grooming. I come home from work and he's all smart and beautiful again, just like that.
Jacqui has been grooming Archie for the past 6 years and from the first visitI knew Archie was in good hands. Archie can be a difficult dog, but Jacqui has him eating out of the palm of her hand - he is calm and well behaved in her presence and enjoys his grooming experience. AllI have to say is "Jacqui and Jaz are here" and he's wagging his tail. I thoroughly recommend Jacqui to all that want their dogs well groomed and happy with the process"
I first met Jacqui in 2004 whenI worked for a boarding kennel. She was the dog-groomer of my employers choice and we had high standards. Since that timeI have utilised Jacqui's skills in grooming my own dogs. I have a pomeranian called Mate, and a german shepherd x called Jess. Jacqui has always done an impeccable groom on both dogs.
Little Mate gets so hot in summer with his thick coat so after a shave she bathes him, dries him, then shaves his coat again. She shapes his face and paws nicely. He looks so smart and feels so much better afterwards. People often stop and ask me, "Who grooms him?" and say "he's is just so cute."
Jess's coat is entirely different. She is 13 years old, moults a lot and has arthritis. Jacqui always takes great care with her and after a brush bathes her and dries her off. It's amazing how many loose hairs come out.
Jacqui always checks their nails, ears and general health while she works and has offered me sound advice.
I would recommed Jacqui to any dog owner. She is caring anda genuine dog lover, and to top it off she comes to you so the dogs feel more comfortable in their own environment.

domain: pet


text:
Effective searching is usually an iterative process. One approach is to try a fairly simple search, quickly identify the best sources in your results based on those records and then adjust your search to identify similar results. Things to look for are wording, source type, subject headings, database, etc.
In addition to looking for useful things in your search results, identify the things that are decreasing the relevance of your results. Look for an option in the filters to just search the disciplines or subject databases relevant for your topic, use the boolean operator NOT to exclude words that you do not want in your results.
Quickly scanning your search results is an important skill that you can develop and grow. It's also useful in all information research, not just when you're searching library resources. Practice by scrolling through the first page of your search results before you click on any of your results. Look for the best results, identify alternate search terms and look for problems in your search. Think about how you may want to adjust your search to improve your results.
Thoughout your search process you are likely to want to track down the full text of articles that you saw cited in other sources. Here is my recomendation for locating the full text:
From the Library home page;

domain: library


text:
Please use this identifier to cite or link to this item:
Effect of Nonsteroidal Aromatase Inhibitor on Sex Reversal of Oreochromis mossambicus (Peters, 1852)
|Title:||Effect of Nonsteroidal Aromatase Inhibitor on Sex Reversal of Oreochromis mossambicus (Peters, 1852)|
|LC Subject Headings:||Fish culture--Israel--Periodicals.|
|Publisher:||Israeli Journal of Aquaculture - BAMIGDEH|
|Citation:||Das R., Rather M.A., Basavaraja N., Sharma R., Udit U.K. (2012). Effect of Nonsteroidal Aromatase Inhibitor on Sex Reversal of Oreochromis mossambicus (Peters, 1852). The Israeli Journal of Aquaculture - Bamidgeh, 64, 9 pp.|
|Series/Report no.:||The Israeli Journal of Aquaculture - Bamidgeh|
|Abstract:||In the present study, the efficacy of letrozole, a potent nonsteroidal aromatase inhibitor, and 17a-methyltestosterone on gondal sex differentiation and sex reversal was examined in Mozambique tilapia (Oreochromis mossambicus). Among the doses tried in the experiment, 100 mg letrozole, 200 mg letrozole, and 50 mg 17a-methyltestosterone/kg produced male dominated populations (97-100% males). The combination of 100 mg letrozole+25 mg 17a-methyltestoster/kg yielded 100% males while the combination of 50 mg letrozole+25 mg 17a-methyltestosterone/kg yielded 92% males. The control group consisted of 48.05% males and 51.95% females, close to the normal sex ratio of 1:1. Survival ranged 85.61-94.31% in the treated groups, significantly higher than 73.83% in the control (p<0.05). In general, the letrozole and combination treatments resulted in a slight alteration in the gonadosomatic index of the tilapia. Administration of letrozole alone or in combination with 17a-MT did not adversely affect the proximate composition of the muscle. Results suggest that letrozole and 17a-methyltestosterone have the potential to produce 100% male populations in Mozambique tilapia and that inhibition of aromatase activity influences sex differentiation in Mozambique tilapia.|
|Appears in Collections:||Volume 64, 2012|
Please contact firstname.lastname@example.org if you need this content in an alternative format.
Items in eVols are protected by copyright, with all rights reserved, unless otherwise indicated.

domain: literature


text:
“Markings... of whatever sort, tend to obliterate, to cancel, by their separate and conflictingpattern, the visibility of the details and boundaries of form....” 1
Both predators and prey use camouflage. It can also be used by neither.
Camouflage and retreat are not tactics of escape, but rather submergence and sublimation. Becoming scenery, background, furniture.
Octopi camouflage themselves and spray ink. Masquerading as a coral, they cloak themselves in a black cloud. The pursuant is confused and disorientated.
Intentional invisibility. Our interior lives cloaked in a mushy material, which creates the contours of our form.
Kneaded into the night.
In Maurice Sendak’s illustrated children’s book In the Night Kitchen (1970) a boy wakes in the middle of the night to the sound of kitchen noises. As he leaves his bed, curious to investigate, he falls into mysterious space. He lands, naked, in a bowl of bread batter, surrounded by plump cooks. He is baked into a costume of bread, and then flies in a bread airplane across the night sky. Finally he drops into a giant bottle filled with creamy milk. Submerged in the milk, he sings: “I’m in the milk and the milk’s in me.”
We do not only cloak, but we transform into monsters. We wear eyes across our skin in order to resemble larger beasts. We simulate patterns and shapes that confuse and dazzle. We maneuver irregularly, resembling street lamps or wobbly broomsticks. We move seamlessly inside and outside the boundaries of our form. We must always become more difficult to track.
Sendak, after writing Where The Wild Things Are (1963), recalls receiving a drawing from a young admiring fan. He was so charmed by the note that he decided to write back. Shortlythereafter, he received a letter back from boy’s mother saying the boy loved the card so much he ate it.
Within this we find our moment of retreat. A letter is not something to be read but to be eaten. Bread is not only something to eat but to exist within. The child is cloaked, but not hidden or fleeing. They are flying. The bread and the milk are also it, and the child is also them. Power and fear, action and agency, collapse into ecstasy and joy. When the child is baked into the bread it isn’t killed, or consumed. The logic of the product isrefused. It’s an implosion of one-ness.
There are predators and prey, but there are also monsters – masquerading, cloaking themselves into the night.
“To be dissolved into something complete and great. When it comes to one, it comes as naturallyas sleep.”2 —
1 Concealing-Coloration in the Animal Kingdom, Abbott Handerson Thayer, 1909
2 My Antonia, Willa Cather, 1919

domain: artistic


text:
Our Blog Posts
Doleshwor Mahadev Temple is a popular Hindu pilgrimage attraction in Bhaktapur Nepal, which is just
Nepal is a highly divergent country with its immense natural beauty. It is inexplicable in words to
Dhampus village (1650 m) is situated on the north from the Pokhara valley which offers gorgeous vie
Buddhist Pilgrimage Sites in Nepal attracts thousands of Buddhist pilgrims from around the world. N
Bandipur village is a living museum of Newari culture, a beautifully preserved village crowning a l
Hindu pilgrimage sites of Nepal are the major sightseeing attractions for those who are looking for
Lord of the Drinks Kathmandu could be the best place for your night hangout in the Kathmandu city.
Pokhara’s music restaurants and clubs are pretty awesome to enjoy the beauty of this living city.
Reason to Travel with us.
Amazing Destinations, Best Holiday Deals, Affordable Prices, Customize Itineraries & Memorable Trips.
Multiple destination options for your holiday trip.
We offer you a customize tour packages on your own choice.
See our trip reviews what our client says.
Let's Travel With Us
We would be more than happy to help you. Our team are 24/7 at your service to help you.
- GET A QUOTE

domain: geography


text:
FDA Issues Warning Letter to OTC Drug Manufacturer For Data Integrity Concerns
The FDA has published a warning letter sent to Ningbo Huize Commodity, an over-the-counter drug manufacturer, citing significant current good manufacturing practice (CGMP) violations including data integrity issues.
The FDA has published a warning letter sent to Ningbo Huize Commodity Co., an over-the-counter drug manufacturer, citing significant current good manufacturing practice (CGMP) violations, including data integrity issues.1
The warning letter specified a failure to have adequate quality control mechanisms in place and the provision of falsified documents to FDA investigators.1 According to the agency, falsified documents included cleaning validation reports, and batch production and control records for multiple drugs. A statement issued by the FDA said the company also admitted to falsifying records showing that they performed the required periodic reviews of their operation to assure quality.
As a result of these CGMP violations found during the FDA inspection in March 2019, all drugs manufactured by Ningbo Huize are adulterated under the Federal Food, Drug, and Cosmetic Act. The FDA statement added that the adulterated products are also considered to be misbranded because the product labels did not include all the required information and directions for use. These products include sunscreen lotions.2
In response to the FDA’s original accusation of falsified documents, Ningbo Huize representatives provided the agency with further CGMP documents in writing. Considering the company’s history of falsified documents, however, the FDA letter expressed concern regarding the document’s validity.
“Your response is inadequate because you failed to fully review the scope of your deficiencies, and provide evidence that you have comprehensively remediated your systems, and to implement procedures and programs that ensure ongoing control over your drug manufacturing operation,” the letter read.2
In response to the letter, the FDA requested several comprehensive assessments and remediation plans, in addition to a full summary of data integrity assessments performed by a third-party consultant. The letter requested this information within 15 working days.
- FDA warns company for putting consumers at risk with drug manufacturing data integrity violations. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-warns-company-putting-consumers-risk-drug-manufacturing-data-integrity-violations. Published August 20, 2019. Accessed August 21, 2019.
- Center for Drug Evaluation and Research. Ningbo Huize Commodity Co., Ltd. -581345- 08/02/2019. U.S. Food and Drug Administration. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/ningbo-huize-commodity-co-ltd-581345-08022019. Published August 20, 2019. Accessed August 21, 2019.


text:
business opportunity with monthly passive income
magic wallet, magic ring.., and short boys to give you money
contact us for your urgent loan now...with 100% guarantee.
get the bank card that gives you free airtime for life
struggling to pay off your debts back monthly?
get a massive loan of up to r250 000
buy any new car for less from r38 per day
**** clinic/pills in soweto call/whatsapp 0728273137
join illuminati in vereeniging 0766733736, how to join
we give out loans up to r500,000.00 and same day appoved.

domain: finance


text:
Norton Fitzwarren Dragon
Here the Roman general Ostorius was said to have killed hundreds of ancient Britons. Over the centuries a dragon is said to have grown from the corruption of the rotting bodies (this spontaneous growth of creatures from rotting matter was a common belief in Medieval times). The dragon took up residence in an Iron Age hill fort and preyed on the populace until Fulk Fitzwarine, a 13th century knight, slew the creature. Despite his brave deed Fulk fell foul of King John and was exiled. He continued his adventures abroad when he saved the Duke of Iberia’s daughter from a dragon near Carthage.
The above was taken from an article by Richard Freeman

domain: history


Our women’s collar and wide leg PJ set featuring a hand-drawn Pink Bows print. A timeless set for winter and beyond.
100% organic cotton, a very soft interlock fabric for maximum night-time comfort.
Knitted ethically and printed in the U.K. using water based inks. Our sleepwear is proudly designed and made in Britain support independent suppliers and factories.
Our pyjamas get softer with age.
Wash at 30 degrees, but please do not tumble dry. The sleepwear should have no more than 5% shrinkage after a couple of washes.
Wash dark colours separately.
Please note we only run small collections each season and sizes do sell out.
Model in photo wears S/M


This is customization with obsessive attention to detail.
If you haven't heard of the Ringbrothers yet have a passion for muscle, we suggest educating yourself at your earliest convenience. Much like tuning firm SpeedKore, this is an outfit obsessed with making old-school metal cooler than ever. The tuner has also worked on some modern machines, but the people who work there have a particular affinity for classic muscle. Over the years, a number of outstanding creations have left the shop, but the latest may eclipse all that came before it. Named CAPTIV, this is a Dodge Charger like no other, and as is fashionable, it packs a Hellcat crate motor with 707 horsepower.
Mated to a six-speed manual transmission from Tremec, the engine powers the rear wheels with the aid of a carbon fiber driveshaft from QA1. Other highlights include custom HRE wheels, Baer six-piston brakes, and Michelin Pilot Sport 4S tires. MoTeC handled the engine management and gauges while Flowmaster provided the custom exhaust system that exits aft of the rear wheels. But as cool as all these parts are, the finer details truly blow you away. Custom-made billet indicator stalks are just a taste of the billet parts throughout the build and are joined by aluminum pedals and an exquisitely retrimmed cabin with loads of leather and a pair of customized Recaro seats. The highlight of the interior has to be the carbon fiber steering wheel though, boasting billet aluminum spokes and hub and a 3D-printed horn button.
The car was built for New Zealand motorsports legend and TV personality Greg Murphy, who had the car disassembled and prepared before shipping it to the States for the overhaul. Here, it was subjected to between 800 and 1,000 hours of bodywork that included making the Challenger a unibody and finishing it in a unique interpretation of Porsche's Signal Yellow, here renamed Pile Up Yellow. The paint has four base coats in white before yellow was applied and topped with six coats of clear. This was then polished to a mirror finish and looks amazing from any angle. Combined with the perfectly centered hole in the hood, the aluminum instrument cluster surround, and just the overall finish of the build's multiple components, we think this could be the best amalgamation of old and new muscle yet.


STAFFORD — Organizers hoping to bring a dog park to town are revisiting their plan to site it next door to the senior center and are now looking for another location where their four-legged friends can play and socialize off leash.
During Tuesday’s Planning and Zoning Commission meeting, organizers of the anticipated Stafford Bark Park formally withdrew their application to establish the park at 15 Buckley Highway, a plot of land owned by Judith and David Mordasky that is adjacent to the Stafford Senior Center and Community Center.
Wendy Tariff, treasurer of the group, said during the meeting that Bark Park Inc. would still like to establish a dog park in town and are looking at other locations.
Tariff and other organizers have been considering 11 Sellars Lane, a former public works dumping ground that was capped and filled years ago and remains vacant. The town owns the property.
She said that the group has been in contact with Bill Warzecha, a remediation specialist from the state Department of Energy and Environmental Protection, who has offered to help Tariff research the background of the property. Tariff also said, if they pursue the property, Bark Park Inc. intends to work with the Stafford Garden Club to try to make the property surrounding the dog park a green space that could include walking trails.
Tariff explained that there were too many obstacles at the Buckley Highway property to continue to pursue that site.
After the dog park was first proposed in June, Senior Center Director Grace Parrow expressed concern about the proximity to the center. Parrow said she had concerns that there could be traffic and parking issues for the center and its members. The initial plan had dog park visitors using the senior center driveway to park in a rear section of the existing parking lot. Parrow said that she was worried there could be overcrowding in the area if a dog park was established, as the center is used for several programs throughout the day.
Another potential wrench in the plans for the Buckley Highway property was that a small plot of land owned by a third party that borders the center and the edge of the Mordasky’s property could have imposed use restrictions on the proposed dog park.
Other than the concerns about the Buckley Highway location, residents who spoke at several public hearings have been overwhelmingly supportive of the idea of an off-leash dog park in town.
Bark Park Inc. has been fundraising to build the park and plans to maintain it once it’s established.
Tariff said that she plans to meet with First Selectwoman Mary Mitta to keep her in the loop, and they hope to resubmit their application.
Before a dog park can be built, it would need a special use permit from the Planning and Zoning Commission, approval from the Board of Selectmen, and ultimately be decided by Stafford residents at a town meeting.


text:
Assam's Flood-Ravaged Village Await New Bridges For 28 Years | Read
PUBLISHED ON: April 11, 2017 | Duration: 2 min, 34 sec
An extremely bumpy drive followed by a pillion ride on a motorcycle over a rickety bamboo bridge is what one has to endure to reach Kalkata village, 25 kilometres from Dhemaji town in Assam. The past few years, Assam has seen a series of floods between May and September. 55-year-old school teacher Tarun Gogoi discusses with his family their crisis management strategy this time around.


text:
Re: Interzone 229 'a sexy prime' issue.
Mannikin was very good, I thought, especially if one is fascinated by the era. Dark Matter was fun too, though I'm sorry to say I found its satire hammer-like in its application.
Haven't read the others yet but I'm sure looking forward to it. Strong turn out from the illustrations, too.

domain: entertainment


text:
Scientific and Manufacturing Challenges in Stem Cell Sourcing
1.1. Stem cell tourism
Advances in stem cell research and media publicity of stem cell potential have raised the hopes of patients with severe disabilities and conditions which lack a cure. While stem-cell-based therapies are the clinical standard of care for a few conditions, such as leukemia and more recently for some burns and corneal disorders, stem cell tourism continues to rise worldwide.
Unfortunately, clinics around the world are exploiting patients’ hopes by offering supposed stem cell therapies, without credible scientific rationale, oversight or patient protections. Occurring particularly in Asia and South America, treatments which are illegal in most counties are being offered for what are often considered incurable conditions, such as brain tumors, congestive heart failure or chronic obstructive pulmonary disease. In addition, countless other conditions are listed as candidates by these clinics including eye disease or orthopedic injuries or disease. In response to this, the International Society for Stem Cell Research (ISSCR) released “The
The general public receives information regarding stem cell potential from mainstream media and does not fully understand the risks associated with unproven treatments. In the most desperate situations, patients may see no other options, or may view the years of continuing research as an obstacle to their potential cure. Yet, untested treatments can be dangerous and years of preclinical and clinical research are required to determine which novel stem-cell based therapies are effective and safe. In one example, brain tumors were discovered in a 9-year old boy who travelled to Russia to receive stem cell treatments to his brain; later it was found that the tumors were the result of cells from at least 2 different donors . Even carefully planned and approved studies can go wrong and have unfortunate results, as in the fatal gene therapy case of Jesse Gelsinger, who received experimental therapy at University of Pennsylvania[3, 4].
Lau et al reported on the clinics around the world that are exploiting patients’ hopes by professing to have effective stem cell therapies for seriously ill patients. These therapies often carry a hefty pricetag. However, they occur in counties which have limited oversight and allow treatment to occur in the absence of credible scientific rationale, transparency, oversight, or patient protections .
Comprehensive government regulations exist in the US, and several other countries. Below, we describe the U.S. and other government regulations associated with the use of human stem cell and tissues in regenerative medicine.
2. Cell Products must follow FDA regulatory guidelines
2.1. FDA’s risk-based approach
To protect the public from risks associated with cell therapies and demonstrate the effectiveness of treatments, the U.S. FDA and other professional societies such as the ISSCR, and the United States Pharmacopia (USP), have established guidelines for therapies using human cellular and tissue-based products (HCT/Ps). The FDA has statutory authority to prevent the spread of communicable diseases granted under Section 361 of the Public Health Service Act (PHS Act, 42 U.S.C. § 264). HCT/Ps are regulated through a risk-based approach outlined predominantly in 21 C.F.R. Part 1271. Some HCT/Ps are regulated solely under Part 1271 while other HCT/Ps are regulated under both Part 1271 and FDA’s Federal Food, Drug, and Cosmetic Act (FDCA, premarket and post- market regulation of medical devices and drugs), & section 351 of the PHS Act for biological products. FDA's regulation focuses on three general areas: 1) limiting the risk of transmission of communicable disease from donors to recipients; 2) establishing manufacturing practices that minimize the risk of contamination; 3) requiring an appropriate demonstration of safety and effectiveness for cells and tissues that present greater risks due to their processing or their use [6, 7].
Stem cell therapies show excellent promise for many types of treatments. However, scientific, manufacturing and safety challenges exist. Once the optimal stem cell type is identified for a given treatment (Table 1), there is a requirement to demonstrate the product’s safety and efficacy in a clinical setting. Cell therapies must overcome several challenges before they can be considered safe for human use. First, most cell therapies will require large numbers of cells. Large cell doses are obtained by increasing cell harvest yields and by increasing ex vivo expansion yields. As cell cultures are expanded over long time periods, they show signs of aging that may be similar to human aging [8, 9]. Lengthy expansion periods can result in ineffective cellular products. Cells may also be manipulated in other manufacturing steps that include cell-selection processes, genetic modifications, or encapsulation with another biological device. Cells that undergo ex vivo manipulation may lose potency, or acquire infectious contaminants, or become transformed / tumorogenic due to the cell culture conditions [11, 12]. Finally, the cells themselves may pose a risk, simply due to the novelty of the therapy and unknowns associated with their behavior in the body.
In 1993, the US FDA began establishing regulatory and guidance documentation for cell therapies with the issuance of Application of Current Statutory Authority to Human Somatic Cell-therapy and Gene-therapy Products  which provided a biologics regulatory framework for the use of HCT/Ps. Table 2 provides a list of other key regulatory and guidance documents. The tiered risk-based approach means that products which present a lower perceived risk will be less regulated, while products with a larger perceived risk will undergo more extensive controls and examination. Both will require the cell products to be manufactured following Good Manufacturing Practices (GMP), and Good Tissue Practices (GTP). Additional regulatory requirements will depend on whether the cell product is minimally manipulated or more-than-minimally manipulated.
|Current good tissue practice for manufacturers of HCT/Ps;
inspection and enforcement; proposed rule
|Human cells, tissues and cellular and tissue-based products
(HCT/Ps); establishment registration and listing; final rule
|Validation of procedures for processing of human tissues
intended for transplantation: final guidance
Minimal manipulation is defined by the FDA for cells or nonstructural tissue as processing that does not alter relevant biological characteristics of cells or tissues. HCT/Ps that meet 1271 criteria for regulation solely under section 361 of the PHS Act and the regulations in Part 1271 are called “361 HCT/Ps”, and are not subject to any premarket review requirements. The Center for Biologics Evaluation and Research (CBER) has jurisdiction over 361 HCT/Ps.
According to 21 CFR 1271.10, minimal manipulation criteria include:
The HCT/P is minimally manipulated;
The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent;
The manufacture of the HCT/P does not involve the combination of the cell or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and
The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:
is for autologous use;
is for allogeneic use in a first-degree or second-degree blood relative; or
is for reproductive use.
For cells, minimal manipulation means processing that does not alter the relevant biological characteristics of cells or tissues. Examples of products regulated as 361 HCT/Ps include bone marrow or blood transplants and organ transplants.
HCT/Ps that do not meet one or more of the four major criteria, are considered more-than-minimally- manipulated HCT/P. FDA has stated that density-gradient separation, cell selection, centrifugation, and cryopreservation constitute minimal manipulation. All processes that manipulate the cell / tissue product such as cell activation, encapsulation, ex vivo expansion, and gene modifications are considered more-than-minimal manipulations. Most advanced cellular therapies meet criteria for the more-than minimally manipulated category . Finally, it is possible to request an informal jurisdictional determination on the level of manipulation from the Tissue Reference Group (TRG), or submit a formal Request for Designation (RFD) from the Office of Combination Products (OCP). Figure 1 is a schematic of regulatory pathway assessment to determine which guidelines apply to a given HCT/Ps product.
2.2. Manufacturing of HCT/Ps requires GTPs
For HCT/Ps that do not meet the criteria established in Section 1271.10, FDA premarket review is required; this includes obtaining FDA license, approval, or clearance.
All steps in the manufacturing of HCT/Ps will require compliance with Current Good Tissue Practice (cGTPs). cGTPs cover manufacturing facilities and processes. The manufacturing process can be broadly described as 1) procurement of HCT/Ps (donor screening and testing, product recovery), 2) processing of HCT/Ps (tissue or cell recovery /isolation, product handling, product labeling), 3) storage (e.g. cryopreservation), and 4) distribution. Many of these steps are common to GTPs and GMPs with the goal of safe and effective products via well-controlled processes and thorough supporting documentation. Requirements for standard operating procedures (SOPs), labeling controls, and storage requirements also exist.
Therapies with HCT/Ps will require a determination of donor eligibility. For the FDA, donor eligibility is determined based on donor screening and testing for relevant communicable disease agents and diseases, and is required for all donors of cells or tissue used in HCT/Ps, with some exceptions listed in C.F.R. Part 1271.90.
As part of clinical or industry compliance with donor testing requirements, procedures to process, store, label, and package cell products also are needed. Hospitals and companies involved in cell/tissue therapeutics manufacturing must establish quality programs which consist of a comprehensive system for manufacturing and tracking HCT/Ps. The quality program must follow CGTP requirements, and be designed to prevent, detect, and correct deficiencies that may lead to circumstances that increase the risk of introduction, transmission, or spread of communicable diseases.[6, 7]
The implementation of a Quality Assurance (QA) program includes principles of good manufacturing practice (GMP) and a quality control (QC) system. A QC system is required to ensure safety and efficacy of cell applications. GMP regulations apply to all phases of cell/tissue collection, processing and expansion, and storage. GMP quality practices are required for HCT/Ps to be used for clinical procedures and INDs. A compliant quality program for record and process control is a critical part of a QC system.
A compliant material control program is essential for FDA licensure. During review of new license applications, clinics and companies are asked to provide detailed descriptions of the manufacturing process and documentation of source country for all materials of animal origin. Additionally, for FDA-regulated products intended for administration to humans, companies must minimize any chance that BSE could be introduced into products during the manufacturing process and ensure that all materials are used as intended in the processing and are contamination free. Subsequently, a program for control of materials used in the process is necessary to meet FDA compliance and product safety.
If the HCT/P product involves cryopreservation, then compliance requires that the process includes an understanding of the shelf-life and how the freezing & storage process affects the HCT/Ps to complete the quality testing program. Banked cells should be stored under conditions shown to be suitable for long-term stability. Cell/tissue stability under the freezing and storage conditions should be validated using cell recovery or viability data. It is expected that establishment of a stability program for a banking process will lead to the development of quality products over a long term storage period and provide confidence that they will be effective in clinical applications.
2.2.4. Distribution testing
For the lot release of patient’s cells/tissues for clinical use, standards for in-process and final product quality must be established. Specifically for FDA licensure, companies must submit their facility controls, process controls, and product standards designed with scientific principles to ensure the safety and effectiveness of all HCT/Ps products. This again is based on SOPs and controls for adherence to the cGTP, Current Good Manufacturing Practice (cGMP) and 21 CFR 1271 requirements. Product lot release specifications ensure that all products are produced in a safe and consistent manner and should be effective in clinical applications. In order to meet HCT/Ps regulations, product lot release specification should include testing for cell phenotype to confirm purity, potency, and identity.
The application for licensure requires that companies demonstrate that the HCT/P product standards and procedures are based on good science, and thorough and extensive data. A comprehensive product characterization program is needed to understand the products and how they may be clinically beneficial. During the application process, the FDA may request that the hospital or company applicant expand on a concept or further explain the rationale/approach or provide additional data. FDA premarket review and licensing is considered a lengthy and arduous process, however new products applicants may benefit by the recent approvals of several cell-based products (Table 3).
|Articular cartilage damage in the knee||Autologous chondrocytes (adult/differentiated)||US FDA approval 1997
|Diabetic foot ulcers and venous leg ulcers||Neonatal foreskin allogeneic keratinocytes and fibroblasts in bovine collagen scaffold||US FDA approval 1998|
|Asypmptomatic or hormone refractory prostate cancer||Autologous dendritic cells (adult/differentiated)||US FDA approval 2010|
|Asypmptomatic or hormone refractory prostate cancer||Autologous dendritic cells (adult/differentiated)||US FDA approval 2010|
|Moderate to severe nasolabial fold wrinkles||Autologous fibroblasts (adult/differentiated)||US FDA approval 2012|
|Single symptomatic cartilage defects in the knee||Autologous chondrocytes (adult/differentiated)||EMEA approval 2009|
|Graft vs. host disease in children who are refractory to steroid therapy post-BMT||Allogeneic mesenchymal stem cells from donor bone marrow||Health Canada/New Zealand grant conditional approval 2012|
|Heart repair post-myocardial infarction||Autologous bone marrow-derived mesenchymal stem cells||Korean approval 2011|
|Traumatic and degenerative osteoarthritis||Allogeneic mesenchymal stem cells from donor umbilical cord blood||Korean approval 2012|
|Anal fistula in Crohn’s Disease||Autologous fat-derived ‘stem cells’||Korean approval 2012|
3. Non-U.S. regulatory systems
The European Union, Australia and Canada and other countries have established similar regulatory systems for the use of post-natal human HCT/Ps.
The European Medicines Agency (EMEA) is the regulating body with authorization and supervision of cell therapy products and other “advanced therapy medicinal products” . As of January 2011, the EMA’s Committee for Advanced Therapies (CAT) recognized the potential of stem cell therapies and released a reflection paper to work in conjunction with the
In Australia, HCT/Ps or products (biologicals) are regulated by the Therapeutic Goods Administration (TGA) which is the Australian equivalent to the FDA. Similar to the FDA approach, the TGA’s regulatory framework for biological imposes varying levels of regulation on the therapy or product depending on risk, extent of manipulation, and whether the intended use of the biological is its
In order for a stem cell therapy to be approved by Health Canada it must meet the regulations as stated in the Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations). The CTO Regulations detail requirements to ensure safety in processing; storage; record keeping; distribution; importation; error, accident and adverse reaction investigation and reporting. Requirements for donor screening, testing, and suitability assessment are described in the processing regulations as well as the testing and measurements performed on the products after retrieval or in preparation for use, preservation, or packaging.
Health Canada, the FDA equivalent in Canada, is the first approving body in the world to approve a manufactured stem cell based drug intended to treat a systemic disease -acute Graft versus Host Disease (aGvHD) . Osiris Therapeutics of Columbia, Maryland developed Prochymal [remestemcel-L, adult human mesenchymal stem cells (hMSCs) for intravenous infusion], a liquid cell suspension of ex vivo cultured adult MSCs derived from the bone marrow of healthy adult donors. Prochymal is the first stem cell therapy approved for clinical use in patients, specifically pediatric patients. Health Canada required Osiris to continue a Risk Management Plan to demonstrate that the benefits of Prochymal continue to outweigh risk, the addition of post-market studies, and maintenance of a treated patient registry for approval.
Table 3 provides a list of cell therapy products that have received U.S. FDA approval or other government approval. Despite extensive stem cell research over the past 15 years, most cell products are not stem cell derived. Only Osiris’ BM-MSC product and 3 Korean products are stem cell based products.
This report examines the different processes involved in HCT/Ps manufacturing and highlights the guidelines that must be followed to obtain FDA or other country specific regulatory approval. Ex vivo expansion, cell selection or gene modification will likely be necessary for most advanced cell and tissue therapies. These modifications increase the risk associated with the treatment and render the product to be regulated under a higher risk category of more-than-minimally-manipulated product. Key to biomanufacturing is the implementation of a QA/QC program including a quality control system and GMP principles which apply to all phases of manufacturing.
Many counties actively regulate the use of stem cell products, however, there are still a number of areas around the world that have little regulations and unregulated treatments pose risk to patients and the careful development of the field. The current challenge to deliver safe cell and tissue therapies and curb unregulated treatments may soon apply to gene therapy and other innovative technologies. Early government regulation and active education by a number of professional organizations should reduce the spread of medical tourism and aid in the development of safe and effective treatments in the field of regenerative medicine.
ISSCR, Guidelines for the Clinical Translation of Stem Cells.International Society for Stem Cell Research, 2008.
Amariglio, N., et al., Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.PLoS Med, 2009. 6(2): p. e1000029.
Liang, B.A. and T. Mackey, Confronting conflict: addressing institutional conflicts of interest in academic medical centers.Am J Law Med, 2010. 36(1): p. 136-87.
Wilson, R.F., The death of Jesse Gelsinger: new evidence of the influence of money and prestige in human research.Am J Law Med, 2010. 36(2-3): p. 295-325.
Lau, D., et al., Stem cell clinics online: the direct-to-consumer portrayal of stem cell medicine.Cell Stem Cell, 2008. 3(6): p. 591-4.
National Academies (U.S.). Committee on Ranking FDA Product Categories Based on Health Consequences Phase II. and National Research Council (U.S.), A risk-characterization framework for decision-making at the Food and Drug Administration. 2011, Washington, D.C.: National Academies Press. xiv, 192 p.
US Food and Drug Administration. Guidance for Industry. Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).2011.
Carlson, M.E. and I.M. Conboy, Loss of stem cell regenerative capacity within aged niches.Aging Cell, 2007. 6(3): p. 371-82.
Gazit, R., I.L. Weissman, and D.J. Rossi, Hematopoietic stem cells and the aging hematopoietic system.Semin Hematol, 2008. 45(4): p. 218-24.
Deasy, B.M., et al., Long-term self-renewal of postnatal muscle-derived stem cells.Mol Biol Cell, 2005. 16(7): p. 3323-33.
Kirouac, D.C. and P.W. Zandstra, The systematic production of cells for cell therapies.Cell Stem Cell, 2008. 3(4): p. 369-81.
Parenteau, N.L., Commercial development of cell-based therapeutics: strategic considerations along the drug to tissue spectrum.Regen Med, 2009. 4(4): p. 601-11.
US Food and Drug Administration. Application of current statutory authority to human somatic cell-therapy and gene-therapy products, in Fed Reg 58:53248-51. 1993.
Burger, S.R., Current regulatory issues in cell and tissue therapy.Cytotherapy, 2003. 5(4): p. 289-98.
Schussler-Lenz, M. and C.K. Schneider, [Clinical trials with advanced therapy medicinal products].Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2010. 53(1): p. 68-74.
Wall, D.M. and H.M. Prince, Regulation of cellular therapies: the Australian perspective.Cytotherapy, 2003. 5(4): p. 284-8.
HealthCanada, GUIDANCE DOCUMENT FOR CELL, TISSUE AND ORGAN ESTABLISHMENTS.Safety of Human Cells, Tissues and Organs for Transplantation, Health Products and Food Branch Guidance Document, Editor. 2009, Minister of Health.
Pollack, A., A Stem-Cell-Based Drug Gets Approval in Canada, in The New York Times. 2012: New York.
HealthCanada, Notice of Decision for Prochymal, in Control Number 150026, Office of Regulatory Affairs Biologics and Genetic Therapies Directorate, Editor. 2012, http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/nd_ad_2012_prochymal_150026-eng.php.
Rada-Iglesias, A. and J. Wysocka, Epigenomics of human embryonic stem cells and induced pluripotent stem cells: insights into pluripotency and implications for disease.Genome Med, 2011. 3(6): p. 36.
Sumer, H., J. Liu, and P.J. Verma, Cellular reprogramming of somatic cells.Indian J Exp Biol, 2011. 49(6): p. 409-15.
Han, J. and K.S. Sidhu, Current concepts in reprogramming somatic cells to pluripotent state.Curr Stem Cell Res Ther, 2008. 3(1): p. 66-74.
Do, J.T., D.W. Han, and H.R. Scholer, Reprogramming somatic gene activity by fusion with pluripotent cells.Stem Cell Rev, 2006. 2(4): p. 257-64.
Zeng, X. and M.S. Rao, Human embryonic stem cells: long term stability, absence of senescence and a potential cell source for neural replacement.Neuroscience, 2007. 145(4): p. 1348-58.
Atkinson, S. and L. Armstrong, Epigenetics in embryonic stem cells: regulation of pluripotency and differentiation.Cell Tissue Res, 2008. 331(1): p. 23-9.
Tavakoli, T., et al., Self-renewal and differentiation capabilities are variable between human embryonic stem cell lines I3, I6 and BG01V.BMC Cell Biol, 2009. 10: p. 44.
Bhattacharya, B., S. Puri, and R.K. Puri, A review of gene expression profiling of human embryonic stem cell lines and their differentiated progeny.Curr Stem Cell Res Ther, 2009. 4(2): p. 98-106.
Guenther, M.G., et al., Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.Cell Stem Cell, 2010. 7(2): p. 249-57.
Yu, J., et al., Induced pluripotent stem cell lines derived from human somatic cells.Science, 2007. 318(5858): p. 1917-20.
Shafa, M., R. Krawetz, and D.E. Rancourt, Returning to the stem state: epigenetics of recapitulating pre-differentiation chromatin structure.Bioessays, 2010. 32(9): p. 791-9.
Newman, A.M. and J.B. Cooper, Lab-specific gene expression signatures in pluripotent stem cells.Cell Stem Cell, 2010. 7(2): p. 258-62.
Hong, S.H., et al., Cell fate potential of human pluripotent stem cells is encoded by histone modifications.Cell Stem Cell, 2011. 9(1): p. 24-36.
Scott, C.T., et al., Democracy Derived? New Trajectories in Pluripotent Stem Cell Research.Cell, 2011. 145(6): p. 820-6.
Lee, H., et al., Induced pluripotent stem cells in regenerative medicine: an argument for continued research on human embryonic stem cells.Regen Med, 2009. 4(5): p. 759-69.
Zavazava, N., Immunity of embryonic stem cell-derived hematopoietic progenitor cells.Semin Immunopathol, 2011.
Broxmeyer, H.E., Will iPS cells enhance therapeutic applicability of cord blood cells and banking?Cell Stem Cell, 2010. 6(1): p. 21-4.
Taylor, C.J., E.M. Bolton, and J.A. Bradley, Immunological considerations for embryonic and induced pluripotent stem cell banking.Philos Trans R Soc Lond B Biol Sci, 2011. 366(1575): p. 2312-22.
Kim, J.B., et al., Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors.Nature, 2008. 454(7204): p. 646-50.
Takahashi, K., et al., Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell, 2007. 131(5): p. 861-72.
Mohamadnejad, M. and E.S. Swenson, Induced pluripotent cells mimicking human embryonic stem cells.Arch Iran Med, 2008. 11(1): p. 125-8.
Ang, Y.S., et al., Stem cells and reprogramming: breaking the epigenetic barrier?Trends Pharmacol Sci, 2011. 32(7): p. 394-401.
Havlas, V., et al., [Comparison of chondrogenic differentiation of adipose tissue-derived mesenchymal stem cells with cultured chondrocytes and bone marrow mesenchymal stem cells].Acta Chir Orthop Traumatol Cech, 2011. 78(2): p. 138-44.
Winter, A., et al., Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells.Arthritis Rheum, 2003. 48(2): p. 418-29.
Shafiee, A., et al., A comparison between osteogenic differentiation of human unrestricted somatic stem cells and mesenchymal stem cells from bone marrow and adipose tissue.Biotechnol Lett, 2011. 33(6): p. 1257-64.
Riekstina, U., et al., Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis.Stem Cell Rev, 2009. 5(4): p. 378-86.
Pournasr, B., et al., In Vitro Differentiation of Human Bone Marrow Mesenchymal Stem Cells into Hepatocyte-like Cells.Arch Iran Med, 2011. 14(4): p. 244-9.
Witkowska-Zimny, M. and K. Walenko, Stem cells from adipose tissue.Cell Mol Biol Lett, 2011. 16(2): p. 236-57.
Mizuno, H., Adipose-derived stem and stromal cells for cell-based therapy: current status of preclinical studies and clinical trials.Curr Opin Mol Ther, 2010. 12(4): p. 442-9.
De Toni, F., et al., Human Adipose-Derived Stromal Cells Efficiently Support Hematopoiesis In Vitro and In Vivo: A Key Step for Therapeutic Studies.Stem Cells Dev, 2011.
Zhu, M., et al., [Cell biological study of adipose-derived stem cells].Nan Fang Yi Ke Da Xue Xue Bao, 2007. 27(4): p. 518-23.
Li, H., et al., Adipogenic Potential of Adipose Stem Cell Subpopulations.Plast Reconstr Surg, 2011.
Szoke, K., K.J. Beckstrom, and J.E. Brinchmann, Human adipose tissue as a source of cells with angiogenic potential.Cell Transplant, 2011.
Lin, C.S., et al., Defining adipose tissue-derived stem cells in tissue and in culture.Histol Histopathol, 2010. 25(6): p. 807-15.
Murohara, T., Autologous adipose tissue as a new source of progenitor cells for therapeutic angiogenesis.J Cardiol, 2009. 53(2): p. 155-63.
He, X., et al., [Morphological characteristics of human adipose-derived stem cells].Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2011. 28(2): p. 337-41.
Bobbert, M., Ethical questions concerning research on human embryos, embryonic stem cells and chimeras.Biotechnol J, 2006. 1(12): p. 1352-69.
Hug, K., Sources of human embryos for stem cell research: ethical problems and their possible solutions.Medicina (Kaunas), 2005. 41(12): p. 1002-10.
Hug, K. and G. Hermeren, Do we Still Need Human Embryonic Stem Cells for Stem Cell-Based Therapies? Epistemic and Ethical Aspects.Stem Cell Rev, 2011.
Knoepfler, P.S., Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine.Stem Cells, 2009. 27(5): p. 1050-6.
Zacharias, D.G., et al., The science and ethics of induced pluripotency: what will become of embryonic stem cells?Mayo Clin Proc, 2011. 86(7): p. 634-40.
Volarevic, V., et al., Human stem cell research and regenerative medicine--present and future.Br Med Bull, 2011.
Lowry, W.E. and W.L. Quan, Roadblocks en route to the clinical application of induced pluripotent stem cells.J Cell Sci, 2010. 123(Pt 5): p. 643-51.
Walia, B., et al., Induced Pluripotent Stem Cells: Fundamentals and Applications of the Reprogramming Process and its Ramifications on Regenerative Medicine.Stem Cell Rev, 2011.
Kiefer, J.C., Primer and interviews: Promises and realities of induced pluripotent stem cells.Dev Dyn, 2011. 240(8): p. 2034-41.
Zhou, H. and S. Ding, Evolution of induced pluripotent stem cell technology.Curr Opin Hematol, 2010. 17(4): p. 276-80.
Amabile, G. and A. Meissner, Induced pluripotent stem cells: current progress and potential for regenerative medicine.Trends Mol Med, 2009. 15(2): p. 59-68.
Deng, W., Exploiting pluripotency for therapeutic gain.Panminerva Med, 2010. 52(2): p. 167-73.
Baker, D.E., et al., Adaptation to culture of human embryonic stem cells and oncogenesis in vivo.Nat Biotechnol, 2007. 25(2): p. 207-15.
Blum, B. and N. Benvenisty, The tumorigenicity of human embryonic stem cells.Adv Cancer Res, 2008. 100: p. 133-58.
Enver, T., et al., Cellular differentiation hierarchies in normal and culture-adapted human embryonic stem cells.Hum Mol Genet, 2005. 14(21): p. 3129-40.
Yang, S., et al., Tumor progression of culture-adapted human embryonic stem cells during long-term culture.Genes Chromosomes Cancer, 2008. 47(8): p. 665-79.
Yuasa, S., et al., Development and migration of Purkinje cells in the mouse cerebellar primordium.Anat Embryol (Berl), 1991. 184(3): p. 195-212.
Aoi, T., et al., Generation of pluripotent stem cells from adult mouse liver and stomach cells.Science, 2008. 321(5889): p. 699-702.
Ghosh, Z., et al., Dissecting the oncogenic and tumorigenic potential of differentiated human induced pluripotent stem cells and human embryonic stem cells.Cancer Res, 2011. 71(14): p. 5030-9.
Gutierrez-Aranda, I., et al., Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection.Stem Cells, 2010. 28(9): p. 1568-70.
Zhao, B.C., et al., Adipose-derived stem cells promote gastric cancer cell growth, migration and invasion through SDF-1/CXCR4 axis.Hepatogastroenterology, 2010. 57(104): p. 1382-9.
Jeon, B.G., et al., Characterization and comparison of telomere length, telomerase and reverse transcriptase activity and gene expression in human mesenchymal stem cells and cancer cells of various origins.Cell Tissue Res, 2011. 345(1): p. 149-61.
Zhang, Y., C.F. Bellows, and M.G. Kolonin, Adipose tissue-derived progenitor cells and cancer.World J Stem Cells, 2010. 2(5): p. 103-13.
Zhang, Y., et al., White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models.Cancer Res, 2009. 69(12): p. 5259-66.
Catalina, P., et al., Human ESCs predisposition to karyotypic instability: Is a matter of culture adaptation or differential vulnerability among hESC lines due to inherent properties?Mol Cancer, 2008. 7: p. 76.
Fu, X. and Y. Xu, Self-renewal and scalability of human embryonic stem cells for human therapy.Regen Med, 2011. 6(3): p. 327-34.
Oh, S.K. and A.B. Choo, Human embryonic stem cells: technological challenges towards therapy.Clin Exp Pharmacol Physiol, 2006. 33(5-6): p. 489-95.
Vallier, L., Serum-free and feeder-free culture conditions for human embryonic stem cells.Methods Mol Biol, 2011. 690: p. 57-66.
Cavallo, C., et al., Comparison of alternative mesenchymal stem cell sources for cell banking and musculoskeletal advanced therapies.J Cell Biochem, 2011. 112(5): p. 1418-30.
Kuroda, Y., et al., Bone Marrow Mesenchymal Cells: How Do They Contribute to Tissue Repair and Are They Really Stem Cells?Arch Immunol Ther Exp (Warsz), 2011.
Undale, A., et al., Induction of fracture repair by mesenchymal cells derived from human embryonic stem cells or bone marrow.J Orthop Res, 2011.
Locke, M., V. Feisst, and P.R. Dunbar, Concise review: human adipose-derived stem cells: separating promise from clinical need.Stem Cells, 2011. 29(3): p. 404-11.
Liu, W., et al., Genetic and epigenetic X-chromosome variations in a parthenogenetic human embryonic stem cell line.J Assist Reprod Genet, 2011. 28(4): p. 303-13.
Noisa, P. and R. Parnpai, Technical challenges in the derivation of human pluripotent cells.Stem Cells Int, 2011. 2011: p. 907961.
Anastasia, L., et al., Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine.Cell Death Differ, 2010. 17(8): p. 1230-7.
Takahashi, K. and S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell, 2006. 126(4): p. 663-76.
Kamata, M., et al., Live cell monitoring of hiPSC generation and differentiation using differential expression of endogenous microRNAs.PLoS One, 2010. 5(7): p. e11834.
Gunaratne, P.H., Embryonic stem cell microRNAs: defining factors in induced pluripotent (iPS) and cancer (CSC) stem cells?Curr Stem Cell Res Ther, 2009. 4(3): p. 168-77.
Hockemeyer, D., et al., Genetic engineering of human pluripotent cells using TALE nucleases.Nat Biotechnol, 2011.
Hoogduijn, M.J., et al., Immunological aspects of allogeneic and autologous mesenchymal stem cell therapies.Hum Gene Ther, 2011.
Drukker, M., Immunological considerations for cell therapy using human embryonic stem cell derivatives.2008.
Drukker, M., Recent advancements towards the derivation of immune-compatible patient-specific human embryonic stem cell lines.Semin Immunol, 2008. 20(2): p. 123-9.
Zhao, T., et al., Immunogenicity of induced pluripotent stem cells.Nature, 2011. 474(7350): p. 212-5.

domain: health


People are interested in the world of the fauna and by whom and how it is presented. For example, what are his biggest and smallest representatives, who lives longer and who eats the most? There is hardly a person who would not be curious to know which is the biggest frog in the world, where it lives and what are the characteristics of its vital activity. Such a creature is actually present in nature, and it is called the frog goliath (Conraua goliath).
The largest frog in the world, like many other exotic animals, hails from Africa. Rather, it lives in its western part, in the tropics of Cameroon and in Equatorial Guinea.
Goliath lives exclusively on the banks and under the canopy of river waterfalls. The largest frog in the world is an amphibian creature that needs to maintain a certain temperature of its body at all times (the temperature of the air in its environment should not be below 22 degrees). Therefore, it is vital for her to always be surrounded by moisture. Goliath avoids open, sunlit places.
When the largest goliath frog is not in the water, it sits on the rocks, merging with their gray color. In this way she gets protection from her enemies. To cling to the slippery rocks from the water, it seems difficult, but the goliath frog is sitting quite confidently on them. Special pads-suckers located on her front fingers help her in this. Participate in this process and hind legs, equipped with special membranes.
Despite its impressive size, the goliath immediately jumps into the water at the slightest sign of danger. He is able to control the territory within 40 meters, and it is rather difficult to get close to an adult goliath. After jumping into the water, the frog stays there for up to 15 minutes, then again goes to the land. In this case, the nose and eyes are first shown above the water, and then the surface of the body.
The largest frog in the world eats scorpions, insects, worms, small rodents and birds. On the hunt, she goes out at night, briskly jumping out of the water for the vending prey. It should be noted that the frog's jump can reach 3 meters in length.
Such a "record" is a very large energy consumption frog. Therefore, after the hunt, it takes a lot of time to rest in order to replenish the wasted forces.
Females of the largest frog on the planet spawn in the offseason, when nature "rests" from the incessantly flowing water streams from the sky. For this, it needs 6 days, during which one individual can “give” up to 10 thousand eggs, each of which reaches the size of a decent pea.
A tadpole is hatching from an egg with a length of 8 mm on average. For 70 days, it should “turn” into a normal frog, having lost its tail and gills. And during this time, the tadpole can eat only plants. Interestingly, in the 45 days of his life, he grows to 48 mm, that is, weight gain and height increase occur, one might say, rapidly.
As for the parameters of an adult individual of a frog, its length can be 30 cm, and its weight - more than 3 kg.
Threats to the Giant Frog
The main threat to the life of the frog comes both directly from the person himself, and from the consequences of his "economic" in its habitats.
The goliath frog has long been the object of persecution by gourmets, collectors and other exotic lovers. In this case, some of it is caught with the aim of putting it in restaurants or in order to cook it yourself. Others hunt for a strange trophy or for an instance for their terrariums. It should be noted that all attempts to breed goliaths in captivity ended in failure.
These giant frogs also suffer from commercial deforestation of tropical forests, which are its habitat. Thus, due to the destruction of trees, the area of residence of frogs is reduced by several thousand hectares annually. In addition, the danger is for her life and unclean water resources, in which poachers throw chemicals to catch fish.
If you do not count the local tribes, whose representatives can hunt frogs to sell it to a restaurant, then tourists who are eager to try frog meat are a great danger. Another meat of these representatives is considered very useful for pregnant women.
The biggest frog (photo)
On the images it is clear that the goliath bears its name for good reason - this frog really impresses with its size. The tribes that live near its habitat, affectionately call these frogs "little boys". Because the adult goliath reaches the size of a normal infant.
It is interesting, but unlike their relatives, for whom a bog is a natural habitat, goliaths like “pass” reservations. They settle exclusively where the water is crystal clear, and this is one of the reasons so many people hunt them.
Now you know which frog is the largest in the world, as well as the peculiarities of its vital activity and everything that threatens its existence.
Appearance of giant frogs
The length of only one body of the Goliath frog, without taking into account the large long legs, is about 32 centimeters, and the body weight can reach up to 3.25 kilograms.
In appearance, these giants in general resemble ordinary frogs. Sexual dimorphism in goliath frogs is expressed in body length: females are larger than males. The skin color is greenish brown, and the inside of the paws and abdomen is whitish or yellowish. The back is covered with wrinkled skin.
Lifestyles of goliath frogs
Since goliath frogs do not tolerate dirty water, they live in fast-flowing tropical rivers and waterfalls. In addition, they are demanding on the temperature of the water. In the rivers and streams where these huge frogs live, water never drops below 22 degrees. In addition, goliaths need high humidity, so they do not come across in well-lit places.
This species of frogs lives in oxygen-enriched water.
Adults are very shy and cautious. Catching such a frog is difficult, because the goliaths have excellent vision, they notice movement over a distance of more than 40 meters. Most of the time, they prefer to hide in the rocks near the waterfalls. If there is any danger, the goliath frog instantly jumps into the frothy water, hiding from the enemy. In the water, it can be about 15 minutes, hiding among the stones at the bottom.
When the danger has passed, the frog slowly emerges, showing the tip of the muzzle above the water, and then bulging eyes, and only then the rest of the body rises. Then the frog leisurely swims to the shore, making short pushes. She jumps, climbing the rapids and ledges of stones. At the same time, the frog always chooses such a position, so that it would be convenient for it to make a jump if necessary, if danger suddenly appears.
The diet of giant frogs
They feed on goliath frogs with various insects, larvae, crustaceans, spiders, worms and other living creatures. Often their victims are smaller frogs. Goliath grabs the victim, making a sharp movement of the head or jump. Like their brethren, the goliaths grab the victim with the jaws and tongue, then press down and swallow it whole.
In addition, goliath frogs are caught from nature and taken abroad.
Population of goliath frogs
Today, goliath frogs within the range are considered an endangered species. From the 80s to the 2000s, the number of these huge frogs decreased by almost 2 times. The main threat to the population is the capture of these frogs by the local population, in order to eat their meat.
Giants-goliath - the largest of the modern frogs.
These giants have long been for people the object of persecution: they are hunted by lovers of the exotic, gourmets and numerous collectors. Being a big frog is quite difficult, the weight and growth of goliaths have become a significant problem for them, since they are slow and cumbersome. Having made only a few jumps, the frog gets tired, so it is easy to catch. These huge frogs have long been the object of attention of zoos and private collectors. A huge number of individuals were captured from nature and taken to the USA, where jump competitions were held between the goliaths.
And of course, a huge damage to the population is caused by the destruction of their habitat habitat, with the goal of farming and deforestation of tropical forests. The habitat of goliath frogs is annually reduced by several thousand hectares due to the destruction of trees. About half of the natural habitats of goliaths are in serious danger. In addition, environmental pollution is a negative factor: poachers pollute water with chemicals for fishing.
For goliaths that can live and lay eggs only in the purest water, this is an environmental disaster.
These frogs are considered to be pure animals, their meat is sweet to the taste, moreover, it is considered useful for pregnant women.
Goliath frogs are in huge quantities supplied to local food markets and restaurants. For a large individual restaurants pay a pretty good price.
It is worth noting that attempts at breeding goliath frogs in artificial conditions end
failures, which is why these defenseless giants need to be cared for by humans.
WWF is trying to preserve the habitat of goliath frogs, which simply melts before our eyes. Recently, 3 zakaznikazhes were created, it is also planned to establish control over the basins of several rivers. If these measures are implemented, it will save unique huge frogs and change the situation of the population in the direction of increasing.
Frog Beelzebub / Beelzebufo ampinga
Let's start with the fossil species, the remains of which were discovered in Madagascar in the Late Cretaceous period, about 60-70 million years ago.
The fragments of the skeleton was able to recreate the appearance of the form, as well as establish the size. At length, this fossil giant reached 41 cm, and weighed about 4.5 kg.
It is believed that she was quite aggressive, attacking from ambush at small animals. Given the size of the frog, it can be assumed that in addition to lizards and small mammals, there were newborn dinosaurs in its diet.
Frog goliath / Conraua goliath
With a body length of 32 cm, it is the largest frog in the world today. Her hind limbs are so strong that a powerful frog jumps 3 meters in length. Note that the largest amphibian, the Chinese salamander, reaches a length of 2 m.
The weight of a frog with such dimensions is more than 3 kg, and the giant frog lives in Africa. As in many species, the female is much larger than the male, and outwardly the goliath is no different from ordinary frogs, but if you do not take into account the size.
It feeds on insects, small crustaceans, spiders. At the moment of danger, it hides under water, and can be under water for 10 to 15 minutes.
Bullfrog / Lithobates catesbeianus
The family of true frogs Lithobates catesbeianus is one of the largest species, since adults grow to 15-25 cm in length, and this is a rather heavy frog, weighing from 800 to 900 g.
The huge frog is found in South and North America, in Europe and Asia, and in Canada, the USA and China has long been an important commercial value.
There are some species differences, depending on the habitat. So, Asian and Australian species are different from their American counterparts. A rather aggressive amphibian that can eat small alligators.
Brazilian slingshot / Ceratophrys aurita
Because of the unusual color of the body of these inhabitants of the Amazon, the Slingshot is also called changeable, and they grow up to 23 cm in length. They are easily identified by a peculiar process over the sockets.
This species has very powerful jaws, capable of chewing small rodents, birds, as well as other representatives of the amphibian world. Sexual dimorphism is also observed, in which the female differs from the male in large size.
Waiting for the victim, Brazilian slingshots burrow into the ground, leaving only the nose and eyes above the surface. Interestingly, these animals do not jump, but walk on the ground.
Tiger frog / hoplobatrachus tigerinus
In the vast world of amphibians, these inhabitants of the swamps of Southeast Asia are distinguished not only by their large size, but also by their exotic coloring.
Their total length ranges from 15 to 17 cm, and the color varies from gray to olive green with dark spots. A yellow stripe runs along the back, and during the mating season, the males inflate with two blue balls around their neck during croaking.
The local population consumes these animals for food, and in the vast expanses of Asia there are even farms where tiger beauties are bred.
Lake Frog / Pelophylax ridibundus
But this representative of the family is one of the most common on the planet, and is considered the largest frog in Russia.
Adult individuals grow up to 13 cm, and their weight is just over 200 grams. It is easy to recognize by its elongated body and slightly pointed muzzle. Through the whole body passes a bright strip of green. Color easily allows the frog to merge with the surrounding nature.
In colder latitudes, when the onset of cold weather hibernates, and in non-freezing waters, they lead an active lifestyle all year round.
Common Frog / Rana temporaria
Medium in size, growing from 6 to 10 cm, the frog lives throughout Europe and in Asia. By population, it is the most common in Europe, and you can meet them from the islands of Britain to remote corners of Siberia.
Note that in Ireland this is the only species of frogs, others have not taken root. But in the Crimea and on the Mediterranean coast you will not meet them. Perhaps it’s too dry and hot for them.
In nature, it identifies 4-6 subspecies, differing among themselves by insignificant traits, formed depending on the habitat.
Purple Frog / Nasikabatrachus sahyadrensis
Having met such a miracle of nature, not immediately and realize that it is a frog. The squat, rounded body has an unusual purple or purple color, and the limbs, unlike other species, are turned outward.
They grow up to 9 cm, but the average size usually does not exceed 7 cm. Adult males are usually painted in purple-lilac color, trying to merge with the ground.
In 2002, one of the publishers of the Chinese online magazine introduced this frog in the Top 20 of the ugliest creatures living on the planet, so that even a photo of this “beauty” can scare.
Garlic Mitt / Pelobates fuscus
The second name of the species is Fathead-headed Travyanka, and this large frog belongs to a large genus of Gesnochnits, and these frogs live practically throughout Europe and in Anterior Asia.
In length they grow up to 8 cm, and weigh from 6 to 25 g. It differs from its counterparts in that it has a vertical pupil, and a peculiar calcaneal tubercle of spatulate shape.
Easily adapted to any environmental conditions, and can live in both deciduous and coniferous forests, and leads mostly terrestrial lifestyle.
From the world of frogs we turn to the kingdom of toads, which also sometimes strike with their size.
Toad Aga / Rhinella marina
Zoological reference books and Wikipedia report that Aga is the largest toad in the world, and the longest specimen recorded in wildlife was 24 cm.
The mass of such a tropical giant is more than 1 kg, and the skin is all warty, covered with small tubercles. Males, as usual, are slightly smaller than females.
These toads live in Central and Latin America, and are considered the most poisonous of the toad family.
Cane Toads / Bufo marinus
According to the species name, it is clear that this species of toads chose reed forests as the place of their location. The fact is that large temperature drops in such places are ideal for blood circulation and heat exchange of amphibians.
The size of these amphibians varies from 15 to 23 cm, and the largest copy, nicknamed "The Prince", weighed 3 kg, and was 54 cm long. Now it is an exhibit of the museum of natural science, but, in fact, an exception to the rules.
Unlike relatives, they have developed hind limbs, due to which they jump superbly.
Blomberg Toad / Rhaebo blombergi
Another inhabitant of South America was named after the Swedish zoologist Rolf Blomberg, who in 1950 opened the world to this wonderful view of toads.
Along with Aga, it is considered one of the largest. After all, the length of the Blomberg's toad can reach 24 cm. It lives at an altitude of 3,000 to 500 m above sea level along the coast of the Pacific Ocean.
Leads an active lifestyle with the onset of twilight and at night, and during the day trying to hide from prying eyes.
Green and brown toads
These species of toads firmly entrenched in 3rd place, because their length reaches more than 20 cm, and in width about 15 cm.
They settled in Central Europe, in the south of Russia, and prefer quiet ponds, peat bogs, silt streams. The color of these amphibians is amazing. Usually they are grassy in color with characteristic white stripes, but there are also individuals with a lilac color.
The view is, of course, unappealing, since the whole body is covered with warts, but they will not cause any harm to health. On the contrary, in the East they are bred for pest control.
Mongolian Toad / Pseudepidalea raddei
Свое видовое наименование Pseudepidalea raddei это земноводное получило в честь русского ученого Густава Радде.
Довольно крупная жаба, вырастающая до 9 см, обитает на Юге Сибири, Дальнем Востоке и в странах Юго-Восточной Азии. В Бурятии Монгольская жаба занесена в Красную книгу.
Окрас изменчив, в зависимости от среды обитания, а туловище плотное с немного заостренной головой. Верхняя часть туловища вся покрыта небольшими бородавками.
Did you know that in some countries frogs are eaten? And often people eat them still alive. About this and other dishes of the world in which food is eaten live, read the article on our website thebiggest.ru. In addition, you can learn a lot of interesting facts about frogs by clicking on the link.
Among the frog world of frogs, the smallest, but small sizes compensate for their incredible color. But among them there are relatively large specimens.
Leggy Litoria / Litoria infrafrenata
In tropical forests off the coast of water bodies, an unusual amphibian from the family of tree frogs with long legs can be found. This feature was noted by zoologists in the name of the species.
This frog grows up to 13 cm in length, and the color of the body and head is surprisingly bright grassy green. But their belly is light.
He spends most of his life in the trees, and most recently discovered that they can’t sleep a mountainous climate, and they settle at an altitude of 1,400 m above sea level.
Cuban frog / Osteopilus septentrionalis
The largest in the world of frogs, so there were instances, the body length of which was 14 cm, although on average the adults of the Cuban frog grow to 9-12.5 cm.
Appearance is quite elegant, thanks to thin elongated fingers, at the ends of which are located a roundish-shaped sucker. They allow frogs to move easily, and most of their lives are spent in dense reed beds of water bodies.
Breed in the rainy season. The female lays from 100 to 1 thousand eggs, and the larva of the tadpole is born in a few hours.
Marsupial frogs / Gastrotheca
A fairly common type of tailless amphibians, whose body length ranges from 3 to 10 cm. The head is moderately large, and in some species pointed or rounded.
Especially love to settle in tropical rainforests, sometimes reaching a height of 4000 meters above sea level. With the help of suction cups on the lamps they freely climb trees.
The diet of marsupial tree frogs mainly consists of insects. Some species hunt flying insects, high-jumping, but in most cases they are content with those insects that are found on the leaves of trees.
So we looked at the largest representatives of the frog world, and found out how much the largest toad weighs, and which frog is considered the largest among its small relatives. Such diversity proves once again that nature is a creator with a rich imagination, creating though not quite attractive, but amazing creatures.
1. Suriname pipa
This frog with a funny name surprises not only with its appearance, but also with its breeding feature. She lives in South America, mainly in the forests of Amazonia. The view is rather large - adult pips can be 20 cm in length. The body of the Suriname pipa is so flat that from a distance it can be completely mistaken for a piece of wood. Her eyes are small. Pipa does not croak like ordinary frogs, but snaps the bones in the throat to bark a partner.
When the male attaches to the female, she jumps out of the water with him and at each such jump releases eggs, which are miraculously embedded in the pores of the back skin. The pipa's female can be called the most caring frog in the world - for 2.5 months, she literally drags a crowd of over a hundred babies on her hump until they hatch through her skin.
2. Glass Frog
The next unusual jump was a glass frog. At first glance, it does not see anything remarkable - the usual brown-green frog. But if you take a closer look at her, you will notice that her body is translucent, especially the skin. Therefore, through her on the belly of the frog, her insides are visible. Sunlight, reflected from the surrounding appearance, passes through the body of the frog, making it less visible to enemies. This is one of the ingenious ways of nature to mask its creatures. But he did not help the glass frog turn into an endangered species. These gentle creatures live in Central and South America, laying eggs on woody leaves near reservoirs, since tadpoles after hatching, they develop their development, as usual, in water.
3. Turtle Frog
In third place was an amazing frog turtle, looking like some kind of mutant with a round body or an alien. She lives in Western Australia. With her powerful, strong legs, she ruins the termites and quickly digs into the sand, where she lays eggs. This species of frogs has a peculiarity in terms of reproduction - there is no tadpole stage here, a “ready” frog is already formed in the egg.
4. Mossy Frog
The next original representative of wahs lives in the tropical jungles of North Vietnam. Mossy frogs look very beautiful, so there are many fans who breed them in their home terrariums. Such a "princess frog" and is, respectively, - up to $ 75.
In their natural habitat, these beauties use the skill of their makeup, not to attract admirers, but for the same disguise. Having noticed some movement from a distance, you might think that a piece of moss came to life. Thanks to the large round suction pads located on the fingers, mossy frogs scramble across rocks or trees and it is no coincidence that they stick their eggs to the trunks and branches of trees and cave walls so that the hatched tadpoles flop directly into the water.
5. Goliath Frog
The name says everything about this species - there is no more frog in the world. In length, it can reach 33 cm, and in weight - 3.25 kg, this is an incomparable heavyweight in the world of frogs, which is twice the size of its closest competitor from the same Africa - also a rather big bull frog. Goliaths live in Cameroon and Equatorial Guinea. If many types of frogs are not too fastidious in matters of water purity, then just not goliath - give him the purest! As a rule, they like to sit near waterfalls, on ledges of rocks, like monuments. But it is worth the goliath to sense the danger, as he headlong rushes into the water jets. Powerful muscular hind legs allow the goliath to make giant leaps up to 3 meters.
Its food is small relatives, snakes, worms, crustaceans. Unfortunately, the close attention of a person to such a big goliath frog put her on the verge of extinction.
6. Tiger Frog
The color of male tiger frogs in the mating season is very remarkable - the skin is bright yellow with two bright blue resonators. They have two rows of inclined powerful teeth. They live in India, Pakistan, Bangladesh, Myanmar, Nepal, Sri Lanka and Afghanistan. They were brought to Madagascar and the Maldives, where they became an invasive species. Prefer wetland freshwater places, usually avoid forest and coastal zones. Mostly they lead a nocturnal lonely lifestyle, preferring to settle in the bushes near water sources. However, they do not spend much time in the water, preferring to hide in the vegetation along the banks of the reservoir.
7. Brazilian slingshot
In the endless tropical forests of the Amazonia there lives an unusual amphibian - the Brazilian slingshot. This horned toad is an outstanding master of reincarnation. The color of her body allows her to dissolve in the environment, which makes her a lucky hunter. She buries herself in the foliage, exposing only her head, and patiently waits for the victim, blithely approaching her. Adults of the Brazilian slingshot can be as long as 20 cm.
This aggressive frog even rushes at people, so the locals walk in rubber boots to protect themselves from its not weak bites. But even such a reputation does not stop some lovers of exotic living creatures from starting Brazilian slingshots as pets.
8. Hairy Frog
The hairy frog was called for thin and closely spaced skin patches 1–1.5 cm long, located on the hind legs and sides of the frog’s body, somewhat resembling wool. They occur only in males and only in the mating period. Why does the frog need such a "wool" is not yet known to scientists. They have one more amazing feature - to protect against predators, they break bones on the toes of their legs, which pierce their skin and turn into a kind of sharp claws. The habitat of the hairy frog is in the west of Central Africa.
9. Purple (purple) frog
This is one of the ugliest creatures on earth. And scientists discovered this frog quite recently - in 2003 in the Western Ghats (mountains in India). It belongs to the category of living minerals. The purple frog has a miserable habitat - only 14 square meters. km They lead a very reclusive life - they spend most of their time underground, and therefore they look like more moles. On the surface, they appear only a couple of weeks a year during the mating period, which falls on the monsoon period. Purple ants and termites feed on purple frogs, looking for them under the ground.
10. Egg Farming Toad
These frog relatives have a very unusual breeding method for amphibians. They do not lay eggs, like most frogs, eggs ripen right in the mother's body, and after some time, fully formed tiny toads appear on the light. There are large glands in the ovoviviparous frogs on the body, near the eyes and paws, which have a bright color that contrasts strongly with the color of the rest of the body. Thanks to this, the toads look very elegant.


Hello Nova Stars! Who better to be our Woman Crush Wednesday than someone with royal taste in clothes ;) That’s right, the one and only Princess Kate Middleton. 22 more words
Tags » WCW
This week on STRAIGHT SHOOT RETRO, we’re heading back down south for the first-ever WCW pay-per-view, Starrcade 1988, and we’re talking about it this Wednesday, August 6, 2014… 503 more words
In honor of #WomenCrushWednesday, we’re featuring the beautiful and talented actress, Scarlett Johansson!
This awesome woman has done a lot of great movies (Lost in Translation, Vicky Cristina Barcelona, anyone?), but recently she’s made her rise into a total badass action star. 103 more words
Last night at the dinner table, I was reading the new issue of Texas Monthly magazine. The story was about “Our Favorite Places” in Texas with answers from famous Texans such as Willie Nelson, Erykah Badu and our former neighbor, Rick Linklater. 64 more words


text:
On September 28, Baccomatto Osteria will serve its final bowl of house-made pasta in the space it’s called home since 2013. The diner, which is part of the Cambridge Hotel complex on Riley Street in Surry Hills, has been on a month-to-month lease for several years because the hotel has been submitting development applications to build towers on the site.
“We didn’t think it would go through,” co-owner Mauro Marcucci tells Broadsheet. “They needed to give us a month’s notice but have given us a bit longer than that.”
Marcucci says the restaurant has developed a loyal local following over the last six-and-a-half years for its menu of pastas, antipasti, cheese and house-made salumi. He wants to keep the patronage and is already in negotiations with a couple of different venues nearby and further afield.
He says the intention is to keep the restaurant format as-is, with a couple of tweaks likely, depending on the new space.
Baccomatto Osteria is slated to close on September 28.

domain: food