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STUDY QUESTION Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? SUMMARY ANSWER Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. WHAT IS KNOWN ALREADY In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. STUDY DESIGN, SIZE, DURATION Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006–2016). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. MAIN RESULTS AND ROLE OF CHANCE Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (−819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: −1265.7, −373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: −21.8%; 95% CI: −37.1%, −2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: −23.8%; 95% CI: −39.9%, −3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. LIMITATIONS, REASONS FOR CAUTION Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. WIDER IMPLICATIONS OF THE FINDINGS Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes? SUMMARY ANSWER In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes. WHAT IS KNOWN ALREADY Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes. STUDY DESIGN, SIZE, DURATION A prospective cohort study of women undergoing IVF from 2009 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence. MAIN RESULTS AND ROLE OF CHANCE In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively. LIMITATIONS, REASONS FOR CAUTION Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results. WIDER IMPLICATIONS OF THE FINDINGS The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Across several medical fields, developing an approach for disease classification is an important challenge. The usual procedure is to fit a model for the longitudinal response in the healthy population, a different model for the longitudinal response in the diseased population, and then apply Bayes' theorem to obtain disease probabilities given the responses. Unfortunately, when substantial heterogeneity exists within each population, this type of Bayes classification may perform poorly. In this article, we develop a new approach by fitting a Bayesian nonparametric model for the joint outcome of disease status and longitudinal response, and then we perform classification through the clustering induced by the Dirichlet process. This approach is highly flexible and allows for multiple subpopulations of healthy, diseased, and possibly mixed membership. In addition, we introduce an Markov chain Monte Carlo sampling scheme that facilitates the assessment of the inference and prediction capabilities of our model. Finally, we demonstrate the method by predicting pregnancy outcomes using longitudinal profiles on the human chorionic gonadotropin beta subunit hormone levels in a sample of Chilean women being treated with assisted reproductive therapy. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. Methods and results We followed 95 465 ever-gravid women participating in the Nurses' Health Study II between 1993 and 2017. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of CVD, including coronary heart disease (CHD), and stroke, according to the occurrence of PL. A mediation analysis was conducted to explore the intermediating effect of subsequent type 2 diabetes, hypertension, or hypercholesterolaemia. During 2 205 392 person-years of follow-up (mean 23.10 years), 2225 (2.3%) incident CVD cases were documented. After adjusting for confounding factors, PL was associated with an HR of 1.21 [95% confidence interval (CI) 1.10–1.33] for CVD during follow-up. A similar association was observed for CHD (HR 1.20; 95% CI 1.07–1.35) and stroke (HR 1.23; 95% CI 1.04–1.44). The risk of CVD increased with the number of PLs [HR 1.18 (95% CI 1.06–1.31) for 1 and 1.34 (95% CI 1.13–1.59) for ≥2 times] and was greater for PL occurring early in reproductive lifespan [HR 1.40 (95% CI 1.21–1.62) for age ≤23 years, 1.25 (95% CI 1.09–1.43) for age 24–29 years, and 1.03 (95% CI 0.88–1.19) for age ≥30 years]. Hypertension, hypercholesterolaemia, and type 2 diabetes all explained <1.80% of the association between PL and CVD. Conclusion PL was associated with a greater CVD risk, independently of subsequent development of metabolic disorders. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has highlighted the inequitable access to resources, leading to a disproportionate burden of disease in vulnerable communities in the USA. However, these inequities in health outcomes are not limited to COVID-19. Approximately 18% of cancers are related to dietary behaviors and excess body weight. Underserved communities, such as minority racial/ethnic groups living in neighborhoods of low socioeconomic status, experience barriers to healthy eating including lack of access to high-quality healthy foods and higher availability of unhealthy foods and beverages in local retail food outlets. Strikingly, these same populations are more likely to die from cancers related to dietary intake and obesity like colorectal, liver, and pancreatic cancers. To reduce cancer inequities, policy makers can act by supporting programs that incentivize healthy food purchases and improve the local food environment in underserved communities. [ABSTRACT FROM AUTHOR]

Summary: Count data are common in many fields such as public health. Hurdle models have been developed to model count data when the zero count could be either inflated or deflated. However, when data are repeatedly collected over time and spatially correlated, it is very challenging to model the data appropriately. For example, to study health professional shortage areas, the number of primary care physicians along with other demographic characteristics are collected at the county level in the USA and over different years. Since the data are repeatedly collected over time, counties are nested within the state, and adjacent counties are geographically correlated, the dependence structure of the data is very complex. We develop a Bayesian hurdle model with multilayered random effects to incorporate this complex structure. We use a time‐varying random effect for each state to capture the time effect at the state level, and a temporal thin plate spline to capture the spatiotemporal correlation across different counties. We use STAN to obtain samples for inference from the posterior distribution. By using the model proposed, we can identify the important factors which impact health professional shortage areas. Simulation studies also confirm the effectiveness of the model. [ABSTRACT FROM AUTHOR]

Study Question: How does ovarian stimulation in an oocyte donor affect the IVF cycle and obstetric outcomes in recipients?Summary Answer: Higher donor oocyte yields may affect the proportion of usable embryos but do not affect live birth delivery rate or obstetric outcomes in oocyte recipients.What Is Known Already: In autologous oocyte fresh IVF cycles, the highest live birth delivery rates occur when ~15-25 oocytes are retrieved, with a decline thereafter, perhaps due to the hormone milieu, with super-physiologic estrogen levels. There are scant data in donor oocyte cycles, wherein the oocyte environment is separated from the uterine environment.Study Design, Size, Duration: This was a retrospective cohort study from 2008 to 2015 of 350 oocyte donors who underwent a total of 553 ovarian stimulations and oocyte retrievals. The oocytes were vitrified and then distributed to 989 recipients who had 1745 embryo transfers. The primary outcome was live birth delivery rate, defined as the number of deliveries that resulted in at least one live birth per embryo transfer cycle.Participants/materials, Setting, Methods: The study included oocyte donors and recipients at a donor oocyte bank, in collaboration with an academic reproductive endocrinology division. Donors with polycystic ovary syndrome and recipients who used gestational carriers were excluded. The donors all underwent conventional ovarian stimulation using antagonist protocols. None of the embryos underwent pre-implantation genetic testing. The average (mean) number of embryos transferred to recipients was 1.4 (range 1-3).Main Results and the Role Of Chance: Per ovarian stimulation cycle, the median number of oocytes retrieved was 30 (range: 9-95). Among the 1745 embryo transfer cycles, 856 of the cycles resulted in a live birth (49.1%). There were no associations between donor oocyte yield and probability of live birth, adjusting for donor age, BMI, race/ethnicity and retrieval year. The results were similar when analyzing by mature oocytes. Although donors with more oocytes retrieved had a higher number of developed embryos overall, there was a relatively lower percentage of usable embryos per oocyte warmed following fertilization and culture. In our model for the average donor in the data set, holding all variables constant, for each additional five oocytes retrieved, there was a 4% (95% CI 1%, 7%) lower odds of fertilization and 5% (95% CI 2%, 7%) lower odds of having a usable embryo per oocyte warmed. There were no associations between donor oocyte yield and risk of preterm delivery (<37 weeks gestation) and low birthweight (<2500 g) among singleton infants.Limitations, Reasons For Caution: Ovarian stimulation was exclusively performed in oocyte donors. This was a retrospective study design, and we were therefore unable to ensure proportional exposure groups. These findings may not generalizable to older or less healthy women who may be vitrifying oocytes for planned fertility delay. There remain significant risks to aggressive ovarian stimulation, including ovarian hyperstimulation. In addition, long-term health outcomes of extreme ovarian stimulation are lacking. Lastly, we did not collect progesterone levels and are unable to evaluate the impact of rising progesterone on outcomes.Wider Implications Of the Findings: Live birth delivery rates remain high with varying amounts of oocytes retrieved in this donor oocyte model. In a vitrified oocyte bank setting, where oocytes are typically sent as a limited number cohort, recipients are not affected by oocyte yields.Study Funding/competing Interest(s): Additional REDCap grant support at Emory was provided through UL1 TR000424. Dr. Audrey Gaskins was supported in part by a career development award from the NIEHS (R00ES026648). [ABSTRACT FROM AUTHOR]

Single‐cell RNA sequencing (scRNA‐seq) technologies are revolutionary tools allowing researchers to examine gene expression at the level of a single cell. Traditionally, transcriptomic data have been analyzed from bulk samples, masking the heterogeneity now seen across individual cells. Even within the same cellular population, genes can be highly expressed in some cells but not expressed (or lowly expressed) in others. Therefore, the computational approaches used to analyze bulk RNA sequencing data are not appropriate for the analysis of scRNA‐seq data. Here, we present a novel statistical model for high dimensional and zero‐inflated scRNA‐seq count data to identify differentially expressed (DE) genes across cell types. Correlated random effects are employed based on an initial clustering of cells to capture the cell‐to‐cell variability within treatment groups. Moreover, this model is flexible and can be easily adapted to an independent random effect structure if needed. We apply our proposed methodology to both simulated and real data and compare results to other popular methods designed for detecting DE genes. Due to the hurdle model's ability to detect differences in the proportion of cells expressed and the average expression level (among the expressed cells), our methods naturally identify some genes as DE that other methods do not, and we demonstrate with real data that these uniquely detected genes are associated with similar biological processes and functions. [ABSTRACT FROM AUTHOR]

Traffic-related air pollution has been linked to higher risks of infertility and miscarriage. We evaluated whether folate intake modified the relationship between air pollution and livebirth among women using assisted reproductive technology (ART). Our study included 304 women (513 cycles) presenting to a fertility center in Boston, Massachusetts (2005–2015). Diet and supplements were assessed by food frequency questionnaire. Spatiotemporal models estimated residence-based daily nitrogen dioxide (NO2), ozone, fine particulate, and black carbon concentrations in the 3 months before ART. We used generalized linear mixed models with interaction terms to evaluate whether the associations between air pollutants and livebirth were modified by folate intake, adjusting for age, body mass index, race, smoking, education, infertility diagnosis, and ART cycle year. Supplemental folate intake significantly modified the association of NO2 exposure and livebirth (P = 0.01). Among women with supplemental folate intakes of <800 μg/day, the odds of livebirth were 24% (95% confidence interval: 2, 42) lower for every 20-parts-per-billion increase in NO2 exposure. There was no association among women with intakes of ≥800 μg/day. There was no effect modification of folate on the associations between other air pollutants and livebirth. High supplemental folate intake might protect against the adverse reproductive consequences of traffic-related air pollution. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between air pollution exposures and the risk of spontaneous abortion (SAB)?Summary Answer: Higher exposure to particulate matter (PM) air pollution above and beyond a woman's average exposure may be associated with greater risk of SAB, particularly among women experiencing at least one SAB during follow-up.What Is Known Already: There is sufficient biologic plausibility to suggest that air pollution adversely affects early pregnancy outcomes, particularly pregnancy loss; however, the evidence is limited.Study Design, Size, Duration: Our prospective cohort study included 19 309 women in the Nurses' Health Study II who contributed a total of 35 025 pregnancies between 1990 and 2008. We also conducted a case-crossover analysis among 3585 women (11 212 pregnancies) with at least one SAB and one live birth during follow-up.Participants/materials, Setting, Methods: Proximity to major roadways and exposure to PM <10 microns (PM10), 2.5-10 microns (PM2.5-10) and <2.5 microns (PM2.5) were determined for residential addresses between 1989 and 2007. Pregnancy outcomes were self-reported biannually throughout follow-up and comprehensively in 2009. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the risk ratios and 95% CIs of SAB. Conditional logistic regression was used for the case-crossover analysis.Main Results and the Role Of Chance: During the 19 years of follow-up, 6599 SABs (18.8% of pregnancies) were reported. In the main analysis, living closer to a major roadway and average exposure to PM10, PM10-2.5 or PM2.5 in the 1 or 2 years prior to pregnancy were not associated with an increased risk of SAB. However, small positive associations between PM exposures and SAB were observed when restricting the analysis to women experiencing at least one SAB during follow-up. In the case-crossover analysis, an increase in PM10 (per 3.9 μg/m3), PM2.5-10 (per 2.3 μg/m3) and PM2.5 (per 2.0 μg/m3) in the year prior to pregnancy was associated with 1.12 (95% CI 1.06, 1.19), 1.09 (95% CI 1.03, 1.14) and 1.10 (95% CI 1.04, 1.17) higher odds of SAB, respectively.Limitations, Reasons For Caution: We did not have information on the month or day of SAB, which precluded our ability to examine specific windows of susceptibility or acute exposures. We also used ambient air pollution exposures as a proxy for personal exposure, potentially leading to exposure misclassification.Wider Implications Of the Findings: In our case-crossover analysis (but not in the entire cohort) we observed positive associations between exposure to all size fractions of PM exposure and risk of SAB. This may suggest that changes in PM exposure confer greater risk of SAB or that women with a history of SAB are a particularly vulnerable subgroup.Study Funding/competing Interest(s): The authors are supported by the following NIH grants UM1CA176726, R00ES026648 and P30ES000002. The authors have no actual or potential competing financial interests to disclose. [ABSTRACT FROM AUTHOR]

Study Question: What is the association of female and male partner marijuana smoking with infertility treatment outcomes with ART?Summary Answer: Women who were marijuana smokers at enrollment had a significantly higher adjusted probability of pregnancy loss during infertility treatment with ART whereas, unexpectedly, there was a suggestion of more favorable treatment outcomes in couples where the man was a marijuana smoker at enrollment.What Is Known Already: Data on the relation of female and male partner marijuana use with outcomes of infertility treatment is scarce despite increased use and legalization worldwide.Study Design, Size, Duration: We followed 421 women who underwent 730 ART cycles while participating in a prospective cohort (the Environment and Reproductive Health Study) at a fertility center between 2004 and 2017. Among them, 200 women (368 cycles) were part of a couple in which their male partner also enrolled in the study.Participants/materials, Setting, Methods: Participants self-reported marijuana smoking at baseline. Clinical endpoints were abstracted from electronic medical records. We used generalized linear mixed models with empirical standard errors to evaluate the association of baseline marijuana smoking with ART outcomes adjusting for participants' age, race, BMI, tobacco smoking, coffee and alcohol consumption, and cocaine use. We estimated the adjusted probability of implantation, clinical pregnancy, and live birth per ART cycle, as well as the probability of pregnancy loss among those with a positive B-hCG.Main Results and the Role Of Chance: The 44% of the women and 61% of the men had ever smoked marijuana; 3% and 12% were marijuana smokers at enrollment, respectively. Among 317 women (395 cycles) with a positive B-hCG, those who were marijuana smokers at enrollment (N = 9, cycles = 16) had more than double the adjusted probability of pregnancy loss than those who were past marijuana smokers or had never smoked marijuana (N = 308, 379 cycles) (54% vs 26%; P = 0.0003). This estimate was based on sparse data. However, couples in which the male partner was a marijuana smoker at enrollment (N = 23, 41 cycles) had a significantly higher adjusted probability of live birth than couples in which the male partner was a past marijuana smoker or had never smoked marijuana (N= 177, 327 cycles) (48% vs 29%; P = 0.04), independently of the women's marijuana smoking status. Treatment outcomes of past marijuana smokers, male and female, did not differ significantly from those who had never smoked marijuana.Limitations, Reasons For Caution: Marijuana smoking was self-reported with possible exposure misclassification. Chance findings cannot be excluded due to the small number of exposed cases. The results may not be generalizable to couples from the general population.Wider Implications Of the Findings: Even though marijuana smoking has not been found in past studies to impact the ability to become pregnant among pregnancy planners in the general population, it may increase the risk of pregnancy loss among couples undergoing infertility treatment. Marijuana smoking by females and males may have opposing effects on outcomes of infertility treatment with ART.Study Funding/competing Interest(s): The project was financed by grants R01ES009718, P30ES000002, and K99ES026648 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms of cytochrome P450 are contributors to variability in individual response to drugs. Within the P450 family, CYP2D6 is responsible for metabolizing hydrocodone, a widely prescribed opioid for pain management. Alternatively, CYP3A4 and CYP3A5 can form norhydrocodone and dihydrocodeine.Wehave previously found that in a postcesarean section cohort, the rate of hydromorphone formation was dependent on the genotype of CYP2D6 and that plasma hydromorphone, not hydrocodone, was predictive of pain relief. Method: Blood was obtained from a postcesarean cohort that were surveyed for pain response and common side effects. Plasma samples were genotyped for CYP3A4/5, and their hydrocodone concentrations were measured by LC-MS. R statistical software was used to check for differences in the outcomes due to CYP3A4/5 and CYP2D6, and a multivariate regression model was fit to determine factors associated with pain score. Results: Two-way ANOVA between CYP3A4/A5 and CYP2D6 phenotypes revealed that the former variants did not have a statistical significance on the outcomes, and only CYP2D6 phenotypes had a significant effect on total dosage (P = 0.041). Furthermore, a 3-way ANOVA analysis showed that CYP2D6 (P = 0.036) had a predictive effect on plasma hydromorphone concentrations, and CYP3A4/A5 did not have any effect on the measured outcomes. Conclusions: With respect to total dosages in a cesarean section population, these results confirm that CYP2D6 phenotypes are predictors for plasma hydromorphone concentration and pain relief, but CYP3A4/A5 phenotypes have no influence on pain relief or on side effects. [ABSTRACT FROM AUTHOR]

Background Though conventionally fractionated chemoradiation (CRT) is well tolerated by selected patients with newly diagnosed glioblastoma (GBM), adverse health-related and nonhealth-related factors can lead to unplanned interruptions in treatment. The effects of prolonged time to completion (TTC) of radiation therapy (RT) on overall survival (OS) for these patients are unclear. Methods The National Cancer Database (NCDB) was queried for all adult patients with newly diagnosed GBM undergoing surgical resection followed by adjuvant CRT with conventionally fractionated RT (6000-6600 cGy in 30-33 fractions) from 2005 to 2012. TTC was defined as the interval from first to last fraction of RT. Recursive partitioning analysis (RPA) was used to determine a threshold for TTC of adjuvant RT. Cox proportional hazards modeling was used to identify covariates associated with OS. Results A total of 13489 patients were included in our cohort. Patients who completed adjuvant RT within the RPA-defined threshold of 46 days from initiation of RT (median OS: 14.0 months, 95% confidence interval (CI) 13.7 to 14.3 months) had significantly improved OS compared to patients with TTC of 47 days or greater (median OS: 12.0 months, 95% CI 11.4 to 12.6 months, P <.001). Delays in completing adjuvant RT were relatively common, with 15.0% of patients in our cohort having a TTC of RT of 47 days or greater. Conclusions Delays in completing adjuvant RT were associated with a worse survival outcome. Any unnecessary delays in completing adjuvant RT should be minimized while ensuring the safe delivery of therapy. [ABSTRACT FROM AUTHOR]

Introduction: Patient-Reported Outcomes Measure System-10 (PROMIS-10) is a brief survey consisting of 10 items that evaluates patients' global physical and mental health. PROMIS-10 was introduced into our burn clinic as a screening tool and serial measure of recovery. We aimed to assess the implementation of PROMIS-10 to improve its equitable use in outpatient clinics. Methods: The PROMIS-10 was implemented in 2014 as part of a packet of other screening tools. The staff were trained in its use. Patients completed English-language surveys via paper/pen upon arrival at each of their burn clinic appointments while waiting to be roomed. Survey results were reviewed by clinic providers and addressed as part of routine care. Survey answers were entered into REDCap and merged with demographic and burn injury information. Data were collected and analyzed using univariate and bivariable statistics to evaluate equitable implementation. Results: A total of 1,963 surveys were collected from 1,606 patients from January 2014 to December 2020 (Figure 1). After excluding patients with missing collection of survey and/or demographic data, our analysis included 1,072 patients. The mean number of surveys completed per visit was 0.53 (SEM=0.007) and 88% of patients completed 1 or more surveys. Patients who required intensive care during their index hospitalization or had an operation had higher mean surveys completed per visit (Highest Level of Care ICU=0.611 ± 0.02; Required an operation = 0.608 ± 0.015), whereas patients requiring an interpreter had lower mean surveys completed per visit (Required an Interpreter = 0.468 ± 0.031). Conclusions: Although the majority of patients completed the PROMIS-10 during at least one clinic visit, there is significant room for improvement given our intent to use it as a screening tool for every encounter and metric of recovery progress over time. Focus on equity in completion is needed (e.g., coordinating interpreter-assisted completion, availability of translated forms, person-assisted completion for limited English proficiency, medical record integration for telemedicine and progress tracking). We did note that patients with markers of high burn severity (ICU stay, requiring an operation) had higher rates of survey completion per visit. This is a patient population in which serial evaluation is particularly helpful in monitoring recovery. Applicability of Research to Practice: Use of PROMIS-10 can successfully be used as a screening and recovery progress metric in the outpatient setting. Equitable implementation should be assessed, and efforts to integrate such screening tools into the medical record should be considered. [ABSTRACT FROM AUTHOR]

Study Question: Is self-reported type of underwear worn associated with markers of testicular function among men at a fertility center?Summary Answer: Men who reported most frequently wearing boxers had higher sperm concentration and total count, and lower FSH levels, compared to men who did not.What Is Known Already: Elevated scrotal temperatures are known to adversely affect testicular function. However, the epidemiologic literature on type of underwear, as a proxy of scrotal temperature, and male testicular function is inconsistent.Study Design, Size, Duration: This is a cross-sectional study including 656 male partners of couples seeking infertility treatment at a fertility center (2000-2017).Participants/materials, Setting, Methods: Self-reported information on type of underwear worn was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone levels and neutral comet assays for sperm DNA damage. We fit linear regression models to evaluate the association between underwear type and testicular function, adjusting for covariates and accounting for multiple semen samples.Main Results and the Role Of Chance: Men had a median (interquartile range) age of 35.5 (32.0, 39.3) years and BMI of 26.3 (24.4, 29.9) kg/m2. About half of the men (53%; n = 345) reported usually wearing boxers. Men who reported primarily wearing boxers had a 25% higher sperm concentration (95% CI = 7, 31%), 17% higher total count (95% CI = 0, 28%) and 14% lower serum FSH levels (95% CI = -27, -1%) than men who reported not primarily wearing boxers. Sperm concentration and total count were inversely related to serum FSH. Furthermore, the differences in sperm concentration and total count according to type of underwear were attenuated after adjustment for serum FSH. No associations with other measured reproductive outcomes were observed.Limitations, Reasons For Caution: Our results may not be generalizable to men from the general population. Underwear use was self-reported in a questionnaire and there may be misclassification of the exposure. The cross-sectional design limits causal inference, and residual confounding is still possible owing to lack of information on other modifiable life styles that can also modify scrotal heat (e.g. type of trousers worn, textile fabric of the underwear). Blood sampling was not limited to the morning and, as a result, we may have missed associations with testosterone or other hormones with significant circadian variation despite statistical adjustment for time of blood draw.Wider Implications Of the Findings: Certain styles of male underwear may impair spermatogenesis and this may result in a compensatory increase in gonadotrophin secretion, as reflected by higher serum FSH levels among men who reported most frequently wearing tight underwear. Confirmation of these findings, and in particular the findings on FSH levels suggesting a compensatory mechanism, is warranted.Study Funding/competing Interest(s): The project was financed by Grants (R01ES022955, R01ES009718, P30ES000002, and K99ES026648) from the National Institutes of Health. None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Background: The advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug.Methods: We analyzed TNF receptor expression in publicly available gene expression profiling data and in thyroid tissue samples. Mice with metastatic FTC-133 and 8505C xenografts and the MEN1 conditional knock-out mice were treated weekly with CYT-21625 and gold nanoparticles with rhTNF only (CYT-6091); controls included mice treated with either paclitaxel or saline. In vivo luciferase activity was used to assess the effects on tumor growth. Computed tomography, magnetic resonance imaging, and 18F-Fludeoxyglucose positron emission tomography were used to study tumor selectivity in mice with insulin-secreting pancreatic neuroendocrine tumors (PNETs). All statistical tests were two-sided.Results: Anaplastic thyroid cancer (ATC) expressed statistically significantly higher levels of TNF receptor superfamily 1A and 1B messenger RNA (n = 11) and protein (n = 6) than control samples (n = 45 and 13, respectively). Mice (n = 5-7 per group) with metastatic ATC (P < .009) and FTC-133 xenografts (P = .03 at week 3, but not statistically significant in week 4 owing to reduced sample size from death in non-CYT-21625 groups) treated with CYT-21625 had a statistically significantly lower tumor burden. Treatment with CYT-21625 resulted in loss of CD34 expression in intratumoral vasculature, decreased proliferating cell nuclear antigen, and increased cleaved caspase-3. Intratumoral vascular leakage occurred only in mice with PNET and ATC treated with CYT-6091 and CYT-21625. CYT-6091 and CYT-21625 preferentially deposited in PNETs and statistically significantly decreased serum insulin levels (n = 3 per group, P < .001). There were no toxicities observed in mice treated with CYT-21625.Conclusions: CYT-21625 is effective in mice with PNETs and metastatic human thyroid cancer with no toxicities. Thus, CYT-21625 should be studied in patients with advanced PNETs and thyroid cancer. [ABSTRACT FROM AUTHOR]

Background Little is known about the predictors of sexual intercourse frequency (SIF) among couples trying to conceive despite the well-established link between SIF and fecundity. Aim To evaluate men's and women's demographic, occupational, and lifestyle predictors of SIF among couples. Methods 469 Couples without a history of infertility participating in the Longitudinal Investigation of Fertility and the Environment Study (2005–2009) were followed up for ≤1 year while trying to conceive. At enrollment, both partners were interviewed about demographic, occupational, lifestyle, and psychological characteristics using standardized questionnaires. Multivariable generalized linear mixed models with Poisson distribution were used to estimate the adjusted percent difference in SIF across exposure categories. Outcomes SIF was recorded in daily journals and summarized as average SIF/mo. Results The median (interquartile range) SIF during follow-up was 6 (4–9) acts/mo. For every year increase in age for women and men, SIF decreased by –0.8% (95% CI –2.5 to 1.0%) and –1.7% (95% CI –3.1 to –0.3%). Women with high school education or less and those of non-white race had 34.4% and 16.0% higher SIF, respectively. A similar trend was seen for men's education and race. Only couples where both partners (but not just 1 partner) worked rotating shifts had –39.1% (95% CI –61.0 to –5.0%) lower SIF compared to couples where neither partner worked rotating shifts. Men's (but not women's) exercise was associated with 13.2% (95% CI 1.7–26.0%) higher SIF. Diagnosis of a mood or anxiety disorder in men (but not women) was associated with a 26.0% (95% CI –42.7 to –4.4%) lower SIF. Household income, smoking status, body mass index, night work, alcohol intake, and psychosocial stress were not associated with SIF. Clinical Translation Even among couples trying to conceive, there was substantial variation in SIF. Both partners' age, education, race, and rotating shift work as well as men's exercise and mental health play an important role in determining SIF. Conclusions As this was a secondary analysis of an existing study, we lacked information on many pertinent psychological and relationship quality variables and the hormonal status of participants, which could have affected SIF. The unique population-based couple design, however, captured both partners' demographics, occupational characteristics, and lifestyle behaviors in advance of their daily, prospective reporting of SIF, which was a major strength. Important predictors of SIF among couples attempting to conceive include men's exercise and mental health and both partners' age, education, race, and rotating shift work. Gaskins AJ, Sundaram R, Buck Louis GM, et al. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med 2018;15:519–528. [ABSTRACT FROM AUTHOR]

Despite improvements in the efficiency of energy, material and water use, the ecological burden of healthcare provision has increased globally.[1] Aside from greenhouse gas (GHG) emissions from power consumption, transportation and service delivery, the healthcare sector and its supply chains contribute to the degradation of the biosphere in less apparent ways. Firstly, the extent to which downstream consequences should influence guideline recommendations designed primarily to improve the health of the individual seeking treatment remains a fraught ethical question. Following this logic, in addition to focusing on proximate effects such as GHG emissions and air pollution, attending to endpoints further down the causal chain becomes critical to appreciate fully the ecological footprint of health care. [Extracted from the article]

Summary: Phosphorylated proteins provide insight into tumor etiology and are used as diagnostic, prognostic, and therapeutic markers of complex diseases. However, pre‐analytic variations, such as freezing delay after biopsy acquisition, often occur in real hospital settings and potentially lead to inaccurate results. The objective of this work is to develop statistical methodology to assess the stability of phosphorylated proteins under short‐time cold ischemia. We consider a hierarchical model to determine if phosphorylation abundance of a protein at a particular phosphorylation site remains constant or not during cold ischemia. When phosphorylation levels vary across time, we estimate the direction of the changes in each protein based on the maximum overall posterior probability and on the pairwise posterior probabilities, respectively. We analyze a dataset of ovarian tumor tissues that suffered cold‐ischemia shock before the proteomic profiling. Gajadhar et al. (2015) applied independent clusterings for each patient because of the high heterogeneity across patients, while our proposed model shares information allowing conclusions for the entire sample population. Using the proposed model, 15 out of 32 proteins show significant changes during 1‐hour cold ischemia. Through simulation studies, we conclude that our proposed methodology has a higher accuracy for detecting changes compared to an order restricted inference method. Our approach provides inference on the stability of these phosphorylated proteins, which is valuable when using these proteins as biomarkers for a disease. [ABSTRACT FROM AUTHOR]

Study Question: Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes?Summary Answer: Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART.What Is Known Already: Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART.Study Design Size, and Duration: This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection.Participants/materials, Setting, Methods: Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth.Main Results and Role Of Chance: The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes.Limitations Reasons For Caution: The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up.Wider Implications Of the Findings: Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART.Study Funding/competing Interests: NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Semen parameters are variable within individuals, but it is unclear whether 1 semen sample could represent a man's long-term average values in epidemiologic studies. Between 2005 and 2014, a total of 329 men from a fertility clinic in Boston, Massachusetts, provided 768 semen samples as part of the Environment and Reproductive Health (EARTH) Study. Total sperm count, sperm concentration, morphology, motility, and ejaculate volume were assessed. We used linear mixed models to compare values from men's first semen samples with their long-term averages and to calculate intraclass correlation coefficients for each parameter. We calculated positive predictive values (PPVs) and negative predictive values (NPVs) by comparing agreement in classification according to World Health Organization reference limits. There were no differences in mean semen parameters between men's first samples and the remaining replicates. Intraclass correlation coefficients ranged from 0.61 for morphology to 0.75 for concentration, indicating consistently greater between-man variability than within-man variability. Nevertheless, using 1 sample alone resulted in high NPVs but low PPVs (range, 43%-91%). The average of 2 samples was needed to achieve high PPVs (range, 86%-100%) and NPVs (range, 91%-100%). We conclude that 1 semen sample may suffice for studies aimed at identifying average differences in semen quality between individuals. Studies aimed at classifying men based on World Health Organization reference limits may benefit from collection of 2 or more samples. [ABSTRACT FROM AUTHOR]

Study Question: Is pre-treatment alcohol and caffeine intake associated with infertility treatment outcomes among women undergoing ART?Summary Answer: Low to moderate alcohol and caffeine intakes in the year prior to infertility treatment were not related to ART outcomes.What Is Known Already: Alcohol and caffeine intake have been found to be associated with infertility in some studies. Nevertheless, data on their relation with outcomes of infertility treatments are scarce and inconsistent.Study Design, Size, Duration: We included 300 women (493 ART cycles) from the Environment and Reproductive Health Study, an ongoing cohort study (2006-2016).Participants/materials, Setting, Methods: Pre-treatment intakes of alcohol and caffeine were assessed retrospectively using a validated food frequency questionnaire. Intermediate and clinical endpoints of ART were abstracted from electronic medical records. Generalized linear mixed models with random intercepts to account for multiple ART cycles per woman were used to evaluate the association with ART outcomes adjusting for age, BMI, smoking status, infertility diagnosis, protocol type, race, dietary patterns, and calories, vitamin B12 and folate intake.Main Results and the Role Of Chance: Median (range) pre-treatment alcohol and caffeine intakes were 5.6 (0.0-85.8) g/day and 124.9 (0.3-642.2) mg/day, respectively. The adjusted percentage of initiated cycles resulting in live birth (95% CI) for women in increasing categories of pre-treatment alcohol intake was 34% (20, 52%) for non-consumers, 46% (36, 57%) for 0.1-6 g/day, 41% (29, 53%) for 6.1-12 g/day, 42% (31, 55%) for 12.1-24 g/day, and 41% (22, 63%) for >24 g/day (P, trend = 0.87). The adjusted percentage of cycles resulting in live birth (95% CI) for women in increasing categories of caffeine intake was 46% (36-57%) for <50 mg/day, 44% (29, 60%) for 50.1-100 mg/day, 42% (31, 53%) for 100.1-200 mg/day, 40% (28, 53%) for 200.1-300 mg/day and 40% (21, 63%) for >300 mg/day (P, trend = 0.34). When specific types of alcoholic and caffeinated beverages were evaluated, no relations with ART treatment outcomes were observed.Limitations, Reasons For Caution: Residual confounding by other diet and lifestyle factors cannot be ruled out owing to the observational nature of this study. It is also unclear how generalizable these results are to women who are conceiving without the assistance of ART.Wider Implications Of the Findings: Our results provide reassurance that low to moderate intakes of alcohol (e.g. ≤12 g/day) and caffeine (e.g. <200 mg/day) in the year prior to infertility treatment initiation do not have an adverse effect on intermediate or clinical outcomes of ART.Study Funding/competing Interest(s): The authors are supported by National Institutes of Health (NIH) grants ES022955, R01ES009718, R01ES000002, P30DK46200 and L50-HD085359. No conflicts of interest to declare.Trial Registration Number: NCT00011713. [ABSTRACT FROM AUTHOR]

Study Question: How are concentrations of plasma homocysteine and serum folate associated with reproductive hormones and anovulation in regularly menstruating women?Summary Answer: Higher homocysteine was associated with sporadic anovulation and hormonal changes that may be indicative of impaired ovulatory function, but higher serum folate was associated only with higher luteal phase progesterone.What Is Known Already: Higher folate levels as well as some variants in genes relevant to one-carbon metabolism, are associated with improved reproductive outcomes and responses to fertility treatment, but only a few small studies have explored the relationship between markers of one-carbon metabolism and menstrual cycle characteristics.Study Design, Size, Duration: The BioCycle Study (2005-2007) is a prospective, longitudinal cohort of 259 regularly menstruating women not using hormonal contraceptives or dietary supplements who were followed for up to two menstrual cycles.Participants/materials, Setting, Methods: Serum folate and reproductive hormones were measured up to eight times per cycle and plasma homocysteine up to three times. Linear mixed models were used to estimate associations between serum folate or plasma homocysteine and log-transformed reproductive hormone levels while accounting for multiple observations and cycles per woman. Generalized estimating equations were used to examine risk of sporadic anovulation. All models were adjusted for age, race, body mass index, cigarette and alcohol use, and energy and fiber intake.Main Results and the Role Of Chance: Higher plasma homocysteine concentrations were associated with lower total estradiol across the cycle (adjusted percent change per unit increase in homocysteine [aPC] -2.3%, 95% CI: -4.2, -0.03), higher follicle stimulating hormone around the time of expected ovulation (aPC 2.4%, 95% CI: 0.2, 4.7) and lower luteal phase progesterone (aPC -6.5%, 95% CI: -11.1, -1.8). Higher serum folate concentrations were associated with higher luteal phase progesterone (aPC per unit increase in folate 1.0%, 95% CI: 0.4, 1.6). Higher homocysteine concentrations at expected ovulation were associated with a 33% increased risk of sporadic anovulation. We observed no risk associated with decreased folate concentrations, but a higher ratio of folate to homocysteine at ovulation was associated with a 10% decreased risk of anovulation.Limitations, Reasons For Caution: Our results are generalizable to healthy women with adequate serum folate levels. The independent influence of homocysteine should be confirmed in larger cohorts and among women with folate deficiency or increased risks of anovulation.Wider Implications Of the Findings: If these findings are confirmed, it is possible that lowering homocysteine with B-vitamins through diet or supplementation could improve ovulatory function in some women.Study Funding/competing Interest(s): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Contract numbers: HHSN275200403394C, HHSN275201100002I and Task one HHSN27500001). None of the authors has any conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

Introduction: Inhalation injury is associated with increased risk of pneumonia. Bronchoscopy with bronchoalveolar lavage (BAL) is commonly used to diagnose and grade inhalation injury while obtaining a microbiological sample. It has been shown that a quarter of patients with inhalation injury have a single bacteria isolated from initial BAL within 12-48 hours of injury. The clinical significance of this and role of antibiotics in this setting are unknown. We investigated the incidence that bacteria isolated during a pneumonia episode were previously isolated on surveillance BAL among patients with inhalation injury. Methods: Among patients with inhalation injury admitted to a large ABA-verified burn center from 2009-2022, microbiological isolates from initial BAL and subsequent culture obtained during a pneumonia episode (BAL, sputum), were extracted from medical records. Abbreviated injury severity score (AIS) was used to grade inhalation injury. Hospital-acquired pneumonia (HAP) was defined using CDC PNU1 criteria, and ventilator-associated pneumonia (VAP) was de- fined using PNU2 criteria with BAL cutoff >10,000 colony forming units (CFU). Results: Two-hundred forty-eight patients with inhalation injury who underwent bronchoscopy for airway inspection and surveillance BAL within 48 hours of injury were included in the analysis. Of the 111 who had a bacterial isolate from initial BAL, 23 (21%) subsequently developed HAP or VAP during the hospitalization. Median (IQR) days between bronchoscopy and pneumonia diagnosis was six (2-8.5). In three of the 11 VAP cases (27%), the organisms identified at pneumonia diagnosis matched the organisms identified on initial BAL. Antibiotic use on admission was not associated with re-culture of initial BAL organism during a subsequent pneumonia episode (p=0.071). Conclusions: Among patients with inhalation injury and bacteria isolated on surveillance BAL, 21% developed pneumonia during their hospital stay, usually with different bacteria than those isolated at initial bronchoscopy. There was no association between empiric antibiotic use and incidence of initial BAL organisms re-cultured during subsequent pneumonia episode. Applicability of Research to Practice: Findings suggest initial BAL isolates cannot guide empiric coverage of pneumonia for patients with inhalation injury. This remains an important area of future research. [ABSTRACT FROM AUTHOR]

Introduction: Inhalation injury is associated with increased incidence of pneumonia. Bacteria are commonly isolated from bronchoalveolar lavage (BAL) within 12-48 hours of injury with unclear clinical significance. We aimed to determine if grade of inhalation injury is associated with different bacterial species isolated from initial BAL, and if higher inhalation injury grade is associated with increased risk of pneumonia. Methods: Abbreviated injury scores (AIS) and clinical microbiology isolates from diagnostic bronchoscopy with BAL performed within 48 hours of injury among adults with inhalation injuries from 2009-2022 were extracted from medical records at an ABA-verified burn center. CDC PNU1 criteria was used to identify pneumonia >48 hours after admission. Modified Poisson regression with robust standard errors was used to assess the association of inhalation injury grade and subsequent pneumonia. Results: Two hundred forty-six patients with inhalation injury who underwent diagnostic bronchoscopy for airway inspection and surveillance BAL within 48 hours of injury were included in this analysis. Fourteen (5.7%) were grade 0, 106 (43.1%) grade 1, 75 (30.5%) grade 2, 51 (20.7%) grade 3-4. The most common bacterial isolate was Streptococcus spp irrespective of AIS grade. Higher AIS grade was associated with increased incidence of pneumonia (IRR 1.3; 95% CI 1.09- 1.61; p = 0.01) after adjustment for age, sex, and total body surface area of burn involvement. Conclusions: Bacterial species isolated did not differ by inhalation injury grade. Higher inhalation injury grade was associated with increased risk of pneumonia. Applicability of Research to Practice: Providers should be vigilant that patients with higher grade of inhalation injury are at increased risk of pneumonia. Further research is urgently needed to assess the clinical significance of organisms isolated on initial BAL and their role -- if any -- on the development of pneumonia. [ABSTRACT FROM AUTHOR]

Study Question: Is there a temporal relationship between endometriosis and infertility?Summary Answer: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years.What Is Known Already: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown.Study Design, Size, Duration: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort.Participants/materials, Setting, Methods: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis.Main Results and the Role Of Chance: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years.Limitations, Reasons For Caution: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates.Wider Implications Of the Findings: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses.Study Funding/competing Interests: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare. [ABSTRACT FROM AUTHOR]

Study Question: Is dairy food consumption associated with live birth among women undergoing infertility treatment?Summary Answer: There was a positive association between total dairy food consumption and live birth among women ≥35 years of age.What Is Known Already: Dairy food intake has been previously related to infertility risk and measures of fertility potential but its relation to infertility treatment outcomes are unknown.Study Design, Size, Duration: Our study population comprised a total of 232 women undergoing 353 in vitro fertilization (IVF) treatment cycles between February 2007 and May 2013, from the Environment and Reproductive Health study, an ongoing prospective cohort.Participants/materials, Setting, Methods: Diet was assessed before assisted reproductive technology (ART) treatment using a validated food frequency questionnaire. Study outcomes included ovarian stimulation outcomes (endometrial thickness, estradiol levels and oocyte yield), fertilization rates, embryo quality measures and clinical outcomes (implantation, clinical pregnancy and live birth rates). We used generalized linear mixed models with random intercepts to account for multiple ART cycles per woman while simultaneously adjusting for age, caloric intake, BMI, race, smoking status, infertility diagnosis, protocol type, alcohol intake and dietary patterns.Main Results and the Role Of Chance: The age- and calorie-adjusted difference in live birth between women in the highest (>3.0 servings/day) and lowest (<1.34 servings/day) quartile of dairy intake was 21% (P = 0.02). However, after adjusting for additional covariates, this association was observed only among women ≥35 years (P, interaction = 0.04). The multivariable-adjusted live birth (95% CI) in increasing quartiles of total dairy intake was 23% (11, 42%), 39% (24, 56%), 29% (17, 47%) and 55% (39, 69%) (P, trend = 0.02) among women ≥35 years old, and ranged from 46 to 54% among women <35 years old (P, trend = 0.69). There was no association between dairy intake and any of the intermediate outcomes.Limitations, Reasons For Caution: The lack of a known biological mechanism linking dairy intake to infertility treatment outcomes calls for caution when interpreting these results and for additional work to corroborate or refute them.Wider Implications Of the Findings: Dairy intake does not appear to harm IVF outcomes and, if anything, is associated with higher chances of live birth.Study Funding/competing Interests: This work was supported by NIH grants R01-ES009718 and R01ES000002 from NIEHS, P30 DK046200 from NIDDK and T32HD060454 from NICHD. M.C.A. was supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from NIDDK. She is currently employed at the Nestlé Research Center, Switzerland and completed this work while at the Harvard School of Public Health. The other authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: Fetal exposure to parental smoking may have long-term impact on the development of disease in adulthood. We examined the association of parental smoking during pregnancy with risk of gestational diabetes mellitus (GDM) in the daughter.Methods: We included 15,665 singleton pregnancies from 10,152 women in the Nurses' Health Study II cohort whose mothers participated in the Nurses' Mothers' Cohort Study. Data on maternal and paternal smoking during pregnancy and associated covariates were recalled by the mothers. GDM diagnosis was self-reported by the daughters and was validated by medical record review in a previous study. We used log-binomial models with generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: We observed a positive association between maternal heavy smoking during pregnancy and risk of GDM in the daughter. The multivariable-adjusted RRs (95% CIs) of GDM among women whose mothers did not smoke during pregnancy, continued smoking 1-14, 15-24, and ≥ 25 cigarettes/day were 1.00 (reference), 1.05 (0.81-1.35), 1.27 (0.95-1.70) and 1.98 (1.18-3.30), respectively (P for trend = 0.01). Further adjustment for the women's perinatal variables, adult-life characteristics and body mass index during various periods of life modestly attenuated the association. No association was observed between paternal smoking during the pregnancy period and risk of GDM in the daughter.Conclusions: Maternal heavy smoking (≥ 25 cigarettes/day) during pregnancy was associated with higher risk of gestational diabetes in the daughter. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Study Question: Are urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting?Summary Answer: Higher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care.What Is Known Already: Experimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown.Study Design, Size, Duration: We examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study.Participants/materials, Setting, Methods: We quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking.Main Results and the Role Of Chance: We observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated.Limitations, Reasons For Caution: We demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals.Wider Implications Of the Findings: Environmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development.Study Funding/competing Interests: Work supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? SUMMARY ANSWER: Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS KNOWN ALREADY: Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION: This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE: The specific gravity-adjusted geometric mean of BPA was 1.87 mg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (<37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (≥37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations. LIMITATIONS, REASONS FOR CAUTION: Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population. WIDER IMPLICATIONS OF THE FINDINGS: Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Is consumption of fruits and vegetables with high levels of pesticide residues associated with lower semen quality? SUMMARY ANSWER: Consumption of fruits and vegetables with high levels of pesticide residues was associated with a lower total sperm count and a lower percentage of morphologically normal sperm among men presenting to a fertility clinic. WHAT IS KNOWN ALREADY: Occupational and environmental exposure to pesticides is associated with lower semen quality. Whether the same is true for exposure through diet is unknown. STUDY DESIGN, SIZE, DURATION: Men enrolled in the Environment and Reproductive Health (EARTH) Study, an ongoing prospective cohort at an academic medical fertility center. Male partners (n = 155) in subfertile couples provided 338 semen samples during 2007-2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen samples were collected over an 18-month period following diet assessment. Sperm concentration and motility were evaluated by computer-aided semen analysis (CASA). Fruits and vegetables were categorized as containing high or low-to-moderate pesticide residues based on data from the annual United States Department of Agriculture Pesticide Data Program. Linear mixed models were used to analyze the association of fruit and vegetable intake with sperm parameters accounting for within-person correlations across repeat samples while adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Total fruit and vegetable intake was unrelated to semen quality parameters. High pesticide residue fruit and vegetable intake, however, was associated with poorer semen quality. On average, men in highest quartile of high pesticide residue fruit and vegetable intake (≥1.5 servings/day) had 49% (95% confidence interval (CI): 31%, 63%) lower total sperm count and 32% (95% CI: 7%, 58%) lower percentage of morphologically normal sperm than men in the lowest quartile of intake (<0.5 servings/day) (P, trend = 0.003 and 0.02, respectively). Low-to-moderate pesticide residue fruit and vegetable intake was associated with a higher percentage of morphologically normal sperm (P, trend = 0.04). LIMITATIONS, REASONS FOR CAUTION: Surveillance data, rather than individual pesticide assessment, was used to assess the pesticide residue status of fruits and vegetables. CASA is a useful method for clinical evaluation but may be considered less favorable for accurate semen analysis in the research setting. Owing to the observational nature of the study, confirmation is required by interventional studies as well. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first report on the consumption of fruits and vegetables with high levels of pesticide residue in relation to semen quality. Further confirmation of these findings is warranted. STUDY FUNDING/COMPETING INTEREST(S): Supported by National Institutes of Health grants ES009718, ES022955, ES000002, P30 DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16. None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Innovative treatments like yoga for men's smoking cessation (SC) are lacking. To examine the feasibility and acceptability of yoga for men's SC. We randomly assigned eligible men (smoker, ≥5 cigarettes/day, age 18-65) to receive cognitive behavioral therapy for SC, plus a yoga or wellness program. Measures included feasibility (recruitment, class attendance) and acceptability (customer satisfaction). We enrolled 38 of 49 eligible men of 167 screened in response to ads (mean age 39.9 years, ±13.7) who smoked on average 18.6 cigarettes/day (±8.3). Wellness (75.8 %) versus yoga (56 %) men attended more SC classes, p < 0.01. Sixty percent attended ≥1 yoga class. Men reported greater satisfaction with in-house versus community yoga classes. Wellness appears to be the preferred intervention; results indicated that it may be more feasible and showed increased attendance at smoking classes. To be fully feasible, yoga + SC may need to be a unified program offering all classes tailored for men and in the same location. [ABSTRACT FROM AUTHOR]

Objective To use routine data from a comprehensive electronic medical record system to predict death among patients with reactive airways disease. Design Retrospective cohort study conducted in an academic primary care internal medicine practice. Subjects were 1,536 adults with reactive airways disease: 542 with asthma and 994 with chronic obstructive pulmonary disease (COPD). Measurements The dependent variable was death from any cause within 3 years following patients' first primary care appointment in 1992. Multivariable logistic regression was used to identify independent predictors of 3-year mortality, with half of the patients used to derive the predictive model and the other half used to assess its predictability. Results Of the 1,536 study patients, 191 (12%) died in the 3-year follow-up period. From information available on or before patients' first primary care visit in 1992, multivariable predictors of 3-year mortality were coincidental heart failure, male sex, presence of COPD, lower weight, low serum albumin concentration level, and a prior arterial PO of less than 60 mmHg; use of an inhaled corticosteroid was protective. The c-statistic (ROC curve area) in the validation cohort was 0.76, indicating good discrimination, and goodness of fit was excellent by Hosmer-Lemeshow chi-square (P > 0.5). Only 24% of the patients in the validation cohort were designated at high risk (estimated ≥15% 3-year mortality), but this group contained more than half of the deaths within 3 years for the entire cohort. Conclusions Data generated during routine care and stored in a comprehensive electronic medical record can accurately predict mortality among patients with reactive airways disease. Such technology can be used by practices to control for severity of illness when assessing clinical practice and to identify high-risk patients for interventions to improve prognosis. [ABSTRACT FROM PUBLISHER]

STUDY QUESTION Is paternal physical activity associated with semen quality parameters and with outcomes of infertility treatment? SUMMARY ANSWER Among men presenting for infertility treatment, weightlifting and outdoor activities were associated with higher sperm concentrations but not with greater reproductive success. WHAT IS ALREADY KNOWN Higher physical activity is related to better semen quality but no studies to date have investigated whether it predicts greater reproductive success. STUDY DESIGN, SIZE, DURATION The Environment and Reproductive Health (EARTH) Study is an on-going prospective cohort study which enrolls subfertile couples presenting at Massachusetts General Hospital (2005–2013). In total, 231 men provided 433 semen samples and 163 couples underwent 421 IVF or intrauterine insemination cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS Leisure time spent in physical and sedentary activities over the past year was self-reported using a validated questionnaire. We used mixed models to analyze the association of physical and sedentary activities with semen quality and with clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE Men in this cohort engaged in a median of 3.2 h/week of moderate-to-vigorous activities. Men in the highest quartile of moderate-to-vigorous activity had 43% (95% confidence interval (CI) 9, 87%) higher sperm concentrations than men in the lowest quartile (P-trend = 0.04). Men in the highest category of outdoor activity (≥1.5 h/week) and weightlifting (≥2 h/week) had 42% (95% CI 10, 84%) and 25% (95% CI −10, 74%) higher sperm concentrations, respectively, compared with men in the lowest category (0 h/week) (P-trend = 0.04 and 0.02). Conversely, men who reported bicycling ≥1.5 h/week had 34% (95% CI 4, 55%) lower sperm concentrations compared with men who reported no bicycling (P-trend = 0.05). Paternal physical and sedentary activities were not related to clinical pregnancy or live birth rates following infertility treatment. LIMITATIONS, REASONS FOR CAUTION The generalizability of the findings on live birth rates to populations not undergoing infertility treatment is limited. WIDER IMPLICATIONS OF THE FINDINGS Certain types of physical activity, specifically weightlifting and outdoor activities, may improve semen quality but may not lead to improved success of infertility treatments. Further research is needed in other non-clinical populations. STUDY FUNDING/COMPETING INTEREST(S) The authors are supported by NIH grants R01-ES009718, ES000002, P30-DK046200, T32-DK007703-16 and ES022955 T32-HD060454. None of the authors has any conflicts of interest to declare. [ABSTRACT FROM PUBLISHER]

Study Question: Is consumption of sugar-sweetened beverages (SSB) associated with semen quality?Summary Answer: Higher consumption of SSB was associated with lower sperm motility among healthy, young men.What Is Known Already: The existing literature on the potential role of SSBs on male reproductive function is scarce and primarily focused on the relation between caffeinated beverages and semen quality. However, a rodent model suggests that SSBs may hamper male fertility.Study Design, Size, Duration: The Rochester Young Men's Study; a cross-sectional study of 189 healthy young men carried out at the University of Rochester during 2009-2010.Participants/materials, Setting, Methods: Men aged 18-22 years provided semen and blood samples, underwent a physical examination and completed a previously validated food frequency questionnaire (FFQ). Linear regression was used to analyze the association of SSBs with sperm parameters and reproductive hormone levels while adjusting for potential confounders.Main Results and the Role Of Chance: SSB intake was inversely related to progressive sperm motility. Men in the highest quartile of SSB intake (≥1.3 serving/day) had 9.8 (95% CI: 1.9,17.8) percentage units lower progressive sperm motility than men in the lowest quartile of intake (<0.2 serving/day) (P, trend = 0.03). This association was stronger among lean men (P, trend = 0.005) but absent among overweight or obese men (P, trend = 0.98). SSB intake was unrelated to other semen quality parameters or reproductive hormones levels.Limitations, Reasons For Caution: As in all cross-sectional studies, causal inference is limited. An additional problem is that only single semen sample was obtained from each subject.Wider Implications Of the Findings: To our knowledge, this is the first report on the relation between SSB intake and low semen quality beyond the contribution of caffeinated beverages. While our findings are in agreement with recent experimental data in rodents, more studies are required to draw conclusions on the relation of SSB with semen quality or male infertility.Study Funding/competing Interest(s): Supported by the European Union Seventh Framework Program (Environment), 'Developmental Effects of Environment on Reproductive Health' (DEER) grant 212844. Grant P30 DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 and T32HD060454 from the National Institutes of Health. None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is increased consumption of dairy foods associated with lower semen quality? SUMMARY ANSWER We found that intake of full-fat dairy was inversely related to sperm motility and morphology. These associations were driven primarily by intake of cheese and were independent of overall dietary patterns. WHAT IS KNOWN ALREADY It has been suggested that environmental estrogens could be responsible for the putative secular decline in sperm counts. Dairy foods contain large amounts of estrogens. While some studies have suggested dairy as a possible contributing factor for decreased semen quality, this finding has not been consistent across studies. STUDY DESIGN, SIZE, DURATION The Rochester Young Men's Study (n = 189) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS/MATERIALS, SETTING, METHODS Men aged 18–22 years were included in this analysis. Diet was assessed via food frequency questionnaire. Linear regression was used to analyze the relation between dairy intake and conventional semen quality parameters (total sperm count, sperm concentration, progressive motility, morphology and ejaculate volume) adjusting for age, abstinence time, race, smoking status, body mass index, recruitment period, moderate-to-intense exercise, TV watching and total calorie intake. MAIN RESULTS AND THE ROLE OF CHANCE Total dairy food intake was inversely related to sperm morphology (P-trend = 0.004). This association was mostly driven by intake of full-fat dairy foods. The adjusted difference (95% confidence interval) in normal sperm morphology percent was −3.2% (−4.5 to −1.8) between men in the upper half and those in the lower half of full-fat dairy intake (P < 0.0001), while the equivalent contrast for low-fat dairy intake was less pronounced [−1.3% (−2.7 to −0.07; P= 0.06)]. Full-fat dairy intake was also associated with significantly lower percent progressively motile sperm (P= 0.05). LIMITATIONS, REASONS FOR CAUTION As it was a cross-sectional study, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS Further research is needed to prove a causal link between a high consumption of full-fat dairy foods and detrimental effects on semen quality. If verified our findings would mean that intake of full-fat dairy foods should be considered in attempts to explain secular trends in semen quality and that men trying to have children should restrict their intake. STUDY FUNDING/COMPETING INTEREST(S) European Union Seventh Framework Program (Environment), ‘Developmental Effects of Environment on Reproductive Health’ (DEER) grant 212844. Grant P30 DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 from the National Institutes of Health. None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) microbiome contributes significantly to host nutrition and health. However, relationships involving GI microbes, their hosts and host macrohabitats remain to be established. Here, we define clear patterns of variation in the GI microbiomes of six groups of Mexican black howler monkeys (Alouatta pigra) occupying a gradation of habitats including a continuous evergreen rainforest, an evergreen rainforest fragment, a continuous semi-deciduous forest and captivity. High throughput microbial 16S ribosomal RNA gene sequencing indicated that diversity, richness and composition of howler GI microbiomes varied with host habitat in relation to diet. Howlers occupying suboptimal habitats consumed less diverse diets and correspondingly had less diverse gut microbiomes. Quantitative real-time PCR also revealed a reduction in the number of genes related to butyrate production and hydrogen metabolism in the microbiomes of howlers occupying suboptimal habitats, which may impact host health. [ABSTRACT FROM AUTHOR]

In the modelling of longitudinal data from several groups, appropriate handling of the dependence structure is of central importance. Standard methods include specifying a single covariance matrix for all groups or independently estimating the covariance matrix for each group without regard to the others, but when these model assumptions are incorrect, these techniques can lead to biased mean effects or loss of efficiency, respectively. Thus, it is desirable to develop methods for simultaneously estimating the covariance matrix for each group that will borrow strength across groups in a way that is ultimately informed by the data. In addition, for several groups with covariance matrices of even medium dimension, it is difficult to manually select a single best parametric model among the huge number of possibilities given by incorporating structural zeros and/or commonality of individual parameters across groups. In this paper we develop a family of nonparametric priors using the matrix stick-breaking process of Dunson et al. (2008) that seeks to accomplish this task by parameterizing the covariance matrices in terms of their modified Cholesky decompositions (Pourahmadi, 1999). We establish some theoretical properties of these priors, examine their effectiveness via a simulation study, and illustrate the priors using data from a longitudinal clinical trial. [ABSTRACT FROM PUBLISHER]

The Fermi-LAT collaboration has recently reported the detection of angular power above the photon noise level in the diffuse gamma-ray background between 1 and 50 GeV. Such signal can be used to constrain a possible contribution from dark matter (DM) induced photons. We estimate the intensity and features of the angular power spectrum (APS) of this potential DM signal, for both decaying and annihilating DM candidates, by constructing template all-sky gamma-ray maps for the emission produced in the galactic halo and its substructures, as well as in extragalactic (sub)haloes. The DM distribution is given by state-of-the-art N-body simulations of cosmic structure formation, namely Millennium-II for extragalactic (sub)haloes, and Aquarius for the galactic halo and its subhaloes. We use a hybrid method of extrapolation to account for (sub)structures that are below the resolution limit of the simulations, allowing us to estimate the total emission all the way down to the minimal self-bound halo mass. We describe in detail the features appearing in the APS of our template maps and we estimate the effect of various uncertainties such as the value of the minimal halo mass, the fraction of substructures hosted in a halo and the shape of the DM density profile. Our results indicate that the fluctuation APS of the DM-induced emission is of the same order as the Fermi-LAT APS, suggesting that one can constrain this hypothetical emission from the comparison with the measured anisotropy. We also quantify the uncertainties affecting our results, finding ‘theoretical error bands’ spanning more than two orders of magnitude and dominated (for a given particle physics model) by our lack of knowledge of the abundance of low-mass (sub)haloes. [ABSTRACT FROM AUTHOR]

Trauma-related invasive mold infections are an emerging threat among US military personnel. Early identification of suspicious wounds, based on injury profile and tissue-based diagnosis, require aggressive surgical and empiric antifungal therapy (liposomal amphotericin B and voriconazole pending histopathology and cultures).Background. Major advances in combat casualty care have led to increased survival of patients with complex extremity trauma. Invasive fungal wound infections (IFIs) are an uncommon, but increasingly recognized, complication following trauma that require greater understanding of risk factors and clinical findings to reduce morbidity.Methods. The patient population includes US military personnel injured during combat from June 2009 through December 2010. Case definition required wound necrosis on successive debridements with IFI evidence by histopathology and/or microbiology (Candida spp excluded). Case finding and data collected through the Trauma Infectious Disease Outcomes Study utilized trauma registry, hospital records or operative reports, and pathologist review of histopathology specimens.Results. A total of 37 cases were identified: proven (angioinvasion, n = 20), probable (nonvascular tissue invasion, n = 4), and possible (positive fungal culture without histopathological evidence, n = 13). In the last quarter surveyed, rates reached 3.5% of trauma admissions. Common findings include blast injury (100%) during foot patrol (92%) occurring in southern Afghanistan (94%) with lower extremity amputation (80%) and large volume blood transfusion (97.2%). Mold isolates were recovered in 83% of cases (order Mucorales, n = 16; Aspergillus spp, n = 16; Fusarium spp, n = 9), commonly with multiple mold species among infected wounds (28%). Clinical outcomes included 3 related deaths (8.1%), frequent debridements (median, 11 cases), and amputation revisions (58%).Conclusions. IFIs are an emerging trauma-related infection leading to significant morbidity. Early identification, using common characteristics of patient injury profile and tissue-based diagnosis, should be accompanied by aggressive surgical and antifungal therapy (liposomal amphotericin B and a broad-spectrum triazole pending mycology results) among patients with suspicious wounds. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are different dietary patterns associated with semen parameters in young men? STUDY ANSWER The consumption of a Prudent dietary pattern was significantly associated with higher progressive sperm motility and unrelated to sperm concentration and morphology. The consumption of a Western dietary pattern was unrelated to conventional semen quality parameters. WHAT IS KNOWN ALREADY Over the past decades there has been evidence of a concomitant decline in sperm and diet quality. Yet whether diet composition influences semen quality remains largely unexplored. STUDY DESIGN, SIZE, DURATION The Rochester Young Men's Study (n= 188) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS, SETTING, METHODS Men aged 18–22 years were included in this analysis. Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns and conventional semen quality parameters (sperm concentration, progressive motility and morphology) adjusting for abstinence time, multivitamin use, race, smoking status, BMI, recruitment period, moderate-to-intense exercise and total calorie intake. RESULTS Two dietary patterns were identified by factor analysis. The ‘Western’ pattern was characterized by high intake of red and processed meat, refined grains, pizza, snacks, high-energy drinks and sweets. The ‘Prudent’ pattern was characterized by high intake of fish, chicken, fruit, vegetables, legumes and whole grains. The Prudent pattern was positively associated with percent progressively motile sperm in multivariate models (P-trend = 0.04). Men in the highest quartile of the Prudent diet had 11.3% (95% CI 1.3, 21.3) higher % progressively motile sperm compared with men in the lowest quartile. The Prudent pattern was unrelated to sperm concentration and morphology. The Western pattern was not associated with any semen parameter. LIMITATIONS This was a cross-sectional and observational study, which limited our ability to determine causality of diet on semen quality parameters. WIDER IMPLICATIONS OF THE FINDINGS Our findings support the suggestion that a diet rich in fruits, vegetables, chicken, fish and whole grains may be an inexpensive and safe way to improve at least one measure of semen quality. STUDY FUNDING/COMPETING INTERESTS The authors are supported by NIH grant T32DK007703-16 and P30DK46200 and European Union DEER Grant 212844. The authors have no competing interests to declare. [ABSTRACT FROM AUTHOR]

Hydrogenotrophic microbiota have a significant impact on colonic health; however, little is known about their diversity and ecology in situ. Here, molecular-based methods and multivariate analyses were used to examine the abundance and diversity of mucosa-associated hydrogenotrophic microbes in 90 biopsies collected from right colon, left colon and rectum of 25 healthy subjects. Functional genes of all three hydrogenotrophic groups were detected in at least one colonic region of all subjects. Methanogenic archaea (MA) constituted approximately one half of the hydrogenotrophic microbiota in each colonic region. Sulfate-reducing bacteria (SRB) were more abundant than acetogens in right colon, while acetogens were more abundant than SRB in left colon and rectum. MA genotypes exhibited low diversity, whereas SRB genotypes were diverse and generally similar across the three regions within subject but significantly variable among subjects. Multivariate cluster analysis defined subject-specific patterns for the diversity of SRB genotypes; however, neither subject- nor region-specific clusters were observed for the abundance of hydrogenotrophic functional genes. Sequence analyses of functional gene clones revealed that mucosa-associated SRB were phylogenetically related to Desulfovibrio piger, Desulfovibrio desulfuricans and Bilophila wadsworthia; whereas MA were related to Methanobrevibacter spp., Mb. smithii and the order Methanomicrobiales. Together these data demonstrate for the first time that the human colonic mucosa is persistently colonized by all three groups of hydrogenotrophic microbes, which exhibit segmental and interindividual variation in abundance and diversity. [ABSTRACT FROM AUTHOR]

BSTRACT Pulsars emerge in the Fermi era as a sizable population of gamma-ray sources. Millisecond pulsars (MSPs) constitute an older subpopulation whose sky distribution extends to high Galactic latitudes, and it has been suggested that unresolved members of this class may contribute a significant fraction of the measured large-scale isotropic gamma-ray background (IGRB). We investigate the possible energy-dependent contribution of unresolved MSPs to the anisotropy of the Fermi-measured IGRB. For observationally motivated MSP population models, we show that the preliminary Fermi anisotropy measurement places an interesting constraint on the abundance of MSPs in the Galaxy and the typical MSP flux, about an order of magnitude stronger than constraints on this population derived from the intensity of the IGRB alone. We also examine the possibility of an MSP component in the IGRB mimicking a dark matter signal in anisotropy-based searches, and conclude that the energy dependence of an anisotropy signature would distinguish MSPs from all but very light dark matter candidates. [ABSTRACT FROM AUTHOR]

Low literacy and chronic pain have been identified as significant problems in the rural USA. Cognitive behavioral therapy (CBT) is a widely used efficacious psychosocial treatment for chronic pain; adaptations for low-literacy rural populations are lacking. This paper reports on preparatory steps implemented to address this deficit. Adapting an existing group, CBT patient workbook for rural adults with low literacy is described, and adaptations to reduce cognitive demand inherent in CBT are explained via cognitive load theory. Adhering to health literacy guidelines, the patient workbook readability was lowered to the fifth grade. Two key informant interviews and four focus groups provided the impetus for structural and procedural adaptations. Using health literacy guidelines and participant feedback, the patient workbook and treatment approach were adapted for implementation in low-literacy rural adult chronic pain populations, setting the stage for proceeding with a larger trial using the adapted materials. [ABSTRACT FROM AUTHOR]

Background: Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation.Methods: The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18-44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles.Results: Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005).Conclusions: These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome. [ABSTRACT FROM AUTHOR]