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Objective We evaluate change in low back pain (LBP) intensity and interference as the mechanism by which chiropractic care affects other biopsychosocial factors in US active-duty military members.Design We conducted secondary, exploratory mediation analysis of pragmatic, multisite, clinical trial (NCT01692275) post results using natural effect modeling. Mediators were the 6-week values of Patient-Reported Outcomes Measurement Information System (PROMIS)-29 pain interference and intensity. Outcomes were 12-week values of other PROMIS-29 biopsychosocial subdomains. Models evaluated overall and individual factor contribution and were adjusted for baseline age, sex, LBP duration, LBP intensity and mediator and outcome values.Setting Three US military treatment facilities.Participants 750 US active-duty military members with LBP.Interventions Trial participants received 6 weeks of treatment with chiropractic care plus usual medical care or usual medical care alone.Results In multiple mediator models, pain interference and pain intensity explained much of the effect of chiropractic care on physical function (proportion mediated=0.77, 95% CI 0.43 to 2.0), fatigue (0.62, 95% CI 0.30 to 1.0), sleep disturbance (0.49, 95% CI 0.31 to 1.5) and social roles (0.81, 95% CI 0.50 to 2.0). Mental health was not evaluable due to the low prevalence of symptoms reported. The combined models of pain interference and pain intensity did not have a higher proportion mediated than the individual pain intensity models except for fatigue outcome models.Conclusion Pain intensity appeared to be the mechanism by which much of the change in biopsychosocial factors occurred and should be considered a key clinical indicator for improvement in biopsychosocial health when chiropractic care is added to usual medical care for US active-duty military members.

Background: Lower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease. Objectives: We evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2). Methods: MPOD was measured with customized heterochromatic flicker photometry in women who attended CAREDS2 (2016–2019) and CAREDS1 (2001–2004) study visits. Manifest POAG at CAREDS2 was assessed using visual fields, disc photos, optical coherence tomography, and medical records. Age-adjusted linear and logistic regression models were used to investigate the cross-sectional association between POAG and MPOD at CAREDS2, and MPOD measured 15 years earlier at CAREDS1. Results: Among 426 CAREDS2 participants (mean age: 80 y; range: 69–98 y), 26 eyes with manifest POAG from 26 participants were identified. Glaucomatous eyes had 25% lower MPOD compared to nonglaucomatous eyes [mean (SE): 0.40 (0.05) compared with 0.53 (0.01)] optical density units (ODU), respectively (P = 0.01). Compared with MPOD quartile 1, odds for POAG were lower for women in quartiles 2–4 (P-trend = 0.01). After excluding eyes with age-related macular degeneration, associations were similar but not statistically significant (P-trend = 0.16). Results were similar for MPOD measured at CAREDS1. Conclusions: Our results add to growing evidence that low MPOD may be a novel glaucoma risk factor and support further studies to assess the utility of dietary interventions for glaucoma prevention.

We present country records and a list of voucher specimens for Mussurana bicolor (Peracca, 1904) (Serpentes, Colubridae) from Bolivia. There is scarce information on museum specimens and locality data from Bolivia for this species in the scientific literature. Additionally, we discuss two newly collected specimens from the Llanos de Moxos, a floodplain in the Beni Department. This account contributes to the knowledge of the northwestern distributional status of M. bicolor and summarizes available data for Bolivia.

La ciencia ciudadana incentiva la participación de las personas en proyectos de investigación científica. Una de las iniciativas más conocidas es el concurso City Nature Challenge, dirigido a registrar la biodiversidad en las ciudades mediante la aplicación iNaturalist. La región metropolitana de La Paz, Bolivia, participó en este concurso en 2019 y 2022 bajo el nombre Reto Ciudad Naturaleza, gracias al impulso de Wildlife Conservation Society (WCS) Bolivia, la Carrera de Biología y el Instituto de Ecología de la Universidad Mayor de San Andrés (UMSA) y el Museo Nacional de Historia Natural (MNHN), los cuales conformaron un comité organizador. El objetivo fue fortalecer los vínculos de la población urbana con la naturaleza, en aras de generar datos sobre el conocimiento y la conservación de la biodiversidad. Las actividades consistieron en la promoción y difusión del concurso, eventos de capacitación en el manejo de iNaturalist, registros fotográficos, identificación taxonómica y entrega de certificados a los participantes. En 2019, La Paz compitió con 158 ciudades y consiguió el octavo lugar en número de especies (3005), el tercer lugar en número de participantes (1500) y el segundo en número de observaciones (46 931). En 2022 participaron 447 ciudades, y La Paz lideró en las tres categorías del concurso, con 137 345 observaciones, 5320 especies y 4296 participantes. Más allá de estos resultados, se destaca el compromiso de la ciudadanía paceña con su biodiversidad, lo que repercute en un vínculo cada vez más estrecho entre la población urbana y su entorno natural.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

We conducted research to understand online trade in jaguar parts and develop tools of utility for jaguars and other species. Our research took place to identify potential trade across 31 online platforms in Spanish, Portuguese, English, Dutch, French, Chinese, and Vietnamese. We identified 230 posts from between 2009 and 2019. We screened the images of animal parts shown in search results to verify if from jaguar; 71 posts on 12 different platforms in four languages were accompanied by images identified as definitely jaguar, including a total of 125 jaguar parts (50.7% posts in Spanish, 25.4% Portuguese, 22.5% Chinese and 1.4% French). Search effort varied among languages due to staff availability. Standardizing for effort across languages by dividing number of posts advertising jaguars by search time and number of individual searches completed via term/platform combinations changed the proportions the rankings of posts adjusted for effort were led by Portuguese, Chinese, and Spanish. Teeth were the most common part; 156 posts offered at least 367 teeth and from these, 95 were assessed as definitely jaguar; 71 of which could be linked to a location, with the majority offered for sale from Mexico, China, Bolivia, and Brazil (26.8, 25.4, 16.9, and 12.7% respectively). The second most traded item, skins and derivative items were only identified from Latin America: Brazil (7), followed by Peru (6), Bolivia (3), Mexico (2 and 1 skin piece), and Nicaragua and Venezuela (1 each). Whether by number of posts or pieces, the most commonly parts were: teeth, skins/pieces of skins, heads, and bodies. Our research took place within a longer-term project to assist law enforcement in host countries to better identify potential illegal trade and presents a snapshot of online jaguar trade and methods that also may have utility for many species traded online.

Aims: Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning. Methods: A total of 54 patients with distal radial fractures were included in the study. Each underwent posteroanterior (PA) and lateral radiographs of the injured wrist with an aluminium step wedge. Overall 27 patients underwent routine DXA scanning of the hip and lumbar spine, with 13 undergoing additional DXA scanning of the uninjured forearm. Analysis of radiographs was performed on ImageJ and Matlab with calculations of cortical measures, cortical indices, combined cortical scores, and aluminium equivalent grading. Results: Cortical measures showed varying correlations with the forearm DXA results (range: Pearson correlation coefficient (r) = 0.343 (p = 0.251) to r = 0.521 (p = 0.068)), with none showing statistically significant correlations. Aluminium equivalent grading showed statistically significant correlations with the forearm DXA of the corresponding region of interest (p < 0.017). Conclusion: Cortical measures, cortical indices, and combined cortical scores did not show a statistically significant correlation to forearm DXA measures. Aluminium-equivalent is an easily applicable method for estimation of BMD from digital radiographs in the preoperative setting. Cite this article: Bone Joint Res 2021;10(12):830–839.

Objectives To research and develop tools and methods for building cohorts of images linked to longitudinal healthcare records from real-world clinical images from the whole Scottish population. To provide this capability for the Scottish Medical Imaging service (provided by the Scottish National Safe Haven) to support research and AI projects. Approach Clinical images, especially when linked to routinely collected health data, are extremely useful for many types of research and AI development. However, finding and using clinical images for research data is challenging because: 1) Existing software used to search for images are designed for clinical care rather than research making it easy to find images for a particular patient. They are not designed to search for all images with particular characteristics e.g. slice thickness/scanning protocol/contrast agent/patient medication. 2) Reuse of clinical images for research requires de-identification, yet identifiable data can be present in many areas of the associated image file. Results The PICTURES (InterdisciPlInary Collaboration for efficienT and effective Use of clinical images in big data health care RESearch) 5-year programme has developed an architecture for building cohorts of images based upon research criteria and providing these in a di-identifiable form within a Safe Haven environment. There are 3 zones: • An identifiable zone which stores the raw image data and a MongoDB database which captures the metadata • A de-identified zone which provides a database and tools for cohort building which do not require imaging data expertise • Several Project Private Zones (PPZs) where researchers can install custom software and access the de-identified images for their project The architecture supports cohort building based upon features within pixel data, image metadata and linking to longitudinal health care records. Conclusion PICTURES is currently enhancing the cohort building user interface used by the National Safe Haven and supporting exemplar projects. The SMI service is live and accepting requests for more information. The software is open source and we welcome the use of the platform by other Safe Havens/research groups.

Objectives The Scottish Medical Imaging (SMI) service provides linkable, population based, “research-ready” real-world medical images for researchers to develop or validate AI algorithms within the Scottish National Safe Haven. The PICTURES research programme is developing novel methods to enhance the SMI service offering through research in cybersecurity and software/data/infrastructure engineering. Approach Additional technical and governance controls were required to enable safe access to medical images. The researcher is isolated from the rest of the trusted research environment (TRE) using a Project Private Zone (PPZ). This enables researchers to build and install their own software stack, and protects the TRE from malicious code. Guidelines are under development for researchers on the safe development of algorithms and the expected relationship between the size of the model and the training dataset. There is associated work on the statistical disclosure control of models to enable safe release of trained models from the TRE. Results A policy enabling the use of “Non-standard software” based on prior research, domain knowledge and experience gained from two contrasting research studies was developed. Additional clauses have been added to the legal control – the eDRIS User Agreement – signed by each researcher and their Head of Department. Penalties for attempting to import or use malware, remove data within models or any attempt to deceive or circumvent such controls are severe, and apply to both the individual and their institution. The process of building and deploying a PPZ has been developed allowing researchers to install their own software. No attempt has yet been made to add additional ethical controls; however, a future service development could be validating the performance of researchers’ algorithms on our training dataset. Conclusion The availability to conduct research using images poses new challenges and risks for those commissioning and operating TREs. The Private Project Zone and our associated governance controls are a huge step towards supporting the needs of researchers in the 21st century.

Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H2 receptor antagonists (H2RA) compared with H2RA nonusers in relatively small studies. We evaluated the association of H2RA use and incident HF in postmenopausal women in the large‐scale WHI (Women’s Health Initiative) study. Methods and Results This study included postmenopausal women from the WHI without a history of HF at baseline. HF was defined as first incident hospitalization for HF and physician adjudicated. Multivariable Cox proportional hazards regression models evaluated the association of H2RA use as a time‐varying exposure with HF risk, after adjustment for demographic, lifestyle, and medical history variables. Sensitivity analyses examined (1) risk of HF stratified by the ARIC (Atherosclerosis Risk in Communities) score, (2) propensity score matching on H2RA use, (3) use of proton pump inhibitors rather than H2RA nonuse as the referent, and (4) exclusion of those taking diuretics at baseline. The primary analysis included 158 854 women after exclusion criteria, of whom 9757 (6.1%) were H2RA users. During median 8.2 years of follow‐up, 376 H2RA users (4.9 events/1000 person‐years) and 3206 nonusers (2.7 events/1000 person‐years) developed incident HF. After multivariable adjustment, there was no association between H2RA use and HF in the primary analysis (hazard ratio, 1.07; 95% CI, 0.94–1.22; P=0.31) or in any of the sensitivity analyses. Conclusions Clinical H2RA use was not associated with incident HF among postmenopausal women. Future studies are needed to evaluate potential effect modification by sex, HF severity, or patterns of use on H2RA exposure and HF risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000611.

BACKGROUND: Urinary incontinence affects >40% of women in the United States, with an annual societal cost of >$12 billion and demonstrated associations with depressive symptoms, social isolation, and loss of work productivity. Weight has been established as an exposure that increases urinary incontinence risk and certain dietary components have been associated with urinary incontinence symptoms. We hypothesized that diet plays a key role in the association between weight and urinary incontinence in US women. OBJECTIVE: This study aimed to examine the effect of a low-fat diet on urinary incontinence in postmenopausal women as a post hoc analysis of a randomized controlled trial of diet modification. STUDY DESIGN: This was a post hoc analysis of the Women's Health Initiative Dietary Modification randomized controlled trial of 48,835 postmenopausal women from 40 US centers assigned to a dietary intervention (20% energy from fat, 5 fruits or vegetable servings, and 6 whole grain servings daily and an intensive behavioral modification program) or to the usual diet comparison group. The outcome was urinary incontinence at 1 year. RESULTS: Of the participants, 60% were randomized to the usual diet comparison group and 40% to the dietary modification intervention. After adjusting for weight change, women assigned to the dietary modification intervention were less likely to report urinary incontinence (odds ratio, 0.94; 95% confidence interval, 0.90–0.98; P=.003), more likely to report urinary incontinence resolution (odds ratio, 1.11; 95% confidence interval, 1.03–1.19; P=.01), and less likely to develop urinary incontinence (odds ratio, 0.92; 95% confidence interval, 0.87–0.98; P=.01) in adjusted models. CONCLUSION: Dietary modification may be a reasonable treatment for postmenopausal women with incontinence and also a urinary incontinence prevention strategy for continent women. Our results provide evidence to support a randomized clinical trial to determine whether a reduced fat-intake dietary modification is an effective intervention for the prevention and treatment of urinary incontinence. In addition to providing further insights into mechanisms of lower urinary tract symptoms, these findings may have a substantial impact on public health based on the evidence that diet seems to be a modifiable risk factor for urinary incontinence.

To date, more than 2400 valid fish species have been recorded in the Amazon basin. However, some regions remain poorly documented. This is the case in the Beni basin and in particular in one of its main sub-basins, the Tuichi, an Andean foothills rivers flowing through the Madidi National Park in the Bolivian Amazonia. The knowledge of its ichthyological diversity is, however, essential for the management and protection of aquatic ecosystems, which are threatened by the development of infrastructures (dams, factories and cities), mining and deforestation. Environmental DNA (eDNA) has been relatively little used so far in the Amazon basin. We sampled eDNA from water in 34 sites in lakes and rivers in the Beni basin including 22 sites in the Tuichi sub-basin, during the dry season. To assess the biogeographical patterns of the amazonian ichthyofauna, we implemented a metabarcoding approach using two pairs of specific primers designed and developed in our laboratory to amplify two partially overlapping CO1 fragments, one of 185bp and another of 285bp. We detected 252 fish taxa (207 at species level) among which 57 are newly identified for the Beni watershed. Species compositions are significantly different between lakes and rivers but also between rivers according to their hydrographic rank and altitude. Furthermore, the diversity patterns are related to the different hydro-ecoregions through which the Tuichi flows. The eDNA approach makes it possible to identify and complete the inventory of the ichthyofauna in this still poorly documented Amazon basin. However, taxonomic identification remains constrained by the lack of reference barcodes in public databases and does not allow the assignment of all OTUs. Our results can be taken into account in conservation and management strategies and could serve as a baseline for future studies, including on other Andean tributaries.

The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.

Identifying fish spawning areas is of great ecological and conservation importance as fishes are suffering increasing threat levels from anthropogenic activities. However, to date very few studies have done so in the Amazon basin. In the Beni River located in the upper Madeira basin, fishers reported that a particular ecotone near the town of Rurrenabaque was a fish reproduction area. To test the importance of this zone as a spawning site, we conducted an ichthyoplankton survey during the month when reproduction is most likely to occur. The specific identification of larvae and eggs was made with a metabarcoding analysis. With this approach 13 different fish species of high importance for regional and local fisheries were identified, including the long-distance migratory gilded catfish (Brachyplatystoma rousseauxii), considered as endangered in the upper Madeira. Combining the development time of morula-gastrula egg stages with the integrated current velocity of the river, we identified a spawning area that ranges between the last gravel beaches close to Altamarani community and the San Miguel del Bala community on top of Suse strait, the last foothill of the Andes. This spawning area further extends upstream in the Madidi and Pilon Lajas protected areas and Tacana and T’simane indigenous communities, when considering eggs in final embryo stage. This portion of the Beni River, at the Andean foothills, is heavily impacted by anthropogenic activities, ranging from unmanaged fisheries to contamination coming from the extraction of fluvial aggregates, upstream gold mining, deforestation associated with a sugar cane mill, an existing downstream dam, and projected upstream dam projects. Some urgent solutions for the conservation of this already impacted area are proposed. Confirming fish spawning zones, although difficult, is crucial to inform the definition of priority areas for conservation and management measures, in particular when these sites host endangered species.

The persistent high deforestation rate and fragmentation of the Amazon forests are the main threats to their biodiversity. To anticipate and mitigate these threats, it is important to understand and predict how species respond to the rapidly changing landscape. The short-eared dog Atelocynus microtis is the only Amazon-endemic canid and one of the most understudied wild dogs worldwide. We investigated short-eared dog habitat associations on two spatial scales. First, we used the largest record database ever compiled for short-eared dogs in combination with species distribution models to map species habitat suitability, estimate its distribution range and predict shifts in species distribution in response to predicted deforestation across the entire Amazon (regional scale). Second, we used systematic camera trap surveys and occupancy models to investigate how forest cover and forest fragmentation affect the space use of this species in the Southern Brazilian Amazon (local scale). Species distribution models suggested that the short-eared dog potentially occurs over an extensive and continuous area, through most of the Amazon region south of the Amazon River. However, approximately 30% of the short-eared dog's current distribution is expected to be lost or suffer sharp declines in habitat suitability by 2027 (within three generations) due to forest loss. This proportion might reach 40% of the species distribution in unprotected areas and exceed 60% in some interfluves (i.e. portions of land separated by large rivers) of the Amazon basin. Our local-scale analysis indicated that the presence of forest positively affected short-eared dog space use, while the density of forest edges had a negative effect. Beyond shedding light on the ecology of the short-eared dog and refining its distribution range, our results stress that forest loss poses a serious threat to the conservation of the species in a short time frame. Hence, we propose a re-assessment of the short-eared dog's current IUCN Red List status (Near Threatened) based on findings presented here. Our study exemplifies how data can be integrated across sources and modelling procedures to improve our knowledge of relatively understudied species.

Abstract Background Motor vehicle crashes remain the leading cause of teen deaths in spite of preventive efforts. Prevention strategies could be advanced through new analytic approaches that allow us to better conceptualize the complex processes underlying teen crash risk. This may help policymakers design appropriate interventions and evaluate their impacts. Methods System Dynamics methodology was used as a new way of representing factors involved in the underlying process of teen crash risk. Systems dynamics modeling is relatively new to public health analytics and is a promising tool to examine relative influence of multiple interacting factors in predicting a health outcome. Dynamics models use explicit statements about the process being studied and depict how the elements within the system interact; this usually leads to discussion and improved insight. A Teen Driver System Model was developed by following an iterative process where causal hypotheses were translated into systems of differential equations. These equations were then simulated to test whether they can reproduce historical teen driving data. The Teen Driver System Model that we developed was calibrated on 47 newly-licensed teen drivers. These teens were recruited and followed over a period of 5-months. A video recording system was used to gather data on their driving events (elevated g-force, near-crash, and crash events) and miles traveled. Results The analysis suggests that natural risky driving improvement curve follows a course of a slow improvement, then a faster improvement, and finally a plateau: that is, an S-shaped decline in driving events. Individual risky driving behavior depends on initial risk and driving exposure. Our analysis also suggests that teen risky driving improvement curve is created endogenously by several feedback mechanisms. A feedback mechanism is a chain of variables interacting with each other in such a way they form a closed path of cause and effect relationships. Conclusions Teen risky driving improvement process is created endogenously by several feedback mechanisms. The model proposed in the present article to reflect this improvement process can spark discussion, which may pinpoint to additional processes that can benefit from further empirical research and result in improved insight.

Abstract Statins have been shown to induce a phosphoprotein signature that modifies MYC (myelocytomatosis viral oncogene) activation and to have anti‐inflammatory activity that may impact the risk of Non‐Hodgkin's lymphoma (NHL). We analyzed the relationship between statins and risk of NHL using data from the Women's Health Initiative (WHI). The study population included 161,563 postmenopausal women ages 50–79 years from which 712 cases of NHL were diagnosed after 10.8 years of follow‐up. Information on statin use and other risk factors was collected by self‐ and interviewer‐administered questionnaires. Multivariable‐adjusted HR and 95% CI evaluating the relationship between statin use at baseline, as well as in a time‐dependent manner and risk of NHL, were computed from Cox proportional hazards analyses. A separate analysis was performed for individual NHL subtypes: diffuse large B‐Cell lymphoma (DLBCL) (n = 228), follicular lymphoma (n = 169), and small lymphocytic lymphoma (n = 74). All statistical tests were two‐sided. There was no significant association between use of statins at baseline and risk of NHL (HR 0.85, 95% C.I. 0.67–1.08). However, in the multivariable‐adjusted time‐dependent models, statin use was associated with a borderline lower risk of NHL (HR 0.81, 95% C.I. 0.66–1.00). Considering subtypes of NHL, statin use was associated with a lower risk of DLBCL (HR 0.62, 95% C.I. 0.42–0.91). This effect was driven by lipophilic statins (HR 0.62, 95% C.I. 0.40–0.96). In the WHI, statins were associated with a lower overall risk of DLBCL, particularly attributable to lipophilic statins. These results may have impact on primary or secondary prevention of NHL, particularly DLBCL.

We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p

Mexico has a long history of parasitological studies in communities of vertebrates. However, the mega diversity of the country makes fauna inventories an ongoing priority. Presently, there is little published on the parasite fauna of gray foxes (Urocyon cinereoargenteus Schereber, 1775) and this study provides new records of parasites for gray foxes in central Mexico. It is a continuation of a series of previous parasitological studies conducted with this carnivore in Mexico from 2003 to the present. A total of 24 foxes in the Parque Nacional El Cimatario (PANEC) were trapped, anaesthetized, and parasites recovered. The species found were Dirofilaria immitis, Ctenocephalides canis, C. felis, Euhoplopsillus glacialis affinis (first report for gray foxes in Mexico) Pulex simulants, and Ixodes sp. Three additional gray fox carcasses were necropsied and the parasites collected were adult nematodes Physaloptera praeputialis and Toxocara canis. The intensive study of the gray fox population selected for the 2013–2015 recent period allowed for a two-fold increase in the number of parasite species recorded for this carnivore since 2003 (nine to 18 parasite species), mainly recording parasitic arthropods, Dirofilaria immitis filariae and adult nematodes. The parasite species recorded are generalists that can survive in anthropic environments; which is characteristic of the present ecological scenario in central Mexico. The close proximity of the PANEC to the city of Santiago de Queretaro suggests possible parasite transmission between the foxes and domestic and feral dogs. Furthermore, packs of feral dogs in the PANEC might have altered habitat use by foxes, with possible impacts on transmission.

We expanded the known distribution of the leaflitter frog Pristimantis ockendeni (Boulenger, 1912) with a new record from Madidi National Park, La Paz, Bolivia. This represents the southernmost record along the Andes for this species. Individuals were found in montane savanna and gallery forest at about 1800 m above sea level close to the Machariapo River near the community of Sarayo.

BackgroundThe 2013 American College of Cardiology/American Heart Association blood cholesterol guideline recommends high‐intensity statin therapy among certain groups of patients, but full implementation of the guideline has not yet been satisfactory. We aimed to investigate the temporal trends and predictors of high‐intensity statin therapy among veterans who had been treated with percutaneous coronary intervention (PCI) and followed up by cardiologists within the Veterans Health Administrative system. Methods and ResultsA retrospective cohort study was conducted at the Veterans Health Administrative system including all patients >18 years old who had their PCI procedure between October 2010 and September 2016. National Veterans Health Administrative databases were used to retrieve study participant's demographics, comorbid conditions, statin type and dose within 90 days before and after the PCI procedure. There were 48 862 patients who underwent a PCI procedure during the study period. High‐intensity statin use at 90 days post‐PCI rose from 23% in 2010 to 37% before release of the 2013 American College of Cardiology/American Heart Association cholesterol guideline, then rose sharply to 80% by 2016. The projected 10‐year risk of arteriosclerotic cardiovascular disease events among our study population was projected to be ≈1841 fewer if the cohort had received high‐intensity statin therapy versus moderate‐intensity statin. ConclusionsBy 2016, the 2013 American College of Cardiology/American Heart Association blood cholesterol guideline was well implemented among veterans who had a PCI procedure in the Veterans Health Administrative system, suggesting systems of care can be improved to increase rates of high‐intensity statin initiation.

ImportanceCarpal tunnel syndrome (CTS) is a common and debilitating condition that commonly affects postmenopausal women.ObjectiveTo determine the effect of menopausal hormone therapy (HT) in healthy postmenopausal women on CTS risk.DesignWe conducted a secondary analysis of the Women's Health Initiative's (WHI) HT trials linked to Medicare claims data. Separate intention-to-treat analyses were performed for the two trials; the conjugated equine estrogens alone (CEE alone) and the trial of CEE plus medroxyprogesterone acetate (MPA) trial. (ClinicalTrials.gov, NCT number): NCT00000611.SettingTwo randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers.ParticipantsThe sample size included in the analysis was 16,053 community-dwelling women aged ≥65 years at study entry or those who later aged into Medicare eligibility, and who were enrolled in Medicare (including Part A and/or Part B coverage).InterventionWomen with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E+P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14203).Main outcome(s)The primary outcome was incident CTS and the secondary outcome was therapeutic CTS procedure occurring during the intervention phases of the trials.ResultsA total of 16,053 women were randomized in both trials. During mean follow up of 4.5 ± 2.8 years in the CEE trial (n = 6,833), there were 203 incident CTS cases in the intervention and 262 incident CTS cases in the placebo group (HR, 0.78; 95% CI, 0.65-0.94; P = 0.009). The CEE+MPA trial (n = 9,220) followed participants for a mean of 3.7 ± 2.3 years. There were 173 incident CTS cases in the intervention compared to 203 cases in the placebo group (HR, 0.80, 95% CI, 0.65-0.97; P = 0.027).ConclusionsThese findings suggest a protective effect of menopausal HT on the incidence of CTS among postmenopausal women. A potential therapeutic role for other forms of estrogen therapy in the management of CTS warrants future research.

Dry immersion (DI) is a Russian-developed, ground-based model to study the physiological effects of microgravity. It accurately reproduces environmental conditions of weightlessness, such as enhanced physical inactivity, suppression of hydrostatic pressure and supportlessness. We aimed to study the integrative physiological responses to a 3-day strict DI protocol in 12 healthy men, and to assess the extent of multi-system deconditioning. We recorded general clinical data, biological data and evaluated body fluid changes. Cardiovascular deconditioning was evaluated using orthostatic tolerance tests (Lower Body Negative Pressure + tilt and progressive tilt). Metabolic state was tested with oral glucose tolerance test. Muscular deconditioning was assessed via muscle tone measurement.Results: Orthostatic tolerance time dropped from 27 ± 1 to 9 ± 2 min after DI. Significant impairment in glucose tolerance was observed. Net insulin response increased by 72 ± 23% on the third day of DI compared to baseline. Global leg muscle tone was approximately 10% reduced under immersion. Day-night changes in temperature, heart rate and blood pressure were preserved on the third day of DI. Day-night variations of urinary K+ diminished, beginning at the second day of immersion, while 24-h K+ excretion remained stable throughout. Urinary cortisol and melatonin metabolite increased with DI, although within normal limits. A positive correlation was observed between lumbar pain intensity, estimated on the second day of DI, and mean 24-h urinary cortisol under DI. In conclusion, DI represents an accurate and rapid model of gravitational deconditioning. The extent of glucose tolerance impairment may be linked to constant enhanced muscle inactivity. Muscle tone reduction may reflect the reaction of postural muscles to withdrawal of support. Relatively modest increases in cortisol suggest that DI induces a moderate stress effect. In prospect, this advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies.

BackgroundThe relationship between light intensity physical activity (PA), which is common in older adults, and cardiovascular disease (CVD) risk factors is unclear. This study examined associations of accelerometer‐measured PA intensity with CVD risk factors in older women of different race‐ethnicities. Methods and ResultsCross‐sectional analyses were conducted in 4832 women (mean age 78.9 years; 52.5% white, 30.5% black, 17.1% Hispanic) who were without known CVD and wore triaxial accelerometers a minimum of 4 of 7 days with ≥10 hours/d awake wear‐time. Vector magnitude counts per 15‐s epoch were used to define time spent in low light (19–225 counts/15 s), high light (226–518), and moderate‐to‐vigorous; ≥519) intensity PA. Fasting CVD biomarkers, resting blood pressure, waist girth, body mass index, and 10‐year predicted CVD risk (Reynolds Risk Score) were measured. After adjusting for age, wear time, race‐ethnicity, and potential confounders, each PA measure was favorably associated with mean high‐density lipoprotein, triglyceride, glucose, C‐reactive protein, body mass index, waist girth, and Reynolds Risk Score (P

BackgroundHow physical activity (PA) and sitting time may change after first myocardial infarction (MI) and the association with mortality in postmenopausal women is unknown. Methods and ResultsParticipants included postmenopausal women in the Women's Health Initiative‐Observational Study, aged 50 to 79 years who experienced a clinical MI during the study. This analysis included 856 women who had adequate data on PA exposure and 533 women for sitting time exposures. Sitting time was self‐reported at baseline, year 3, and year 6. Self‐reported PA was reported at baseline through year 8. Change in PA and sitting time were calculated as the difference between the cumulative average immediately following MI and the cumulative average immediately preceding MI. The 4 categories of change were: maintained low, decreased, increased, and maintained high. The cut points were ≥7.5 metabolic equivalent of task hours/week versus

BackgroundPsychosocial characteristics have a strong effect on risk of depression, and their direct treatment with behavioral interventions reduces rates of depression. Because new‐onset poststroke depression (NPSD) is frequent, devastating, and often treatment‐resistant, novel preventive efforts are needed. As a first step toward developing behavioral interventions for NPSD, we investigated whether prestroke psychosocial factors influenced rates of NPSD in a manner similar to the general population. Methods and ResultsUsing the Women's Health Initiative, we analyzed 1424 respondents who were stroke‐free at enrollment and had no self‐reported history of depression from enrollment to their nonfatal ischemic stroke based on initiation of treatment for depression or the Burnam screening instrument for detecting depressive disorders. NPSD was assessed using the same method during the 5‐year poststroke period. Logistic regression provided odds ratios of NPSD controlling for multiple covariates. NPSD occurred in 21.4% (305/1424) of the analytic cohort and varied by stroke severity as measured by the Glasgow scale, ranging from 16.7% of those with good recovery to 31.6% of those severely disabled. Women with total anterior circulation infarction had the highest level (31.4%) of NPSD while those with lacunar infarction had the lowest (16.1%). Prestroke psychosocial measures had different associations with NPSD depending on functional recovery of the individual. ConclusionsThere is a difference in the relationship of prestroke psychosocial status and risk of NPSD depending on stroke severity; thus it may be that the same preventive interventions might not work for all stroke patients. One size does not fit all.

The Chrysomelidae (Coleoptera) is a highly speciose family that has been poorly studied at the regional level in Mexico. In the present study, we estimated species richness and diversity in oak-pine forest, Tamaulipan thorny scrub and in tropical deciduous forests in Peregrina Canyon within the Altas Cumbres Protected Area of the northeastern state of Tamaulipas, Mexico. Sampling of Chrysomelidae consisted of five sweep net samples (200 net sweeps) within each of three sites during four sample periods: early dry season, late dry season, early wet season, and late wet season. Species were identified and total numbers per species were recorded for each sample. A total of 2,226 specimens were collected belonging to six subfamilies, 81 genera and 157 species of Chrysomelidae from the study area. Galerucinae was the most abundant subfamily with 1,828 specimens, representing 82.1% of total abundance in the study area. Lower abundance was recorded in Cassidinae (8.5%), Eumolpinae (3.6%), Cryptocephalinae (2.2%), Chrysomelinae (2.2%), and finally Criocerinae (1.3%). The highest species richness was also presented in the subfamily Galerucinae with 49% of the total obtained species followed by Cassidinae (20%), Cryptocephalinae (9.7%), Eumolpinae (9.7%), Chrysomelinae (6.5%) and Criocerinae (5.2%). The most common species were Centralaphthona fulvipennis Jacoby (412 individuals), Centralaphthona diversa (Baly) (248), Margaridisa sp.1 (219), Acallepitrix sp.1 (134), Longitarsus sp.1 (104), Heterispa vinula (Erichson) (91), Epitrix sp.1 (84) and Chaetocnema sp.1 (72). Twenty-two species were doubletons (1.97% of total abundance) and 52 were singletons (2.33%). The estimated overall density value obtained was 0.0037 individuals/m2. The greatest abundance and density of individuals were recorded at the lowest elevation site. However, alpha diversity increased with increasing altitude. Similarity values were less than 50% among the three sites indicating that each site had distinct species assemblages of Chrysomelidae. The highest abundance was obtained during the late dry season, whereas diversity indices were highest during the early wet season. The present work represents the first report of the altitudinal variation in richness, abundance, and diversity of Chrysomelidae in Mexico. These results highlight the importance of conservation of this heterogeneous habitat and establish baseline data for Chrysomelidae richness and diversity for the region.

There are numerous and important coral reefs in the Mexican Pacific, but scarce studies of brittle stars conducted in these ecosystems. In this regard, this work provides the first annotated checklist of brittle stars associated with coral communities and reefs in the Mexican Pacific and an illustrated key to identify the species. We also provide taxonomic descriptions, spatial and bathymetric distributions and some important remarks of the species. We report a total of 14 species of brittle stars belonging to nine genera and seven families. Ophiocnida hispida in Jalisco, Ophiophragmus papillatus in Guerrero, and Ophiothrix (Ophiothrix) spiculata and Ophiactis simplex in Colima are new distribution records. The record of O. papillatus is remarkable because the species has not been reported since its description in 1940. The brittle stars collected in this study, represent 22.2% of the total species previously reported from the Mexican Pacific. Presently, anthropogenic activities on the coral reefs of the Mexican Pacific have increased, thus the biodiversity of brittle stars in these ecosystems may be threatened.

Se evaluó la contribución de Apis mellifera L. y Chrysoperla carnea S. como polinizadores del cultivo de la fresa, utilizando flores primarias de la variedad Festival en un experimento realizado en Irapuato, Guanajuato, México. Los tratamientos utilizados fueron: autogamia (SF), polinización abierta (OP), Apis mellifera (AM) y Chrysoperla carnea (CC). La tasa de polinización mostró que hubo diferencias significativas en el tratamiento AM (85.20 ± 2.41) en comparación con SF (41.51 ± 3.92), OP (77.98 ± 2.11) y CC (48.46 ± 2.97). Igualmente se encontraron diferencias significativas en el grado de malformación en AM (16.78 ± 1.20) en comparación con el SF (52.53 ± 1.54), OP (23.34 ± 1.03) y CC (47.88 ± 2.02). El total de antocianinas, peso, diámetro y sólidos totales solubles de los frutos fueron significativamente mayores en AM comparados con los tratamientos SF, OP y CC. El número de óvulos fertilizados se correlacionó positivamente con el peso de la fruta. Se considera a Chrysoperla carnea como deficiente polinizador, pero en contraparte se concluye que la utilización de Apis mellifera puede ser una alternativa para incrementar la producción y calidad de la fruta en los cultivos de la fresa establecidos en Irapuato, Guanajuato, México.

This article distinguishes five, and then three, mostly political issues raised in Sophokles’ Antigone. (1) Can a traitor to his community be honorably buried? (2) Can a family member be valued ahead of the community? (3) Do underworld gods of the family come before public safety concerns? (4) Can civil authorities rightly be challenged by individual citizens? (5) Can «unwritten ordinances» of the gods supercede the city’s laws? Antigone answers yes to these questions, chiefly because in the 440s Athens’ democratic polity was strengthening at the expense of aristocratic families, but Sophokles was aristocratic, no friend of Perikles, and here sometimes candidly hostile to the masses. (6) What is the significance of Kreon’s degeneration into tyrannical behavior? Sophokles always worried about too powerful magistrates. (7) Haimon’s better behavior reflects Athens’ «generation gap», contrasting older democrats with the more conservative young. Finally, (8) what is the proper public role of women? While Antigone herself is personally offensive, she proves to be right. As elsewhere, Sophokles rejects Kreon’s and democratic Athens’ harsh treatment of women. The play was successful because Athens’ democratic society itself was changing, especially as regards the status of women.

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4) and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

There is increasing interest in the development of non-invasive tools for studying the properties of skin, due to the potential for non-destructive sampling, reduced ethical concerns and the potential comparability of results in vivo and in vitro. The present research focuses on the use of a range of non-invasive approaches for studying skin and skin barrier properties in human skin and human skin equivalents (HSE). Analytical methods used include pH measurements, electrical sensing of the epidermis and detection of volatile metabolic skin products. Standard probe based measurements of pH and the tissue dielectric constant (TDC) are used. Two other more novel approaches that utilise wearable platforms are also demonstrated here that can assess the electrical properties of skin and to profile skin volatile species. The potential utility of these wearable tools that permit repeatability of testing and comparability of results is considered through application of our recently reported impedance-based tattoo sensors and volatile samplers on both human participants and HSEs. The HSE exhibited a higher pH (6.5) and TDC (56) than human skin (pH 4.9–5.6, TDC 29–36), and the tattoo sensor revealed a lower impedance signal for HSEs, suggesting the model could maintain homeostasis, but in a different manner to human skin, which demonstrated a more highly resistive barrier. Characterisation of volatiles showed a variety of compound classes emanating from skin, with 16 and 27 compounds identified in HSEs and participants respectively. The continuing development of these tools offers potential for improved quality and relevance of data, and potential for detection of changes that are undetectable in traditional palpable and visual assessments, permitting early detection of irritant reactions.

Se evaluó la contribución de Apis mellifera L. y Chrysoperla carnea S. como polinizadores del cultivo de la fresa, utilizando flores primarias de la variedad Festival en un experimento realizado en Irapuato, Guanajuato, México. Los tratamientos utilizados fueron: autogamia (SF), polinización abierta (OP), Apis mellifera (AM) y Chrysoperla carnea (CC). La tasa de polinización mostró que hubo diferencias significativas en el tratamiento AM (85.20 ± 2.41) en comparación con SF (41.51 ± 3.92), OP (77.98 ± 2.11) y CC (48.46 ± 2.97). Igualmente se encontraron diferencias significativas en el grado de malformación en AM (16.78 ± 1.20) en comparación con el SF (52.53 ± 1.54), OP (23.34 ± 1.03) y CC (47.88 ± 2.02). El total de antocianinas, peso, diámetro y sólidos totales solubles de los frutos fueron significativamente mayores en AM comparados con los tratamientos SF, OP y CC. El número de óvulos fertilizados se correlacionó positivamente con el peso de la fruta. Se considera a Chrysoperla carnea como deficiente polinizador, pero en contraparte se concluye que la utilización de Apis mellifera puede ser una alternativa para incrementar la producción y calidad de la fruta en los cultivos de la fresa establecidos en Irapuato, Guanajuato, México.

Aging is a natural process involving complex interplay between environment, metabolism, and genes. Sirtuin genes and their downstream targets have been associated with lifespan in numerous organisms from nematodes to humans. Several target proteins of the sirtuin genes are key sensors and/or effectors of oxidative stress pathways including FOXO3, SOD3, and AKT1. To examine the relationship between single nucleotide polymorphisms (SNP) at candidate genes in these pathways and human lifespan, we performed a molecular epidemiologic study of an elderly cohort (≥65 years old.). Using age at death as a continuous outcome variable and assuming a co-dominant genetic model within the framework of multi-variable linear regression analysis, the genotype-specific adjusted mean age at death was estimated for individual SNP genotypes while controlling for age-related risk factors including smoking, body mass index, alcohol consumption and co-morbidity. Significant associations were detected between human lifespan and SNPs in genes SIRT3, SIRT5, SIRT6, FOXO3 and SOD3. Individuals with either the CC or CT genotype at rs107251 within SIRT6 displayed >5-year mean survival advantages compared to the TT genotype (5.5 and 5.9 years, respectively; q-value = 0.012). Other SNPs revealed genotype-specific mean survival advantages ranging from 0.5 to 1.6 years. Gender also modified the effect of SNPs in SIRT3, SIRT5 and AKT1 on lifespan. Our novel findings highlight the impact of sirtuins and sirtuin-related genotypes on lifespan, the importance of evaluating gender and the advantage of using age as a continuous variable in analyses to report mean age at death.