Development of a Diagnostic Biosensor Method of Hypersensitivity Pneumonitis towards a Point-of-Care Biosensor.

In spite of a current increasing trend in the development of miniaturized, standalone point-of-care (PoC) biosensing platforms in the literature, the actual implementation of such systems in the field is far from being a reality although deeply needed. In the particular case of the population screenings for local or regional diseases related to specific pathogens, the diagnosis of the presence of specific antibodies could drastically modify therapies and even the organization of public policies. The aim of this work was to develop a fast, cost-effective detection method based on the manipulation of functionalized magnetic beads for an efficient diagnosis of hypersensitivity pneumonitis (HP), looking for the presence of anti-pigeon antigen antibodies (APAA) in a patient's serum. We presented a Diagnostic Biosensor Method (DBM) in detail, with validation by comparison with a traditional high-throughput platform (ELISA assay). We also demonstrated that it was compatible with a microfluidic chip that could be eventually incorporated into a PoC for easy and broad deployment using portable optical detectors. After standardization of the different reaction steps, we constructed and validated a plastic chip that could easily be scaled to high-volume manufacturing in the future. The solution proved comparable to conventional ELISA assays traditionally performed by the clinicians in their laboratory and should be compatible with other antibody detection directly from patient samples.

Determination by Relaxation Tests of the Mechanical Properties of Soft Polyacrylamide Gels Made for Mechanobiology Studies.

Following the general aim of recapitulating the native mechanical properties of tissues and organs in vitro, the field of materials science and engineering has benefited from recent progress in developing compliant substrates with physical and chemical properties similar to those of biological materials. In particular, in the field of mechanobiology, soft hydrogels can now reproduce the precise range of stiffnesses of healthy and pathological tissues to study the mechanisms behind cell responses to mechanics. However, it was shown that biological tissues are not only elastic but also relax at different timescales. Cells can, indeed, perceive this dissipation and actually need it because it is a critical signal integrated with other signals to define adhesion, spreading and even more complicated functions. The mechanical characterization of hydrogels used in mechanobiology is, however, commonly limited to the elastic stiffness (Young's modulus) and this value is known to depend greatly on the measurement conditions that are rarely reported in great detail. Here, we report that a simple relaxation test performed under well-defined conditions can provide all the necessary information for characterizing soft materials mechanically, by fitting the dissipation behavior with a generalized Maxwell model (GMM). The simple method was validated using soft polyacrylamide hydrogels and proved to be very useful to readily unveil precise mechanical properties of gels that cells can sense and offer a set of characteristic values that can be compared with what is typically reported from microindentation tests.

Graphic Depictions: Portrayals of Mental Illness in Video Games.

Although studies have examined portrayals of mental illness in the mass media, little attention has been paid to such portrayals in video games. In this descriptive study, the fifty highest-selling video games in each year from 2011 to 2013 were surveyed through application of search terms to the Wikia search engine, with subsequent review of relevant footage on YouTube. Depiction categories were then assigned based on the extent of portrayal and qualitative characteristics compared against mental illness stereotypes in cinema. Twenty-three of the 96 surveyed games depicted at least one character with mental illness. Forty-two characters were identified as portraying mental illness, with most characters classified under a "homicidal maniac" stereotype, although many characters did not clearly reflect cinema stereotypes and were subcategorized based on the shared traits. Video games contain frequent and varied portrayals of mental illness, with depictions most commonly linking mental illness to dangerous and violent behaviors.

Commentary. Oligognostic mega-analysis. Is Archie turning in his grave?

The Cochrane Collaboration has developed guidelines for the conduct of meta-analyses and systematic reviews. When applied to well-conducted short-duration randomized controlled trials, meta-analysis can be informative, but seldom in prolonged trials, because of "unblinding", non-adherence, losses to follow-up, and "crossovers". The meta-analysis of observational studies is beset by problems of bias, confounding, variable methodology, and lack of transparency, and is seldom valid. For the evaluation of partly quantitative or non-quantitative studies, systematic reviews using standardized methods have been developed. However, such reviews are inferior to well-conducted qualitative reviews tailored to the specific topics at issue.

Misrepresentation of the risk of ovarian cancer among women using menopausal hormones. Spurious findings in a meta-analysis.

BACKGROUND: Based on a meta-analysis of 52 studies, and principally on a meta-analysis of 17 follow-up studies, it has been claimed that current-or-recent use (last use <5 years previously) of menopausal hormones causes ovarian cancer, even if the duration of use was <5 years, and that women aged about 50 years who use hormones for >5 years have about one extra case per 1000 users, and one extra fatal case per 1700 users. OBJECTIVE: To evaluate the validity of the evidence. METHODS: Generally accepted epidemiological principles of causation were applied to the evidence. FINDINGS: The study base included hysterectomised women, an unknown proportion of whom were oophorectomised, and not at risk for ovarian cancer. The findings did not satisfy the criteria of time order, bias, confounding, strength of association, dose-response, duration-response, consistency, and biological plausibility. CONCLUSIONS: The meta-analysis did not establish that current-or-recent use of menopausal hormones causes ovarian cancer. The strong likelihood is that early symptoms of as yet undiagnosed ovarian cancer "caused" current-or-recent short-duration hormone use, not the reverse. The representation of the number of extra cases, and fatal cases, among hormone users was misleading and alarmist.

Union status and sexual risk behavior among men in their 30s.

CONTEXT: Understanding the relationship between union status and men's sexual risk behavior in their 30s is important to ensure appropriate reproductive health services for men in middle adulthood. METHODS: Data from 1,083 men aged 34-41 who participated in the 2008-2010 wave of the National Survey of Adolescent Males were used to examine differentials in sexual risk behaviors by union status, past risk behavior and selected characteristics. Bivariate tabulations were done to assess relationships between current risk behavior and background variables, multinomial regression analysis was conducted to identify associations between union status and past risk behavior, and logistic regression analysis was used to assess associations between current behavior and both union status and past behavior. RESULTS: Eight percent of men in their 30s had had three or more sexual partners in the last 12 months, 10% had had at least one risky partner and 8% had had concurrent partners. Men living outside co-residential unions reported higher levels of these behaviors (24%, 29% and 24%, respectively) than did married men (1-2%) or cohabiting men (7-12%). In multivariate analyses that controlled for past risk behavior, married men were less likely than cohabiting men to have had at least one risky partner or concurrent partners in the last year (odds ratio, 0.2 for each), while men who were not in a co-residential union had an increased likelihood of reporting each risk behavior (2.2-5.3). CONCLUSIONS: Men in their 30s, especially those who are not married, engage in risky sexual behaviors. Further studies are needed to assess what contributes to behavioral differences by union status and what types of services might help men in this age-group reduce their risk.

Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies.

BACKGROUND: Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study, it is claimed that hormone replacement therapy (HRT) is an established cause of breast cancer. The authors have previously reviewed those studies (Parts 1-4). The WHI findings were first published in 2002, following which the use of HRT rapidly declined. A correspondingly rapid decline in the incidence of breast cancer has been reported, and attributed to the drop in the use of HRT. The evidence, however, is conflicting. METHODS: Using generally accepted causal criteria, in this article (Part 5) the authors evaluate reported trends in the incidence of breast cancer. RESULTS: The evidence to suggest a correlated decline in the incidence of breast cancer following a decline in the use of HRT has not adequately satisfied the criteria of time order, detection bias, confounding, statistical stability and strength of association, internal consistency, and external consistency; biological plausibility is difficult to assess. CONCLUSIONS: Based on the observed trends in the incidence of breast cancer following the decline in HRT use, the ecological evidence is too limited either to support or refute the possibility that HRT causes breast cancer.

Combined hormonal contraceptives and the risk of venous and arterial thromboembolism and cardiovascular death: misuse of automated databases.

BACKGROUND: In December 2011, the US Food and Drug Administration (FDA) convened a public Advisory Committee meeting to review evidence from a study commissioned by the agency. An analysis of findings derived from four databases was published on the FDA website, and presented at the meeting. Among users of combined hormonal contraceptives containing ethinylestradiol (EE) plus drospirenone (DRSP) the risks of venous (VTE) and arterial thromboembolism (ATE) were higher than among users of older reference contraceptives containing other progestogens. The findings have now been published in a peer-reviewed journal. OBJECTIVE: To evaluate the published evidence. METHODS: Generally accepted epidemiological principles of causality are applied. RESULTS: The findings did not satisfy the criteria of time order, bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency, or biological plausibility. CONCLUSIONS: The best evidence continues to suggest that the increased risk of VTE in combined hormonal contraceptive users is dependent on the dose of estrogen, and independent of the progestogen used. The best evidence also suggests that DRSP does not increase the risk of ATE, and may reduce it.

Invited commentary: Immunization and Bell's palsy in children.

Based on case reports, it has been speculated that certain vaccines may increase the risk of Bell's palsy. In a study using a novel approach (case-centered analysis) among children aged 18 years or less, results of which appear in this issue of the Journal, Rowhani-Rahbar et al. (Am J Epidemiol. 2012;175(9):878-885) found no association between immunization with trivalent influenza vaccine (TIV), hepatitis B virus (HBV) vaccine, or any vaccine (all vaccines combined) and Bell's palsy (definite and probable cases combined). In this commentary, the author evaluates the validity of the case-centered approach. In the study by Rowhani-Rahbar et al., the study population was not representative of the population of children at risk. The analytical approach resulted in the loss of information for 72% of the cases. There were insufficient data to assess TIV and HBV. Only the risk for all vaccines could be assessed, and only if it was assumed that the findings could be generalized. Possible effect modification by antecedent vaccination could not be assessed. The author concludes that a nested case-control study would have been more statistically robust and more informative.

Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies. Part 4: the Million Women Study.

BACKGROUND: Based principally on findings in three studies, the collaborative reanalysis (CR), the Women's Health Initiative (WHI) and the Million Women Study (MWS), it is claimed that hormone replacement therapy (HRT) with estrogen plus progestogen (E+P) is now an established cause of breast cancer; the CR and MWS investigators claim that unopposed estrogen therapy (ET) also increases the risk, but to a lesser degree than does E+P. The authors have previously reviewed the findings in the CR and WHI (Parts 1-3). OBJECTIVE: To evaluate the evidence for causality in the MWS. METHODS: Using generally accepted causal criteria, in this article (Part 4) the authors evaluate the findings in the MWS for E+P and for ET. RESULTS: Despite the massive size of the MWS the findings for E+P and for ET did not adequately satisfy the criteria of time order, information bias, detection bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency or biological plausibility. Had detection bias resulted in the identification in women aged 50-55 years of 0.3 additional cases of breast cancer in ET users per 1000 per year, or 1.2 in E+P users, it would have nullified the apparent risks reported. CONCLUSION: HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does.

Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: part 3. The Women's Health Initiative: unopposed estrogen.

BACKGROUND: Studies from the Women's Health Initiative have reported an increased risk of breast cancer in users of estrogen plus progestogen. Among users of estrogen alone an increased risk was not observed. OBJECTIVE: To evaluate the evidence for unopposed estrogen. METHODS: In a related article (Part 2) the authors apply generally accepted causal criteria to the findings for estrogen plus progestogen. Here (Part 3) the authors apply the criteria to the findings for unopposed estrogen, as reported in a clinical trial, and in combined data from the trial and an observational study. RESULTS: In the clinical trial, after 7.1 years of follow-up the relative risk (RR) of invasive breast cancer for women assigned to estrogen was 0.77 in an 'intention-to-treat' analysis (95% CI 0.59-1.01) and 0.67 (95% CI 0.47-0.97) in an 'as treated' analysis; after 10.7 years the risk reduction persisted. Time order was correctly specified; detection bias was minimal; in the 'as treated' analysis confounding was unlikely; duration-response and internal consistency could be evaluated only to a limited extent because of scanty data; the findings were discordant with increased risks observed in the Collaborative Reanalysis and the Million Women Study; biological plausibility could not be assessed. In the combined analysis, among women who had previously used estrogen soon after the menopause there was no clear evidence of either a reduction or an increase in the risk of breast cancer among women assigned to estrogen during the trial, or among women who were using estrogen in the observational study when follow-up commenced. The combined analysis did not satisfy the criteria of time order, bias, confounding, statistical stability and strength of association, duration-response, and internal consistency; biological plausibility could not be assessed. CONCLUSIONS: The evidence from the clinical trial suggests that unopposed estrogen does not increase the risk of breast cancer, and may even reduce it. The latter possibility, however, is based on statistically borderline evidence.

Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: part 2. The Women's Health Initiative: estrogen plus progestogen.

BACKGROUND: Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study (MWS), it is claimed that combined hormone replacement therapy (HRT) with estrogen plus progestogen is now an established cause of breast cancer. For unopposed estrogen therapy the evidence in the three studies is conflicting: the CR and MWS have reported increased risks in estrogen users, while the WHI has not. The authors have previously reviewed the findings in the CR (Part 1). OBJECTIVE: To evaluate the evidence for causality in the WHI studies. METHODS: Using generally accepted causal criteria, in this paper (Part 2) the authors evaluate the findings in the WHI for estrogen plus progestogen; in a related paper (Part 3) the authors evaluate the findings for unopposed estrogen. An evaluation of the MWS (Part 4), and of trends in breast cancer incidence following publication of the WHI findings in 2002 (Part 5) will follow. RESULTS: For estrogen plus progestogen the findings did not adequately satisfy the criteria of bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency or biological plausibility. CONCLUSION: HRT with estrogen plus progestogen may or may not increase the risk of breast cancer, but the WHI did not establish that it does.