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BackgroundMost longitudinal studies of COVID-19 incidence have used unlinked samples. The city of Manaus, Brazil, has a blood donation program which allows sample linkage, and was struck by two large COVID-19 epidemic waves between mid-2020 and early 2021.MethodsWe estimated the changing force of infection, i.e. incidence in susceptible individuals. Seroconversion was inferred by a mixture model for serial values from the Abbott Architect SARS-CoV-2 nucleocapsid (N) IgG assay. We estimated the number of suspected COVID-19 hospitalizations arising from each infection over calendar time.ResultsWhole blood donations between April 2020 and March 2021 were included from 6734 people, 2747 with two or more donations. The inferred criterion for seroconversion, and thus an incident infection, was a 6.07 fold increase in N IgG reactivity. The overall force of infection was 1.19 per person year (95% confidence interval 1.14-1.24) during the two main waves. The estimated number of suspected hospitalizations per infection, was approximately 4.1 times higher in the second wave than in the first.ConclusionsSerial values from this assay can be used to infer seroconversion over time, and in Manaus show a higher number of suspected COVID-19 hospitalizations per infection in the second wave relative to the first.

Objectives To determine SARS-CoV-2 seroprevalence over time and risk factors among pregnant women at delivery in São Paulo, Brazil; and to evaluate the suitability of pregnant women as a sentinel population for SARS-CoV-2 serosurveillance. Methods Unselected consecutive pregnant women presenting at the labor ward of a single large hospital between July 20th 2020 to February 21st 2021 were enrolled and tested for SARS-CoV-2 serology using two assays: the rapid chromatic Wondfo One Step (for total IgA and IgG detection) and Roche Elecsys assay (detecting anti-nucleoprotein [N] IgG). SARS-CoV-2 seroprevalence was computed as smooth spline function over time with 95% confidence intervals (CI). Risk factors were evaluated for positivity by each assay. We compared timepoint seroprevalence by the two assays with four concomitant community household surveys (HHS), in which the Roche assay was used, to determine the sensitivity and relevance of the pregnant women population as sentinel population. Results Overall SARS-CoV-2 seroprevalence was 28.9% (221/763) by Roche and 17.9% (137/763) by Wondfo. Reported symptoms experienced during pregnancy were all significantly correlated with being SARS-CoV-2 seropositive at delivery with any assay (with odds-ratios ranging from 3.0 [95% CI: 2.1–4.3] for coryza to 22.8 [95% CI: 12.3–46.6] for ageusia). Seropositivity by either assay was high in women at delivery in the early period of the pandemic (June 2020), compared with seropositivity in women from the concomitant HHS: 44.1% (95% CI: 21.8–66.4) for Roche, 54.1% (30.9–78.5) for Wondfo, versus 11.4% (95% CI: 9.2–13.6) for HHS. For later periods (October 2020 and January 2021), the seropositivity in women at delivery measured by Roche corresponded well with the prevalence found among women in the HHS using the same assay, whilst prevalence measured by Wondfo dropped. Conclusions Women at delivery represent a highly exposed and readily accessible population for sentinel surveillance of emerging infections such as SARS-CoV-2.

Introduction There is insufficient evidence supporting the use of rapid diagnostic tests (RDTs) for syphilis in people living with HIV (PLWH). We evaluated the diagnostic performance of two commercially available RDTs (Bioline and Determine) in PLWH in Cali, Colombia. Methods A cross-sectional field validation study on consecutive adults with confirmed HIV diagnosis attending three outpatient clinics. Both RDTs were performed on capillary blood (CB), obtained by finger prick, and sera, by venipuncture. A combination of treponemal enzyme linked immunosorbent assay (ELISA) and Treponema pallidum haemagglutination assay (TPHA) on serum samples was the reference standard. Rapid plasma reagin (RPR) and clinical criteria were added to define active syphilis. Sensitivity and specificity, predictive values and likelihood ratios (LR) of RDTs were estimated with their corresponding 95% confidence interval (95% CI). Stratified analyses by sample type, patient characteristics, non-treponemal titers, operator and re-training were performed. Results 244 PLWH were enrolled, of whom 112 (46%) had positive treponemal reference tests and 26/234 (11.1%) had active syphilis. The sensitivities of Bioline on CB and sera were similar (96.4% vs 94.6%, p = 0.6). In contrast, Determine had a lower sensitivity on CB than sera (87.5% vs 99.1%, p 95% in most analyses. Predictive values were 90% or higher. For active syphilis, the RDTs showed a similar performance pattern but with decreased specificities. Conclusion The studied RDTs have an excellent performance in PLWH to screen for syphilis and potentially for active syphilis, yet Determine performs better on sera than CB. Patient characteristics and potential difficulties operators may face in acquiring enough blood volume from finger pricks should be considered for the implementation and the interpretation of RDTs.

Dengue is hyperendemic in most Southeast Asian countries including Thailand, where all four dengue virus serotypes (DENV-1 to -4) have circulated over different periods and regions. Despite dengue cases being annually reported in all regions of Thailand, there is limited data on the relationship of epidemic DENV infection between humans and mosquitoes, and about the dynamics of DENV during outbreaks in the northeastern region. The present study was conducted in this region to investigate the molecular epidemiology of DENV and explore the relationships of DENV infection in humans and in mosquitoes during 2016-2018. A total of 292 dengue suspected patients from 11 hospitals and 902 individual mosquitoes (at patient's houses and neighboring houses) were recruited and investigated for DENV serotypes infection using PCR. A total of 103 patients and 149 individual mosquitoes were DENV -positive. Among patients, the predominant DENV serotypes in 2016 and 2018 were DENV-4 (74%) and DENV-3 (53%) respectively, whereas in 2017, DENV-1, -3 and -4 had similar prevalence (38%). Additionally, only 19% of DENV infections in humans and mosquitoes at surrounding houses were serotypically matched, while 81% of infections were serotypically mismatched, suggesting that mosquitoes outside the residence may be an important factor of endemic dengue transmission. Phylogenetic analyses based on envelope gene sequences showed the genotype I of both DENV-1 and DENV-4, and co-circulation of the Cosmopolitan and Asian I genotypes of DENV-2. These strains were closely related to concurrent strains in other parts of Thailand and also similar to strains in previous epidemiological profiles in Thailand and elsewhere in Southeast Asia. These findings highlight genomic data of DENV in this region and suggest that people's movement in urban environments may result in mosquitoes far away from the residential area being key determinants of DENV epidemic dynamics.

BackgroundThe force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs.Methods and findingsWe present Bayesian methods for estimating force of infection using serological surveys of infections which produce a lasting immune response, accounting for imperfections of the test, and uncertainty in such imperfections. In this estimation, the sensitivity and specificity can either be fixed, or belief distributions of their values can be elicited to allow for uncertainty. We analyse data from two published serological studies of dengue, one in Colombo, Sri Lanka, with a single survey and one in Medellin, Colombia, with repeated surveys in the same individuals. For the Colombo study, we illustrate how the inferred force of infection increases as the sensitivity decreases, and the reverse for specificity. When 100% sensitivity and specificity are assumed, the results are very similar to those from a standard analysis with binomial regression. For the Medellin study, the elicited distribution for sensitivity had a lower mean and higher variance than the one for specificity. Consequently, taking uncertainty in sensitivity into account resulted in a wide credible interval for the force of infection.ConclusionsThese methods can make more realistic estimates of force of infection, and help inform the choice of serological tests for future serosurveys.

BackgroundAdequate testing is critically important for control of the SARS-CoV-2 pandemic. Antibody testing is an option for case management and epidemiologic studies, with high specificity and variable sensitivity. However, characteristics of local populations may affect performance of these tests. For this reason, the National Institute of Health (INS) and regulatory agencies in Colombia require verification of diagnostic accuracy of tests introduced to the Colombian market.MethodsWe conducted a validation study of the Abbott SARS-CoV-2 test for qualitative detection of IgG using the Abbott Architect i2000SR. Participants and retrospective samples were included from patients with suspected SARS-CoV-2 infection, age ≥18 years, and ≥8 days elapsed since initiation of symptoms. Pre-pandemic plasma samples (taken before October 2019) were used as controls. We estimated the sensitivity, specificity and agreement (kappa) of the Abbott IgG test compared to the gold standard (RT-PCR).ResultsThe overall sensitivity was 83.1% (95% CI: 75.4-100). Sensitivity among patients with ≥14 days since the start of symptoms was 85.7%, reaching 88% in samples collected from patients with COVID-19 symptoms onset >60 days. Specificity was 100% and the kappa index of agreement was 0.804 (95% CI: 0.642-0.965).ConclusionsOur findings show high sensitivity and specificity of the Abbott IgG test in a Colombian population, which meet the criteria set by the Colombian INS to aid in the diagnosis of COVID-19. Data from our patient groups also suggest that IgG response is detectable in a high proportion of individuals (88.1%) during the first two months following onset of symptoms.

RationaleMultiple clinical trials support the effectiveness of cardiac resynchronization therapy (CRT); however, optimal patient selection remains challenging due to substantial treatment heterogeneity among patients who meet the clinical practice guidelines.ObjectiveTo apply machine learning to create an algorithm that predicts CRT outcome using electronic health record (EHR) data avaible before the procedure.Methods and resultsWe applied machine learning and natural language processing to the EHR of 990 patients who received CRT at two academic hospitals between 2004-2015. The primary outcome was reduced CRT benefit, defined as ConclusionsA machine learning model that leveraged readily available EHR data and clinical notes identified a subset of CRT patients who may not benefit from CRT before the procedure.

BACKGROUND: Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably. Since water content can influence signal intensity on CT and MRI scans, its assessment may provide indirect clues about clot composition. This study aimed to elucidate the correlation between water content and clot composition using human clots retrieved from stroke patients and experimentally generated ovine clots. MATERIALS AND METHODS: This study involved an analysis of ten clots retrieved from patients with AIS undergoing MT. Additionally, we created ten red blood cells (RBC)-rich and ten fibrin-rich ovine blood clots, which were placed in a human intracranial vascular model under realistic flow conditions. The water content and compositions of these clots were evaluated, and linear regression analyses were performed to determine the relationship between clot composition and water content. RESULTS: The regression analysis in human stroke clots revealed a significant negative association between RBC concentration and water content. We also observed a positive correlation between water content and both fibrin and platelets in ovine blood clots. Conclusion.

[This corrects the article DOI: 10.1371/journal.pone.0166486.].

Tobacco smoke exposure dramatically alters DNA methylation in blood cells and may mediate smoking-associated complex diseases through effects on immune cell function. However, knowledge of smoking effects in specific leukocyte subtypes is limited. To better characterize smoking-associated methylation changes in whole blood and leukocyte subtypes, we used Illumina 450K arrays and Reduced Representation Bisulfite Sequencing (RRBS) to assess genome-wide DNA methylation. Differential methylation analysis in whole blood DNA from 172 smokers and 81 nonsmokers revealed 738 CpGs, including 616 previously unreported CpGs, genome-wide significantly associated with current smoking (p 22 cigarettes/day, n = 86) which might relate to long-term heavy-smoking pathology. In purified leukocyte subtypes from an independent group of 20 smokers and 14 nonsmokers we further examined methylation and gene expression for selected genes among CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, and CD2+ T cells. In 10 smokers and 10 nonsmokers we used RRBS to fine map differential methylation in CD4+ T cells, CD8+ T cells, CD14+, CD15+, CD19+, and CD56+ natural killer cells. Distinct cell-type differences in smoking-associated methylation and gene expression were identified. AHRR (cg05575921), ALPPL2 (cg21566642), GFI1 (cg09935388), IER3 (cg06126421) and F2RL3 (cg03636183) showed a distinct pattern of significant smoking-associated methylation differences across cell types: granulocytes> monocytes>> B cells. In contrast GPR15 (cg19859270) was highly significant in T and B cells and ITGAL (cg09099830) significant only in T cells. Numerous other CpGs displayed distinctive cell-type responses to tobacco smoke exposure that were not apparent in whole blood DNA. Assessing the overlap between these CpG sites and differential methylated regions (DMRs) with RRBS in 6 cell types, we confirmed cell-type specificity in the context of DMRs. We identified new CpGs associated with current smoking, pack-years, duration, and revealed unique profiles of smoking-associated DNA methylation and gene expression among immune cell types, providing potential clues to hematopoietic lineage-specific effects in disease etiology.

The World Health Organization recommends that malaria be confirmed by parasitological diagnosis before treatment using Artemisinin-based Combination Therapy (ACT). Despite this, many health workers in malaria endemic countries continue to diagnose malaria based on symptoms alone. This study evaluates interventions to help bridge this gap between guidelines and provider practice. A stratified cluster-randomized trial in 42 communities in Enugu state compared 3 scenarios: Rapid Diagnostic Tests (RDTs) with basic instruction (control); RDTs with provider training (provider arm); and RDTs with provider training plus a school-based community intervention (provider-school arm). The primary outcome was the proportion of patients treated according to guidelines, a composite indicator requiring patients to be tested for malaria and given treatment consistent with the test result. The primary outcome was evaluated among 4946 (93%) of the 5311 patients invited to participate. A total of 40 communities (12 in control, 14 per intervention arm) were included in the analysis. There was no evidence of differences between the three arms in terms of our composite indicator (p = 0.36): stratified risk difference was 14% (95% CI -8.3%, 35.8%; p = 0.26) in the provider arm and 1% (95% CI -21.1%, 22.9%; p = 0.19) in the provider-school arm, compared with control. The level of testing was low across all arms (34% in control; 48% provider arm; 37% provider-school arm; p = 0.47). Presumptive treatment of uncomplicated malaria remains an ingrained behaviour that is difficult to change. With or without extensive supporting interventions, levels of testing in this study remained critically low. Governments and researchers must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines.ClinicalTrials.gov NCT01350752.

BACKGROUND: Uterine leiomyomas and adenomyosis are both common and often associated with abnormal uterine bleeding (AUB), including the symptom of heavy menstrual bleeding (HMB). Understanding the prevalence of adenomyosis in women with uterine leiomyomas could inform clinicians and patients in a way that may improve therapeutic approaches. OBJECTIVE: To explore the prevalence of adenomyosis in a group of women who underwent hysterectomy for AUB-L, to determine the prevalence of submucous leiomyomas, and to examine the utility of preoperative ultrasound to detect the presence of adenomyosis. METHODS: The Kaiser Permanente Hysterectomy Database (KPHD) was searched for women aged 18-52 undergoing hysterectomy for leiomyoma-associated chronic AUB (AUB-L) in 2018 and 2019. A target sample of 400 comprised those with at least 3 years in the Health System. Radiologists evaluated preoperative pelvic ultrasound images to determine leiomyoma size and level 2 FIGO type (submucous or other), and the linked electronic medical record abstracted for clinical features, including histopathological evidence of adenomyosis. RESULTS: Of the 370 subjects that met the study criteria, adenomyosis was identified via histopathology in 170 (45.9%). There was no difference in the adenomyosis prevalence with (47.1%) and without (43.0%) at least one submucous leiomyoma. Subgroup analysis of ultrasound images by an expert radiologist for the presence of adenomyosis demonstrated a positive predictive value of 54.0% and a negative predictive value of 43.4%. CONCLUSIONS: Adenomyosis was present in almost half of this AUB-L cohort undergoing hysterectomy and was equally prevalent in those with and without submucous leiomyomas as determined by sonographic evaluation. The imaging findings are in accord with prior investigators and demonstrate that 2-D ultrasound is insensitive to the presence of adenomyosis when the uterus is affected by leiomyomas. Further research is necessary to determine the impact of various adenomyosis phenotypes on the presence and severity of the symptom of HMB.

The use of publicly available sequencing datasets as controls (hereafter, "public controls") in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we leveraged both public controls, gnomAD v2.1 and several datasets sequenced in our laboratory to systematically investigate factors that could contribute to the false-positive discovery, as measured by λΔ95, a measure to quantify the degree of inflation in statistical significance. Analyses of datasets in this investigation found that 1) the significantly inflated distribution of test statistics decreased substantially when the same variant caller and filtering pipelines were employed, 2) differences in library prep kits and sequencers did not affect the false-positive discovery rate and, 3) joint vs. separate variant-calling of cases and controls did not contribute to the inflation of test statistics. Currently available methods do not adequately adjust for the high false-positive discovery. These results, especially if replicated, emphasize the risks of using public controls for rare-variant association tests in which individual-level data and the computational pipeline are not readily accessible, which prevents the use of the same variant-calling and filtering pipelines on both cases and controls. A plausible solution exists with the emergence of cloud-based computing, which can make it possible to bring containerized analytical pipelines to the data (rather than the data to the pipeline) and could avert or minimize these issues. It is suggested that future reports account for this issue and provide this as a limitation in reporting new findings based on studies that cannot practically analyze all data on a single pipeline.

A critical function of singing by male songbirds is to attract a female mate. Previous studies have suggested that the anterior forebrain system is involved in this courtship behavior. Neural activity in this system, including the striatal Area X, is strikingly dependent on the function of male singing. When males sing to attract a female bird rather than while alone, less variable neural activity results in less variable song spectral features, which may be attractive to the female. These characteristics of neural activity and singing thus may reflect a male's motivation for courtship. Here, we compared the variability of neural activity and song features between courtship singing directed to a female with whom a male had previously formed a pair-bond or to other females. Surprisingly, across all units, there was no clear tendency for a difference in variability of neural activity or song features between courtship of paired females, nonpaired females, or dummy females. However, across the population of recordings, there was a significant relationship between the relative variability of syllable frequency and neural activity: when syllable frequency was less variable to paired than nonpaired females, neural activity was also less variable (and vice-versa). These results show that the lower variability of neural activity and syllable frequency during directed singing is not a binary distinction from undirected singing, but can vary in intensity, possibly related to the relative preference of a male for his singing target.

The herpes simplex virus type 1 (HSV-1) immediate early protein, ICP4, participates in the regulation of viral gene expression by both activating and repressing RNA polII transcription. We used affinity purification of ICP4 expressed in infected cells followed by mass spectrometry and western blot analysis to determine the composition of cellular complexes associated with ICP4 throughout infection. ICP4 was associated with TFIID complexes containing a distinct set of TAFs. These complexes were most abundant early, but were detected throughout infection, whereas Mediator was found in ICP4 containing complexes later in infection, indicating a temporal pattern for the utilization of these complexes for the transcription of the viral genome. The form of Mediator copurifying with ICP4 was enriched for the kinase domain and also lacked the activator-specific component, Med26, suggesting that Mediator-ICP4 interactions may be involved in repression of viral transcription. The N-terminal 774 amino acids of ICP4, which retains partial function, were sufficient to form complexes with TFIID and Mediator, although these interactions were not as strong as with full-length ICP4. Additionally, components involved in transcription elongation, chromatin remodeling, and mRNA processing were isolated with ICP4. Together our data indicate that ICP4 plays a more integrated role in mediating HSV transcription, possibly affecting multiple steps in transcription and gene expression.

The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam.A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0).This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data.

Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase.

BackgroundThe asexual blood stages of the human malaria parasite Plasmodium falciparum produce highly immunogenic polymorphic antigens that are expressed on the surface of the host cell. In contrast, few studies have examined the surface of the gametocyte-infected erythrocyte.Methodology/principal findingsWe used flow cytometry to detect antibodies recognising the surface of live cultured erythrocytes infected with gametocytes of P. falciparum strain 3D7 in the plasma of 200 Gambian children. The majority of children had been identified as carrying gametocytes after treatment for malaria, and each donated blood for mosquito-feeding experiments. None of the plasma recognised the surface of erythrocytes infected with developmental stages of gametocytes (I-IV), but 66 of 194 (34.0%) plasma contained IgG that recognised the surface of erythrocytes infected with mature (stage V) gametocytes. Thirty-four (17.0%) of 200 plasma tested recognised erythrocytes infected with trophozoites and schizonts, but there was no association with recognition of the surface of gametocyte-infected erythrocytes (odds ratio 1.08, 95% C.I. 0.434-2.57; P = 0.851). Plasma antibodies with the ability to recognise gametocyte surface antigens (GSA) were associated with the presence of antibodies that recognise the gamete antigen Pfs 230, but not Pfs48/45. Antibodies recognising GSA were associated with donors having lower gametocyte densities 4 weeks after antimalarial treatment.Conclusions/significanceWe provide evidence that GSA are distinct from antigens detected on the surface of asexual 3D7 parasites. Our findings suggest a novel strategy for the development of transmission-blocking vaccines.

Synaptic transmission onto dopaminergic neurons of the mammalian ventral tegmental area (VTA) can be potentiated by acute or chronic exposure to addictive drugs. Because rewarding behavior, such as social affiliation, can activate the same neural circuitry as addictive drugs, we tested whether the intense social interaction of songbird courtship may also potentiate VTA synaptic function. We recorded glutamatergic synaptic currents from VTA of male zebra finches who had experienced distinct social and behavioral conditions during the previous hour. The level of synaptic transmission to VTA neurons, as assayed by the ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D-aspartic acid (NMDA) glutamate receptor mediated synaptic currents, was increased after males sang to females, and also after they saw females without singing, but not after they sang while alone. Potentiation after female exposure alone did not appear to result from stress, as it was not blocked by inhibition of glucocorticoid receptors. This potentiation was restricted to synapses of dopaminergic projection neurons, and appeared to be expressed postsynaptically. This study supports a model in which VTA dopaminergic neurons are more strongly activated during singing used for courtship than during non-courtship singing, and thus can provide social context-dependent modulation to forebrain areas. More generally, these results demonstrate that an intense social encounter can trigger the same pathways of neuronal plasticity as addictive drugs.

This cross-sectional study assessed how traditional eating relates to cultural and community factors. Alaska Native adults from the Norton Sound region were recruited and surveyed between 2015-2018 for a randomized clinical trial of multiple risk behavior change interventions for cardiovascular disease prevention. Participants (n = 291) were 49% female with a mean age of 47 years (SD = 14). A 34-item food frequency questionnaire assessed consumption of foods traditional and nontraditional to the regional Alaska Native diet. A novel measure, termed the "traditional foods index", was computed as weekly servings of culturally traditional food consumption divided by total foods reported. Overall, the sample's traditional foods index averaged 21%±16%, with higher values reported by participants assessed in summer (23%±17%) than winter (19%±15%, p

BackgroundRespiratory heat exchange is an important physiological process occurring in the upper and lower respiratory tract and is usually completed when inspired gases reach the alveoli. Animal and human studies demonstrated that heat exchange can be modulated by altering pulmonary ventilation and perfusion. The purpose of this study was to examine the effect of acute ventilation-perfusion (V/Q) mismatch on respiratory heat exchange. In clinical practice, monitoring respiratory heat exchange might offer the possibility of real-time tracking of acute V/Q-mismatch.MethodsIn 11 anesthetized, mechanically ventilated pigs, V/Q-mismatch was established by means of four interventions: single lung ventilation, high cardiac output, occlusion of the left pulmonary artery and repeated whole-lung lavage. V/Q-distributions were determined by the multiple inert gas elimination technique (MIGET). Respiratory heat exchange was measured as respiratory enthalpy using the novel, pre-commercial VQm™ monitor (development stage, Rostrum Medical Innovations, Vancouver, CA). According to MIGET, shunt perfusion of low V/Q compartments increased during single lung ventilation, high cardiac output and whole-lung lavage, whereas dead space and ventilation of high V/Q compartments increased during occlusion of the left pulmonary artery and whole-lung lavage.ResultsBohr dead space increased after pulmonary artery occlusion and whole-lung lavage, venous admixture increased during single lung ventilation and whole-lung lavage, PaO2/FiO2 was decreased during all interventions. MIGET confirmed acute V/Q-mismatch. Respiratory enthalpy did not change significantly despite significant acute V/Q-mismatch.ConclusionClinically relevant V/Q-mismatch does not impair respiratory heat exchange in the absence of additional thermal stressors and may not have clinical utility in the detection of acute changes.

The Open Payments database reports payments made to physicians by industry. Given the potential for financial conflicts of interest relating to patient outcomes, further scrutiny of these data is valuable. Therefore, the objective of this study was to analyze physician-industry relationships by specialty type, payment type, geospatial trend, and longitudinal trend between 2014-2018. We conducted an observational, retrospective data analysis of payments from the Open Payments database for licensed United States physicians listed in the National Plan & Provider Enumeration System (NPPES). Datasets from 2013-2018 were joined using the Python programming language. Aggregation and sub-setting by characteristics of interest was done in R to calculate means and frequencies of reported general physician payments from industry across different specialties, locations, timeframes, and payment types. Normalization was applied for numbers of physicians or payments. Geospatial statistical hot spot analysis was conducted in ArcGIS. 51.73 million payment records were analyzed. In total, 50,047,930 payments were issued to 771,113 allopathic or osteopathic physicians, representing $8,702,631,264 transferred from industry to physicians over the five-year period between 2014 and 2018. The mean payment amount was $179, with a standard deviation of $12,685. Variability in physicians' financial relationships with industry were apparent across specialties, regions, time, and payment type. A limited match rate between records in the NPPES and Open Payments databases may have resulted in selection bias of trends related to physician characteristics. Further research is necessary, particularly in the context of changing industry payment trends and public perceptions of the appropriateness of these relationships.

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at

IntroductionFrom late 2014 through 2015, Scott County, Indiana faced an HIV outbreak triggered by opioid abuse and transition to injection drug use. Investigating the origins, risk factors, and responses related to this outbreak is critical to inform future surveillance, interventions, and policymaking. In response, this retrospective infoveillance study identifies and characterizes user-generated messages related to opioid abuse, heroin injection drug use, and HIV status using natural language processing (NLP) among Twitter users in Indiana during the period of this HIV outbreak.Materials and methodsOur study consisted of two phases: data collection and processing, and data analysis. We collected Indiana geolocated tweets from the public Twitter API using Amazon Web Services EC2 instances filtered for geocoded messages in the immediate pre and post period of the outbreak. In the data analysis phase we applied an unsupervised machine learning approach using NLP called the Biterm Topic Model (BTM) to identify tweets related to opioid, heroin/injection, and HIV behavior and then examined these messages for HIV risk-related topics that could be associated with the outbreak.ResultsMore than 10 million geocoded tweets occurring in Indiana during the immediate pre and post period of the outbreak were collected for analysis. Using BTM, we identified 1350 tweets thought to be relevant to the outbreak and then confirmed 358 tweets using human annotation. The most prevalent themes identified were tweets related to self-reported abuse of illicit and prescription drugs, opioid use disorder, self-reported HIV status, and public sentiment regarding the outbreak. Geospatial analysis found that these messages clustered in population dense areas outside of the outbreak, including Indianapolis and neighboring Clark County.DiscussionThis infoveillance study characterized the social media conversations of communities in Indiana in the pre and post period of the 2015 HIV outbreak. Behavioral themes detected reflect discussion about risk factors related to HIV transmission stemming from opioid and heroin abuse for priority populations, and also help identify community attitudes that could have motivated or detracted the use of HIV prevention methods, along with helping identify factors that can impede access to prevention services.ConclusionsInfoveillance approaches, such as the analysis conducted in this study, represent a possibly strategy to detect "signal" of the emergence of risk factors associated with an outbreak though may be limited in their scope and generalizability. Our results, in conjunction with other forms of public health surveillance, can leverage the growing ubiquity of social media platforms to better detect opioid-related HIV risk knowledge, attitudes and behavior, as well as inform future prevention efforts.

Recently emerging evidence indicates accelerated age-related changes in the structure and function of the brain in schizophrenia, raising a question about its potential consequences on cognitive function. Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patients show accelerated age-related decline in cognition and whether an age-related effect differ between females and males. We utilized data of 1,415 schizophrenia patients and 1,062 healthy community collected by the second phase of the Consortium on the Genetics of Schizophrenia (COGS-2). A battery of cognitive tasks included the Letter-Number Span Task, two forms of the Continuous Performance Test, the California Verbal Learning Test, Second Edition, the Penn Emotion Identification Test and the Penn Facial Memory Test. The effect of age and gender on cognitive performance was examined with a general linear model. We observed age-related changes on most cognitive measures, which was similar between males and females. Compared to controls, patients showed greater deterioration in performance on attention/vigilance and greater slowness of processing social information with increasing age. However, controls showed greater age-related changes in working memory and verbal memory compared to patients. Age-related changes (η2p of 0.001 to .008) were much smaller than between-group differences (η2p of 0.005 to .037). This study found that patients showed continued decline of cognition on some domains but stable impairment or even less decline on other domains with increasing age. These findings indicate that age-related changes in cognition in schizophrenia are subtle and not uniform across multiple cognitive domains.

Alzheimer's disease and related dementias (ADRD) present a significant global disease burden that is only expected to grow in the future. As such, there is a need to develop and investigate biomarkers that identify individuals at risk of developing ADRD with the goal of providing early interventions and treatments. Non-human primate (NHP) models of neurodegeneration present opportunities to examine such biomarkers in a preclinical model with the ability to control several confounding factors present in research with humans. Baboons naturally develop several ADRD-related neuropathologies that humans also exhibit, including age-related tau and amyloid deposition. However, to our knowledge, there are no data characterizing fluid biomarkers relevant to neurodegeneration or ADRD in baboons. We collected plasma (N = 139) and cerebrospinal fluid (CSF, N = 44) from captive baboons ranging in age from 3–19 years old. We characterized biomarkers as a function of age, sex, and rearing status in baboons using a bead-based bioplex human assay (Thermo Fisher Scientific's Neuroscience 18-Plex Human ProcartaPlex™ Panel). Fluid biomarkers were more detectable in CSF compared to plasma. Additionally, while sex and rearing did not significantly predict biomarkers in baboons, age significantly predicted levels of eight of the 12 biomarkers detected in the assay. Linear regressions showed that CSF levels of total tau, pTau181, NGF-beta, GFAP, NF-H, and S100B were higher in older baboons, as were plasma levels of NGF-beta. Lastly, older baboons showed a higher incidence of co-occurrence of multiple biomarkers as measured in CSF, but not in plasma. These data show that baboons exhibit age-dependent changes in biomarkers used in humans for clinical screening, diagnosis, and prognosis of ADRD, thereby further demonstrating the value of baboons as a model of aging and, possibly, ADRD. [ABSTRACT FROM AUTHOR]

Aliya®Pulsed Electric Field (PEF) technology is an emerging strategy in the field of cancer treatment, offering a novel approach to ablation therapy that does not rely on thermal mechanisms. By employing a multi-stage experimental setup, including potato tuber, porcine liver, and murine breast cancer models, we explored the dose-response relationship on ablation and immune modulation by varying the pulse packets delivered from 20 to 100. The biologic response observed with 60 packets represented a minimum effective dose yielding reproducible ablation parameters, immune response, and efficacy which could be augmented with immune checkpoint blockade. This pre-clinical analysis provides a first step toward understanding the therapeutic index for PEF technology beyond ablation, a consideration that will require robust clinical validation in well-designed prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: To assess physiological metrics during the use of a commercially available bilateral active ankle exoskeleton during a challenging military-relevant task and if use of the exoskeleton during this task influences: metabolic load, physiological measures or rate of perceived exertion. Methods: Nine healthy volunteers (5M, 4F) completed this randomized cross-over design trial, with a baseline visit and two randomized test sessions (with/without the exoskeleton). Variables included impact on time to exhaustion during walking on a treadmill at varying speeds and gradients (0–15%) at 26.7°C, 50% humidity with a loaded rucksack (30% body weight). The primary outcome measure was change in metabolic cost with/without the exoskeleton (O2 consumption, metabolic equivalents); secondary outcomes were change in heart rate and perceived exertion between conditions. Results: Participants averaged 22.4 ± 4.5 years old, 173.7 ± 7.4 cm tall, weighed 80.9 ± 13.9 kg, and VO2max of 43.8 ± 10.6 mL/kg/min. Total kcals did not differ between conditions (with/without exoskeleton; t = 0.98; p = 0.357). Kcals/min were significantly lower (1.06 kcals/min) with the exoskeleton (t = 3.94; p = 0.004). Average oxygen consumption (VO2) was significantly lower (2.36 mL/kg/min) with the exoskeleton (t = 2.81; p = 0.023), and peak VO2 was 3.33 mL/kg/min lower with the exoskeleton (t = 2.37; p = 0.045). Peak and Average METS were also lower with the exoskeleton by 0.98 (t = 2.61; p = 0.031) and 1.23 (t = 2.39; p = 0.044) respectively. Conclusions: Results suggest a powered ankle exoskeleton may decrease energy consumption during military relevant tasks when conducted in a laboratory environment. There may also be physiological benefits such as reduced core temperate and heart rate. Replication of this work in the field environment is warranted. [ABSTRACT FROM AUTHOR]

Background: Most longitudinal studies of COVID-19 incidence have used unlinked samples. The city of Manaus, Brazil, has a blood donation program which allows sample linkage, and was struck by two large COVID-19 epidemic waves between mid-2020 and early 2021. Methods: We estimated the changing force of infection, i.e. incidence in susceptible individuals. Seroconversion was inferred by a mixture model for serial values from the Abbott Architect SARS-CoV-2 nucleocapsid (N) IgG assay. We estimated the number of suspected COVID-19 hospitalizations arising from each infection over calendar time. Results: Whole blood donations between April 2020 and March 2021 were included from 6734 people, 2747 with two or more donations. The inferred criterion for seroconversion, and thus an incident infection, was a 6.07 fold increase in N IgG reactivity. The overall force of infection was 1.19 per person year (95% confidence interval 1.14–1.24) during the two main waves. The estimated number of suspected hospitalizations per infection, was approximately 4.1 times higher in the second wave than in the first. Conclusions: Serial values from this assay can be used to infer seroconversion over time, and in Manaus show a higher number of suspected COVID-19 hospitalizations per infection in the second wave relative to the first. [ABSTRACT FROM AUTHOR]

Purpose: Implicit, unconscious biases in medicine are personal attitudes about race, ethnicity, gender, and other characteristics that may lead to discriminatory patterns of care. However, there is no consensus on whether implicit bias represents a true predictor of differential care given an absence of real-world studies. We conducted the first real-world pilot study of provider implicit bias by evaluating treatment parity in prostate cancer using unstructured data–the most common way providers document granular details of the patient encounter. Methods and findings: Patients ≥18 years with a diagnosis of very-low to favorable intermediate-risk prostate cancer followed by 3 urologic oncologists from 2010 through 2021. The race Implicit Association Test was administered to all providers. Natural language processing screened human annotation using validated regex ontologies evaluated each provider's care on four prostate cancer quality indicators: (1) active surveillance utilization; (2) molecular biomarker discussion; (3) urinary function evaluation; and (4) sexual function evaluation. The chi-squared test and phi coefficient were utilized to respectively measure the statistical significance and the strength of association between race and four quality indicators. 1,094 patients were included. While Providers A and B demonstrated no preference on the race Implicit Association Test, Provider C showed preference for White patients. Provider C recommended active surveillance (p<0.01, φ = 0.175) and considered biomarkers (p = 0.047, φ = 0.127) more often in White men than expected, suggestive of treatment imparity. Provider A considered biomarkers (p<0.01, φ = 0.179) more often in White men than expected. Provider B demonstrated treatment parity in all evaluated quality indicators (p>0.05). Conclusions: In this pilot study, providers' practice patterns were associated with both patient race and implicit racial preferences in prostate cancer. Alerting providers of existing implicit bias may restore parity, however future assessments are needed to validate this concept. [ABSTRACT FROM AUTHOR]

Associations between vitamin D biochemical status and cancer may be modified by vitamin D binding protein isoforms which are encoded by GC (group-specific component). We examined interactions between serum 25-hydroxyvitamin D [25(OH)D], the Gc isoforms Gc1-1, Gc1-2, and Gc2-2, and cancer risk within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort based on 3,795 cases and 3,856 controls. Multivariable-adjusted logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer risk according to 25(OH)D quantiles, stratified by Gc isoform. Separately, the GC-cancer risk association was examined using proportional hazards regression among 109,746 individuals with genetic data and 26,713 diagnosed with cancer. Specific vitamin D binding protein isoform subtypes were delineated and analyzed, including Gc1-1 subtypes (Gc1s-Gc1s, Gc1f-Gc1s, and Gc1f-Gc1f) and Gc2 subtypes (Gc1s-Gc2, Gc1f-Gc2, and Gc2-Gc2). For most cancers, the GC genotype did not modify the risk associations for 25(OH)D; e.g., the OR for high vs. low vitamin D quintile was 1.09 (0.89–1.33) for overall cancer risk among individuals with the Gc1-1 isoform and 1.04 (0.83–1.31) among those with either the Gc1-2 or Gc2-2 isoforms. ORs for high compared to low vitamin D tertile for colorectal, lung, breast, and prostate cancer among those with the Gc1-1 vs. any Gc2 isoforms were, respectively, 0.60 vs. 0.73, 1.96 vs. 1.03, 1.30 vs. 1.18, and 1.19 vs. 1.22 (all p-interaction ≥0.36). However, GC qualitatively modified the vitamin D-bladder cancer risk association: OR = 1.70 (95% CI 0.96–2.98) among those with the Gc1-1 isoform and 0.52 (0.28–0.96) among those with any Gc2 isoforms (p-interaction = 0.03). When modeled without regard for 25(OH)D, Gc isoforms were generally not associated with cancer risk, although melanoma risk was significantly lower among individuals with the "f" subtype of the Gc1-1 isoform, specifically HR = 0.83 (95% CI 0.70–0.98) for Gc1f-1s and 0.67 (0.45–1.00) for Gc1f-1f, compared to individuals with the Gc1s-Gc1s isoform. Vitamin D binding protein genetic isoforms may be associated with melanoma risk but do not modify the association between vitamin D status and cancer, with the possible exception of bladder cancer. [ABSTRACT FROM AUTHOR]

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

[This corrects the article DOI: 10.1371/journal.pone.0025598.].

Based on original ethnographic and ethnobotanical research, we share how in the cosmology of Tanna, an island in Vanuatu's southernmost province of Tafea, the Sun is viewed as a living, interactive being. Our initial interviews explored knowledge and beliefs concerning individual plant species, then subsequent follow-up interviews further explored topics that emerged therefrom. The results of these interviews are a series of oral narratives of the mytho-historical past involving the Sun, and the description of contemporary practices which are influenced by the Sun. In traditional narratives, the Sun is both a creative and destructive force which is sometimes viewed as an active, personified character, and in other circumstances appears as an instrument created and utilized by greater powers. People from Tanna recount—and we adopt as a hypothesis—that the Sun's physical manifestation and role in the world has changed since the earliest days of its mythological creation, and that it remains an active player in Tanna's biocultural landscape within practices including time-reckoning, agriculture, and architecture. Through its relationships with humans and non-humans alike, the Sun ultimately shapes the cultural practices and even the landscape of Tanna. The nature of these relationships is changing as linguistic and cultural practices shift alongside people's relationship with the land, but the Sun remains a critical factor in lives and livelihoods of Tanna today. [ABSTRACT FROM AUTHOR]

Weighted networks are information-rich and highly-flexible, but they can be difficult to analyze because the interpretation of edges weights is often ambiguous. Specifically, the meaning of a given edge's weight is locally contingent, so that a given weight may be strong for one dyad, but weak for other dyad, even in the same network. I use backbone models to distinguish strong and weak edges in a corpus of 110 weighted networks, and used the results to examine the magnitude of this ambiguity. Although strong edges have larger weights than weak edges on average, a large fraction of edges' weights provide ambiguous information about whether it is strong or weak. Based on these results, I recommend that strong edges should be identified by applying an appropriate backbone model, and that once strong edges have been identified using a backbone model, their original weights should not be directly interpreted or used in subsequent analysis. [ABSTRACT FROM AUTHOR]

BackgroundIn recent decades the overall smoking prevalence in the US has fallen steadily. This study examines whether the same trend is seen in the Medicaid population.Methods and findingsNational Health Interview Survey (NHIS) data from 17 consecutive annual surveys from 1997 to 2013 (combined N = 514,043) were used to compare smoking trends for 4 insurance groups: Medicaid, the Uninsured, Private Insurance, and Other Coverage. Rates of chronic disease and psychological distress were also compared.ResultsAdjusted smoking prevalence showed no detectable decline in the Medicaid population (from 33.8% in 1997 to 31.8% in 2013, trend test P = 0.13), while prevalence in the other insurance groups showed significant declines (38.6%-34.7% for the Uninsured, 21.3%-15.8% for Private Insurance, and 22.6%-16.8% for Other Coverage; all P's

ConclusionHigher vitamin D status was not beneficially associated with responses to therapy; if anything, patients with higher vitamin D concentrations were less likely to attain SVR. Our data do not support a role for vitamin D supplementation as an adjuvant therapy for HCV.

Global climate change and other anthropogenic stressors have heightened the need to rapidly characterize ecological changes in marine benthic communities across large scales. Digital photography enables rapid collection of survey images to meet this need, but the subsequent image annotation is typically a time consuming, manual task. We investigated the feasibility of using automated point-annotation to expedite cover estimation of the 17 dominant benthic categories from survey-images captured at four Pacific coral reefs. Inter- and intra- annotator variability among six human experts was quantified and compared to semi- and fully- automated annotation methods, which are made available at coralnet.ucsd.edu. Our results indicate high expert agreement for identification of coral genera, but lower agreement for algal functional groups, in particular between turf algae and crustose coralline algae. This indicates the need for unequivocal definitions of algal groups, careful training of multiple annotators, and enhanced imaging technology. Semi-automated annotation, where 50% of the annotation decisions were performed automatically, yielded cover estimate errors comparable to those of the human experts. Furthermore, fully-automated annotation yielded rapid, unbiased cover estimates but with increased variance. These results show that automated annotation can increase spatial coverage and decrease time and financial outlay for image-based reef surveys.

BackgroundThe prevalence of hypertension is known to differ by racial group in adults in the United States (US), but findings in children are scarce and inconsistent. The objective of this study was to assess the racial differences in pediatric hypertension and to explore whether these differences, if any, can be explained by low birth weight (LBW) and obesity.MethodsAnalyses were performed for participants aged 8-17 years (N = 9,250) included in the 1999-2010 National Health and Nutrition Examination Survey. Multivariate logistic regressions and weighted analysis were carried out considering the complex survey design.ResultsCompared to non-Hispanic White youth, the crude prevalence of hypertension was significantly higher in non-Hispanic Blacks (7.1% vs. 5.6%; P = 0.04), but not in Mexican Americans (5.4% vs. 5.6%; P = 0.77). Blacks also had higher rates of LBW (14.6% vs. 5.9%; P

The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses (≥ 45 Gy), few studies have been conducted at much lower doses (≤ 2 Gy), where the response of the CNS (like many other tissues) may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT) animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios.

The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: The overall goal of this work is to produce a set of recommendations (SoNHR–Social Networks in Health Research) that will improve the reporting and dissemination of social network concepts, methods, data, and analytic results within health sciences research. Methods: This study used a modified-Delphi approach for recommendation development consistent with best practices suggested by the EQUATOR health sciences reporting guidelines network. An initial set of 28 reporting recommendations was developed by the author team. A group of 67 (of 147 surveyed) experienced network and health scientists participated in an online feedback survey. They rated the clarity and importance of the individual recommendations, and provided qualitative feedback on the coverage, usability, and dissemination opportunities of the full set of recommendations. After examining the feedback, a final set of 18 recommendations was produced. Results: The final SoNHR reporting guidelines are comprised of 18 recommendations organized within five domains: conceptualization (how study research questions are linked to network conceptions or theories), operationalization (how network science portions of the study are defined and operationalized), data collection & management (how network data are collected and managed), analyses & results (how network results are analyzed, visualized, and reported), and ethics & equity (how network-specific human subjects, equity, and social justice concerns are reported). We also present a set of exemplar published network studies which can be helpful for seeing how to apply the SoNHR recommendations in research papers. Finally, we discuss how different audiences can use these reporting guidelines. Conclusions: These are the first set of formal reporting recommendations of network methods in the health sciences. Consistent with EQUATOR goals, these network reporting recommendations may in time improve the quality, consistency, and replicability of network science across a wide variety of important health research areas. [ABSTRACT FROM AUTHOR]

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.