Faster than a sluggish bureaucracy. More powerful than enemy radar. Able to scale tall buildings with a single engine. Up on the screen in the forthcoming Superman reboot, it's – it's – it's the debut of the F-35 Joint Strike Fighter, the most expensive weapons program in human history.
Long before the family of stealth jets known as the F-35 Joint Strike Fighter will ever fly a combat mission, the F-35 will appear in theaters for the first time next summer in Man of Steel, Zach Snyder's anticipated re-imagining of the Superman franchise. It's perhaps the best cinematic debut possible for an aircraft program that's suffered numerous budgetary and engineering woes.
"It was a target of opportunity," Phil Strub, the Pentagon's Hollywood liaison, tells Danger Room. When the filmmakers visited California's Edwards Air Force Base in January to get shots of military aircraft for a scene, they were excited to learn that the base hosted a complement of F-35s for flight testing. The base arranged for two of them to be towed into the shot.
"They liked the idea of having the most modern, the newest fighter aircraft in the background," says Strub, who was on location with Man of Steel at Edwards. The F-35 had been digitally rendered in movies previously, including a scene in The Avengers when the Hulk tears it apart, but this was its first screen test for the actual plane. And it took only a few hours to film.
Offscreen, the F-35 is in about as much trouble as a superhero in the third act of an action movie. The advanced stealth fighter – intended to be the backbone of the Air Force, Navy and Marines' future combat air fleets – is estimated to cost as much as $1.5 trillion over its half-century lifespan. It's several years late and several hundred million dollars over budget. Its software is complicated, its engineering flaws are numerous, and the Pentagon no longer predicts when it will enter service. The Navy appears to be hedging its bets against the program ultimately collapsing under the weight of its costs – and inside the Pentagon, there's concern over whether the F-35 remains, as Sen. Claire McCaskill once called it, "too big to fail."


text:
No significant difference was observed between amlodipine (the red line) and chlorthalidone (the blue line) for the primary outcome. The relative risk for amlodipine compared to chlorthalidone was 0.98, with a 95% confidence interval of 0.90-1.07. Also, no significant difference was observed between lisinopril (the green line) and chlorthalidone for the primary outcome. The relative risk was 0.99, with a 95% confidence interval of 0.91-1.08.
The three core messages for the ALLHAT antihypertensive trial are: Diuretics should be the drug of choice for first step therapy of hypertension For the patient who cannot take a diuretic (which should be an unusual circumstance), CCB’s and ACEI’s may be considered. Most hypertensive patients require more than one drug. Diuretics should generally be part of the antihypertensive regimen. Lifestyle advice should also be provided.
Combination therapy reduced blood pressure by 12/5 mm Hg and reduced stroke risk by 43% - the benefit was similar in hypertensive patients as well as normotensives. By contrast, single-drug therapy reduced blood pressure by 5/3 mm Hg with no statistically significant reduction in stroke risk, although the confidence interval is wide a risk reduction of up to 23% for stroke cannot be ruled out. It is important to remember that patients were randomized between active agent and placebo - active agent could have been single or combination therapy as determined by the patients physician. Therefore, the study was powered to detect reductions in stroke risk in the active treatment group. There was not a sufficient patient base receiving single agent to detect a statistically significant risk reduction in stroke.
C:\Cema\HipertensióN Arterial Curso 2008 2
Hipertensión Arterial 2008
Enfermedad cardiovascular

HTA es el principal factor que contribuye al riesgo de enfermedad cardiovascular.

El segundo contribuyente al mayor riesgo es que la población llega a mayor edad y tiene mayor obesidad

White-Coat Effect with Age Mansoor et al. J Hum Hypertens 1996;10:87
Enfermedad Cardiovascular

Tercer factor que contribuye es el inadecuado control de la Hipertensión:

EEUU : 29 %

Canadá : 17 %

Europa : < 10 % (Inglaterra, Alemania Italia ,España y suecia )

Definición operacional Hipertensión Arterial

Hipertension es ... “el nivel de Presion sanguinea en donde los beneficios de la accion (i.e. intervencion terapeutica) exceden a los de la inaction.”

Evans and Rose Brit Med Bull 1971;27:37-42

Treatment Strategies and Risk Stratification JNC 6
Classification and Management of BP for adults *Treatment determined by highest BP category. † Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡ Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. JNC 7 slideset Two-drug combination for most † (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). Yes or > 100 > 160 Stage 2 Hypertension Drug(s) for the compelling indications. ‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Yes or 90–99 140–159 Stage 1 Hypertension Drug(s) for compelling indications. ‡ No antihypertensive drug indicated. Yes or 80–89 120–139 Prehypertension Encourage and <80 <120 Normal With compelling indications Without compelling indication Initial drug therapy Lifestyle modification DBP* mmHg SBP* mmHg BP classification
Sudden Deaths by Time of Day Peckova et al. Circulation 1998;98:31
Low Dose Diuretics vs. Others From Psaty BM et al. JAMA 2003;289:2534
The Reasons Why Low-Dose Diuretics Should be Initial Therapy 1. They reduce cardiovascular morbidity and mortality. 2. They lower blood pressure, particularly in patients consuming excessive sodium. 3. They enhance the antihypertensive efficacy of all other antihypertensive drugs. 4. They rarely cause side effects. 5. They reduce calcium loss and osteoporosis. 6. They are relatively inexpensive.
Results of Different Levels of Blood Pressure Control in Hypertensive Patients with Type 2 Diabetes : B-Blocker compared with ACE Inhibitor-Based Treatment Program

8.4-year follow-up of 1148 subjects (achieved blood pressure of 144/82 mm Hg compared with 154/87 mm Hg)

Reduced risk of:

Stroke (44%)

Fatal strokes (58%)

Death related to diabetes (32%)

Heart failure (56%)

Fatal and nonfatal coronary heart disease events (21%) (trend but not significant)

No difference in outcome between a captopril-based and

an atenolol based treatment program

UKPDS . BMJ 1998;317:703-713
CV Events in Swedish Trial in Old Persons (Stop-2) Conventional Rx (diuretics and B-blockers) compared to ACE-Is and CCBs No difference in BP outcomes No overall difference in EVENTS Lancet 1999;354:751
Results of An ARB-Based (Losartan Compared to a B-Blocker Based (Atenolol) Treatment Program in Hypertensive Patients with LVH (LIFE Study)

 Losartan Atenolol Goal BPs

Achieved BP (mm Hg) 144/82 145/82 45-50% SBP <140

 89% DBP <90

% Difference Losartan vs Atenolol

Primary endpoint P Value

(CV death, MI, Stroke) -13* .02

Stroke -25* .001

MI +07 NS

CV mortality -11 NS

Total mortality -10 NS

New onset diabetes -25* .001

Lancet 2002;359:1004 *Statistically significant

Percentage of Type 2 Diabetic Patients with End-Stage Renal Disease in the RENAAL Study

Losartan – therapy with ARB plus other medications; placebo – therapy with medications other than an ARB or ACE inhibitor. (Risk reduction, 28%; P = 0.002)

Brenner BM, et al. N Engl J Med 2001;345:865

Months of Study End-Stage Renal Disease (%) 0 12 24 36 48 30 20 10 0 Placebo Losartan
Heart Outcomes Preventions Evaluation (HOPE) Study Events ACE-1 (Ramipril)* Regimen that did not include an ACE-1 No. Randomized 4645 4652 % Reduction in Risk - Ramipril:Other therapy MI, Stroke, CVD 22 CV death 25 MI 20 Stroke 31 Non-CV death +3 (NS) All cause mortality 16 *10 mg/day - 62.5% remained on Rx at 4.5 years New Engl J Med 11/10/99
Relative Risk of Cardiovascular Mortality and Morbidity for ACEIs vs Calcium Antagonists ( STOP-2 Study )

* Significant difference.

Hansson L et al. Lancet. 1999;354:1751-1756

En pacientes de alto riesgo (HOPE, IRMA, IDNT, RENAAL, and LIFE), el uso de un IECA (o un ARA) usualmente con un diuretico) reducen eventos CV mas que un regimen que no incluye estas medicaciones.
2003 The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT),
Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril Years to CHD Event 0 1 2 3 4 5 6 7 Cumulative CHD Event Rate 0 .04 .08 .12 .16 .2 0.81 0.99 (0.91-1.08) L / C 0.65 0.98 (0.90-1.07) A / C p value RR (95% CI)
Implications of ALLHAT

Diuretics should be the drug of choice for first

step therapy of hypertension in most patients*

Most hypertensive patients require more than one drug. Diuretics should generally be part of the antihypertensive regimen.

*[BP levels were lower in diuretic treated patients ]

Possible Advantages of Low-Dose Combination Therapy Compared to High-Dose Monotherapy

Blood pressure response is greater

Percentage of responders is higher

Side effects may be less

Titration to effective dose is simplified- Goal BP achieved sooner

Adherence is improved

Stroke

Combination 43%

Single Drug 5% (-19 to 23)

Total Stroke 28%

Combination versus Monotherapy Favors active Favors placebo Risk Reduction ( 95%CI ) 0.4 1.0 2.0 Hazard Ratio PROGESS Study
Combination Therapy

In the LIFE trial treatment to goal was aggressively pursued

90% of patients required multiple medications

Benefits of Lowering BP by Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure 50% -12 -4-5 About mmHg

domain: literature


text:
Writer/director Darren Aronofsky follows up his critically-acclaimed feature debut "Pi", with REQUIEM FOR A DREAM, adapted from the 1978 novel by celebrated author Hubert Selby, Jr. (Last Exit to Brooklyn). Set in the rusted mean streets of Coney Island, Brooklyn, the film is a harrowing journey into the psyches of four human beings addicted to their visions of a happier life. The delusions fostered by drug use cause them to deny reality until they are eye to eye with their worst nightmares. The film stars Academy Award-winner Ellen Burstyn, Jared Leto, Marlon Wayans and Jennifer Connally, and is released by Artisan Entertainment (Blair Witch Project, Buena Vista Social Club). The music for REQUIEM is by Clint Mansell - originally the front man for the pioneering English band Pop Will Eat Itself - who composed the noted original score for Pi. Mainly electronic, it includes string quartet performances by the Kronos Quartet.
Mansell previously worked with director Darren Aronofsky on Pi
where the electronica was powerfully raw. Enlisting the Kronos Quartet, this is proof of a far more intellectual process to create a through-scored piece. Both on screen and album, the music undergoes a perceivable development. Here it is given three sections ("Summer", "Fall" and "Winter"), and therefore attempts an almost symphonic form. "Summer Overture" introduces a repeatedly impressive central motif. The quartet excels in its sawing performance of it, and by the time of the first of two congas closing this initial seasonal section, you'll be prepared for the unexpected explosions of dissonance to follow. The final third ("Winter") puts a new motif through inventive stages of growth. From "Southern Hospitality" to "Meltdown" the sampled strings incessantly build in pitch until the desired unnerving effect has been well and truly achieved. This is music to match the most unshakeably nightmarish of dreams. --Paul Tonks

domain: entertainment


text:
Photography, Fourth Edition A Cultural History, by Marien, Mary Warner
Note: Supplemental materials are not guaranteed with Rental or Used book purchases.
- ISBN: 9781780673325 | 1780673329
- Cover: Paperback
- Copyright: 7/7/2020
The fourth edition of this comprehensive history of photography spans the entire history of the medium, from its early development to current practice, and provides a focused understanding of the cultural contexts in which photographers have lived and worked. Mary Warner Marien discusses photography from a truly global viewpoint and examines a wide-range of images through the lenses of art, science, travel, war, fashion, the mass media, and individual photographers. Professional, amateur,and art photographers are all represented, with "Portrait" boxes devoted to highlighting important individuals and "Focus" boxes charting particular cultural debates. This indispensable book shows how photography has charted, shaped, and sharpened our perception of the world.

domain: library


Maxiscoot is a sort of scooter to which you’ll make use of quite a few abilities for making the complete deal begin from the scooter only to the helmets and different equipment. For starting with the same, you need to perform a little research work by way of the internet. You can sketch out the particular design utilizing relevant colours. Your inventive skills and imagination power is simply required.
Even once we’re away from the home or office, most of us stay linked to our cell telephones or pagers. We stay in a society where communication is made simple, however privateness and real down-time are becoming less and fewer of an choice. Electric : Wheel Base
First Class Automotive
There are every kind of ranges of quality in leather-based jackets and all kinds of protection ranges. There’s the very cheapest leather-based jacket which could look great for an evening out however provides you with no protection on your bike to the best high quality jacket that meet pro racing standards.
This Honda CB Trigger is likely one of the thunderstruck introduction which is powered by the identical engine of the Dazzler, that guarantees to ship thirteen.81 BHP of power at 8500 RPM and 12.6 Nm of torque at 6500 RPM. In addition, the amazing power readily in a position to influence every rider with its astounded efficiency and mileage ratio in the long term without hassle. Therefore, the CB Set off is astringently proven its worth of engine capability and captivates to deliver a mileage of 60 km/l in the long run.
is an excellent place so that you can buy Motorcycle components ( Guangzhou Wangyi Trade Co., Ltd.) Established in 2010, Guangzhou, China. Our business was start from sells Motorcycle elements and Motorbike fairings on Ebay since 2008,we’ve served thousands of motorcycle rider worldwide and get thousands of fine overview.During these years we’ve acquired a number of bike parts promoting exper.Thanks for going to , during which you can see out a massive amount of Motorcycle components and automobile components provided at superb wholesale prices. A fast start wanting near to our web site will reveal our monumental broad vary of first-rate goods, be they aftermarket elements ,Bike fairings, or Bike Equipment.
Automotive Services Department Letter
Verify the bike state before you ship: The moment you hand over your bike, at all times notice down the state of affairs during which you have got given your bike to the transport firm. That is typically finished with a form wherein you might be required to give the exact situations on the time of shipping and get it signed by them.
In actual fact if we glance up on the listing of features this new Mahindra Duro is bringing with it self we are going to find that it is holding a few of the best features in it, as it’s coming with a 1246cc -stroke petrol engine which is able to offering a power of up to 8 Bhp at 7000 RPM and the utmost torque power of as much as 9 NM at 5500 RPM. Spinning bike tires on take off or holding the brake on emergency stops must be checked.
25 years old Amusement Center Manager Jarvis from McBride, has hobbies and interests for example beadwork, . and texting. Has signed up for a world contiki trip. Is very excited specifically about visiting Yin Xu.


This machine is suitable for 1color 6 color 8 color 10 color 12 color plasticine packaging This machine is suitable color plasticine clay automatic packaging, it can be done automatically plasticine molding cutting and packing and automatic print date
Has a high degree of automation, packaging, speed and stability characteristics. servo system controls small footprint, simple operation, easy to use.
This machine is through extrusion, forming, cutting, and then automatic packaging, printing date, the whole process of automation,with the characteristics of fast packaging, beautiful packaging products, saving labor costs. It is the first one in China to adopt a servo extrusion and cutting device with a weight of about plus or minus 3% G, with high measurement accuracy, simple cutting, open box structure, convenient and quick cleaning suitable for the molding and cutting packaging of light clay and ultra-light clay, and the first one to adopt a new servo cutting system, with fast packaging speed, accurate tracking, and difficulty to solve the waste of packaging materials in domestic mud packaging The machines are easy to operate and easy to use(it can also be customized for all kinds of single-color or multi-color molding and packaging students)Production line).
1). 3 Servo Motor control, flexible bag length cutting. Save time and film.
2). 7 inch touch screen, easy operation and multiple language for choice.
3). Smart PLC system, machine performance is stable, convenient for change parameter
4). Self diagnosis failure function, machine error can be clearly displayed in the touch screen.
5). Separate PID temperature controller, suitable for various packing materials
6). High sensitivity optical photocell for eye mark tracking, digital input for cutting position.
7). Position stop function, no adhesive and no waste of membrane and protect cutter.
8). Simple driving system, stable performance and convenient maintenance.
9). According to different product, the input conveyor can use pusher, belt or film for transportation.
10). High sensitive sensor to track the color mark, so the position of sealing and cutting will be more accuracy.
11).Automatic Detect the products, if no product feeding into the film, the machine will stop, no empty bag and no cutting the products.
12). No limit for product length
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AirDepot offers air conditioning and furnace maintenance in Sugar Land, TX, which is essential to making sure your HVAC works properly. Maintaining your heating and cooling lowers your energy bills while keeping your home comfortable.
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Our maintenance package includes the following services to help you make the most of your home’s HVAC system.
Planned HVAC maintenance
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Our AC maintenance includes checking elements such as the relays, voltage, and condensate drain. We also pay attention to vibrations and noise to determine if anything feels or sounds unusual.
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When you need an AC inspection or furnace maintenance, be sure to contact [company name] in Sugar Land.


text:
there are times when the pup crawls into my lap and i have to stop doing whatever it is that i am doing and i just look at him and pet him.
after a few seconds of this, it usually hits me: there is nothing else i'd rather be doing than just being with him in that moment.
it hits me how precious of a moment it is.
precious for a number of reasons, but it feels most precious because it is a moment, a happy moment, and those come and go.
those happy moments come and go.
those moments when you actually feel good come and go.
moments when you actually feel content. when you actually feel love. when you actually feel warmth. when you actually feel grounded. when you actually feel like yourself.
those moments are so precious.
i want to hold them close and breathe them in.
i've started to try to do that when i notice the precious moment.
when i can, i close my eyes...or open them even more...and see, taste, feel, hear, smell the moment. i want it to become a part of me.
i want to carry it, them, these precious moments in my bones.

domain: psychology


text:
Showing 1 - 4 of 4 results
Research on human sleep and circadian rhythms.
Mount Allison University
Research on designing and studying boron compounds
Promotes research and hands-on training in the applications of mass spectrometry to diverse problems in the chemical, biological, and clinical sciences, including metabolomics, lipidomics, and proteomics
Research and development of low-cost, high-volume polymer matrix composite structures

domain: chemistry


text:
Obscura Arborea - Telegraph Brewing Company
Displayed for educational use only; do not reuse.
Ratings: 38 | Reviews: 26 | Display Reviews Only:
4/5 rDev +18.3%
I read elsewhere this was a gusher, so I opened this after it was chilled to about 45 degrees. Cork loosened with a resounding champagne pop, but no gushing. Hard to pour this one without the head expanding voluminously. About a 2 inch head was the best I could do, which was eggshell white, thick and foamy. Has pretty good head retention, and leaves lots of sticky lace on the glass.
Smells of lemon, dark cherries, brown sugar, barnyard funk, and old wood.
I like how this beer tastes, and it is not disappointing, but it doesn't exactly fit the brewer's style objective of a sour cherry Oude Bruin. it is not as sour as Oude Bruins typically are, such as Rodenbach. The lacto takes it in a lemony sour direction, yet it is also characterized by a dark caramel malt sweetness, accompanied by a metallic cola taste and spiciness, reminding me of an abbey ale with a lacto fermentation. It has a husky and spicy dark fruit character in the finish, probably dried dark cherries. The flavor cherry only comes through in the long dry finish. Oak is there to lend some smoothness but it isn't that prominent in the taste. This beer crosses style boundaries, but it ends up being a smooth and balanced beer.
The carbonation is pretty vigorous, much like champagne when the beer is first poured. Together with the sourness, the carbonation gives it a nicely refreshing mouthfeel.
Telegraph has been bending styles for awhile now. This is an interesting dark, slightly sour beer that comes off pretty smooth in the end. I'd definitely have this again.
07-09-2011 17:48:24 | More by Beerenauslese
4.05/5 rDev +19.8%
This is the most violently carbonated beer I've ever opened. Just loosening the cage starts the cork sliding out, and once it comes out (with a very loud pop), foam immediately starts gushing out of the bottle. I had a glass ready, as I had been warned, but once that was filled up with foam and the bottle showed no signs of stopping, I had to scramble for a second glass. There was foam coming out of the bottle for several full minutes, with me trying to pour out enough to get it to stop without losing too much, and still more ended up down the drain than I would have liked. Crazy.
A: If you can get it poured, it's a dark slightly translucent brown amber, with mountains of sticky off white head. Head retains for a while, and leaves solid walls of lacing.
S: Tart funkiness, with citrus backed by a solid malty sweetness.
T: Nicely balanced blend of sweet and tart, with a fair amount of funk on top. The alcohol is very well hidden.
M: Very very highly carbonated, medium to full body.
Overall this was pretty interesting; tasty, but unique. If I have it again I'll need a bigger glass around to catch the first 1/3 of a bottle or so that comes out in foam.
07-30-2011 02:05:09 | More by seand
4.13/5 rDev +22.2%
750 mL bottle poured into a Mikasa tulip glass
The beer is creamed-copper in appearance (if that's a legitimate color description) with a huge pillow-y head that never recedes. Tones of woodsy dank and unripe berries float about, but in the ether - the nose lingers and takes a few whiffs to pull it in.
The taste is much more pronounced with toffee-like malts playing against tart cherries. There are notes of drying oak that mix well with a subtle hop snap, keeping the sweet aspects in check. Alcohol is apparent but not aggressive. Finishes long, sweet and sour.
I don't get the low (or average) reviews here. My bottle's been aging for a little over a year (maybe longer) so that might be what 'smoothed' it out, but I don't think that's the entire reason. The brew produces a super-sudsy head, almost billowy, but it doesn't FEEL over-carbonated, something I can't stand. Over-carbing wouldn't get better with age. And I'm trying to pinpoint why the consensus feels this has a disjointed flavor profile - I'm getting a pretty smooth play of sweet and sour and bitter washing over the palate. Hmm...maybe I got a good batch? Or there's a bit of group-think here on BA? Well, no need to speculate...I've been drinking a lot of this style lately and this beer, at least my bottle, is a good example.
11-15-2012 06:00:41 | More by rand
3.55/5 rDev +5%
Pours a milk chocolate brown with a ridicously foamy head though the bottle wasnt the gusher others said it was. Nose has simple lemony citrus, rhubarb, sour cherry and an earthiness to it. The taste is a bit muddied by old wood that didnt seem to integrate its flavors well, bright tart citrus and rhubarb pie with almost a creaminess to it. Very nice carbonation to balance the sour acidity and the wood actually plays well in the mouthfeel as well as the abv being very hidden. A simple easy drinking 9% beer.
06-26-2011 06:12:13 | More by Trilogy31
3.65/5 rDev +8%
Appearance: Light brown color, tons of thick off-white head that fades slowly. The pressure in the bottle blew the cork out as soon as the cage was removed. Tons of lacing.
Smell: Tart, malty undertones, earthy, dark fruit, sour cherries.
Taste: Tart, sour cherries, dark fruit, earthy, oak, caramel, raisins, plums.
Mouthfeel: medium bodied, moderate carbonation, silky, creamy, somewhat tart.
Overall: Another tasty beer from Telegraph. Not as sour as I'd have liked, but very drinkable.
03-07-2012 06:03:01 | More by phichifiji00
4.22/5 rDev +24.9%
Poured out and all turned into foam, once in started to settle down. It was a very deep dark orange leaving spotty lacing around the glass.
smells of carmel and fruit. then just a hint of malt
The only way i can think to describe the taste is, like an apple juice with an ale bite to it. Can definitely taste the alc. in it.
mouth feel in med to full body. little bit dry afterwards.
overall the is a good beer. have to give it a little time for the foam to settle down but is worth the wait
10-22-2011 23:03:02 | More by rtaps
2.05/5 rDev -39.3%
Poured into a styro coffee cup in a hotel room--better than out of the bottle me thinks. Couldn't really tell you the color due to the cup plus 3" foamy head that refused to subside. Wasn't a gusher, but highly carbed and ready to foam at the slightest hint of a nucleation site. You've been warned.
Smells like highly diluted balsamic vinegar. And that's about it. Very one-noted. Just kinda blahhh.
Tastes was a little less blahhh. Maybe more of a blah. With the target being Flanders Oude Bruin, both the sweet and sour were way off the mark. More precise, though there is some sour there, there is really no sweet balance. In fact, this finishes unpleasantly bitter... oddly enough, a coffee bitter, with the coffee likely coming from the roasted malts and the bitter from the oak. It is not very refreshing as a result.
Not my cup o' brew.
10-05-2011 04:23:15 | More by jwjon1
2.93/5 rDev -13.3%
I went to the store excited to get a local sour beer on my travels here in southern California, and was excited to try this beer because I will be going to Santa Barbara soon. Unfortunately I was very dissapointed. I may be too harsh of a critic, but it seems too young/commercial - but not so professional. Granted the sour taste is there- it just seems like they are just getting started on this project. It is very cloudy/chill haze. It seems rushed, and is WAY over carbonated in the bottle i got- making for a 1 inch pour into a snifter full of foam. really dissapointed- should have stuck with Russian River, or lost Abbey.
I left it in the fridge over night after that review to see if the rest of the bottle would get better with a little fresh air- Still way over carbonated, but the beer did get better.. still hazy though
06-17-2011 03:13:20 | More by guausullivan8
Obscura Arborea from Telegraph Brewing Company
79 out of 100 based on 38 ratings.

domain: hobby


text:
As we come to the close of 2023, and ready ourselves for an exciting 2024, the consulting team at
Courtemanche & Associates wanted to provide you with our list of 12 “ To Do’s” in 2024!
Top 12 for 2024
1. Evaluate your Health Equity and Disparities Program
Review your organizational assessment and the specific areas identified by your organization where opportunity for improvement exists. Assess your progress with your 2023 action plans and determine if you have had a positive impact. Be certain to plan additional actions for 2024. Use this evaluation as the foundation for your annual stakeholders report.
2. Review and Update your Survey Execution Plan
With the changes that were made to comply with CMS expectations, organizations should review their plan and adjust them to ensure a smooth process. Remember, no pre-survey notification, no blackout dates, and on-site surveys in response to complaints will mean your organizational plan will need to change.
3. USP 797 Gap Assessment
The final version of USP 797 was released in mid-2023, and TJC has published and posted its crosswalk for compliance expectations on its website. Use the crosswalk to determine where your organizational gaps exist and make modifications to ensure compliance.
4. Review your Competency Assessment Program
The Joint Commission Glossary contains definitions of education, training, and competency. Review your competency program to ensure that when you say you are assessing competency, you really are assessing the application of the SKILLS needed to complete the task. Consider revisiting the competency assessment process that was used during the Pandemic and ensure that the competency of staff recruited during the Pandemic was adequately assessed.
5. Review of your Live Plants Policy in the Patient Care Area
It is important to remember that immunocompromised patients have a higher likelihood of developing an infection than healthy individuals and may be vulnerable when exposed to live plants and soil. Review your live plant policy to determine if your patients are at risk. Consider these precautions that can be implemented in the patient-care setting, especially if there are immunocompromised patients:
- Limiting flower and plant care to staff with no direct patient contact
- Advising healthcare staff to wear gloves when handling plants
- Washing hands after handling plants
- Changing vase water every two days and discharging the water into a sink outside the immediate patient environment
- Cleaning and disinfecting the vases after use
6. Evaluate Inspection of Surgical Instrumentation
Ensuring that all instruments are inspected before sterilization is important for protecting the patient and the life of the instrumentation. Checking and inspecting all reuseable instruments for things such as rust, pitting, discoloration, retained bioburden, sharpness, smooth operation, loose, damaged or corroded connectors, overall instrument functionality and sharpness is essential to patient safety. Following the Manufacturer’s instructions for use and cleaning procedures is vital to ensure patient safety and prevent infection.
7. Review Rounding for Patient Safety
It is important to round in your organization to stay abreast of patient safety and regulatory issues in all areas of the facility. Review your current rounding practice to ensure you are evaluating all patient care areas consistently. Review rounding data to determine trends of opportunities. Ensure you evaluate for opportunities in the environment, quality and performance improvement, patient safety, and regulatory
8. Point of Use Cleaning (POU) Evaluation
Point of Use cleaning is required before transporting contaminated instrumentation from the OR, procedure rooms, nursing units, or departments. Evaluate your current practices to determine if your practice is aligned with policy and evidence-based practice. This should include removing visible bioburden (blood, bone, etc.) from the instrument, keeping the instrument wet by spraying the instruments with an enzymatic spray/gel at the point of use (or using a water-soaked towel), and transporting them in a leak-proof, puncture-proof container with a biohazard sticker on it.
9. Instructions for Use (IFU)
IFUs are essential to provide staff information on how to operate, maintain, and clean medical equipment. Evaluate if your staff have access to the IFU for equipment they use or are in charge of managing. Is the IFU current? Do staff know how to access their IFUs?
10. Surgical Fire Risk
Fires during surgical procedures still occur despite advances in fire prevention. There is a recommittal by accrediting organizations in evaluating surgical fire risk prevention. Evaluate your current posture in your prevention efforts. Ensure your policy is in place and up to date. Are staff evaluated on their prevention practices (fire risk assessments, drying times for flammable antiseptics, safe use of cautery and heat sources)? Are staff evaluated on surgical fire response, including evacuation? Are all areas at risk participating in risk prevention and response?
11. Workplace Violence
Workplace violence in healthcare facilities continues to be a persistent issue. It’s important for organizations to evaluate their practices and incident data to determine
how to address their own risks. Consider the following as part of your evaluation:
- What does your annual analysis of workplace violence incidents indicate as risks for your organization?
- Have you developed a mitigation plan based on these risks?
- Have you communicated risks and prevention efforts to your staff?
- Have you evaluated your staff's perception of personal safety from workplace violence, and what does the data show?
12. Tissue Transplant Safety
The management of transplantable tissues is critical. Evaluate your current practice for monitoring temperatures of tissue storage. Are there gaps in measures? Are there unaddressed excursions of temperature from acceptable ranges? Ensure your temperature logs are accessible if requested by the survey team. Are your thermometers and refrigerators/freezers maintained and calibrated per the manufacturer’s instructions for use? Are your tissue logs complete with all required information, including identification of diluents in the event of a recall? Are all documentation elements present to support the bi-directional tracing of tissue/diluent to the patient?
From the staff at Courtemanche and Associates: We wish you a safe holiday and a productive New Year and look forward to serving you in 2024
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domain: medical


text:
Resverlogix and Medison Pharma Ltd. Announce Strategic Licensing Agreement
Alliance to focus on regulatory approval, commercialization and marketing of novel apabetalone therapy in Israel
CALGARY, Alberta, Jan. 08, 2018 (GLOBE NEWSWIRE) -- Resverlogix Corp. ("Resverlogix" or the "Company") (TSX:RVX) today announced that it has entered into a licensing agreement with Medison Pharma Ltd. ("Medison") for the Company's lead therapeutic candidate, apabetalone (RVX-208), in Israel and the Palestine Authority. Apabetalone is currently in development for the treatment of high-risk cardiovascular disease (CVD) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), and potential expanded indications.
Under the terms of the agreement, Medison has the exclusive rights to distribute and market apabetalone in Israel. Resverlogix is eligible to receive from Medison, ascending double digit royalties based on future net sales of the product in the region. If certain sales milestones are reached total royalty payments are estimated to potentially reach in excess of US$100 million over the entire patent life in the region. Medison will be responsible for all regulatory, sales and marketing costs for apabetalone in the Israel region.
"This partnership with Medison is an important validation for our lead molecule apabetalone and our BET inhibition technology," stated Donald McCaffrey, President and CEO of Resverlogix. "Patients in Israel have access to an innovative world class health care system. Having Medison as a leading partner is instrumental in the commercialization and marketing of apabetalone for the many high-risk vascular disease patients in the Israel national health system," McCaffrey added.
"Apabetalone represents a potential new and important therapeutic approach to risk reduction for areas of critical unmet need in Israel such as CVD, diabetes, and CKD. We look forward to the continued clinical success of apabetalone and working with Resverlogix in fulfilling Medison's vision to provide innovative treatments to patients in Israel," stated Meir Jakobsohn, CEO and founder of Medison.
"Israel represents an important market for medical innovation," stated Kenneth Lebioda, Senior Vice President of Business and Corporate Development at Resverlogix. "We will continue to work closely and strengthen our ongoing collaboration with Medison to ensure successful regulatory approval and commercialization of apabetalone in Israel," Mr. Lebioda added.
Medison is Israel's leading marketing group, representing innovative niche healthcare solutions to companies such as Biogen, Amgen, Shire and Ipsen. Employing a comprehensive approach to sales and service, Medison supplies and maintains long-standing relations with HMOs (Health Maintenance Organizations), local medical centers and physicians. Backed by three generations of experience in the healthcare industry since 1937, Medison is uniquely qualified to provide the complete spectrum of integrated services for international companies looking to enter or expand their presence in the Israeli healthcare market.
Resverlogix is developing apabetalone (RVX-208), a first-in-class, small molecule that is a selective BET (bromodomain and extra-terminal) inhibitor. BET bromodomain inhibition is an epigenetic mechanism that can regulate disease-causing genes. Apabetalone is the first and only BET inhibitor selective for the second bromodomain (BD2) within the BET protein called BRD4. This selective inhibition of apabetalone on BD2 produces a specific set of biological effects with potentially important benefits for patients with high-risk cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease, end-stage renal disease treated with hemodialysis, neurodegenerative disease, Fabry disease, peripheral artery disease and other orphan diseases, while maintaining a well described safety profile. Apabetalone is the only selective BET bromodomain inhibitor in human clinical trials. Apabetalone is currently being studied in a Phase 3 trial, BETonMACE, in high-risk CVD patients with type 2 DM and low high-density lipoprotein (HDL), and is expected to be initiated in a Phase 2a kidney dialysis trial designed to evaluate biomarker changes and safety parameters in up to 30 patients with end-stage renal disease treated with hemodialysis.
Resverlogix common shares trade on the Toronto Stock Exchange (TSX:RVX).
Follow us on Twitter: @Resverlogix_RVX (https://twitter.com/resverlogix_rvx )
This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information relating to estimated royalty payments pursuant to the licensing agreement with Medison, the Company's Phase 3 clinical trial and the potential role of apabetalone in the treatment of CVD, DM, chronic kidney disease, end-stage renal disease treated with hemodialysis, neurodegenerative disease, Fabry disease, peripheral artery disease and other Orphan diseases. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our Annual Information Form and most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com . The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. The Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
For further information, please contact:
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All summer long, the city of Medias sponsored weekly organ concerts at the oldest church in town, Biserica Sf. Margareta (Margarethenkirche). Medias is a medieval city in the province of Transilvania, Romania.
The concerts were held every Monday night at 7 pm. We attended one of them on September 7, 2009. A wide selection of music was played for 1 ½ hours, from medieval pieces to Bach, and all the way to a modern piece written in the 1940s. I lost the program note, so I can’t go into the details, but overall, the concert was good, and some pieces were great. I’m definitely looking forward to attending more of these recitals next summer.


text:
Massive Disneyland Attraction Database
A kind view of Tonka's Go Device when it's not hidden in darkness
Tonka's Go Device
April 23, 1972
Avg. queue length:
This rollerdevice -- the fastest in Toontown -- is designed for mice of all heights.
- Warning: after the Christmas season, this attraction will be crammed full of monorail pilots.
Guest Policies and Alerts
- Guests may get tired on this attraction.
- This attraction is based on a film made before you were born.
- Strollers may not be brought aboard this attraction.
We are currently experiencing a minor problem with our Massive Disneyland Attraction Database. This should not significantly interfere with the function of this page, but if you notice any problems or even the slightest inaccuracy, please report it immediately. Thank you for your understanding.


DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click HERE
to register or log in.
Damage Mechanisms/Failure Mechanics of Carbon-Carbon Composite Materials.
WYOMING UNIV LARAMIE DEPT OF MECHANICAL ENGINEERING
Pagination or Media Count:
A 100 millimeter 4in cubic billet of 3-dimensional cartesian weave carbon-carbon material was received in late December, 1977. A series of tests were performed to measure mechanical properties during uniaxial tension, compression, and shear loading. Extensive test development was required as standard tests for these materials do not exist. Strain gages and extensometers were used to measure strain during loading for determination of elastic coefficients. Acoustic emission measurements were performed on selected tests to determine damage thresholds. Failure surfaces were examined in a scanning electron microscope to study failure modes. Author
APPROVED FOR PUBLIC RELEASE


text:
The effects of USF's 28-24 last minute loss to Houston were felt in the national polls on Sunday.
As you can see, C. now assumes the spot as the highest ranked Group of Five team being slotted at #14 in the Coaches and #15 in the AP.
Also from the American comes Memphis, who moved up to #21 in the Coaches and #22 in the AP.
More importantly, the College Football Playoff committee will release their first set of Top 25 rankings on Tuesday so we'll see if the Bulls are somehow included in those.
-At the same exact time that USF going down to the wire with Houston, chaos was ensuing all around college football.
J.T. Barrett marched Ohio State down the field to complete their comeback on Penn State. Iowa State set the Big 12 standings on fire by upsetting TCU. Sparty messed around and got clipped by Northwestern in three overtimes. CHAOS!
-Georgia pummeled Florida 42-7, a win that earned them a spot at #2 in both polls and got Jim McElwain fired.
-BEDLAM is this week as #8 Oklahoma battles #11 Oklahoma State for Big XII supremacy...until they meet about a month later in the Big XII's unnecessary championship game, because that's totally going to happen.
-Hey look, Arizona is bowl eligible and ranked #23! Rich Rod saved his job...for now.

domain: sports


text:
4 questions to ask before choosing a wealth and investment management service
Wealth management plays a vital role in ensuring that a new business succeeds and an established business organization maintains its consistency. From the perspective of an affluent businessman, wealth and investment management involves enhancing their financial situation or solving various finance-related issues that business organizations usually face. Furthermore, in context of the wealth and investment management services that these organizations hire, wealth and investment management involves making use of the skills of the financial advisors to deliver a full range of varied financial services and products their clients might need.
One of the prime factors a prospective client needs to understand about wealth and investment management services is that all the services are offered in a consultative manner, and the wealth managers are highly client-centered. They ensure that their clients receive every bit of financial and investment advice they need. Some wealth managers even provide banking services or advice on different philanthropic activities.
Wealth and investment management is a broad field and immensely benefits those who opt for it. Read on to know more about wealth and investment services and how to determine you have made the right choice.
Are wealth management and investment banking the same?
- Wealth management and investment banking are considered to be two distinct businesses, and the factor that differentiates one from the other is their client base.
- Investment banking deals with corporate entities and the prime duties of an investment banker are to offer financial services and advice to their clients, so that the clients can handle different financial situations, such as acquisitions or mergers and even certain forms of business finance restructuring, efficiently. Moreover, an investment banker also has to handle the initial public offering, stock pits, and issues with stocks or bonds.
- A wealth manager, on the other hand, deals with the finances of high net-worth individuals. Wealth management involves various money management techniques that combine financial and investment advice, retirement planning, legal or estate planning, accounting and tax services, and more.
- So, it is imperative to gauge one’s needs before determining whether they wish to opt for wealth and investment management services or investment banking services, as each of these caters to different audiences.
What are the duties of a wealth manager?
- A wealth manager is a professional who offers financial and investment advice to their clients. These services also include various accounting and tax services, legal and estate planning, and retirement planning.
- The wealth manager will coordinate the inputs they receive from other financial experts and can even consult the client’s own attorney, accountant, and insurance agent while formulating various wealth management techniques.
- It is the wealth manager’s vital duty to develop a financial plan based on the client’s current financial situation, goals, and comfort level with risks. Once this plan is developed, the wealth manager has to meet up with their clients regularly for updating them about the goals, reviewing and rebalancing the financial portfolio, and determining whether they need additional services.
How much does it cost to hire wealth and investment management services?
- The cost of availing the service of a wealth manager varies from one wealth and investment management service to another. Usually, the fee charged involves a percentage of the assets that are under the wealth manager for management purposes.
- However, there are instances when the fee schedule scales vary and, usually, wealth and investment management services charge less for wealthier clients. For instance, clients with $1 million might be charged around 1% of their assets per year, whereas, those with $10 million might have to pay 0.7% per year.
- Certain wealth and investment management services would charge their clients hourly rates for their services, which implies that you will have to pay more if you need more advice in dealing with your finances.
How does one choose the right wealth and investment management services?
Choosing the right wealth and investment management services have a great impact on how successfully the individual or the firm manage their finances. Therefore, here are essential tips to choose the best wealth and investment management services:
- Before zeroing in on a particular wealth and investment management firm, you need to determine whether the firm is competent enough to yield desirable results. The firm’s experience in this particular field can prove useful in gauging its effectiveness.
- You need to determine whether the particular wealth and investment management service have the required resources to guide you through any unforeseen financial turmoil.
- One of the prime determining factors that allows you to make the right choice is the firm’s performance. You need to check whether the particular firm has yielded consistent results in effectively managing their client’s wealth over an extended period of time.
Tags- wealth investment management services

domain: economics


Gettle's Guns is here to help you make the best decision on what firearm suits you. Contact us for whatever you need and we'll give you our best deal.
The GLOCK 23 combines compact dimensions for both open and concealed carry with minimum weight despite its large magazine capacity in .40 caliber. Having survived durability tests and use by U.S. Law Enforcement agencies the G23 pistol has repeatedly demonstrated its world-class durability and reliability in even the most unfavorable conditions. That's why countless police authorities continue to adopt the GLOCK 23 as their official service pistol. - Length: 187 mm / 7.36 in. - Width: 30.00 mm / 1.18 in. - Length Between Sights: 153 mm / 6.02 in. - Height: 127 mm / 4.99 in. - Barrel Height: 32 mm / 1.26 in. - Barrel Length: 102 mm / 4.01 in. - Weights: Unloaded: 670 g / 23.65 oz.-Loaded: 880 g / 31.06 oz. - Trigger Pull: ~2.5 kg / ~5.5 lbs. - Trigger Travel: ~12.5 mm / ~0.49 in. - Barrel Rifling: right hand hexagonal - Length of Twist: 250 mm / 9.84 in. - Magazine Capacity: Standard: 13 Optional: 10/15/22
|STOCK FRAME GRIPS||-|
|FEATURES||Type: Pistol Action: Double Caliber: 40 S&W Barrel Length: 4.01" Capacity: 10+1 Safety: Trigger/Firing Pin/Drop Grips: Black Polymer Grip/Frame Sight Configuration: Fixed Weight: 21.2 oz Frame Finish: Black Frame Material: Polymer Barrel Type: Cold Hammer-Forged Polygonal Rifled Slide Description: Black Case Type: Hard Sight Style: Fixed Barrel Length Range: 4.00" to 4.99" Weight Range: 16.00 oz to 31.99 oz|
|PROP 65||WARNING: This product can expose you to chemicals including lead, which is known to the State of California to cause cancer and birth defects or other reproductive harm. For more information go to www.P65Warnings.ca.gov.|


More than a decade ago Jaguar decided it wanted to become a serious rival to Mercedes-Benz, BMW and Audi in terms of raw numbers. And thus the X-Type was born as a rival to the popular C-Class, 3 Series and A4 small sedans.
The move was a result of Ford's buy-out of the troubled British brand and, really, that was the start of the X-Type's problems.
You see, rather than invest the billions of dollars into developing a clean-sheet compact-luxury design, Ford's bean counters insisted the car should use existing Ford architecture with a Jaguar-spec body draped over it.
And the only existing Ford that really fitted the bill was the Mondeo. But it was front-wheel-drive, so some money was spent on making the car all-wheel-drive (ironically, going all-wheel-drive was cheaper than turning the platform into a rear-wheel-drive one) and the X-Type's rather derivative sedan body was sketched up.
It's now a matter of history that the car Jaguar promised would never happen - a front-wheel-drive X-Type - did, in fact, happen and that by 2011, the X-Type would be on the endangered list after another ownership change (this time to India's biggest conglomerate, the Tata Group).
But the X-Type's last gasp - from 2008 to 2010 - amounted to the car's peak, technically speaking, and, you could argue, its swan-song was also its finest hour. The changes to the car for the 2008 model year numbered more than 500. Obviously, most of them were small refinements because even Tata, with its enthusiasm for its new brand, couldn't justify spending the money to completely redesign the X-Type.
Engine choices remained much as they had before, with a 3.0-litre petrol V6 providing the excitement, a 2.1-litre V6 aimed at the budget-Jaguar buyer and, in line with the facelift, a 2.2-litre turbo-diesel developed primarily for Europe joining the local line-up. The bigger V6 made 172kW while the smaller V6 was good for 117kW but was buttery smooth into the bargain.
The five-speed automatic transmissions for either were also carried over from the pre-facelift cars, but the big difference between the two petrol models was that the 3.0-litre was all-wheel-drive while the smaller V6 was front-wheel-drive. It shows in the way they drive, too, but the front-drive layout certainly helped keep costs down.
The turbo diesel got a newer gearbox - a six-speed automatic - and although the engine made just 107kW, with 366Nm of pulling power, it out-grunted even the 3.0-litre (284Nm). The only catch was that the turbo-diesel was a front-wheel-drive rather than an all-wheel-drive. In the real world, this mattered little.
Against an up-spec C-Class or 3-Series, the X-Type can feel a bit underdone, but it's always a smooth, relaxed performer and, in all-wheel-drive form, it has the grip to make trips to the snow entirely viable. And in turbo-diesel form, it's even more unruffled at speed and capable of seriously good fuel economy.
The Jaguar brand has long been associated with dodgy reliability, but that degree of mechanical recalcitrance doesn't really affect these later cars.
The Mondeo underpinnings are well proven and the V6 petrol engines also seem pretty well sorted. Even so, we'd recommend a thorough pre-purchase inspection to make sure that all is well beneath the waterline.
The all-wheel-drive system adds strain to various driveline parts so make sure the driveshafts are all in good condition. Any clicking or clunking when turning or accelerating could be evidence of wear in this area.
Make sure any prospective purchase has a fully stamped and up-to-date service handbook. Jaguars have often appealed to those who want the badge and then discover they can't afford to keep the thing properly (this was one of the major problems Jaguar had over the decades).
Bear in mind, too, that a turbo-diesel version, while capable of stunning fuel economy, will require more expensive servicing over its lifespan. So, if you aren't covering big annual distances, you might find that the economics of going diesel don't add up as convincingly as you may have imagined.
The diesel version was also recalled for a cruise-control problem that could see the cruise refusing to cancel in any of the usual ways (braking, changing gear or hitting the cancel button). Only switching the ignition off would cancel the cruise, so it could be a real problem in the heat of the moment. Make sure any diesel X-Type has been checked and, if necessary, rectified.
Our score: 3/5
- V6 engines are smooth
- Turbo diesel punchy and frugal
- An alternative to the German pack
- Suffers undeservedly, from Jaguar's poor reliability record of many years ago
- Styling, while different, could be accused of being derivative of other bigger models in the range
- Front-wheel-drive creates its own stigma


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As age kicks in, loss of collagen and elastin leads to wrinkles and sagging skin. But with today’s advanced radiofrequency treatment, you can get your youthful glow back. Forma and Forma plus is a modern technology that helps in the generation of new collagen and elastin. It’s a non-invasive and non-surgical treatment that uses radiofrequency waves to provide contraction in the deep skin layers of the skin to stimulate collagen formation and skin elasticity.
Now available at Doux Papillon MediSkin, this treatment is ideal to improve skin laxity, tighten skin and reduce wrinkles.
What Areas can be Treated?
Forma is used on small areas while Forma plus is used on larger areas. It’s used to treat face and neck areas including the forehead, face, smile lines and necklines. It is also applicable to other parts of the body including abdomen, hips, thighs, upper arm, knees and other areas that have loose skin.
The treatment is suitable for all skin types. Therefore, those who want a non-surgical and non-invasive method for improving their skin can get the treatment at our clinic.
How Forma and Forma Plus Works
Forma uses radiofrequency to penetrate deep layers of the skin. This energy causes the collagen strands to remould into tighter lines while stimulating the growth of new ones. Since collagen is the building block of the skin firmness, this process leads to significant improvement of the skin tone and texture over time.
What the Treatment Entails
Our physicians apply a gel to the treatment area, and then glide the Forma device on the treatment area and move it in small circles. The dermal clinician controls the temperature using the gauge to ensure no area is under or overheated. The treatment is painless with no downtime. It leaves your skin rejuvenated with no mark. Patients undergoing this procedure feel a heat soothing sensation similar to a hot stone massage. Treatment is done once a week for around 6-8 treatments depending on the area being treated.
Recovery and Results
The treatment leaves no visible mark except for slight redness in some circumstances which subsides in a few hours. Results are visible within two weeks after the first visit and progress to improve with each visit. Having a maintenance program will have long-lasting results.
At Doux Papillon MediSkin Clinic, we offer a comprehensive skin assessment, and customized, safe and effective treatment plans for your skin needs. Contact us today for a consultation.


Amazon.com and the U.S. Postal Service are teaming up to offer Sunday delivery as the world’s biggest online retailer seeks to broaden its reach by getting packages to customers on any day of the week.
Customers in New York, Los Angeles and parts of San Diego County, can start choosing Sunday delivery at no extra cost starting this week.
Amazon spokeswoman Mary Osako was unable to say which areas of San Diego County will be able to take advantage of the new seven-day delivery, but confirmed it will be “a large portion” of the county.
The Sunday delivery means any shipments taking place over the weekend will be delivered a day sooner than in the past, she explained.
“What we’re doing essentially is making every day an Amazon delivery day,” she said. “The Sunday delivery means that customers can receive their orders faster than ever.”
The service will expand to Dallas, Houston, Phoenix, New Orleans and other cities next year, Amazon said.
While Amazon is seeking to siphon away customers from Target and other retailers, it’s also facing competition from online-shopping sites that are rolling out new services to get products to customers more quickly and efficiently. EBay offers deliveries under an hour, seven days a week, for some products, and Walmart operates a same-day delivery service for groceries and household goods.
“What really drives the company — it’s all about selection growth, lower costs and increased speed,” said Dave Clark, Amazon’s vice president of worldwide operations and customer service. “Thousands of people around the world spend every day working on those three things in operations, and a big piece of speed for us is adding seven-day delivery.
“For Prime members, it’s free; for non-Prime members, it’s like any other delivery day of the week,” said Clark.
Amazon won’t change shipping prices for customers, adding to fulfillment costs that made up the largest portion of the company’s expenses in the third quarter.
Investors have endorsed the investment in capacity — spending increased 35 percent to $2.03 billion — pushing up the company’s shares 40 percent this year even as the Seattle-based retailer posts losses.
The online retailer’s partnership with the U.S. Postal Service means faster delivery for Internet shoppers, especially Amazon Prime members who pay $79 a year for unlimited two-day shipping — a promise the company previously couldn’t fulfill if someone ordered a product on Friday afternoon.
For the U.S. Postal Service, the alliance means more packages flowing through its network, which generates more revenue than flat mail. The Prime service also offers access to Amazon’s TV and movie streaming service.
By investing in fulfillment centers — massive warehouses that store and package everything from books to garden furniture — Amazon has improved its ability to sort packages so that they reach shoppers more quickly and efficiently.
Sunday delivery is part of Amazon’s strategy to keep shoppers coming back to buy products on its Web store. The company had 89 warehouses in 2012 and is planning seven more this year.
Amazon also unveiled plans in July to increase staff by 5,000 in 17 centers this year, and is hiring 70,000 seasonal workers in the U.S. to meet holiday demand.
Amazon does offer limited Sunday delivery currently through its Amazon Fresh online grocery service in Seattle and Los Angeles.
On Nov. 26 last year, Amazon’s peak shopping day, customers ordered more than 26.5 million items worldwide, or 306 items per second. About 57 percent of Amazon’s sales last year were in North America.
The postal service, too, offers limited Sunday package delivery during the holidays. It sends out carriers on the three Sundays before Christmas in major metropolitan markets.
Financial terms of the arrangement were not disclosed, but the deal is likely to give the financially ailing service a boost. The agency, which lost $16 billion last year, had tried but failed to end Saturday mail delivery as a cost-saving measure.
Despite the diminishing economics of standard mail delivery, package delivery is booming for the postal service. USPS spokeswoman Sue Brennan said it expects to deliver 420 million packages between Thanksgiving and Christmas, up 12 percent from last year.
Staff writer Katherine Poythress, The Seattle Times and The Associated Press contributed to this report.


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A 37-year-old Macon man was charged with kidnapping Monday afternoon after allegedly jumping into a womans car on Thomaston Road near Interstate 475.
DeAngelos Sherad Dennis was arrested at the Motel 6 on Harrison Road, where he had been banned from the property for panhandling, according to a news release from the Bibb County Sheriffs Office.
Witnesses told investigators Dennis told the female driver he needed fuel for his tractor trailer, but said he forgot his gas card when they arrived at the gas station shortly after 2 p.m.
He allegedly told the woman to drive to the motel, where she went in and asked the clerk for help.
Dennis followed her into the office, started arguing with the clerk and the victim ran out of the building and drove away in her car, the release stated.
Deputies urge motorists to keep their car doors locked with windows rolled up, and watch for people walking up to their vehicles.
Leaving enough space between vehicles at a light or intersection, will allow you to make a quick getaway, the release stated.

domain: news


text:
(A version of this posting appeared recently on www.hamiltonjustice.ca)
The study called “One Step Forward, Two Steps Back” documents widespread employment standards violations facing Chinese workers. http://www.workersactioncentre.org/updates/survey-shows-widespread-esa-violations-including-pay-below-minimum-wage/
For example of the workers surveyed:
**Twenty percent were paid less than minimum wage.
**Only half received public holiday pay.
**Seventy-seven percent said they never receive overtime.
An earlier report by the Workers Action Centre documented similar abuses. The fact that 1 in 3 low-wage workers had experienced unpaid wages in the previous 5 years was indeed shocking. http://www.workersactioncentre.org/wp-content/uploads/2011/12/pb_unpaidwagesunprotectedworkers_eng.pdf
The Worker’s Action Centre wants to immediately increase fines and penalties for employers who break the law and make it mandatory for all employers with a confirmed violation to face a fine.
This just makes sense.


Annotation: This paper proposes an astatic frequency-locked loop with the improved noise immunity and dynamic accuracy compared with the static frequency-locked loop. Improved noise immunity has been achieved through radiopulse spectrum conversion of an input harmonic signal. It allows reducing the self-tuning band of the narrow-band voltage-controlled oscillator follow-up filter, implemented on the basis of the developed frequency-locked loop, by several orders of magnitude. Simple analytic expressions for estimating the improvement of noise immunity and dynamic accuracy of the developed system are given allowing to compare it with the static frequency-locked loop of the voltage-controlled oscillator. An implementation of the harmonic signal spectrum radio pulse converter on the basis of present hardware components is proposed.


text:
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domain: pet


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domain: travel


text:
Cathy Smith Bowers is author of three poetry collections, including The Love That Ended Yesterday in Texas, which was the first winner of the Texas Tech University Press Poetry Award Series, subsequently named for Walt McDonald. Her other books are Traveling in Time of Danger and her most recent, A Book of Minutes, from Iris Press. A native of South Carolina, she has received a South Carolina Poetry Fellowship and was a winner of the 1990 General Electric Award for Younger Writers. Her poems appear in The Atlantic Monthly, Poetry, The Georgia Review, Shenandoah, The Southern Review, Kenyon Review, and The Gettysburg Review, among other journals. She teaches in the Low-Residency MFA Program at Queens University of Charlotte. I spoke with her in Tryon, North Carolina, her new town of residence, which offers a view of the Blue Ridge Mountains.
Julie Funderburk: I’d like to ask you about narrative structure. In an essay first published in Poetry, “Fear of Narrative and the Skittery Poem of Our Moment,” poet Tony Hoagland describes the current shift away from narrative, noting that “many persons think that ours is simply not a narrative age; that contemporary experience is too multitracked, too visual, too manifold and simultaneous to be confined to the linearity of narrative.” Your first two books show a dedication to story. You have written that “our major task is writing a poem is to shine a light on a moment of intensity.” How does narrative help you do this?
Cathy Smith Bowers: I believe that every moment of intensity is a moment inside some narrative. The essence of our lives is story.
JF: How do you respond, then, to the current trend toward the fragmented, the nonlinear, the disassociative poems that Hoagland is describing?
CSB: Basically, to me [the style] can feel overly intellectual, cerebral, and not from the heart.
JF: When you say “heart,” do you also mean spirit? The theme of spirituality recurs in your poetry, with speakers and characters trying on a variety of religions. Do you think it necessary that poetry speak to the spirit?
CSB: Especially now, we are in a culture deprived of spirituality. We hunger for it and are always looking for ways of having the spirit fed. In the best poetry, the spirit will be fed, and it’s the spirit that should be—not the brain. The mind is also a part of it—but [the mind] is the machine that gets the reader to the spirit of the poem. I like to think of a poem as a river of spirit, and every once in a while there comes a current of intellect. I like smart poems, but I don’t want the smartness of the poem to be the main thing. I want to not even notice the smartness of a poem until many readings later.
JF: Will you name a poet who serves as a model for you in this?
CSB: Who always comes to mind is Gerard Manley Hopkins. I don’t even have to care whether his poems are about anything. They sweep me away, touch me with language and with sound. And then, after being swept away by that, I want to know and am willing to work at it, and realize that yes, indeed, the poems are intelligent—they are brilliant. But what I was first swept away by had to do with the heart and the spirit. I’ve lent out my books and they haven’t been returned yet, but Franz Wright is doing something that is stunning to me in its quietness. You don’t know whether he’s writing a poem or praying.
JF: Do you make a distinction, then, between spirituality and religion?
CSB: Well, if you’ve ever read my poem “Learning How to Pray,” you see what my religion is like! The word “spirituality” is thrown around a lot these days and is almost becoming one of the words you’re scared to use, especially in the presence of academics.
JF: There’s plenty of words I’m afraid to use in the presence of academics.
CSB: Hell yeah, why do you think I fled?
JF: How has writing in the form you use in A Book of Minutes changed your writing? For our readers: the form is a “minute,” a stanzaic and syllabic poem, with each stanza keeping a syllabic count of 8/4/4/4, for a total of 60 syllables. How does this form help you “shine a light”?
CSB: The form is also one of rhymed couplets. My intention was to always adhere to the rhyme scheme. But when it’s a perfect rhyme or an almost-perfect rhyme, that’s the surprise, rather than the off-rhyme being a surprise. The tension occurs when I have finally somehow adhered to the [rhyme] form, rather than the traditional practice of veering away from the form.
JF: You’ve also got lyrics here—celebratory and mock-celebratory, addressed to herbs and to saints. And what happens to the narrative in this form? In poems such as “The Anatomy of a Southern Kiss”?
CSB: It forces you to really reduce the subject to its essence.
JF: A distilled narrative.
CSB: Yes. And the titles in those poems—I used them for all they were worth. Because I had only sixty syllables.
JF: In the preface to this book, you mention issues of control when dealing with such a form, both in poetry and in handling personal material. I wonder whether the decision to include such a preface is also related to this.
CSB: Absolutely. I knew this book was so different from my first two books, that people were going to wonder what the hell happened to me, and I wanted to have some say in how they read that book. I wanted my hand in it.
JF: Let’s discuss the South and its influence on language. You grew up in South Carolina, and your earlier books mention mills, and the mill worker’s life. You’ve written poems about Southern diction—in “A Southern Rhetoric” where the speaker’s Mama uses the phrases “a sight in this world” and “don’t you forget who it was / learned you to talk.” And in A Book of Minutes, “My Mother’s Lexicon.”
CSB: That’s probably been my biggest challenge. I mean, growing up in a world where . . . It was hard for me, for instance, just to get an education. We always hear people say “pull yourself up by the bootstraps.” Some people don’t even have any bootstraps. And it is hard. So all my life, even after being educated, I have been judged by my accent. It’s not really more difficult for Southern poets until we speak in public, which is why I don’t travel out of the South very often. [Colleagues] used to tease me for saying “I been knowin’ him a long time.” Sounded right to me! The little neighborhood I grew up in . . . my family didn’t have a car, so I lived right by the mill, right by the railroad tracks; I did not go out of my neighborhood until I was bussed to junior high. So you don’t get rid of an accent that you have spent 14 years inadvertently perfecting. So what you do instead is you stay in safe territory, which means anywhere where you can hear this tune: [mimics the sound of a banjo].
JF: But there are so many countries to which you have traveled—France, Italy, but also Indonesia, Korea. All over the world. Has traveling mattered to your writing?
CSB: There’s my poem “Touring the Berliner Dom,” where the moment of grace was seeing a man tie his wife’s shoe . . . Traveling—Though people complain about Americans who are flag-waving patriots . . . whatever I disagree with, with our administration, what’s going on in our country . . . I feel so lucky.
JF: Here, you have the freedom to write. Does it seem that you have a separate language for speaking and a separate language for writing?
CSB: I have many separate languages. The most over-the-top it gets is when I’m with my youngest sister Rosie. It definitely depends on my audience.
JF: In A Book of Minutes, some poems showcase humor. The rhyme can almost serve as a punch-line in poems such as “How I Became an Existentialist.” And in longer narratives, the end is funny, as in “The Ascension,” where the guru-esque lover steals the truck. Other poems begin with a joke and end wistfully or full of the weary world. I’ve heard you read before, and I know you enjoy making the audience laugh. Your subjects, though, are often heavy—grief, bitterness. How do you think humor functions in your verse?
CSB: This is not exactly what you’re asking, but I will say this: I started writing in [the minute] form after my brother died, and I worked in that form for four years. And I noticed that after about three years, I started writing those funny, silly poems. And I thought: hmm, this is interesting because they say that it takes about three years to grieve a tremendous loss. So just on that level, I took it as a sign I had moved to a place where I could feel joy and even silliness again. But that little form really works for humor because jokes are short, and jokes rely on brevity and timing, which are also a big part of that form.
JF: Was writing in this form, and writing lyrics inspired by saints and herbs, was this easier, since you’ve said that the moment of intensity you’re most interested in is the one within a narrative? If you are drawing from personal experience . . .
CSB: Yes, but at the time I didn’t really realize. When I discovered that form I was so deep in my grief, I was just sort of putting one foot in front of the other. I was teaching at a conference in Oklahoma City. And a woman was reading these short poems she called “minutes,” and as she told about the form, I jotted it down. It was just to get to the next minute, the next hour. I had planned on staying out there a few extra days after the conference was over, to see if I could get back to my own writing. And so I woke up Sunday morning, and there I was, confronted with this time, and I remembered writing down that little form, and so I tried to work with some images from my brother’s illness and death. And I know now that the form kept me in both sides of my brain. Before, after I had written my early drafts, for a long time in the writing of a poem, I would make myself stay in that right brain, that intuitive, that emotional, mysterious place. But I think that the subjects of my brother’s illness and death were too heavy for me to be in that place. So this form kept me in the emotional and the rational at the same time. It kept me balanced so that I could go back to those moments of intensity and work with them . . . My idea was just to work in that form in order to get back into my writing. My plan was just to go back to free verse. But I got hooked on the form and started liking some of the little poems that came out of it, and then they started being accepted by really good places like The Atlantic Monthly and The Southern Reviewand Shenandoah.
JF: Maybe I should start writing minutes.
CSB: Since my book came out, people all over are writing in that form, and I have seen at least two books written in that form. That’s one of the reasons I wanted to write the preface, because people were thinking that I had invented that form. And I wanted to make sure credit went where credit was due. My publisher was the one who did some research and found out who actually invented it.
JF: Your poem “Kingdom” addresses your brother’s death from AIDS. Do you think writing about AIDS is crucial for some reason?—this is related to whether poetry has a direct political or social role.
CSB: I didn’t see it as [political]. I’m sort of too small-minded, and I’m not saying that to be disingenuous or to come across as naïve, but my scope is pretty narrow—it’s just that one of my philosophies is to write the poems that need to be written, and that’s what my family was dealing with. It was the hardest thing we had ever been confronted with, the most painful, and so those were the poems that needed to be written. I didn’t think at all that this is the subject that needs to be out there. Usually when I think, “Here’s something a poem needs to be written about,” I get as far away from pen and paper as I possibly can.
JF: Here’s a related question then. Is it important for white Southern writers, given the horrors of the past, to write about race?
CSB: I wish that people would be more honest about that. It’s hard to write about honest experience without using language which is just a fact of our history . . . this is probably dangerous to say, but I don’t know how anybody brought up in the South could not have those remnants of emotional reaction to racial issues.
JF: This seems very much a matter of generation as well as place.
CSB: I grew up with the mythology that blacks were inferior. I grew up with that mythology from the neighborhood. I always heard mixed things. On the one hand: everybody’s equal. Then I would see and hear things that made me think: well, that doesn’t sound like everybody’s equal. It was like looking at a table and being told you were looking at a chair. And when you grow up with that, it doesn’t go away, on an unconscious level. But then you become aware of it, do a double take and say, “This is not rational, this is old stuff.” You have to be aware of that mythology you grew up in, and realize that it was a false mythology.
JF: Now that you’re teaching in the Low-Residency MFA Program at Queens University of Charlotte, has teaching graduates and being involved in that program changed you? Has it altered the relationship between your teaching work and your writing work?
CSB: I think it has. In the past, and I hate to say this because I had such wonderful students when I taught undergraduates at Queens, but I felt sometimes I was too much of a cheerleader for their writing. And I’m not a cheerleader anymore. Because these students are already serious about it. They are writers, they are not people I have to convince of anything, and I don’t even have to convince them of my theories of poetry and what a poem is. I give it to them as mine, and whether they buy it or not, it’s not any of my business.
JF: There’s so many different faculty in a low-residency program, a lot of different styles.
CSB: That used to worry me about my undergraduate work, because I was the only one, I was the creative writing department, and it bothered me that the students were not presented with other styles. Nobody could be any different from me than, say, Sally Keith in the MFA Program, and it makes me more comfortable with my students because I know they’ll move on from what they’ve experienced with me to other people, and they’ll get this broad experience of styles and philosophies, which is another reason I can just relax and do what I believe in.

domain: artistic


text:
Amateur Baseball: Nisswa starts playoffs hot
Victory League roundup
Nisswa 11, St. Mathias 0
NISSWA — Jeremiah Piepkorn went 3-for-4 with a home run and five RBIs to help the top-seeded Nisswa Lightning knock off the No. 8 St. Mathias Devils 11-0 in the North/East Division Playoffs Saturday, July 23.
Chris Pederson went 2-2 with a double and two RBIs for the Lightning. Matt Casperson had two hits and three RBIs.
Aaron Jenkins was the winning pitcher and struck out four in six innings.
St. Mathias 0 3 0
Nisswa 11 13 0
WP: Aaron Jenkins. LP: Luke Zontelli. 2B: N-Kody Ruedisili, Chris Pederson, Matt Casperson. HR: N-Jeremiah Piepkorn.
Nisswa 10, Buckman 4
NISSWA — Nicholas Nelson went 3-for-5 with two home runs as top-seeded Nisswa defeated Buckman 10-4 in the Winner’s Bracket of the North/East Division Playoffs Sunday, July 24.
Kody Ruedisili went 3-5 with a home run for the Lightning as well. Aaron Jenkins also launched a home run in the win.
Jack Suska and Joe Kahl blasted home runs for Buckman in the loss.
Nate DeChaine pitched a complete game with five strikeouts to get the win.
Buckman 4 8 0
Nisswa 10 14 0
WP: Nate DeChaine. LP: Todd Robinson. HR: N-Kody Ruedisili, Nicholas Nelson (2), Aaron Jenkins; B-Joe Kahl, Jack Suska.
Buckman 11, Foley 6
FOLEY — Buckman’s Andrew Rueckert blasted two home runs in the Buckman Billygoats 11-6 win over the Foley Lumberjacks Saturday, July 23.
Noah Boser tallied four hits and Matt Tautges got the complete game win.
Buckman 11 12 2
Foley 6 8 5
WP: Matt Tautges. LP: Alex Foss.
Lakers 5, Brewers 4
PIERZ — Ryan Diers went 2-for-2 with two doubles as he helped the No. 3 Pierz Lakers defeat the No. 6 Pierz Brewers 5-4 in the first round of the North/East Division Playoffs Saturday, July 23.
Noah Cekalla got the win with six innings pitched and eight strikeouts.
The Brewers were led by Michael Leidenfrost who ripped a double and Rylee Rauch with a triple.
Ryan Stuckmayer tallied three hits for the Brewers in the loss. Cody Kimman suffered the loss and struck out five in six innings pitched.
Brewers 4 8 0
Lakers 5 9 0
WP: Noah Cekalla. LP: Cody Kimman. 2B: B-Micahel Leidenfrost, L-Paul Herman, Ryan Diers (2). 3B: B-Rylee Rauch.
St. Mathias 6, Bulldogs 3
ST. MATHIAS — Hunter Wicklund went 4-for-5 with four stolen bases to help the No. 8 St. Mathias Devils defeat the Pierz Bulldogs 6-3 in the North/East Division Playoffs Saturday, July 23.
Dillon Solid picked up the win with two strikeouts.
Pierz was led by Chase Becker who went 2-3 with two walks.
Pierz 3 8 3
St. Mathias 6 5 1
WP: Dillon Solid. LP: Max Barclay. SV: Alex Guggisberg.
Lakers 4, Fort Ripley 2
FORT RIPLEY — Preston Rocheleau went 1-for-2 with a double and two RBIs for the No. 3 Pierz Lakers in their 4-2 win over the No. 2 Fort Ripley Rebels in the Winner’s Bracket of the North/East Division Playoffs Sunday, July 24.
Noah Cekalla and Brady Petron also had doubles for the Lakers in the win.
Carter Petron struckout 11 batters in the win for the Lakers.
Fort Ripley was led by Alex Haapajoki who went 2-for-4 with an RBI.
Lakers 4 8 0
Fort Ripley 2 4 0
WP: Carter Petron. LP: Bryce Flanagan. SV: Ryan Diers. 2B: L-Noah Cekalla, Preston Rocheleau, Brady Petron.
Brewers 10, Aitkin 3
PIERZ — Preston Veith recorded a double and drove in three runs for the No. 6 Pierz Brewers in their 10-3 win over the No. 7 Aitkin Steam in the Loser’s Bracket of the North/East Division Playoffs Sunday, July 24.
Peter Schommer got the win and struck out six with seven innings pitched.
Aitkin was led by Landon Janzan who went 4-for-4 with two doubles and a home run.
Aitkin 3 8 0
Brewers 10 6 0
WP: Peter Schommer. LP: Jesse Goettig. 2B: A-Landon Janzen (2), Nathan Ehnstrom, Carson Kullhem; B-Preston Veith. HR: A-Landon Janzen.
Fort Ripley 8, Aitkin 7
FORT RIPLEY — The Fort Ripley Rebels beat the Aitkin Steam 8-7 Saturday, July 23. Fort Ripley tallied nine hits while the Steam recorded 12.


text:
- An international research team identified a novel molecular pathway believed to cause gout and its progression to erosion of joint tissue.
- Researchers believe lubricin, a protein found in joint fluid, may serve as a novel therapeutic target for prevention and treatment of gout.
- Researchers made the discovery, in part, by studying a woman who had developed urate crystal deposits and joint erosion but did not show high urate levels in her blood.
Gout, a common form of inflammatory arthritis, can cause intense pain, swelling, and stiffness in the joints.
A torment on humanity since ancient times, gout typically affects one joint at a time, often the joint at the base of the big toe.
The condition impacts more than 3 million people in the United States, according to the American College of Rheumatology.
The affliction occurs more frequently in men, post-menopausal women, and people with kidney disease.
An international research team led by University of California San Diego School of Medicine, has identified a novel molecular pathway that causes gout and its progression to erosion of joint tissue.
The researchers published their
Hyperuricemia, an elevated level of uric acid in the blood, can lead to the development of crystals of uric acid forming within a joint, which causes inflammation.
Individuals with gout also often have high levels of uric acid in their
However, hyperuricemia doesn’t always cause gout.
“There are factors well beyond having a high serum rate to determine who gets gout, who doesn’t get gout,” Dr, Robert Terkeltaub, a professor at the University of California San Diego School of Medicine, the section chief of rheumatology at the Veterans Affairs San Diego Healthcare System, and senior author of the study, told Medical News Today.
In their paper, the researchers discussed their study of a 22-year-old woman with an unusual case of gout. She had developed urate crystal deposits and had erosion in her joints but did not show high levels of urate in her blood.
For their study, researchers used
They also utilized quantitative proteomic methods, a technique that allows for a comprehensive analysis of proteins, to identify a molecular pathway causing the patient’s condition.
They tested specimens from the young woman, her parents, and others not associated with the case.
Ultimately, researchers identified a molecular pathway that was disrupted in the young woman. Their findings centered on
Researchers identified numerous proteins that were lower in the woman’s joint fluid than the joint fluid of either of her parents and lower than pooled results from four healthy controls.
“We looked for something that would either be tenfold decreased in the patient… relative to the mother or father and the control or tenfold increased in the patient relative to the mother or the father and the healthy control. And we found about a dozen proteins that were markedly decreased in the patient, Terkeltaub said.
One of those proteins was lubricin. Researchers then looked at 18 people with common gout and uncontrolled hyperuricemia. Of those, five also had low levels of lubricin.
“it’s been unclear why uric acid is so enriched in the joint fluid in gout patients compared to blood and we found a mechanism whereby cells and the lining of the joint actually respond to inflammation by increasing the production of uric acid in the joint and lubricin inhibits that… inhibits the ability of the crystals to deposit, inhibits the ability of uric acid to get raised in the joint itself and was already appreciated to decrease the ability of the crystals to stimulate cells. So this is a novel pathway that probably helps in a major way to explain why some people get gout, and most others don’t… and why gout progresses in some people to be a disease that really damages the joints,” Terkeltaub said.
In another part of the study, researchers used mice engineered to not have lubricin and mice with lubricin. They injected Interleukin-1β, an inflammatory cytokine, into the knee joints of the rodents.
“In the mice that didn’t make lubricin, there was an enrichment of the key enzyme that actually makes uric acid, xanthine oxidase, in the cells called macrophages in the joint lining,” Terkeltaub explained.
The experiment suggests lubricin suppresses the secretion of urate and xanthine oxidase by activated white blood cells, and also blocks urate from crystallizing in the joint.
The study indicates lubricin could work as a biomarker for gout, Dr. Puja Paul Khanna, an associate professor in the department of Internal Medicine at the University of Michigan Medical School, told MNT. She was not involved with the study.
“In the mouse models, they are seeing that even if you did not have a high level of uric acid, but you are seeing damage because of those tiny little, you know, monosodium urate crystals happening already. That’s the pathway that we could block because we’ve identified lubricin as the reason,” Khanna said. “If the mice are deficient, meaning [they] lack lubricin, the [monosodium urate] crystals have a higher likelihood of depositing themselves and damaging that joint. Right? And the same needs to be studied further in humans.”
Terkeltaub stressed that the study shows the role of lubricin goes beyond lubricating joint tissues.
“Lubricin is something that’s really involved in the what we call the homeostasis of uric acid in the joint and also does a whole bunch of other things: inhibits inflammation caused by the crystals and it limits the crystals from forming,” he said.
Whether or not a person who has hyperuricemia develops gout, Terkeltaub explained, may be influenced by gene variants that the individual has for lubricin and other molecules that control lubricin.
Dr. Theodore Fields, a rheumatologist at Weill Cornell Medicine and Hospital for Special Surgery in New York who was not involved in the study, told MNT that this study illustrates more can be learned about the pathogenesis of gout.
“It makes perfect sense that factors such as lubricin deficiency play a role in some patients because we continue to have major knowledge gaps about why some patients get gout and some don’t, even if both have the same level of serum urate,” he said.
Terkeltaub plans to do future research exploring biomarkers for gout and looking at whether lubricin could work as a novel therapeutic target for the prevention and treatment of gout.