Seriously. Can you blame the guy?
Sam Raimi created the first modern trilogy in CBM history. It was acclaimed by fans and initially, lauded by critics. Spider-Man 2 is still among the top five in everyone’s comic book movie history, and that was 2004.
Sure, Spider-Man 3 carried a big sack of suck with a less-than-impressive Venom, which is what many nerds really wanted to see. Nonetheless, his vision of the friendly neighborhood guy set the standard for what a modern CBM should be (due respect to the Donner cuts of Superman and Elfman’s quintessential classic Batman).
So, why didn’t he get a fourth? Why dump that vision and give us a reboot and arguably the best director/movie duo — The Amazing Spider-Man and Marc Webb (in name only)?
Answer: Who the hell knows. That includes Sam Raimi who sat down with Ethan Alter of Yahoo! Entertainment (yes, Yahoo is still a thing).
15 Years Later and Still Butthurt
It has been 15 years since Sam Raimi was thanked for his Marvel service; yet, he still bemoans the day they let him go. While out promoting his latest production work, Crawl, the topic of the Webhead came up because nerds:
“I think about it all the time,” Raimi shared with Yahoo! “It’s hard not to, because each summer another Spider-Man film comes out! So when you have an unborn one, you can’t help but think what might have been. But I try to focus on what will be, and not look into the past.”
Spider-Man 4 was supposed to be the culmination of his original vision, but because the aforementioned fart-and-fall-down moment that was Spider-Man 3, the next film in the saga seemed a little cursed.
He was planning on bringing back Tobey to play Peter Parker. And Michael Keaton who? Raimi envisioned a more grizzled version of Peter’s biggest challenge in ‘Vulture’, to be played by the magnificent John Malkovich. Did you know Anne Hathaway was considered for SM4? As ‘Black Cat’ though. Oh yeah, if you know Raimi, you know The Evil Dead. Raimi wanted his cult hero Bruce Campbell to play Mysterio.
As you may know, Raimi wasn’t the biggest fan of the script and ghosted the project. Don’t like The Amazing Spider-Man? It was Raimi who blessed it and the reboot.
Raimi’s friend and fabled storyboard artist Jeffrey Henderson recently published some drawings on his website about the “what could have been” project along with some revealing thoughts:
“It would’ve been one absolutely kick ass movie,” he wrote. “We were working on some crazy cool stuff, because everyone…felt that Spidey 3 was a bit of a ‘missed opportunity’, [and[ really wanted to help Sam take SM4 to another level so he could end the series on a high note.”
Just look at this!
Kinda like the torture Zack Snyder is causing DC stans, huh? That’s what you could have had, Spidey fans. Ah well, let’s pour some out to what could have been and hope Raimi comes back to Marvel in some fashion. His vision was beyond reproach, something Kevin Feige has mastered.
Sleep well, Marvel stans.
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To investigate the olfactory/gustatory functions of patients with inflammatory bowel disease (IBD) by smell/taste tests, and to determine if disease activity or medication might influence the olfactory/gustatory functions of patients.
Patients and Methods
In total, 59 IBD patients (37 Crohn's disease (CD) and 22 ulcerative colitis (UC) patients) were studied using “Sniffin' sticks” and “taste strips” for olfactory and gustatory tests, respectively, and compared to healthy controls and published normative data.
Among IBD (CD and UC) patients, the values for odor threshold, but not for odor identification or discrimination, were significantly lower than that of the normative data. Further, these patients showed lower values than the normative taste values and the control group for all tastes, except sour; 57.6% of the IBD patients were hyposmic, while 30.5% were hypogeusic. Subjective self-assessments showed that the patients were not aware of their reduced olfactory/gustatory functions. There were no relevant differences in taste and smell abilities between the CD and UC patients. Disease activity and treatment did not influence the olfactory/gustatory functions.
IBD (CD and UC) patients exhibited significant reductions in the olfactory and gustatory functions. Therefore, patients should be tested by smell/taste tests, in order to be adequately informed of their olfactory/gustatory functions and provided an understanding of how to overcome their limitations, and thus improve their quality of life.
Citation: Steinbach S, Reindl W, Dempfle A, Schuster A, Wolf P, Hundt W, et al. (2013) Smell and Taste in Inflammatory Bowel Disease. PLoS ONE 8(9): e73454. https://doi.org/10.1371/journal.pone.0073454
Editor: John I. Glendinning, Barnard College, Columbia University, United States of America
Received: January 29, 2013; Accepted: July 21, 2013; Published: September 25, 2013
Copyright: © 2013 Steinbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Inflammatory bowel disease (IBD), consisting of the main clinical phenotypes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing inflammatory disorder of the gastrointestinal tract. CD and UC are complex diseases arising from the interaction of multiple mutations in genes relevant for the regulation of the intestinal immune system, a set of yet poorly defined environmental factors, and the patients' intestinal microbiota . The environmental factors influencing the pathogenesis of IBD are still not fully understood. However, epidemiological studies have shown that the incidence of IBD rises in developing populations adopting industrialized urban lifestyles , . The consumption of foods that are low in fiber, high in sugar, and high in animal fat has been proposed to increase the risk for IBD , . In particular, CD patients have been shown to consume large amounts of sucrose and refined carbohydrates, whereas they consume few fruits and vegetables –. CD patients commonly have weight loss and nutritional impairment at diagnosis . In CD, 70% of children suffer from weight loss; in UC, 34% of children are affected . In children, IBD, and particularly CD, can lead to an impairment of growth and development. In adults, weight loss is assumed in 65–75% of CD patients and in 18–62% of UC patients . The inflammatory response in IBD patients leads to a reduced resorption of iron; a patient who has a fistula, stenosis, and inflammation can have impaired nutrition leading to significant weight loss, even though the patient might have a relatively large area of uninvolved mucosa in the small intestine. However, some patients continue to experience difficulties in gaining weight, even while they are in complete remission. Although weight loss is a common problem in IBD, some patients gain excessive weight, masking malnutrition problems, such as reduced bone mass or nutritional deficiencies.
Temmel et al.  described that patients with reductions in or loss of smell have problems with cooking (73.25%) or appetite loss (56.25%) and often eat rotten (50%) or burnt (30%) food. Thus, such patients often lose weight . However, other patients gain weight . Taste consists of the following qualities: sweet, sour, salty, bitter, and umami. Odors from the food or in the oral cavity reach the olfactory receptor cells in the nose through the retronasal way; all odors are smelled in this manner. It is assumed that 80% of the information in a meal is transmitted through the sense of smell . Therefore, smell seems to be critical to experience a food's flavor. Regarding the higher sucrose consumption in CD patients, the question arises if IBD patients suffer from reductions in the olfactory and gustatory functions and thus consume more sucrose to overcome the deficits and make their meals more interesting. To our knowledge of existing literature the olfactory function (odor identification, discrimination, and threshold) of IBD patients has not been investigated by smell tests so far. Additionally, in this study, the gustatory function of IBD patients was tested by a new taste test employing impregnated taste strips. Former investigations of the gustatory function in CD patients used the Henkin's pipette method , –. In this study, the UC patients were also investigated for the olfactory and gustatory functions, and the effects of medication and disease activity on smell and taste were evaluated.
Patients and Methods
In this case-control study, 59 IBD patients (37 CD and 22 UC patients) from a specialized IBD outpatient unit were included. All patients provided written consent for their participation in this study. Ethical approval was obtained for the conduct of the study from the Ethics Committee of the Faculty of Medicine at the Technical University of Munich (Number: 1677/06, amendment 3).
Twenty-three healthy volunteers, frequency-matched for age and sex to the patient samples, were used as a control group for the taste evaluation. They underwent exactly the same taste testing procedure as the patients (see below). Twenty-two healthy female volunteers (mean age, 43.6±5.9 years; range, 36–55 years) were tested by the same “Sniffin' Sticks” test battery that was used in the IBD patients to validate whether the smell test results for the IBD patients were comparable with those of the more than 3,000 healthy individuals investigated by Hummel et al. . As there were no significant and relevant differences between the values of the healthy female volunteers (mean values: odor identification, 14.1±1.4; odor discrimination, 13.1±1.4; odor threshold, 9.5±1.9) and the values of the age-matched female group investigated by Hummel et al. , the values of IBD patients could be compared with that of the normative data from Hummel et al. .
After ear, nose, and throat examinations, the patients assessed subjective topics, such as appetite or the ability to perceive smell and taste. The assessments were based on a visual analogue scale (VAS), with the score for each variable ranging from 0 to 100 (0 = complete loss of appetite and perception of smell or taste; 100 = excellent appetite and perception of smell or taste). Thereafter, smell and taste testing was performed.
Smell testing was performed using “Sniffin' Sticks”. This test battery consists of 3 subtests for odor identification (ID), odor discrimination (DIS), and odor threshold (THR) and is well validated and highly recommended by the “Working Group Olfaction and Gustation” of the German Society for Otorhinolaryngology, Head and Neck Surgery . Odors were presented in felt-tip pens, the cap was removed, and the tip was positioned approximately 2 cm in front of patient's nostrils for 3 s.
For the ID test, patients separately sniffed 16 pens of different odors. Patients were asked to select the source substance that matched the presented odor from 4 different items in a forced-choice procedure (4-alternative-forced choice). The DIS test kit contained 48 pens arranged in 16 triplets. In each triplet, 2 of the pens contained the same odor, while the third pen contained a different odor. Patients were asked to identify the pen with the different odor (3-alternative-forced choice). The THR kit also contained 48 pens arranged in 16 triplets. In each triplet, 2 of the pens contained a solvent, but the third pen was impregnated with different concentrations of an n-butanol solution with a concentration range starting from 4%. The triplets were presented to the patients from the lowest to highest n-butanol concentration. From each set, the patients were prompted to choose the pen that differed in smell from the others. They did not need to experience an actual odor, only a slight subtle effect such as a difference in intensity. After choosing the pen containing n-butanol from the triplet, the same 3 pens were shuffled and presented again in a random order. If the patient correctly chose the n-butanol pen in a triplet the second time, a reversal of the staircase was initiated, until the patient could no longer identify the n-butanol pen in the triplet. The THR value is represented as the mean of the last 4 out of the 7 staircase reversal test values. Patients were blindfolded during the THR and DIS tests to avoid visual identification of the pens. Normative values: Hummel et al.  published normative values for the “Sniffin' Sticks” after investigating more than 3,000 healthy individuals. Both sexes, as well as 4 defined age groups, were considered separately. Additionally, hyposmia was defined as a 10th percentile value or less in healthy individuals aged 16–35 years. Thus, THR values of 6.5 or less in women and of 6.0 or less in men were suggestive of hyposmia (versus normosmia).
Taste testing was performed using “taste strips”. A total of 16 filter paper strips were impregnated at 1 end with 1 of the 4 types of taste (sweet, sour, salty, and bitter) in 1 of the following 4 concentrations: 0.05, 0.1, 0.2, or 0.4 g/mL of sucrose (sweet); 0.05, 0.09, 0.165, or 0.3 g/mL of citric acid (sour); 0.016, 0.04, 0.1, or 0.25 g/mL of sodium chloride (salty); and 0.0004, 0.0009, 0.0024, or 0.006 g/mL of quinine hydrochloride (bitter) . Taste strips were placed on 2 sides of the patient's tongue, approximately 1.5 cm from the tip. Patients were instructed to keep their tongues protruded during testing. They were asked to identify the taste stimuli by forced-choice procedures. Correct identification of each taste was scored on a scale of 0–4, with a total of 16 points for 1 side of the tongue and 32 points for both sides of the tongue. Normative values: Mueller et al.  published normative values for the “taste strips” after investigating 69 healthy individuals. Landis et al.  defined hypogeusia as a 10th percentile value or less in healthy individuals aged 18–40 years using a bilateral taste strip test. A value less than 19 in women and less than 17 in men (range, 0–32) would be regarded as hypogeusic (versus normogeusic).
Statistical analysis was performed using SPSS software (version 16.0, SPSS Inc., Chicago, IL, USA) and R, version 2.14.1. Descriptive data are presented as absolute and relative frequencies for categorical data and as mean ± standard deviation or median (range) for continuous data. The relationship between the smell and taste test results and the subjective assessment of smell and taste (VAS) was performed using the Spearman's rho correlation coefficient. To compare the patients' smell values with the normative smell data , we performed a three-way ANOVA with the factors group (patient or control), sex, and age group to account for the specific age and sex-distributions of our sample. For the comparison of taste values with the normative data , the mean of the left and right sides of the tongue was used for the patients, as only unilateral data were available for the published control sample. Total taste values (sum of the 4 taste qualities) of the patients were compared with the normative data using a two-sample t-test, as the normative taste values were not available by sex or age group. Following a significant test of total taste values, post-hoc two-sample t-tests were performed for each individual taste quality to compare the patients' data with the normative data. For comparison of the taste values with our own healthy control group or within subgroups of IBD patients, taste values for the left and right sides of the tongue were added for each individual. Taste values of all 4 taste qualities simultaneously (sweet, sour, salty, and bitter) were compared between the patients and our own healthy control group by multivariate ANOVA (MANOVA), again with the factors group (patient or control) and the sex and covariate age (continuous), using the Pillai-Bartlett statistic. Following a significant MANOVA, univariate post hoc linear models with the same variables were used. For subgroup comparisons (CD versus UC; subgroups based on disease activity, clinical variables, or treatment), analogous MANOVAs were performed for the taste and smell tests. All reported p-values were nominal and should be compared to an adequate significance level to account for multiple testing. For the 2 pre-specified hypotheses that the olfactory and gustatory functions are reduced in patients with IBD, an adequate significance level would be an α = 0.025 each (comparison of smell and taste in the patients versus the control groups). Within the IBD group, subgroup comparisons were performed, covering a total of 28 exploratory hypotheses regarding the influence of 14 independent variables (disease activity, clinical variables or treatment) on 2 dependent variables each (taste and smell). Consequently, these should all be evaluated against a significance level of α = 0.0018.
The patients' characteristics, duration and severity of disease, and treatments are summarized in Table 1. No patient had hypo- or hyperactivity of the thyroid gland, diabetes, neurological disorders, tumors or nasal operations in the medical history. Two CD patients and 1 UC patient used angiotensin-converting-enzyme-inhibitor for high blood pressure. None of the patients took medications for depression.
Smell and taste test results based on subjective self-evaluation
Table 2 summarizes the subjective assessment results of smell, taste, appetite, parosmia, and phantosmia on VAS. There was no significant correlation between the smell and taste test values and the VAS-assessed results in the IBD patients.
Smell test results compared to the normative data
IBD patients had significantly lower THR values than those of the healthy controls  (p = 4 * 10−12, ANOVA adjusted for age group and sex). This effect was also significant if the UC (p = 9 * 10−5) and CD (p = 5 * 10−9) subgroups were compared separately to the published normative data (Table 3). The values of ID and DIS were not significantly different from that of the normative data (p = 0.56 for ID and p = 0.42 for DIS, adjusted for age group and sex).
Taste test results compared to the normative data
The values of total taste were significantly lower in IBD patients than that of the normative data, as reported by Mueller et al.  (p = 0.002, t-test). If the UC and CD subgroups were compared separately to the published normative data, the effects were of a similar size but were only marginally significant because of the smaller sample size (p = 0.046 for UC; p = 0.01 for CD). Sweet, sour, salty, and bitter tastes differed slightly between the IBD patients and the published normative data (p = 0.10, p = 0.017, p = 0.016, and p = 0.008 respectively, Table 4). However, the sample by Mueller et al.  involved younger participants than the IDB patients in this study (Table 5), and taste ability has been shown to decrease with age , thus the observed lower gustatory function could be due to the fact that the patients were older than the controls. Therefore, 23 healthy controls (frequency-matched for sex and age) were tested using taste strips (Table 5). Their taste values were compared with those of the IBD patients, who exhibited significantly lower total taste values (p = 0.001, linear model adjusted for age and sex) and significantly lower values for the individual taste qualities (p = 1.7*10−5, MANOVA, and p = 0.002 (sweet), p = 0.0004 (salty), p = 0.0002 (bitter) for post-hoc linear models adjusted for age and sex), except for sour (p = 0.15) (Table 6). The UC and CD patients also separately showed reduced gustatory function in comparison to the healthy controls (p = 0.008 for UC; p = 4.8*10−6 for CD, MANOVA).
Hyposmia and hypogeusia
Of the 59 IBD patients, 34 (57.6%) were hyposmic (THR value below the 10th percentile ), 13 of the UC patients (59.1%) and 21 of the CD patients (56.8%). Similarly, 18 of the 59 IBD patients (30.5%) were hypogeusic (total taste score below the 10th percentile ), 7 of the UC patients (31.8%) and 11 of the CD patients (29.7%).
Smell and taste test results in relation to diagnosis, disease activity, and treatment
The UC and CD patients did not differ significantly in their smell test results (p = 0.17, MANOVA, adjusted for age and sex) and their taste test results (p = 0.56, MANOVA, adjusted for age and sex). Age (p = 0.52) and sex (p = 0.04) had no great influence on the smell test results in this sample (MANOVA for age and sex). As expected, taste ability decreased significantly with age (p = 1.4*10−5, MANOVA), while there was no relevant effect related to sex (p = 0.08) in our combined case-control sample. Disease activity, as measured using the Truelove-Witts index, the Rachmilewitz index, or the Crohn's disease activity index (CDAI), did not influence the smell and taste test values (all p>0.17, MANOVA models adjusted for age and sex). Further, the values of C-reactive protein, leukocyte count, duration of disease, fistula, stenosis, or operations had no significant influence on the olfactory and gustatory functions in the patients. An extraintestinal manifestation of disease did not influence olfactory function (p = 0.9), but was associated with a slightly differing gustatory function (p = 0.009, MANOVA, adjusted for age and sex), in particular, an improved ability to taste sour (p = 0.0008, post-hoc linear model) but not the other taste qualities (all p >0.14). The use of low-dose cortisone, azathioprine, or 5-aminosalicylic acid (5-ASA) did not influence the olfactory and gustatory functions of the patients (all p >0.12).
This is the first study to investigate the olfactory and gustatory functions in IBD (CD and UC) patients by using validated smell and taste tests. It could clearly be shown that the values of THR, but not ID or DIS, were lower in IBD (CD and UC) patients than those of the healthy individuals. Assuming that the values of THR reflect the peripheral olfactory functions in patients to higher degrees than that of the values of ID or DIS , , the patients exhibited reduced olfactory functions. By definition, 57.6% of the IBD (CD and UC) patients were hyposmic. Regarding taste, the IBD (CD and UC) patients had lower total taste test values than the participants investigated by Mueller et al.  and the healthy control group (matched for age and sex). This reduction in gustatory function was particularly strong for salty and bitter tastes and lower for sweet and sour tastes. By definition, 30.5% of the patients were hypogeusic. In routine clinical practice, taste strips have the major advantages of a long shelf-life, convenience of administration, a short time needed for testing, and possible whole mouth or lateralized taste testing. However, Mueller et al.  noticed that the sour taste quality in its lowest concentration was correctly identified by 36% of participants, whereas sweet, salty, and bitter taste qualities were correctly identified by 54%, 51%, and 52%, respectively. This might explain the difficulty that our control group had in correctly identifying the sour taste quality in comparison with the other taste qualities. In addition, Mueller et al.  described that some individuals confuse salty and sour. Individual taste blindness must be considered in interpreting taste test values. Although the patients showed reduced functions in the smell and taste tests, they subjectively rated their olfactory and gustatory functions as not being limited on a visual analog scale (VAS). The CD patients rated their olfactory and gustatory functions on the VAS (0 = no perception of smell and taste; 100 = excellent perception of smell and taste) as 79.7±26.2 and 80.4±24.5, respectively. Additionally, the UC patients rated their olfactory and gustatory functions on the VAS as 80.3±18.0 and 79.3±18.5, respectively. Using the same method, Fasunla et al.  assessed olfactory and gustatory functions on the VAS in 16 healthy individuals and reported values of 83.8±10.4 for smell and of 83.5±10.4 for taste. In addition, Steinbach et al.  reported values of 85.9±10.6 for smell and of 82.9±19.2 for taste in 87 patients with gynecological tumors after the operations and before the initiation of chemotherapy. However, patients suffering from Wegener's granulomatosis  or hereditary hemorrhagic telangiectasia  reported values of 65.7±36.8 or 65.3±27.7, respectively, for smell and 67.2±30.0 or 68.1±25.1, respectively, for taste. This means that IBD patients are hardly aware of their objectively reduced olfactory and gustatory functions. Therefore, it is necessary to test the olfactory and gustatory functions of IBD patients by smell and taste tests, to increase the patients' awareness of their olfactory and gustatory functions, and to discuss the possibilities of overcoming the deficits to improve their quality of life.
On VAS, the CD patients subjectively assessed their appetites as reduced and reported to use more sweeteners and salt for their foods, whereas the UC patients preferred more fatty meals. A low intake of fiber and a high intake of unsaturated fat, as well as high intakes of mono- and disaccharides, have been proposed to have an increased risk for CD and UC , , . These results confirm the role of diet in the pathogenesis of CD and UC, yet the pathomechanism is still unclear. The interaction of the intestinal microbiota with the intestinal immune system is an essential step in the pathogenesis of CD and UC , and new data show the strong influences of diet on the gut microbiota . However, patients suffering from hyposmia and hypogeusia may have higher consumptions of sugar, salt, and fat to make eating more pleasurable. Therefore, some patients with distorted olfactory and gustatory functions gain weight , while others complain about having low appetite and weight loss . Distorted olfactory and gustatory functions affect a patients' lives substantially (e.g., malnutrition, reduced detection of environmental hazards, social isolation, and depression) ; however, the distorted olfactory and gustatory functions are often not outwardly present.
Among the various dietary interventions for IBD patients, none has shown a striking efficacy, with the possible exception of complete enteral nutrition. Enteral nutrition appears effective in both active and quiescent CD , yet it seems to be more effective in pediatric patients . Enteral nutrition may possibly interrupt oral malnutrition in IBD patients, thereby improving the quality of life for these patients. However, for those patients suffering from active CD, corticosteroids have been shown to be superior to enteral nutrition , . Although enteral nutrition can be helpful for CD patients, it is limited by inadequate patient compliance and the high cost of enteral formula . It would be worthwhile to investigate in further studies if IBD patients with reduced olfactory and gustatory functions have improvements in their quality of life and in nutritional behavior when adding small amounts of herbs and spices (trigeminal input), glutamate, or other flavors to their foods –. Perhaps taste could be improved by prescribing oral zinc , .
CD patients can suffer from oral lesions and symptoms (e.g., halitosis, reflux, dry mouth, buccal mucosal swelling or cobblestoning, mucogingivitis, deep linear ulceration, and mucosal tags) , , whereas nasal involvement is extremely rare and reported only in a few cases of CD , . However, in our study, a large proportion of the CD and UC patients were not only hypogeusic, but also hyposmic. It appears that the inflammatory response may possibly cause the distortion of olfactory and gustatory functions. Extraintestinal manifestations show that IBD can affect tissues far away from the site of active intestinal inflammation. Circulating proinflammatory cytokines and activated immune cells trigger these symptoms , . Decreased olfactory function is associated with autoimmune disorders such as systemic lupus erythematosus and Sjögren's syndrome . TNF-a has been shown to lead to a reduced olfactory regeneration . Increased levels of circulating TNF-a  are present in IBD patients' serum and saliva ; therefore, a comparable pathomechanism can be assumed for the effects seen in this study. Recent genetic data  suggest a substantial overlap of genetic susceptibility in IBD, as well as other autoimmune diseases such as psoriasis and ankylosing spondylitis. Olfactory receptor gene clusters are located in proximity to key loci for susceptibility to autoimmune diseases, such as the major histocompatibility complex. As with a chromosomal linkage, a functional association may exist. In our study, duration of disease, severity of disease, fistula, stenosis, or operations did not significantly influence the olfactory and gustatory functions in the patients. This is consistent with a study by Zopf et al. 2009 , that showed an increased taste threshold for the detection of all 4 taste qualities in 31 active and 27 inactive CD patients, while assessing taste by a 3-drop method with exceeding dilution tests. Decreased taste perception in CD patients was also independent of disease severity in terms of inflammation . However, odorants and taste molecules seem to activate enterochromaffin cells in the bowel tract. Braun et al.  found an expression of 4 olfactory receptors in micro-dissected, human, mucosal, enterochromaffin cells, whereas Kidd et al.  identified transcripts for bitter and olfactory receptors, as well as transporters for glutamine, glucose, and bile salts in enterochromaffin cells. In the study by Braun et al. , an activation of the olfactory receptors in the enterochromaffin cells caused an elevation of the intracellular Ca2+ level and a serotonin release. Serotonin release can influence gut motility and secretion. Assuming that the olfactory receptors are equal in the nose and the bowel, decreased THR values in the smell and taste tests may possibly suggest disturbed bowel functions.
It is reported that patients with rheumatoid arthritis (RA) were often hyposmic and hypogeusic . As 9 CD patients and 5 UC patients suffered from arthritis as sources of extraintestinal manifestations (Table 1), we investigated whether patients with and without extraintestinal manifestations showed differences in olfactory and gustatory functions. Only sour taste ability was better in those with an extraintestinal manifestation. The effects of treatment with low-dose oral cortisone, azathioprine, or 5-ASA on olfactory and gustatory functions were minimal and non-significant in our patient sample. A previously published study investigating RA patients showed lower values of THR in patients taking low-dose oral cortisone . However, high doses of oral cortisone are known to be helpful in patients suffering from olfactory dysfunctions . Additionally, reversible dysgeusia has been reported as a negative side effect of azathioprine .
It is still not possible to objectively measure parosmia and phantosmia. In our study, patients were asked to subjectively assess parosmia and phantosmia on a VAS (0 = no parosmia/phantosmia; 100 = strong parosmia/phantosmia). The CD and UC patients assessed parosmia as low, whereas the UC patients (10.3±18.5) assumed phantosmia much more intensive than the CD patients (1.8±8.6) or the patients suffering from irritable bowel syndrome (6.4±18.5) and Wegener's granulomatosis (0.5±2.0), using the same method based on a VAS , . Reden et al.  did, however, show that phantosmia has no prognostic significance in patients suffering from olfactory dysfunctions. In addition, Landis et al.  concluded that idiopathic phantosmia does not seem to be a reliable predictor of severe disease.
IBD (CD and UC) patients exhibited a significant reduction in the olfactory and gustatory functions and a large proportion were hyposmic, hypogeusic, or both. Although the patients had reduced values in the smell and taste tests, they rated their chemosensory functions as not limited on a VAS. Therefore, smell and taste tests should be recommended for IBD patients to measure such deficits, to inform them of the results, and to give them advice on how to overcome limitations and improve their quality of life.
Conceived and designed the experiments: SS WR W. Huber W. Hundt. Performed the experiments: SS AS W. Huber W. Hundt. Analyzed the data: AD PW. Contributed reagents/materials/analysis tools: SS. Wrote the paper: SS WR AD PW.
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- 23. Landis BN, Welge-Luessen A, Brämerson A, Bende M, Mueller CA, et al. (2009) “Taste strips” – a rapid, lateralized, gustatory bedside identification test based on impregnated filter papers. J Neurol 256: 242–248.
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- 26. Fasunla JA, Hundt W, Lutz J, Förger F, Thürmel K, et al. (2012) Evaluation of smell and taste in patients with Wegener's granulomatosis. Eur Arch Otorhinolaryngol 269: 179–186.
- 27. Steinbach S, Hummel T, Böhner C, Berktold S, Hundt W, et al. (2009) Qualitative and quantitative assessment of taste and smell changes in patients undergoing chemotherapy for breast cancer or gynecologic malignancies. J Clin Oncol 10: 1899–1905.
- 28. Steinbach S, Fasunla AJ, Schäfers SP, Lahme CM, Geisthoff UW, et al. (2012) Does hereditary hemorrhagic telangiectasia affect olfactory or gustatory function ? Am J Rhinol Allergol. 26: 463–468.
- 29. Hou JK, Abraham B, El-Serag H (2011) Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 106: 563–573.
- 30. Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM, et al. (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488: 178–184.
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- 36. Schiffmann SS, Sattely-Miller EA, Taylor EL, Graham BG, Landerman LR, et al. (2007) Combination of flavor enhancement and chemosensory education improves nutritional status in older cancer patients. J Nutr Health Aging 11: 439–454.
- 37. Yeomans MR, Gould NJ, Mobini S, Prescott J (2008) Acquired flavor acceptance and intake facilitated by monosodium glutamate in humans. Physiol Behav 93: 958–966.
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- 45. Adams DH, Eksteen B (2006) Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol 6: 244–251.
- 46. Perricone C, Shoenfeld N, Agmon-Levin N, de Carolis C, Perricone R, et al. (2013) Smell and Autoimmunity: A Comprehensive Review. Clin Rev Allergy Immunol 45: 87–96.
- 47. Turner JH, Liang KL, May L, Lane AP (2010) Tumor necrosis factor alpha inhibits olfactory regeneration in a transgenic model of chronic rhinosinusitis-associated olfactory loss. Am J Rhinol Allergy 24: 336–340.
- 48. Murch SH, Lamkin VA, Savage MO, Walker-Smith JA, MacDonald TT (1991) Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut 32: 913–917.
- 49. Szczeklik K, Owczarek D, Pytko-Polonczyk J, Kesek B, Mach TH (2012) Proinflammatory cytokines in the saliva of patients with active and non-active Crohn's disease. Pol Arch Med Wewn 122: 200–208.
- 50. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, et al. (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491: 119–124.
- 51. Braun T, Voland P, Kunz L, Prinz C, Gratzl M (2007) Enterochromaffine cells of the human gut: sensors for spices and odorants. Gastroenterology 132: 1890–1901.
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- 53. Steinbach S, Proft F, Schulze-Koops H, Hundt W, Heinrich P, et al. (2011) Gustatory and olfactory function in rheumatoid arthritis. Scand J Rheumatol 40: 169–177.
- 54. Steinbach S, Hundt W, Zahnert T (2008) The sense of smell in daily life. Laryngorhinootologie 87: 657–668.
- 55. Ellul P, Vella V, Vassallo M (2007) Reversible dysgeusia attributed to azathioprine. Am J Gastroenterol 102: 689.
- 56. Steinbach S, Reindl W, Kessel C, Ott R, Zahnert T, et al. (2010) Olfactory and gustatory function in irritable bowel syndrome. Eur Arch Otorhinolaryngol 267: 1081–1087.
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domain: literature


text:
View of excavations on the west side of Trench 54 where brick robbers had removed several massive Harappan Period baked brick walls (c.
Ancient Indus walls.
In 2001, excavation of perimeter wall  was extended to the Northwest. Here the surface of the wall is being cleared and the bricks outlined. Note the excavation in the foreground left where there was no mud-brick.
View of the preserved surface of perimeter wall  excavated in 2001 looking Southeast toward the area excavated from 1993 to1997.
Lateral view of remnants of brick walls and massive mud brick platforms of the Harappan and Early Harappan (Kot Diji) Periods on the west side of Trench 54. Looking North.
Plan view of the portion of perimeter wall  excavated in 2001. The pattern of the bricks suggests a complicated series of additions to the inside of the structure that are not yet well understood.
North-South section plan of Harappan (Period 3) and Early Harappan (Period 2) wall remnants and mud brick platforms on the west side of Trench 54.
Overview of the excavations showing the Harappan (Period 3) and Early Harappan (Period 2) walls on the west side of Trench 54. North is to the right.

domain: geography


text:
CNN A growing number of women and men say they are bisexual, according to the latest national survey by the Centers for Disease Control and Prevention. Chat with us in Facebook Messenger. Find out what's happening in the world as it unfolds. Photos: Know your identity terms. New terms are entering the cultural lexicon as people endeavor to codify their sexual orientation or gender.
Kinsey scale Klein grid. The guys were so used to pornography and thinking of sex and relationships as entirely focused on them, that they did not know how to satisfy a woman emotionally or sexually. Despite the visibility and acceptance of bisexuality Bi sexual fad by the effects of bisexual chic, this phenomenon ffad been criticised for its "trendy" property rather than a genuine act of advocating bisexual equality. Oh, Webcam sex vids. Men are just as likely to be bi as women. Researchers at Cornell University, examining data collected from a representative sampling of young Americans Bi sexual fad included more than 20, individuals in 80 communities across the United States, found that
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Bisexual chic is a phrase used to describe the public acknowledgment of bisexuality or increased public interest or acceptance of bisexuality.
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Verified by Psychology Today. Sax on Sex. You've probably heard about Constance McMillen by now. She's the openly-gay high school senior who wanted to take her girlfriend to the high school prom at Itawamba High School in northern Mississippi. The principal told the girls that all prom couples have to be boy-girl. In response, the school board canceled the prom.
District Court Judge Glen Davidson to intervene and reinstate the prom. The judge ruled that although the school had violated Ms. McMillen's civil rights, he wouldn't force them to hold a prom.
On Friday, April 2, Ms. According to the Associated Press, her girlfriend's parents wouldn't allow the year-old girlfriend to go, so McMillen escorted another young woman instead. To make the story even worse, it turns out that the alternative prom at the Fulton County Country Club was a fake , with only seven kids attending, according to McMillen. The real prom, i.
The story continues to attract national attention because it's just so darn quaint. Imagine: There are still people who get upset when they see girls kissing other girls! Who knew? Not any more. As a physician and a psychologist, what I found missing in the noise surrounding the Constance McMillen story was any serious discussion of why a growing number of girls self-identify as lesbian or bisexual. Not that there's anything wrong with that, as Seinfeld might say.
But why are young women today at least three times more likely than their brothers to identify as bisexual or homosexual? There is no comparable crowd of young male celebrities rushing to assure us that they go both ways.
Imagine a young man singing "I kissed a boy and I liked it. Why not? Over the past seven years, I've posed this question to hundreds of teenagers and young adults across the United States.
The most common answer I get isn't really an answer. They're just doing it for attention. It's not for real. I point out, as gently as I can, that that response doesn't answer my question. Pretending to be lesbian or bisexual doesn't explain why a growing proportion of young women are lesbian or bisexual. Female sexuality is different from male sexuality. If a straight boy kissed another boy, perhaps to amuse some girls who might be watching, he would be unlikely to undergo a change in sexual orientation as a result.
But, as Professor Roy Baumeister at Florida State University and others have shown, sexual attraction in many women seems to be more malleable see note 3 below. If a teenage girl kisses another teenage girl, for whatever reason, and she finds that she likes it—then things can happen, and things can change. If a young woman finds her soulmate, and her soulmate happens to be female, then she may begin to experience feelings she's never felt before. Which brings me to the second point I've encountered in my interviews with young people.
Twenty years ago, when I opened my practice in a suburb of Washington DC, it was rare to find year-old boys who were looking at pornography every day. Today it's common—in fact, it's becoming the norm.
When I meet with a group of year-old boys and I ask them, "how many of you guys subscribe to a porn site? I don't believe them. But today, no boy wants to admit that he's the weirdo who doesn't look at online porn.
Twenty years ago, hardcore pornography was tucked away in adult bookstores. Today any year-old can access such photos online in seconds. Maybe there is. A young woman told me how her boyfriend several years ago suggested that she shave her pubic hair so that she might more closely resemble the porn stars who were this young man's most consistent source of sexual arousal. She now identifies herself as bisexual. I don't know a guy who could even comprehend the conversations we have. I wish Constance McMillen and her girlfriend all the best.
But I have to wonder: Are there so many girl-girl couples out there because the guys are such losers? Note 1: How common has bisexual and lesbian sexual orientation been among women, historically? He implies that this figure has been generally valid over time, a finding which he acknowledges poses an as-yet-unsolved mystery for evolutionary psychology.
Popular accounts of homosexual behavior often suggest that these behaviors make evolutionary sense because the people practicing these behaviors make better aunts and uncles than heterosexuals do, a theory first advanced by E.
Wilson back in the s. However, studies published in the past 20 years have provided little support for this hypothesis, and have often directly refuted it, particularly for male homosexuals. It's very difficult to estimate accurately the "true" proportion of lesbian or bisexual women 50 years ago or years ago.
In many jurisdictions 50 years ago, lesbian behavior would have been a criminal offense. In that era and in those jurisdictions, asking a woman whether she was a lesbian was equivalent to asking her whether she had committed a crime. Even when assured of confidentiality, women might reasonably under-report the true incidence of bisexual or lesbian orientation.
However, it's hard to deny that lesbian and bisexual behavior has become much more visible in our time compared with one or two generations ago. Researchers at Cornell University, examining data collected from a representative sampling of young Americans which included more than 20, individuals in 80 communities across the United States, found that Among young men, Ream, "Prevalence and stability of sexual orientation components during adolescence and young adulthood," Archives of Sexual Behavior, volume 36, pp.
The proportions in Europe might be higher. Hegna, "Sexual orientation and suicide attempt: A longitudinal study of the general Norwegian adolescent population," Journal of Abnormal Psychology , volume , pp. In a study from New Zealand, Dickson and colleagues, "Same-sex attraction in a birth cohort: prevalence and persistence in early adulthood", Social Science and Medicine , volume 56, pp.
Note 3: Maybe a straight woman is just a woman who hasn't yet met — the right woman? Professor Roy Baumeister's most relevant article about erotic plasticity is " Gender differences in erotic plasticity: the female sex drive as socially flexible and responsive," Psychological Bulletin , volume , pp. Professor Lisa Diamond has made a compelling case that many women don't discover their "true" sexual identity until their 20s, 30s or even 40s.
A woman may reach her 40s, believe that she is a straight woman, and then find herself falling in love with her soulmate—who happens to be a woman. Here are three of Professor Diamond's most relevant articles:. Note 4: John Mayer said what? John Mayer's current preference for pornography over sex with real women wasn't well-known until his interview with Rolling Stone February 4, and his March interview with Playboy magazine , in which he also explained why he now prefers porn over sex with actual women: because masturbation allows him to be in complete control.
He said: "As soon as I lose that control, once I have to deal with someone else's desires, I cut and run I'm more comfortable in my imagination than I am in actual human discovery.
Seems to me that comparing current studies of YOUNG women with older studies of the entire female population is comparing apples and oranges. You really mean to tell me that young women during the flower child era weren't all sleeping with each other too? Sure sounds like it to hear some of them talk. This comment by Anonymous is one of several written in response to my blog which share the same underlying assumption: namely, that teenage girls and young women are more likely than older women to identify as lesbian or bisexual.
Other comments below include terms such as BUG Bisexual Until Graduation , reflecting the assumption that teenage girls and young women who identify as bisexual are just "going through a phase" and that most of those women will eventually settle down as heterosexual. The scholarly research on this topic does not provide strong evidence in support of this assumption.
On the contrary, the most careful, longitudinal studies - in which researchers keep track of the same women for many years - suggests just the opposite. You will find the full citation for this study in Note 3, at the end of page 2 of my blog.
I'm a little confused now The "boys adrift" phenomenon - i. I suggest you read Chapter 6, "End Result: Failure to Launch", in my book Boys Adrift, where I describe the growing proportion of something young men who seem to care more about video games than they care about real-world interaction with young women.
You ask "why didn't all of these older lesbians identify as such when they were younger? But Professor Diamond has documented that women also go the other way, from homosexual to bisexual.
Please read Professor Diamond's articles see my Note 3, on page 2 of my blog, for the full citations. The best answer to your question appears to be that sexual orientation may simply be more fluid and more plastic in women than it is in men. A woman who divorces a "loser" husband at the age of 26, and then discovers another woman with whom she has a genuine connection, may discover that she also has the ability to experience and enjoy sexual intimacy with another woman.
If you read through the other comments, below, you will find several women who describe just such an experience. Again, please read the scholarly citations listed in my Note 3, beginning perhaps with Professor Roy Baumeister's paper. The one thing you didn't go into much in your article is sexuality and the messages being sent by the media.
Being a lesbian or bisexual is cool and hip. It's a fantasy for men of being with two women if something is good, double of something is even better. This of course reinforces to women that being a 'lesbian' or 'bisexual' is not only acceptable and that sexuality isn't a hard and fast concept , but it's also an attractive attribute to the other sex.
If a young man meets twins who are somehow the EXACT same in every aspect including personality but one twin is straight and the other bisexual, the overwhelming amount of adolescents and young-men would prefer the bisexual, due in part to the notion pornography reinforces of the threesome an ultimate conquer for a man.
Factor in the prevalence of sex toys women have and their increasing acceptance in society at least among young women and the incredible advances these sex toys specifically dildos have undergone being bisexual or lesbian doesn't have to be very much the same as the definition. Just some random thoughts about the matter.
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Why so many young people say they're bisexual | Daily Mail Online
More people than ever before in the United States identify as something other than heterosexual, a trend that signals an increase in sexual fluidity and a cultural shift toward more acceptance of diverse sexual orientations. Recently released data shows that one-third of 18 to year-olds are not heterosexual, according to research from YouGov , an international Internet-based market research and data analytics firm from the U.
The data also revealed that the number of people who identify outside of heterosexuality is steadily rising, up 5 percent since This change might be due to the growing acceptability of same-sex sexual relationships in both culture and in law, Carrie Baker, director of Smith College's Program for the Study of Women and Gender, told Newsweek.
Within the last few years, there have been more depictions of same-sex couples in movies and television, as well as more public conversations about sexual orientation and same-sex attraction. Changes in legislation have altered the context in which we live. The U. Supreme Court's landmark same-sex marriage decision and the removal of "don't ask don't tell" spurred more conversations in the media around same-sex relationships. With all of these political and cultural changes, it's possible that people simply feel more comfortable expressing their desires in this social climate, Baker explained.
Participants in the YouGov survey were asked to rate themselves on the Kinsey scale, where 0 is completely heterosexual and 6 is completely gay. Alfred Kinsey invented the scale in thes as a way to study human sexuality. The data was compared to another similar survey that was conducted by the research firm in The results were clear. One-quarter of people of all age groups identified as something other than completely heterosexual, compared to 20 percent of people in This could indicate that sexuality exists on a spectrum and it is not fixed over a lifetime, you might identify as heterosexual early in life, but later in life that might evolve, said Baker.
The context of someone's life might also influence their desires. Exposure to popular culture, movies and television that show depictions of same-sex encounters might have an influence on people.
Same-sex environments like prison and the military might also sway someone to act or have sexual feelings about someone of the same sex, said Baker. Weekly magazine, delivered Daily Newsletter Website access.

domain: sociology


text:
A substitute for Dromana Toppings which is sometimes not available and can change colour with different loads
A replacement for Lilydale Toppings. Unfortunately Lilydale is no longer produced. This is the closest copy and customers have had good results blending it with the old when topping up.
This is the easiest to use. If you have a landscaping project that could use a light grey colour, this is what you need.
A great money saving alternative. Depending on what is quarried at the time (as it can vary) it can really look good. It is probably the best crushed rock, gravel aggregate for a driveway, so you really should come and have a look at what is available.
Provides homeowners with a lot of flexibility in terms of their driveway design preferences.
A key advantage to working with loose fill materials like crushed granite is that it’s easy to create interesting shapes. All you have to do is imagine the layout and fill it in with the desired stone aggregate materials.
Crushed granite is also great for constructing a unique driveway because of the many different colours available. The colours associated with granite can accentuate other landscaping features and will work well with a wide range of natural edging materials for added beauty.
We stock four varieties including, Tyabb Brown, Lilycan, which is a replacement for Lilydale , which is no longer produced.
A 20mm crushed rock which is mainly used for under road bases, concrete slabs and as base for laying pavers. However it is also a cheaper alternative and can look great in the right landscaping situation.
We also have a 5mm Grey colour crushed granite which we find to be the easiest to use – it screeds and levels out very easily and will pack super hard. However, when choosing which material to use, the easiest product to use may not be the best product but a product that suits and enhances your landcaping design.
As a side note, a lot of people attest that crushed granite will stop any weed growth. Some people even suggest laying weed mat underneath. As someone who has a lot on his own property I can tell you this is not the case. The weed seeds will grow in the dirt which gathers on top and grow right down through the rock. So please be aware that it is a great cheap, easy to lay product but it will still require weed killer to be applied every 12 months or so.
A little thought should also be given to existing colours of your house, surrounding landscaping and neighborhood character.

domain: design


text:
On a newly constructed wall at the Nogales part of Mexico marking the US border hung white crosses with the names of those who died crossing and braving the vast unforgiving Sonora desert. Fr. Peter Neeley SJ said that he had performed several blessings of headless bodies or bones found scattered in the wasteland. They said that cayotes would carry the head of the victims to their burrows because it was the best part.
In 1691, Jesuit missionary Fr. Eusebio Francisco Kino SJ came to this area invited by the Sobaipuri Indians who wanted to know more about his religion. This was the time when the desert was a part of Spain, then Mexico, before it became American territory. Still later, it became a part of Arizona. He built some of the beautiful Spanish mission churches like Tumacacori and San Xavier del Bac (see succeeding post).
Three hundred years later, the Jesuits still work at the frontiers. Today, we are at the border of the same desert Fr. Kino once thread. However, the work is at the other side of the wall the Americans built. We wait for deportees whose dreams of a better life has been crushed to death.
Introducing us to the Kino Border Initiative mission, Fr. Neeley gave us a taste of what the illegal immigrants experienced. When we went to the Mexican immigration processing center, we were treated rudely. The people who were dumped by the US border patrol bus said that even their own people treated them like desert animals.
Even the hardened criminals deserved some humanity. To be there waiting for the migrants, which Fr. Peter do every day, was risky. I honestly was scared.
Then we walked through the streets of Nogales, passed by the cemetery where the deportees sometimes spent the night. Some of them recognized us from the breakfast earlier at the comedor, where we served hot rice coffee (kape grano), a plate of filling Mexican pasta, beans and tortillas. At some days, mass was celebrated there since they were mostly Catholic.
But some things don’t change from Fr. Kino’s time to this day. Jesuit life is marked by being at the borders, at the frontiers. Risk is what we eat.
Miles from this border, but still in the Sonoran desert, Fr. Kino’s church, the San Xavier del Bac stands majestically white; from afar, a weary native American in the 16th century would like look like the waiting arms of the father of the wayward son of the Gospels. Around 1622 in Cartagena, Columbia, St. Peter Claver SJ also waited, protected, and nursed newly-arrived African slaves. Today, the Kino Initiative waits with open arms to serve the ostracized and the persecuted.
On the road from the Mexican Immigration we took the Nogales bus. Mexican buses were like large Philippine jeepneys: seats were located at the sides, passengers faced each other. One passenger talked to Fr. John Murphy SJ my tertian master. Another who recognized me at the comedor said, “AhGonzales! Speedy Gonzales! Arriba, arriba!” We both laugh, and the guy seated across me joined in laughter. We didn’t know each other, but everyone joined the conversation as if we were friends.
The risk was making ourselves vulnerable to the possibility of persecution in living a radical truth: in the name of compassion, there are no borders. In the vision of eternity, we are all one family riding a bus towards the same destination.


Nihar Neelakanti, CEO of Ecosapiens, on Blockchain-Based Carbon Tracking and more
Nihar Neelakanti is the Co-Founder and CEO of Ecosapiens, a VC-backed platform enabling consumers to fight climate change through the world’s first carbon-backed NFT. Nihar previously worked in venture capital, spending several years at VCs, including Correlation Ventures, Kauffman Fellows, and most recently, at the prestigious Menlo Ventures, where he helped develop the climate thesis that sparked the idea for Ecosapiens. He is deeply fascinated by the opportunity to rethink economics in a way that regenerates the planet rather than extracts from it.
In this conversation, we discuss:
– Are we back?
– Crypto VC landscape
– Carbon tracking on the blockchain
– Web3 tech powering eco-conscious consumerism
– Invest in the environment
– How businesses can achieve their climate goals
– Growing in a bear market
– Using NFTs to solve climate problems
– Climate tech


Google may well be working on its Google Project Glass augmented reality visors, but British defence company BAE Systems has delivered its Tornado Helmet Mounted Cueing System to the Royal Air Force, proving that heads-up displays are already fully operational in the military.
Now operational on Tornado GR4 aircraft utilised in Afghanistan, the HMCS projects live data in front of the pilot's eye, allowing them instantly to access points of interest. It should also help them immediately to identify allied forces, helping to cut down on "friendly fire" incidents.
"The Tornado HMCS capability has greatly enhanced the crews’ situational awareness and resource management, enabling the rapid identification of points of interest in the homogeneous Afghan environment," said Wing Commander Kurt Hill, FAST Tornado capability manager.
Martin Taylor, BAE Systems’ combat air support director, added: "Over the coming months, we will continue to work with the customer, to provide the capability across the wider Tornado fleet."
BAE Systems already utilises helmet-mounted display (HMD) technology in other military applications, including helmet-mounted night vision systems, helmet-mounted sighting systems, and monocular and binocular displays.


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Hey, wealthy foreigners! Want to live in the U.S.? Buy a home here.
International purchases of American homes are ramping up, and a new Senate bill designed to boost the ailing real-estate market would encourage globe-trotting investors to buy even more.
The bill, co-sponsored by Charles Schumer (D-N.Y.) and Mike Lee (R.-Utah) would grant a U.S. visa to international investors who agree to spend at least $500,000 on residential real estate here.
If passed, the legislation could add to a surge in homebuying by international purchasers over the past year or two that’s already given some local U.S. markets a welcome boost.
Foreigners spent $82 billion buying up U.S. homes in the 12 months ended in March, up 24% from a year earlier, according to the National Association of Realtors (NAR). That represents 8% of total U.S. sales.
In places like South Florida, international buyers already account for a whopping 25% of the market. California, Texas and Arizona also attract many foreign buyers, as do Hawaii and New York.
South Florida condo sales have been surprisingly strong,Â said Brad Hunter, chief economist for Metrostudy, a housing analytics company. “And the majority of those sales are to South Americans and Canadians,” he said.
All that international buyer activity has been a tonic for the anemic Florida market. Housing starts were up nearly 20% in the three months ended Sept. 30, according to Metrostudy.
In Manhattan, there’s been a steady baseline of foreign condo buyers, said Jonathan Miller, CEO of Miller Samuel, a New York appraisal firm. They generally account for about 15% of investors, but in recent years, the buyer mix in New York City has shifted, he said.
When the euro was strong in the mid-2000s, buyers from Western Europe — and particularly Ireland — dominated.
The Irish “economy was so strong back home — the ‘Celtic Tiger’ years — that many were flush and wanted to invest and take advantage of the spread between currencies,” said Miller. “There were marketing groups that would go to Ireland and sell packages of condos here.”
Now, said Miller, the New York market now attracts more Asian and Latin American buyers than in the past.
Wei Min Tan, a real-estate agent with Charles Rutenburg Realty who specializes in selling Manhattan real estate to Asians, said his volume has more than doubled this year.
“I tell [buyers] it’s going to be a stable investment that should go up 10% a year,” he said. That’s “not as much as they might get in Hong Kong or Shanghai,” but there’s less volatility, he said.
Even better for homeowners, foreign sales can be very easy: The buyers are often affluent and buy more expensive homes. The median sale price of $175,000 they pay in Florida, for example, is well above the median sales price of $136,500 for all transactions.
There’s also no hassle over financing or waiting around for a mortgage lender to approve the deal: Overwhelmingly, international buyers pay cash.
Indeed, the Senate bill would require buyers to pay cash for the homes to qualify for the new “homeowner” visa. They’d also need to pay U.S. taxes and spend at 180 days a year in the country, and can’t work here or take out home-equity loans against the properties. In return, they’d get to live here for at least three years.
The program could improve the housing market nationwide, said Schumer.
“We think a very significant number of people will be brought in,” he said. “They’ll sop up the extra supply of homes we have right now that has been dragging down the economy.”
Foreigners seem to have more confidence in the U.S. real estate market than Americans do. Almost half of buyers surveyed by NAR cited the profitability or safety of their investments as the main factor that persuaded them to buy.
“With the economic distress in Europe,” said Miller, “people are still looking for safe havens for investing and the U.S. is perceived globally as safe.”


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"I’m Feeling Really Run Down": Amy Schumer Is Going Through IVF In Hope For Having A Second Child
January 13, 2020 12:38
A question for a day: is Amy Schumer planning a second baby? In May 2019, the comedian welcomed her first-ever child, named Gene, with her husband, Chris Fischer. The couple married eight months prior to the childbirth of their son.
Schumer had a baby boy at the age of 37, but will she be giving birth naturally for the second time if she decides to become a mum again?

domain: entertainment


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Fiocruz releases today a new step in international communication of the institution, with the release of Fiocruz Internacional newsletter. Edited by the Coordination of Social Communication (CCS) with the Center for International Relations in Health (Cris/Fiocruz), the new publication will gather news of the international activities of all units of Fiocruz, highlighting the activities of the Foundation on issues such as global health, international cooperation agreements, Sustainable Development Goals, partnerships, South-South cooperation, and more. Access here.
The new bulletin replaces CrisInforma, publication by Cris/Fiocruz edited between 2012 and 2015, with 21 issues. The former publication registered significant moments of the international performance of Fiocruz over the past three years, as the tripartite scientific partnership signed with the Pasteur Institute and the University of São Paulo (USP), the seminar on ebola promoted in partnership with the Union of South American Nations (Unasur) and the creation of the Technical Chamber of International Cooperation.
Fiocruz Internacional continues the international coverage of the international activities of the Foundation, bringing also some news. The language passes from PDF to HTML; the periodicity is no longer bi-monthly to become monthly; the activities of all units of the Fiocruz gain more and more importance.
The publication is also the first product to be released in partnership by the CCS and Fiocruz Portal, of the Institute of Communication and Information in Health Science and Technology (Icict/Fiocruz). While editing the content was in charge of the CCS, the design and development were the charge of Icict/Fiocruz.
In addition to the internal public, about 3000 members of international health agencies, academics, diplomats, NGOs and others interested in global health should be reached already in the first edition. This audience should increase even more next year, when an English version is planned.
The first Edition makes a retrospective of important events of international relations at Fiocruz, including participation in the Multisectoral Forum on Science, Technology and Innovation for the Sustainable Development Goals at the United Nations in New York, the second meeting of the High-level Committee to Evaluate Equity and Inequalities in Health in the Americas, the Pan American Health Organization (Paho) and the award given by Unesco to the Director of Fiocruz Bahia , Manoel Barral-Netto.

domain: news


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Peterborough Cathedral has been awarded a grant of £2,464,300 from the Heritage Lottery Fund (HLF) for its “Peterborough 900: Letting it speak for itself” project.
Peterborough Cathedral has received an award from the Heritage Lottery Fund (HLF) meaning that up to £500,000 is available to the Cathedral, but we must match every £1 of theirs with every £1 we can raise by 30th June 2017.


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Long Drop Earrings
Designer: Fierce Deer
- These earrings are one piece and are as long in the front as they are in the back
- Made with gold plated brass
- Lightweight enough to wear everyday, these earrings make a statement and elevate any outfit!
- Choose between a wider front bar with a textured surface, or a thin dainty bar


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All types of fiber can be good for the heart. The American Heart Association says that dietary fiber can improve cholesterol, and lower the risk of heart disease, stroke, type 2 diabetes, and obesity.
Psyllium’s unique 70:30 ratio of soluble to insoluble fiber not only provides digestive benefits, but it also supports a healthy heart. The soluble fibers found in psyllium fiber have shown to be particularly effective in reducing blood triglycerides (a type of fat), blood pressure, and the risk of heart disease.
The US Food and Drug Administration authorized a health claim that soluble fibers from psyllium husk, beta glucan in oats, and beta-glucan in barley can reduce the risk of heart disease. The reason psyllium is so good for your heart is because of its ability to lower blood total- and LDL-cholesterol levels.
How Can Psyllium Husk Help Lower Cholesterol?
So how does psyllium husk lower cholesterol levels? Psyllium binds to fat and bile acids in the digestive tract, helping your body to excrete them. This prompts the liver to create more bile acids. In order to do this, the liver uses stored cholesterol, thereby decreasing overall cholesterol in your body.
Clinical studies on psyllium husk supplementation have discovered significant benefits for the following conditions:
*Reduced blood total- and LDL-cholesterol levels in those with high cholesterol levels
*Increased HDL levels in patients with type 2 diabetes
*Decreased LDL levels for healthy subjects
*Substantially decreased blood triglyceride levels in patients with type 2 diabetes
*Significantly improved blood pressure levels in hypertensive, overweight, and obese patients
100% organic, non-GMO whole husk sylly is an excellent dietary supplement to promote a healthy heart and lower LDL cholesterol.
- American Heart Association: Whole Grains, Refined Grains, and Dietary Fiber
- Psyllium (Plantago ovata) Husk: A Wonder Food for Good Health
- FDA: Health Claims: Soluble Fiber from Certain Foods and Risk of Coronary Heart Disease (CHD)
- Effect of Psyllium (Plantago ovata) Fiber on LDL cholesterol and Alternative Lipid Targets, Non-HDL Cholesterol and Apolipoprotein B
- Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health Benefits, Part 1
- Fiber Supplements and Clinically Proven Health Benefits: How to Recognize and Recommend an Effective Fiber Therapy

domain: health


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Best price found
Fastest flight time
Airports in Bangkok
When travelling from Maroochydore to Bangkok, the most popular airport to fly into is Bangkok Suvarnabhumi Airport. The majority of travellers flying into Bangkok Suvarnabhumi Airport from Maroochydore are departing from Maroochydore Sunshine Coast Airport. If you are looking for an alternate airport near Maroochydore Sunshine Coast Airport, Brisbane Airport is a great option and is located in Brisbane. If you are looking for alternate airports to fly into when travelling from Maroochydore, you can try Bangkok Don Mueang Intl Airport or Rayong Utapao Rayong Pattaya Airport which are located in Bangkok and Rayong respectively. In December, $747 is typically the cheapest round trip price you’ll find from Maroochydore to Bangkok which you can find when you fly BNE — BKK.
|Jetstar||PriceFrom $868||Free cancellation||Rating|
|Qantas Airways||PriceFrom $1,265||Free cancellation||Rating|
There are 7234.6 km between Maroochydore Sunshine Coast and Bangkok. A reasonable flight in good conditions will take 12h 55m.
Prices for flights from Maroochydore Sunshine Coast Airport to Bangkok refresh daily.
There are 2 operators available for flights from Maroochydore Sunshine Coast Airport to Bangkok as of December 2023.
The minimum age for a child to fly alone is five, but airlines that offer an unaccompanied minor (UNMR) service may have their own age limitations. Flight duration, scheduling, and stopovers are among the considerations that may influence age limits. We recommend that you double-check with the airline you are booking with for travel from Maroochydore Sunshine Coast Airport to Bangkok.
The travel and health documents you'll need for your trip to Bangkok may differ based on your itinerary and personal situation. Typically, you should have several documents on hand, such as a national ID card or driver's licence and a passport that is valid for six months after your intended arrival at Bangkok. It is always advisable to seek advice from your airline or a trusted third party, such as IATA.
Finding the right flight to Bangkok from Maroochydore is quick and easy when you have a range of options in front of you, from reputable agents and recognisable airlines. Options that can then be filtered down to find the best fit. That is what momondo does. We make finding flights to Bangkok quick and easy, saving you time and money.
Yes. All flights to Bangkok from Maroochydore on momondo can be compared and filtered by various policies on offer, including flexible booking.
momondo helps you find the best flight between Maroochydore and Bangkok by providing filters to narrow your choice of flights to those matching your criteria. You can select flights based on numerous factors such as price, departure and landing times, airport and airline.
Yes. momondo can track prices for Maroochydore to Bangkok flights and alert you when they change. Perform a search to set up the price alert. All that is required is a valid email address.


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YCBA Collections Search
- Kyan, John Howard, 1774-1850
- On the elements of light and their identity with those of matter, radiant and fixed
- Constable, John, 1776-1837
- Various subjects of landscape, characteristic of English scenery
- Leslie, Charles Robert, 1794-1859
- Memoirs of the life of John Constable ...

domain: library


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The World Health Organization (WHO) reports that over sixteen million deaths occur worldwide each year due to cardiovascular disease, and more than half of those deaths occur in developing countries where plant-based diets high in legumes and starches are eaten by the vast majority of the people.
Yet “everyone knows” plant-based diets prevent heart disease. Indeed this myth is repeated so often that massive numbers of educated, health-conscious individuals in first world countries are consciously adopting third world style diets in the hope of preventing disease, optimizing health and maximizing longevity. But if the WHO statistics are correct, plant-based diets might not be protective at all. And today’s fashionable experiment in veganism could end very badly indeed.
HOMOCYSTEINE AND HEART DISEASE
A study published in the August 26, 2001 issue of the journal Nutrition makes a strong case against plant-based diets for prevention of heart disease. The title alone, “Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis,” sounds a significant warning. The article establishes why subjects who eat mostly vegetarian diets develop morbidity and mortality from cardiovascular disease unrelated to vitamin B status and Framingham criteria.
Co-author Kilmer S. McCully, MD, “Father of the Homocysteine Theory of Heart Disease,” is familiar to WAPF members as a winner of the Linus Pauling Award, WAPF’s Integrity in Science Award, and author of numerous articles published in peer-reviewed journals as well as the popular books The Homocysteine Revolution and The Heart Revolution. In 2009 Dr. McCully was one of the signers of the Weston A. Price Foundation’s petition to the FDA in which we asked the agency to retract its unwarranted 1999 soy/heart disease health claim. (See www.westonaprice.org/soy-alert/soy-heart-health-claim.)
Dr. McCully teamed up with Yves Ingenbleek, MD, of Université Louis Pasteur in Strasbourg, France, which funded the research. Dr. Ingenbleek is well known for his work on malnutrition, the essential role sulfur plays along with nitrogen in metabolism, and sulfur deficiency as a cause of hyperhomocysteinemia.
The study took place in Chad, and involved twenty-four rural male subjects ages eighteen to thirty, and fifteen urban male controls, ages eighteen to twenty-nine. (Women in this region of Chad could not be studied because of their animistic beliefs and proscriptions against collecting their urine.)
The rural men were apparently healthy, physically active farmers with good lipid profiles. Their staple foods included cassava, sweet potatoes, beans, millet and ground nuts. Cassava leaves, cabbages and carrots provided good levels of carotenes, folates and pyridoxine (B6). The rural Chadian diet is plant-based because of a shortage of grazing lands and livestock, but subjects occasionally consume some B12-containing foods, mostly poultry and eggs, though very little dairy or meat. Their diet could be described as high carb, high fiber, low in both protein and fat, and low in the sulfur-containing amino acids. In brief, this diet is the very one recommended by many of today’s nutritional “experts” for overall good health and heart disease prevention.
The urban controls were likewise healthy and ate a similar diet, but with beef, smoked fish and canned or powdered milk regularly on the menus. Their diet was thus higher in protein, fat and the sulfur-containing amino acids, though roughly equivalent in calories.
Dr. McCully’s research over the past forty years on the pathogenesis of atherosclerosis has shown the role of homocysteine in free radical damage and the protective effect of vitamins B6, B12 and folate. Indeed, many doctors today recommend taking this trio of B vitamins as an inexpensive heart disease “insurance policy.”
In Chad, both groups showed adequate levels of B6 and folate. The B12 levels of the vegetarian group were lower, but the difference was only of “borderline significance.” However, as the researchers point out, “A previous study undertaken in the same Chadian area in a larger group of sixty rural participants did demonstrate a weak inverse correlation between B12 and homocysteine concentrations in the twenty subjects most severely protein depleted . . . It is therefore likely that the hyperhomocysteinemia status of some of our rural subjects in the present survey might have resulted from combined B12 and protein deficiencies. The correlation of B12 deficiency with hyperhomocysteinemia could well reach statistical significance if a larger group of subjects were studied.”
ANIMAL PROTEIN AND SULFUR
Clearly it’s wise for people on plant-based diets to supplement their diets with B12, but protein malnutrition must also be addressed. And the issue is not just getting enough protein to eat, but the right kind. The bottom line is we must eat protein rich in bioavailable, sulfur-containing amino acids—and that means animal products. Vegans at this point will surely claim the issue is insufficient protein and trot out soy as the solution. Soy is indeed a complete plant-based protein, but notoriously low in methionine. It does contain decent levels of cysteine, but the cysteine is bound up in protease inhibitors, making it largely biounavailable. (For more information, read my book The Whole Soy Story: The Dark Side of America’s Favorite Health Food, endorsed by Dr. McCully, as well as our petition to the FDA noted above.)
So what did Drs. Ingenbleek and McCully find among the study group of protein-deficient people? Higher levels of homocysteine, of course. Also significant alterations in body composition, lean body mass, body mass index and plasma transthyretin levels. In plain English, the near-vegetarian subjects were thinner, with poorer muscle tone, and showed subclinical signs of protein malnutrition. (So much for popular ideas of extreme thinness being healthy.)
The plant-based diet of the study group was low in all of the sulfur-containing amino acids. As would be expected, labwork on these men showed lower plasma cysteine and glutathione levels compared to the controls. Methionine levels, however, tested comparably. The explanation for this is “adaptive response.” In brief, mammals trying to function with insufficient sulfur-containing amino acids will do whatever is necessary to survive. Given the essential role of methionine in metabolic processes, that means deregulating the transsulfuration pathway, increasing homocysteine levels, and methylating homocysteine to make methionine.
Ultimately, it all boils down to our need for sulfur. As Stephanie Seneff, PhD, and many others have written in Wise Traditions and on the WAPF website, sulfur is vital for disease prevention and maintenance of good health. In terms of heart disease, Drs. Ingenbleek and McCully have shown sulfur deficiency not only leads to high homocysteine levels, but is the likeliest reason some clinical trials using B6, B12 and folate interventions have proved ineffective for the prevention of cardiovascular and cerebrovascular diseases. Over the past few years, headlines from such studies have led to widespread dismissal of Dr. McCully’s “Homocysteine Theory of Heart Disease” and renewed media focus on cholesterol, C-reactive protein and other possible culprits that can be treated by statins and other profitable drugs. In contrast, the research of Drs. McCully and Ingenbleek suggests we can better prevent heart disease with three inexpensive B vitamins and traditional diets rich in the sulfur-containing amino acids found in animal foods.
In the blaze of publicity surrounding the video Forks Over Knives and other blasts of vegan propaganda, few people are likely to hear about this study. That’s sad, for it provides an important missing piece in our knowledge of heart disease development, a strong argument against the plant-based dietary fad, and a bright new chapter in what the New York Times has called “The Fall and Rise of Kilmer McCully.”
This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Winter 2011.🖨 Print post

domain: medical


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San Diego Zoo Celebrates Kids Free in October!
San Diego truly is a great city to be in if you are a kid! There are so many wonderful attractions and educational programs to engage in and so many different ways to enjoy them. Great weather and tons of local attractions means that the possibilities are endless.Take a trip to San Diego and enjoy the sun with us, you can still book a San Diego vacation with peace of mind.
One of the biggest and most popular attractions is, of course, the San Diego Zoo. The San Diego Zoo has lead so many educational attractions such as the Keeper Talks and Cheetah run. We are continually impressed with the San Diego Zoo's dedication to connecting kids with nature! The Zoo's newest attraction is none other than Robert the Zebra which will be accessible hourly starting at 11am until 3pm.
Best yet? During the month of October your little ones can come see the all the amazing attractions for free! Kids Free Month is presented by Mission Fed and has been a tradition at the San Diego Zoo for years.
So, the question is - What is Kids Free Month and What Does it Entail?
- What: Kids Free Month allows anyone 11 and under into the park for free, as long as they are accompanied by a paid adult.
- When: October 1st through October 31st, 2016. The San Diego Zoo and Safari park hours are 9am to 6pm for the month of October..
- Where: Both the San Diego Zoo and the Safari Park are participating!
By taking advantage of the San Diego Zoo and Safari Park's participation in Kids Free October, your little ones can check out the Centennial Treasure Hunt by following clues on the special map and discover some of the San Diego Zoo's wildlife treasures.
Of course all of the San Diego Zoo and Safari Park's usual exhibits are also covered with your kids' free admission, so get ready to have a wild time when you visit America's Finest City and its world famous San Diego Zoo. Kids can participate in the Camp Critters show at the Zoo, or "Race" a cheetah at the Safari Park.
Don't forget to check out the Animal Encounters which usually run at least once or twice per day, depending on which enclosure you're visiting. Animal Encounters allow Zoo visitor's to meet an animal ambassador up close and personal - get ready for the best kind of close encounter!
Kids can also enjoy some Beast Treats in various locations around the park. Watch as your kids engage with the animals and their special treats.


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Mark Levin explains Reagan to Tea Party Patriots
A few weeks ago, Tea Party Patriots launched its Patriot Town Hall series. The series, which brings former Ronald Reagan staffers and a Reagan biographer to Tea Party activists across the nation, is designed to bring the principles and strategies of the nation’s greatest modern President to a new generation of activists.
Last night, nationally syndicated radio talk show host Mark Levin joined Tea Party Patriots to explain how President Reagan overcame the establishment and media bias in his day. According to Levin, Reagan didn’t just beat the establishment – he ran it over in the style of the Tea Party. He didn’t just talk over Democrats in Congress to reach the American people; he talked over the establishment moderates in his own party who were the “grandparents” of today’s establishment.
One critical point Levin made is the left’s misrepresentation of President Reagan’s policies and principles. Levin rejected the narrative that President Reagan would not survive in today’s GOP, and said the Tea Party and Reagan are definitely aligned when it comes to principles and policies to reduce the size and scope of government.
When asked by a listener about taxes, Levin explained that, yes, President Reagan raised taxes. However, the sizeable cuts the President made in tax rates far outweighed the increases. The increases were almost negligible in comparison, said Levin, and the cuts were across the board, for the poor, the middle-class, the wealthy, corporations, etc.
A common theme among the speakers thus far has been Reagan’s attitude. Anger was not a part of his repertoire. Petty partisan politics was not a tool he used. He didn’t worry about racial or ethnic differences. For Reagan, it was important to always look to a brighter future and bring all Americans to that brighter future with him. In this respect, President Obama is similar to Reagan. Unlike the current President, however, Reagan understood a President merely provides inspiration and certain leadership qualities and policies. The American people do the rest.
Over the next two weeks, more Reagan staffers will offer their own advice. Becky Norton Dunlop will provide insights next Sunday from her former perch as a high-ranking official in the Department of the Interior. Be sure to sign up for these calls at Patriottownhall.com. Also, once you sign up, you can hear Mark Levin’s presentation in full.


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I do not own any CULT NAILS nail polish or else, and Ive been seeing a lot of really good reviews and pictures of several Cult NAils polish !! and OMG I cant wait to join the cult nails family.
BUUUUT !! I need your help , I want this to be fun sooo Im going to let you guys introduce me to CULT NAILS who can I trust better than all my fellow nail polish lovers.
Ok all you have to do is write the name of the color below and the color that gets called out the most , that will be the winner and my 1st CULT NAILS purchase :D
I NEED YOUR HELP !
SO , WHICH CULT NAILS NAIL POLISH
WOULD YOU RECOMMEND FOR ME ???

domain: hobby