Diversity in the organization of elastin bundles and intramembranous muscles in bat wings

Unlike birds and insects, bats fly with wings composed of thin skin that envelops the bones of the forelimb and spans the area between the limbs, digits, and sometimes the tail. This skin is complex and unusual; it is thinner than typical mammalian skin and contains organized bundles of elastin and embedded skeletal muscles. These elements are likely responsible for controlling the shape of the wing during flight and contributing to the aerodynamic capabilities of bats. We examined the arrangement of two macroscopic architectural elements in bat wings, elastin bundles and wing membrane muscles, to assess the diversity in bat wing skin morphology. We characterized the plagiopatagium and dactylopatagium of 130 species from 17 families of bats using cross‐polarized light imaging. This method revealed structures with distinctive relative birefringence, heterogeneity of birefringence, variation in size, and degree of branching. We used previously published anatomical studies and tissue histology to identify birefringent structures, and we analyzed their architecture across taxa. Elastin bundles, muscles, neurovasculature, and collagenous fibers are present in all species. Elastin bundles are oriented in a predominantly spanwise or proximodistal direction, and there are five characteristic muscle arrays that occur within the plagiopatagium, far more muscle than typically recognized. These results inform recent functional studies of wing membrane architecture, support the functional hypothesis that elastin bundles aid wing folding and unfolding, and further suggest that all bats may use these architectural elements for flight. All species also possess numerous muscles within the wing membrane, but the architecture of muscle arrays within the plagiopatagium varies among families. To facilitate present and future discussion of these muscle arrays, we refine wing membrane muscle nomenclature in a manner that reflects this morphological diversity. The architecture of the constituents of the skin of the wing likely plays a key role in shaping wings during flight

General practitioners' views and preferences about quality improvement feedback in preventive care: a cross-sectional study in Switzerland and France.

Feedback is widely used as a strategy to improve the quality of care in primary care settings. As part of a study conducted to explore the quality of preventive care, we investigated general practitioners' (GPs) views on the usefulness of feedback and their preferences regarding how feedback is provided. This cross-sectional study was conducted in 2015 among randomly selected community-based GPs in two regions of Switzerland and France. GPs were asked to complete an anonymous questionnaire about how often they provided 12 measures of preventive care: blood pressure, weight and height measurements, screening for dyslipidemia, at-risk drinking (and advice to reduce for at-risk drinkers), smoking (and advice to stop for smokers), colon and prostate cancer, and influenza immunization for patients >65 years and at-risk patients. They were also asked to estimate the usefulness of a feedback regarding their preventive care practice, reason(s) for which a feedback could be useful, and finally, to state which type of feedback they would like to receive. Chi-square tests were used to compare frequencies. Multivariate logistic regression was used to identify factors associated with GPs considering feedback as useful. Five hundred eighteen of 1100 GPs (47.1%) returned the questionnaire. They were predominantly men (62.5%) and most (40.1%) were aged between 55 and 64 years old. Overall, 44.3% stated that a feedback would be useful. Younger GPs and those carrying out more measures of preventive care were more likely to consider feedback useful. The two main reasons for being interested in feedback were to receive knowledge about the study results and to modify or improve practice. The two preferred feedback interventions were a brief report and a report with specific information regarding prevention best practice, whereas less than 1% would like to discuss the results face-to-face with the study investigators. These findings suggest that GPs have preferences regarding the types of feedback they would like to receive. Because the implementation of guidelines is highly related to the acceptance of feedback, we strongly encourage decision makers to take GPs' preferences into account when developing strategies to implement guidelines, in order to improve the quality of primary care

Rates, Delays, and Completeness of General Practitioners' Responses to a Postal Versus Web-Based Survey: A Randomized Trial.

Web-based surveys have become a new and popular method for collecting data, but only a few studies have directly compared postal and Web-based surveys among physicians, and none to our knowledge among general practitioners (GPs). Our aim is to compare two modes of survey delivery (postal and Web-based) in terms of participation rates, response times, and completeness of questionnaires in a study assessing GPs' preventive practices. This randomized study was conducted in Western Switzerland (Geneva and Vaud) and in France (Alsace and Pays de la Loire) in 2015. A random selection of community-based GPs (1000 GPs in Switzerland and 2400 GPs in France) were randomly allocated to receive a questionnaire about preventive care activities either by post (n=700 in Switzerland, n=400 in France) or by email (n=300 in Switzerland, n=2000 in France). Reminder messages were sent once in the postal group and twice in the Web-based group. Any GPs practicing only complementary and alternative medicine were excluded from the study. Among the 3400 contacted GPs, 764 (22.47%, 95% CI 21.07%-23.87%) returned the questionnaire. Compared to the postal group, the participation rate in the Web-based group was more than four times lower (246/2300, 10.70% vs 518/1100, 47.09%, P<.001), but median response time was much shorter (1 day vs 1-3 weeks, P<.001) and the number of GPs having fully completed the questionnaire was almost twice as high (157/246, 63.8% vs 179/518, 34.6%, P<.001). Web-based surveys offer many advantages such as reduced response time, higher completeness of data, and large cost savings, but our findings suggest that postal surveys can be still considered for GP research. The use of mixed-mode approaches is probably a good strategy to increase GPs' participation in surveys while reducing costs

TILs in ER+/HER2- breast cancer

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Smoking as a cofactor for causation of chronic pancreatitis: a meta-analysis.

OBJECTIVES: To assess the evidence for tobacco smoking as a risk factor for the causation of chronic pancreatitis. METHODS: We performed a meta-analysis with random-effects models to estimate pooled relative risks (RRs) of chronic pancreatitis for current, former, and ever smokers, in comparison to never smokers. We also performed dose-response, heterogeneity, publication bias, and sensitivity analyses. RESULTS: Ten case-control studies and 2 cohort studies that evaluated, overall, 1705 patients with chronic pancreatitis satisfied the inclusion criteria. When contrasted to never smokers, the pooled risk estimates for current smokers was 2.8 (95% confidence interval [CI], 1.8-4.2) overall and 2.5 (95% CI, 1.3-4.6) when data were adjusted for alcohol consumption. A dose-response effect of tobacco use on the risk was ascertained: the RR for subjects smoking less than 1 pack per day was 2.4 (95% CI, 0.9-6.6) and increased to 3.3 (95% CI, 1.4-7.9) in those smoking 1 or more packs per day. The risk diminished significantly after smoking cessation, as the RR estimate for former smokers dropped to a value of 1.4 (95% CI, 1.1-1.9). CONCLUSIONS: Tobacco smoking may enhance the risk of developing chronic pancreatitis. Recommendation for smoking cessation, besides alcohol abstinence, should be incorporated in the management of patients with chronic pancreatitis

Cancer Risk in Waterpipe Smokers: a Meta-analysis

OBJECTIVES: To quantify by meta-analysis the relationship between waterpipe smoking and cancer, including cancer of the head and neck, esophagus, stomach, lung and bladder. METHODS: We performed a systematic literature search to identify relevant studies, scored their quality, used fixed and random-effect models to estimate summary relative risks (SRR), evaluated heterogeneity and publication bias. RESULTS: We retrieved information from 28 published reports. Considering only highquality studies, waterpipe smoking was associated with increased risk of head and neck cancer (SRR 2.97; 95 % CI 2.26-3.90), esophageal cancer (1.84; 1.42-2.38) and lung cancer (2.22; 1.24-3.97), with no evidence of heterogeneity or publication bias. Increased risk was also observed for stomach and bladder cancer but based mainly on poor-quality studies. For colorectum, liver and for all sites combined risk estimates were elevated, but there were insufficient reports to perform a meta-analysis. CONCLUSIONS: Contrary to the perception of the relative safety of waterpipe smoking, this meta-analysis provides quantitative estimates of its association with cancers of the head and neck, esophagus and lung. The scarcity and limited quality of available reports point out the need for larger carefully designed studies in well-defined populations

Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes

INTRODUCTION: Ki-67 labeling index assessed by immunohistochemical assays has been shown useful in assessing the risk of recurrence for estrogen receptor (ER)-positive HER2-negative breast cancers (BC) and distinguishing Luminal A-like from Luminal B-like tumors. We aimed to assess the performance of the Ventana CONFIRM anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody. METHODS: We constructed a case-cohort design based on a random sample (n\u2009=\u2009679) of all patients operated on for a first primary, non-metastatic, ER-positive, HER2-negative BC at the European Institute of Oncology (IEO) Milan, Italy during 1998-2002 and all additional patients (n\u2009=\u2009303) operated during the same period, who developed an event (metastasis in distant organs or death due to BC as primary event) and were not included in the previous subset. Multivariable Cox proportional hazards regression with inverse subcohort sampling probability weighting was used to evaluate the risk of event according to Ki-67 (30-9) and derived intrinsic molecular subtype, using previously defined cutoff values, i.e., respectively 14% and 20%. RESULTS: Ki-67 was\u2009<\u200914% in 318 patients (32.4%), comprised between 14 and 19% in 245 patients (24.9%) and\u2009 65\u200920 in 419 patients (42.7%). At multivariable analysis, the risk of developing distant disease was 1.88 (95% CI 1.20-2.93; P\u2009=\u20090.006) for those with Ki-67 comprised between 14 and 19%, and 3.06 (95% CI 1.93-4.84; P\u2009<\u20090.0001) for those with Ki-67\u2009 65\u200920% compared to those with Ki-67\u2009<\u200914%. Patients with Luminal B-like BC had an approximate twofold risk of developing distant disease (HR\u2009=\u20091.91; 95% CI 1.35-2.71; P\u2009=\u20090.0003) than patients with Luminal A-like BC defined using Ki-67 (30-9). CONCLUSIONS: Ki-67 evaluation using the 30-9 rabbit monoclonal primary antibody was able to stratify patients with ER-positive HER2-negative BC into prognostically distinct groups. Ki-67 assessment, with strict adherence to the international recommendations, should be included among the clinically useful biological parameters for the best treatment of patients with BC

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity

How do general practitioners put preventive care recommendations into practice? A cross-sectional study in Switzerland and France.

We previously identified that general practitioners (GPs) in French-speaking regions of Europe had a variable uptake of common preventive recommendations. In this study, we describe GPs' reports of how they put different preventive recommendations into practice. Cross-sectional study conducted in 2015 in Switzerland and France. 3400 randomly selected GPs were asked to complete a postal (n=1100) or online (n=2300) questionnaire. GPs who exclusively practiced complementary and alternative medicine were not eligible for the study. 764 GPs (response rate: postal 47%, online 11%) returned the questionnaire (428 in Switzerland and 336 in France). We investigated how the GPs performed five preventive practices (screening for dyslipidaemia, colorectal and prostate cancer, identification of hazardous alcohol consumption and brief intervention), examining which age group they selected, the screening frequency, the test they used, whether they favoured shared decision for prostate cancer screening and their definition of hazardous alcohol use. A large variability was observed in the way in which GPs provide these practices. 41% reported screening yearly for cholesterol, starting and stopping at variable ages. 82% did not use any test to identify hazardous drinking. The most common responses for defining hazardous drinking were, for men, ≥21 drinks/week (24%) and ≥4 drinks/occasion for binge drinking (20%), and for women, ≥14 drinks/week (28%) and ≥3 drinks/occasion (21%). Screening for colorectal cancer, mainly with colonoscopy in Switzerland (86%) and stool-based tests in France (93%), was provided every 10 years in Switzerland (65%) and 2 years in France (91%) to patients between 50 years (87%) and 75 years (67%). Prostate cancer screening, usually with shared decision (82%), was provided yearly (62%) to patients between 50 years (74%) and 75-80 years (32%-34%). The large diversity in the way these practices are provided needs to be addressed, as it could be related to some misunderstandingof the current guidelines, to barriers for guideline uptake or, more likely, to the absence of agreement between the various recommendations