Associations between birth defects with neural crest cell origins and pediatric embryonal tumors.

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. RESULTS: The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors. CONCLUSIONS: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.

Outcomes after assisted reproductive technology in women with cancer: a systematic review and meta-analysis.

STUDY QUESTION: What are the associations between a history of cancer and outcomes after ART? SUMMARY ANSWER: Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART. WHAT IS KNOWN ALREADY: Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes. STUDY DESIGN, SIZE, DURATION: We conducted a systematic review with meta-analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-and-fill method to assess funnel plot asymmetry. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage. LIMITATIONS, REASONS FOR CAUTION: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests. REGISTRATION NUMBER: N/A.

Case-control matching on confounders revisited.

Matching by a confounder in a case-control study nearly always produces a control-selection bias that mixes with the confounding to produce a net bias. Previous theoretical work has assumed that control for a single confounder, the matching factor, is sufficient to remove all the confounding and that the confounder-exposure, confounder-outcome and exposure-outcome associations are monotonic. Under these conditions: (a) The net bias is toward the null if the exposure affects the outcome and nil if it does not. (b) If the confounding is away from the null, the selection bias is toward the null. (c) If the confounding is toward the null, the selection bias can be in any direction or even nil. If more than one confounder needs to be controlled to remove all the confounding, the net bias from matching by one of them can be away from the null, whether the exposure affects the outcome or not. An influential heuristic, that matching controls to cases by a variable associated with exposure always brings the marginal exposure distributions of the case and control groups closer together, turns out to be faulty. The implications of matching by confounders in case-control studies are less straightforward than previously thought. Suggestions are offered for advancing the methodologic literature on this topic.

A twenty-first century perspective on concepts of modern epidemiology in Ignaz Philipp Semmelweis' work on puerperal sepsis.

We aimed to review Semmelweis's complete work on puerperal sepsis mortality in maternity wards in relation to exposure to cadavers and chlorine handwashing and other factors from the perspective of modern epidemiological methods. We reviewed Semmelweis' complete work and data as published by von Györy 1905 according to current standards. We paid particular attention to Semmelweis's definition of mortality in and of itself, to concepts of modern epidemiology that were already recognizable in Semmelweis's work, and to bias sources. We did several quantitative bias analyses to address selection bias and information bias from outcome measurement error. Semmelweis addressed biases that have become known to modern epidemiology, such as confounding, selection bias and bias from outcome misclassification. Our bias analysis shows that differential loss to follow-up is an unlikely explanation for his results. Bias due to outcome misclassification would only be relevant if misclassification differed between time periods. Confounding by health status was likely but could not be quantitatively addressed. Semmelweis was aware that cause-specific mortality is a function of incidence and prognosis. He reasoned in potential outcome terms to estimate the reduced number of deaths from an intervention. He advanced a hypothesis of clinic overcrowding as a risk factor for puerperal sepsis mortality that turns out to be wrong. Semmelweis' data provide a great pool for illustrating the logic of scientific discovery by use of the numerical method. The explanatory power of his work was strong and Semmelweis was able to refute several previous causal explanations.

Meta-Analysis and Sparse-Data Bias.

Meta-analyses are undertaken to combine information from a set of studies, often in settings where some of the individual study-specific estimates are based on relatively small study samples. Finite sample bias may occur when maximum likelihood estimates of associations are obtained by fitting logistic regression models to sparse data sets. Here we show that combining information from small studies by undertaking a meta-analytical summary of logistic regression estimates can propagate such sparse-data bias. In simulations, we illustrate 2 challenges encountered in meta-analyses of logistic regression results in settings of sparse data: 1) bias in the summary meta-analytical result and 2) confidence interval coverage that can worsen rather than improve, in terms of being less than nominal, as the number of studies in the meta-analysis increases.

The Importance of Making Assumptions in Bias Analysis.

Quantitative bias analyses allow researchers to adjust for uncontrolled confounding, given specification of certain bias parameters. When researchers are concerned about unknown confounders, plausible values for these bias parameters will be difficult to specify. Ding and VanderWeele developed bounding factor and E-value approaches that require the user to specify only some of the bias parameters. We describe the mathematical meaning of bounding factors and E-values and the plausibility of these methods in an applied context. We encourage researchers to pay particular attention to the assumption made, when using E-values, that the prevalence of the uncontrolled confounder among the exposed is 100% (or, equivalently, the prevalence of the exposure among those without the confounder is 0%). We contrast methods that attempt to bound biases or effects and alternative approaches such as quantitative bias analysis. We provide an example where failure to make this distinction led to erroneous statements. If the primary concern in an analysis is with known but unmeasured potential confounders, then E-values are not needed and may be misleading. In cases where the concern is with unknown confounders, the E-value assumption of an extreme possible prevalence of the confounder limits its practical utility.

Propensity score trimming mitigates bias due to covariate measurement error in inverse probability of treatment weighted analyses: A plasmode simulation.

BACKGROUND: Inverse probability of treatment weighting (IPTW) may be biased by influential observations, which can occur from misclassification of strong exposure predictors. METHODS: We evaluated bias and precision of IPTW estimators in the presence of a misclassified confounder and assessed the effect of propensity score (PS) trimming. We generated 1000 plasmode cohorts of size N = 10 000, sampled with replacement from 6063 NHANES respondents (1999-2014) age 40 to 79 with labs and no statin use. We simulated statin exposure as a function of demographics and CVD risk factors; and outcomes as a function of 10-year CVD risk score and statin exposure (rate ratio [RR] = 0.5). For 5% of the people in selected populations (eg, all patients, exposed, those with outcomes), we randomly misclassified a confounder that strongly predicted exposure. We fit PS models and estimated RRs using IPTW and 1:1 PS matching, with and without asymmetric trimming. RESULTS: IPTW bias was substantial when misclassification was differential by outcome (RR range: 0.38-0.63) and otherwise minimal (RR range: 0.51-0.53). However, trimming reduced bias for IPTW, nearly eliminating it at 5% trimming (RR range: 0.49-0.52). In one scenario, when the confounder was misclassified for 5% of those with outcomes (0.3% of cohort), untrimmed IPTW was more biased and less precise (RR = 0.37 [SE(logRR) = 0.21]) than matching (RR = 0.50 [SE(logRR) = 0.13]). After 1% trimming, IPTW estimates were unbiased and more precise (RR = 0.49 [SE(logRR) = 0.12]) than matching (RR = 0.51 [SE(logRR) = 0.14]). CONCLUSIONS: Differential misclassification of a strong predictor of exposure resulted in biased and imprecise IPTW estimates. Asymmetric trimming reduced bias, with more precise estimates than matching.

Statistical inference in abstracts of three influential clinical pharmacology journals analyzed using a text-mining algorithm.

AIM: To describe the trend in the prevalence of statistical inference in three influential clinical pharmacology journals METHODS: We applied a computer-based algorithm to abstracts of three clinical pharmacology journals published in 1976 to 2016 to identify statistical inference and its subtypes. Furthermore, we manually reviewed a random sample of 300 articles to access algorithm's performance in finding statistical inference in abstracts and as a screening tool for presence and absence of statistical inference in full text. RESULT: The algorithm identified 59% (13,375/22,516 [mid p 95% CI, 59%-60%]) article abstracts with statistical inference. The percentage of abstracts with statistical inference was similar in 1976 and 2016, 48% (179/377 [mid p 95%CI, 42%-52%]) versus 49% (386/791 [mid p 95%CI, 45%-52%]). Statistical reporting pattern varied among journals. Among abstracts containing any statistical inference in the publications from 1976 to 2016 null-hypothesis significance testing was the most prevalent reported statistical inference. The algorithm had high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for finding statistical inferences in abstract. While PPV for predicting the statistical inference in full text (including abstract, text, tables and figures) was high, NPV was low. CONCLUSION: Despite journal's editorials and statistical associations' guidelines, most authors focused on testing rather than estimation. In future, a better statistical reporting might be ensured by improving the statistical knowledge of authors and an addition of statistical guides to journals' instruction to authors to the extent that editors would like their statistical inference preferences to be incorporated into submitted manuscripts.

Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta-analysis.

BACKGROUND/RATIONALE: Long-term treatment with anticholinergic agents may increase the risk of cognitive impairment or dementia. This systematic literature review and meta-analysis aimed to assess the impact of ≥3 months of exposure to anticholinergics as a class on the risk of dementia, mild cognitive impairment, and change in cognitive function. The impact of anticholinergic agents specifically used to treat overactive bladder was also evaluated. MATERIALS AND METHODS: A systematic literature review was conducted to identify English language articles evaluating the impact of anticholinergic use for ≥3 months on dementia or cognitive function in adult patients. Databases searched included PubMed, Embase, and the Cochrane Library. Meta-analyses were conducted using random-effects models; 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were reported. RESULTS: A total of 2122 records were identified. Out of those, 21 studies underwent qualitative synthesis and 6 reported endpoints relevant for inclusion in a meta-analysis assessing the risk of incident dementia. The overall rate ratio for incident dementia was 1.46 (95% CI: 1.17-1.81; 95% PI: 0.70-3.04; n = 6). The risk of incident dementia increased with increasing exposure (n = 3). In addition, two studies from the meta-analysis reported an increased risk of dementia with ≥3 months of use of bladder antimuscarinics (adjusted odds ratios ranged from 1.21 to 1.65, depending on exposure category). CONCLUSION: Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics.

Reweighting Oranges to Apples: Transported RE-LY Trial Versus Nonexperimental Effect Estimates of Anticoagulation in Atrial Fibrillation.

BACKGROUND: Results from trials and nonexperimental studies are often directly compared, with little attention paid to differences between study populations. When target and trial population data are available, accounting for these differences through transporting trial results to target populations of interest provides useful perspective. We aimed to compare two-year risk differences (RDs) for ischemic stroke, mortality, and gastrointestinal bleeding in older adults with atrial fibrillation initiating dabigatran and warfarin when using trial transport methods versus nonexperimental methods. METHODS: We identified Medicare beneficiaries who initiated warfarin or dabigatran from a 20% nationwide sample. To transport treatment effects observed in the randomized evaluation of long-term anticoagulation trial, we applied inverse odds weights to standardize estimates to two Medicare target populations of interest, initiators of: (1) dabigatran and (2) warfarin. Separately, we conducted a nonexperimental study in the Medicare populations using standardized morbidity ratio weighting to control measured confounding. RESULTS: Comparing dabigatran to warfarin, estimated two-year RDs for ischemic stroke were similar with trial transport and nonexperimental methods. However, two-year mortality RDs were closer to the null when using trial transport versus nonexperimental methods for the dabigatran target population (transported RD: -0.57%; nonexperimental RD: -1.9%). Estimated gastrointestinal bleeding RDs from trial transport (dabigatran initiator RD: 1.8%; warfarin initiator RD: 1.9%) appeared more harmful than nonexperimental results (dabigatran initiator RD: 0.14%; warfarin initiator RD: 0.57%). CONCLUSIONS: Differences in study populations can and should be considered quantitatively to ensure results are relevant to populations of interest, particularly when comparing trial with nonexperimental findings. See video abstract: http://links.lww.com/EDE/B703.

Incidence of venous thromboembolism following initiation of non-steroidal anti-inflammatory drugs in U.S. women.

OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE, i.e. deep vein thrombosis or pulmonary embolism, or both) following new use of NSAIDs in a long-term cohort of U.S. women. METHODS: We investigated initiation of coxibs and traditional NSAIDs (excluding aspirin) and incident VTE in 39 876 women enrolled in the Women's Health Study from 1993-95 and followed with yearly questionnaires until 2012. We defined initiation as the first reported use of NSAIDs for ≥4 days per month. Incident VTE was confirmed by an end point committee. We estimated hazard ratios (HRs) and risk differences (RDs, expressed as percentages) comparing NSAID initiation with non-initiation and acetaminophen initiation (active comparator) via standardization using a propensity score that incorporated age, BMI, calendar time, and relevant medical, behavioural, and socioeconomic variables updated over time. RESULTS: The HR (95% CI) for risk of VTE in the as treated analyses comparing initiation with non-initiation, was 1.5 (1.2, 1.8) for any NSAID, 1.3 (1.1, 1.7) for traditional NSAIDs, and 2.0 (1.3, 3.1) for coxibs, with 2-year RDs 0.11, 0.08 and 0.32, respectively. When comparing the risk of VTE after initiation of any NSAID with that after acetaminophen initiation, the HRs were 0.9 (0.6, 1.5), 0.9 (0.5, 1.5) and 1.4 (0.6, 3.4), with 2-year RDs 0.03, -0.01, and 0.13, respectively. CONCLUSION: New use of NSAIDs was associated with increased VTE risk compared with non-use, but the association was null or diminished when compared with acetaminophen initiation. Elevated VTE risks associated with NSAID use in observational studies may in part reflect different baseline risks among individuals who need analgesics and may overstate the risk patients incur compared with pharmacologic alternatives.

High-risk Human Papillomavirus Messenger RNA Testing in Wet and Dry Self-collected Specimens for High-grade Cervical Lesion Detection in Mombasa, Kenya.

BACKGROUND: Self-collection for high-risk human papillomavirus (hr-HPV) messenger RNA (mRNA) testing may improve cervical cancer screening. High-risk HPV mRNA with self-collected specimens stored dry could enhance feasibility and acceptance of specimen collection and storage; however, its performance is unknown. We compared the performance of hr-HPV mRNA testing with dry- as compared with wet-stored self-collected specimens for detecting high-grade squamous intraepithelial lesion or more severe (≥HSIL). METHODS: A total of 400 female sex workers in Kenya participated (2013-2018), of which 50% were HIV positive based on enrollment procedures. Participants provided 2 self-collected specimens: one stored dry (sc-DRY) using a Viba brush (Rovers) and one stored wet (sc-WET) with Aptima media (Hologic) using an Evalyn brush (Rovers). Physician-collected specimens were collected for HPV mRNA testing (Aptima) and conventional cytology. We estimated test characteristics for each hr-HPV screening method using conventional cytology as the reference standard (≥HSIL detection). We also examined participant preference for sc-DRY and sc-WET collection. RESULTS: High-risk HPV mRNA positivity was higher in sc-WET (36.8%) than sc-DRY samples (31.8%). Prevalence of ≥HSIL was 6.9% (10.3% HIV positive, 4.0% HIV negative). Sensitivity of hr-HPV mRNA for detecting ≥HSIL was similar in sc-WET (85%; 95% confidence interval [CI], 66%-96%), sc-DRY specimens (78%; 95% CI, 58%-91%), and physician-collected specimens (93%; 95% CI, 76%-99%). Overall, the specificity of hr-HPV mRNA for ≥HSIL detection was similar when comparing sc-WET with physician collection. However, specificity was lower for sc-WET (66% [61%-71%]) than sc-DRY (71% [66%-76%]). Women preferred sc-DRY specimen collection (46.1%) compared with sc-WET (31.1%). However, more women preferred physician collection (63.9%) compared with self-collection (36.1%). CONCLUSIONS: Self-collected stored-dry specimens seemed to perform similarly to sc-WET for the detection of ≥HSIL.

Real-world on-treatment and initial treatment absolute risk differences for dabigatran vs warfarin in older US adults.

PURPOSE: Trials and past observational work compared dabigatran and warfarin in patients with atrial fibrillation, but few reported estimates of absolute harm and benefit under real-world adherence patterns, particularly in older adults that may have differing benefit-harm profiles. We aimed to estimate risk differences for ischemic stroke, death, and gastrointestinal bleeding after initiating dabigatran and warfarin in older adults (a) when patients adhere to treatment and (b) under real-world adherence patterns. METHODS: In a 20% sample of nationwide Medicare claims from 2010 to 2015, we identified beneficiaries aged 66 years and older initiating warfarin and dabigatran. We followed individuals from initiation until death or October 2015 (initial treatment, IT) and separately censored individuals' follow-up after drug switches and gaps in supply (on-treatment, OT). We applied inverse probability of treatment and standardized morbidity ratio weights, as well as inverse probability of censoring weights, to estimate two-year risk differences (RDs) for dabigatran vs warfarin. RESULTS: We identified 10,717 dabigatran and 74,891 warfarin initiators. Weighted OT RDs suggested decreased ischemic stroke risk for dabigatran vs warfarin; IT RDs indicated increased or no change in ischemic stroke risk. Regardless of follow-up approach and weighting strategy, risk of death appeared lower and risk of gastrointestinal bleeding appeared higher when comparing dabigatran vs warfarin. CONCLUSIONS: Dabigatran use was associated with lower risks of mortality and ischemic stroke in routine care when older adults stayed on treatment. IT analyses suggested that these benefits may be diminished under real-world patterns of switching and discontinuation.

Comparison of alternative approaches to trim subjects in the tails of the propensity score distribution.

PURPOSE: In nonexperimental comparative effectiveness research, restricting analysis to subjects with better overlap of covariate distributions, hence greater treatment equipoise, helps balance the groups compared and can improve validity. Three alternative approaches, derived from different perspectives, implement restriction by trimming observations in the tails of the propensity score (PS). Across approaches, we compared the relationships between the overlap in treatment-specific PS distributions and the size of the balanced study population after trimming. METHODS: The three trimming approaches considered were absolute trimming to the range 0.1

Changing predictors of statin initiation in US women over two decades.

PURPOSE: To describe changing roles of predictors of statin initiation before and after incident coronary heart disease, and before and after publication of National Cholesterol Education Program Adult Treatment Panel-III (ATP-III) guidelines in a cohort of US women. METHODS: We identified 34 382 women enrolled into the Women's Health Study from 1993 to 1995 and followed up until 2012. Proportions of previous nonusers initiating statins were described over time. We used multivariable linear regression models to estimate adjusted initiation proportion differences (IPDs) for initiation overall, separately before and after incident coronary heart disease, and separately for ATP-II and ATP-III time periods. RESULTS: Key predictors of initiation overall were self-reported total cholesterol, and previous incident coronary heart disease, cerebrovascular disease, and diabetes. Adjusted IPDs (percentage) for total cholesterol > 240 vs <200 mg/dL were 7.5 (95% confidence interval [CI], 7.0-8.0) and 9.3 (95% CI, 8.7-9.9) during ATP-II and ATP-III time periods, respectively. Adjusted IPDs in women with diabetes were 7.0 (95% CI, 6.3-7.8) and 11.9 (95% CI, 6.7-17.0) for primary and secondary prevention, respectively, and 3.1 (95% CI, 2.1-4.0) and 9.2 (95% CI 8.2-10.2) for before and after ATP-III, respectively. CONCLUSIONS: Secular trends reflected evolution toward risk factor-based treatment indications for statin initiation with increased initiation among diabetics and women with normal and borderline cholesterol. The role of serum cholesterol changed over time, though the character was scale (multiplicative vs additive) dependent. In pharmacoepidemiologic studies of statins, strength of confounding by important variables sometimes unmeasured in claims data, such as cholesterol level, may be calendar time dependent.

Mechanical analysis of an MgB2 1.5 T MRI main magnet protected using Coupling Loss Induced Quench.

Mechanical analysis of the stress and strains developed in the coils were calculated for a ten coil 1.5 T MRI magnet design with magnesium diboride (MgB2) wire protected with Coupling Loss Induced Quench (CLIQ). The temperature distribution inside the coils was first simulated in MATLAB to solve the governing heat and circuit equations. Simulations were performed on the magnet, in which each coil was divided into two subsections, with two CLIQ units while the capacitor ranged from 5 to 20 mF and the initial charging voltage ranged from 2.6 kV to 1.3 kV in order to keep the total stored energy in the CLIQ system constant. The wire's filamentary twist pitch remained constant at 5 cm for all simulations. The exported temperature distribution was expanded to form a representative unit cell (RUC) representing the wire composite and then imported into ANSYS to calculate the 1st principle strain in the MgB2 filament and shear stress across the epoxy for the coils. A peak temperature of 191 K occurred inside the coil with the initial quench when the CLIQ unit had a 20 mF capacitor charged to 1.3 kV. According to the mechanical simulations, the largest resulting peak strain in the wire was 0.034%, and peak shear stress was 44 MPa.

Exposure to Human-Associated Chemical Markers of Fecal Contamination and Self-Reported Illness among Swimmers at Recreational Beaches.

Anthropogenic chemicals have been proposed as potential markers of human fecal contamination in recreational water. However, to date, there are no published studies describing their relationships with illness risks. Using a cohort of swimmers at seven U.S. beaches, we examined potential associations between the presence of chemical markers of human fecal pollution and self-reported gastrointestinal (GI) illness, diarrhea, and respiratory illness. Swimmers were surveyed about their beach activities, water exposure, and baseline symptoms on the day of their beach visit, and about any illness experienced 10-12 days later. Risk differences were estimated using model-based standardization and adjusted for the swimmer's age, beach site, sand contact, rainfall, and water temperature. Sixty-two chemical markers were analyzed from daily water samples at freshwater and marine beaches. Of those, 20 were found consistently. With the possible exception of bisphenol A and cholesterol, no chemicals were consistently associated with increased risks of illness. These two chemicals were suggestively associated with 2% and 1% increased risks of GI illness and diarrhea in both freshwater and marine beaches. Additional research using the more sensitive analytic methods currently available for a wider suite of analytes is needed to support the use of chemical biomarkers to quantify illness risk and identify fecal pollution sources.

Case study in major quotation errors: a critical commentary on the Newcastle-Ottawa scale.

The Newcastle-Ottawa scale (NOS) is one of many scales used to judge the quality of observational studies in systematic reviews. It was criticized for its arbitrary definitions of quality items in a commentary in 2010 in this journal. That commentary was cited 1,250 times through December 2016. We examined the citation history of this commentary in a random sample of 100 full papers citing it, according to the Web of Science. Of these, 96 were systematic reviews, none of which quoted the commentary directly. All but 2 of the 96 indirect quotations (98%) portrayed the commentary as supporting use of the NOS in systematic reviews when, in fact, the opposite was the case. It appears that the vast majority of systematic review authors who cited this commentary did not read it. Journal reviewers and editors did not recognize and correct these major quotation errors. Authors should read each source they cite to make sure their direct and indirect quotations are accurate. Reviewers and editors should do a better job of checking citations and quotations for accuracy. It might help somewhat for commentaries to include abstracts, so that the basic content can be conveyed by PubMed and other bibliographic resources.

Classifying medical histories in US Medicare beneficiaries using fixed vs all-available look-back approaches.

PURPOSE: Evaluate use of fixed and all-available look-backs to identify eligibility criteria and confounders among Medicare beneficiaries. METHODS: We identified outpatient visits (2007-2012) with recently documented (≤180 days) cardiovascular risk and classified patients according to whether the exposure (statin) was initiated within 14 days. We selected each beneficiary's first eligible visit (in each treatment group) that met criteria during the respective look-backs: continuous enrollment (1 or 3 years for fixed look-back; 180 days for all-available), no cancer history, and no statin claims. We estimated crude and standardized mortality ratio weighted hazard ratios (HRs) for the effect of statin initiation on incident 6-month cancer (a known null effect) and 2-year mortality, separately, adjusting for covariates assessed by using each look-back. RESULTS: Analyzing short-term cancer, the estimated HR from the all-available approach (HR = 0.90, 95% CI: 0.83, 0.98) was less biased than the 1-year look-back (HR = 0.79, 95% CI: 0.73, 0.84), which included beneficiaries with prevalent cancer. The 3-year look-back (HR = 1.05, 95% CI: 0.90, 1.21) was somewhat less biased than the all-available estimate but less precise due the exclusion of a large proportion of observations without sufficient continuous enrollment (62.0% and 59.9% of initiators and non-initiators, respectively). All approaches produced similar estimates of the effect on all-cause mortality. Alternative look-backs did not differ in their ability to control confounding. CONCLUSIONS: The all-available look-back performed nearly as well as the 3-year fixed, which produced the least biased point estimate. If 3-year look-backs are infeasible (eg, due to power/sample), all-available look-backs may be preferable to short (1-year) fixed look-backs.

Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.