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There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.

Abstract A 15‐year‐old male neutered mixed breed dog weighing 28 kg presented to a referral center after developing severe tremors and altered mentation. There was hypocalcemia and hypernatremia after oral administration of sodium phosphate as a bowel cleansing agent in preparation for colonoscopy. The dog was treated intravenously with low sodium fluids and calcium gluconate. Neurologic status and electrolyte derangements normalized over the next 12 hours. Oral administration of sodium phosphate appeared to cause clinical electrolyte derangements in this dog.

Abstract Background Transgenerational epigenetic risks associated with complex health outcomes, such as autism spectrum disorder (ASD), have attracted increasing attention. Transgenerational environmental risk exposures with potential for epigenetic effects can be effectively identified using space-time clustering. Specifically applied to ancestors of individuals with disease outcomes, space-time clustering characterized for vulnerable developmental stages of growth can provide a measure of relative risk for disease outcomes in descendants. Objectives (1) Identify space-time clusters of ancestors with a descendent with a clinical ASD diagnosis and matched controls. (2) Identify developmental windows of ancestors with the highest relative risk for ASD in descendants. (3) Identify how the relative risk may vary through the maternal or paternal line. Methods Family pedigrees linked to residential locations of ASD cases in Utah have been used to identify space-time clusters of ancestors. Control family pedigrees of none-cases based on age and sex have been matched to cases 2:1. The data have been categorized by maternal or paternal lineage at birth, childhood, and adolescence. A total of 3957 children, both parents, and maternal and paternal grandparents were identified. Bernoulli space-time binomial relative risk (RR) scan statistic was used to identify clusters. Monte Carlo simulation was used for statistical significance testing. Results Twenty statistically significant clusters were identified. Thirteen increased RR (> 1.0) space-time clusters were identified from the maternal and paternal lines at a p-value

Introduction: Despite progress in whole-organ decellularization and recellularization, maintaining long-term perfusion in vivo remains a hurdle to realizing clinical translation of bioengineered kidney grafts. The objectives for the present study were to define a threshold glucose consumption rate (GCR) that could be used to predict in vivo graft hemocompatibility and utilize this threshold to assess the in vivo performance of clinically relevant decellularized porcine kidney grafts recellularized with human umbilical vein endothelial cells (HUVECs).Materials and methods: Twenty-two porcine kidneys were decellularized and 19 were re-endothelialized using HUVECs. Functional revascularization of control decellularized (n = 3) and re-endothelialized porcine kidneys (n = 16) was tested using an ex vivo porcine blood flow model to define an appropriate metabolic glucose consumption rate (GCR) threshold above which would sustain patent blood flow. Re-endothelialized grafts (n = 9) were then transplanted into immunosuppressed pigs with perfusion measured using angiography post-implant and on days 3 and 7 with 3 native kidneys used as controls. Patent recellularized kidney grafts underwent histological analysis following explant.Results: The glucose consumption rate of recellularized kidney grafts reached a peak of 39.9 ± 9.7 mg/h at 21 ± 5 days, at which point the grafts were determined to have sufficient histological vascular coverage with endothelial cells. Based on these results, a minimum glucose consumption rate threshold of 20 mg/h was set. The revascularized kidneys had a mean perfusion percentage of 87.7% ± 10.3%, 80.9% ± 33.1%, and 68.5% ± 38.6% post-reperfusion on Days 0, 3 and 7, respectively. The 3 native kidneys had a mean post-perfusion percentage of 98.4% ± 1.6%. These results were not statistically significant.Conclusion: This study is the first to demonstrate that human-scale bioengineered porcine kidney grafts developed via perfusion decellularization and subsequent re-endothelialization using HUVEC can maintain patency with consistent blood flow for up to 7 days in vivo. These results lay the foundation for future research to produce human-scale recellularized kidney grafts for transplantation.

Abstract In-vivo estimation of mechanical properties of the myocardium is essential for patient-specific diagnosis and prognosis of cardiac disease involving myocardial remodeling, including myocardial infarction and heart failure with preserved ejection fraction. Current approaches use time-consuming finite-element (FE) inverse methods that involve reconstructing and meshing the heart geometry, imposing measured loading, and conducting computationally expensive iterative FE simulations. In this paper, we propose a machine learning (ML) model that feasibly and accurately predicts passive myocardial properties directly from select geometric, architectural, and hemodynamic measures, thus bypassing exhaustive steps commonly required in cardiac FE inverse problems. Geometric and fiber-orientation features were chosen to be readily obtainable from standard cardiac imaging protocols. The end-diastolic pressure-volume relationship (EDPVR), which can be obtained using a single-point pressure-volume measurement, was used as a hemodynamic (loading) feature. A comprehensive ML training dataset in the geometry-architecture-loading space was generated, including a wide variety of partially synthesized rodent heart geometry and myofiber helicity possibilities, and a broad range of EDPVRs obtained using forward FE simulations. Latin hypercube sampling was used to create 2500 examples for training, validation, and testing. A multi-layer feed-forward neural network (MFNN) was used as a deep learning agent to train the ML model. The model showed excellent performance in predicting stiffness parameters $$a_f$$ a f and $$b_f$$ b f associated with fiber direction ( $$R^2_{a_f}=99.471\%$$ R a f 2 = 99.471 % and $$R^2_{b_f}=92.837\%$$ R b f 2 = 92.837 % ). After conducting permutation feature importance analysis, the ML performance further improved for $$b_f$$ b f ( $$R^2_{b_f}=96.240\%$$ R b f 2 = 96.240 % ), and the left ventricular volume and endocardial area were found to be the most critical geometric features for accurate predictions. The ML model predictions were evaluated further in two cases: (i) rat-specific stiffness data measured using ex-vivo mechanical testing, and (ii) patient-specific estimation using FE inverse modeling. Excellent agreements with ML predictions were found for both cases. The trained ML model offers a feasible technology to estimate patient-specific myocardial properties, thus, bridging the gap between EDPVR, as a confounded organ-level metric for tissue stiffness, and intrinsic tissue-level properties. These properties provide incremental information relative to traditional organ-level indices for cardiac function, improving the clinical assessment and prognosis of cardiac diseases.

Abstract The development of suitable safe adjuvants to enhance appropriate antigen-driven immune responses remains a challenge. Here we describe the adjuvant properties of a small molecule activator of the integrins αLβ2 and α4β1, named 7HP349, which can be safely delivered systemically independent of antigen. 7HP349 directly activates integrin cell adhesion receptors crucial for the generation of an immune response. When delivered systemically in a model of Chagas disease following immunization with a DNA subunit vaccine encoding candidate T. cruzi antigens, TcG2 and TcG4, 7HP349 enhanced the vaccine efficacy in both prophylactic and therapeutic settings. In a prophylactic setting, mice immunized with 7HP349 adjuvanted vaccine exhibited significantly improved control of acute parasite burden in cardiac and skeletal muscle as compared to vaccination alone. When administered with vaccine therapeutically, parasite burden was again decreased, with the greatest adjuvant effect of 7HP349 being noted in skeletal muscle. In both settings, adjuvantation with 7HP349 was effective in decreasing pathological inflammatory infiltrate, improving the integrity of tissue, and controlling tissue fibrosis in the heart and skeletal muscle of acutely and chronically infected Chagas mice. The positive effects correlated with increased splenic frequencies of CD8+T effector cells and an increase in the production of IFN-γ and cytolytic molecules (perforin and granzyme) by the CD4+ and CD8+ effector and central memory subsets in response to challenge infection. This demonstrates that 7HP349 can serve as a systemically administered adjuvant to enhance T cell-mediated immune responses to vaccines. This approach could be applied to numerous vaccines with no reformulation of existing stockpiles.

The inability of CD8+ effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function–associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response. 7HP349 monotherapy had modest effects on anti–programmed death 1–resistant (anti–PD-1–resistant) tumors, whereas combinatorial treatment with anti–cytotoxic T lymphocyte–associated protein 4 (anti–CTLA-4) increased CD8+ Teff intratumoral sequestration and synergized in cooperation with neutrophils in inducing cancer regression. 7HP349 intratumoral CD8+ Teff enrichment activity depended on CXCL12. We analyzed gene expression profiles using RNA from baseline and on treatment tumor samples of 14 melanoma patients. We identified baseline CXCL12 gene expression as possibly improving the likelihood or response to anti–CTLA-4 therapies. Our results provide a proof-of-principle demonstration that LFA-1 activation could convert a T cell–exclusionary TME to a T cell–enriched TME through mechanisms involving cooperation with innate immune cells.

In Pakistan, antimicrobial resistance (AMR) is expected to greatly increase the already high mortality and morbidity rates attributed to infections, making AMR surveillance and prevention a priority in the country. The aims of the project were to characterize the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facility sink drains in Pakistan and to characterize how physical characteristics of sinks and healthcare facility rooms were associated with CRE in those sinks. The study took place in 40 healthcare facilities in Jamshoro Pakistan. Swabs were collected from sink drains in each facility that had a sink, and structured observations of sinks and facilities were performed at each facility. Swabs were plated on CHROMagar KPC to screen for carbapenem-resistant Enterobacteriaceae, which were then isolated on Mueller-Hinton agar plates. Antibiotic susceptibility was determined using the disk diffusion method to assess resistance to carbapenems, cephalosporins, and fluoroquinolones. Thirty-seven of the healthcare facilities had at least one sink, and thirty-nine total sinks were present and sampled from those healthcare facilities. Sinks in these facilities varied in quality; at the time of sampling 68% had water available, 51% had soap/alcohol cleanser at the sink, 28% appeared clean, and 64% drained completely. Twenty-five (64%) of the sink samples grew Enterobacteriaceae on CHROMagar KPC, sixteen (41%) of which were clinically non-susceptible to ertapenem. Seven of the 39 sampled sinks (18%) produced Enterobacteriaceae that were resistant to all three antibiotic classes tested. Several facilities and sink characteristics were associated with CRE. Sinks and drains can serve as undetected reservoirs for carbapenem-resistant Enterobacteriaceae. Control and remediation of such environments will require both systemic strategies and physical improvements to clinical environments.

Background: Despite increasing evidence that particulate air pollution has adverse effects on human semen quality, few studies examine the impact of air pollution on clinically relevant thresholds used to diagnose male fertility problems. Furthermore, exposure is often assessed using average air pollution levels in a geographic area rather than individualized estimates. Finally, physiologically-informed exposure windows are inconsistent. Objectives: We sought to test the hypothesis that airborne particulate exposures during early-phase spermatogenesis will have a differential impact on spermatogenic formation compared to late-phase exposures, using an individualized model of exposure to particulate matter ≤ 2.5 µm and ≤ 10 µm (PM2.5 and PM10, respectively). Methods: From an original cohort of 183 couples, we conducted a retrospective analysis of 130 healthy males seeking to become parents, using spermatogenesis-relevant exposure windows of 77–34 days and 37–0 days prior to semen collection to encompass sperm development stages of mitosis/meiosis and spermiogenesis, respectively. Individualized residential exposure to PM2.5 and PM10 was estimated by selecting multiple air pollution sensors within the same geographic air basin as participants and employing inverse distance weighting to calculate mean daily exposure levels. We used multiple logistic regression to assess the association between pollution, temperature, and dichotomized World Health Organization semen parameters. Results: During the early phase of spermatogenesis, air pollution exposure is associated with 1.52 (95% CI: 1.04–2.32) times greater odds of

Leukocyte inflammatory responses require integrin cell-adhesion molecule signaling through spleen tyrosine kinase (Syk), a non-receptor kinase that binds directly to integrin β-chain cytoplasmic domains. Here, we developed a high-throughput screen to identify small molecule inhibitors of the Syk-integrin cytoplasmic domain interactions. Screening small molecule compound libraries identified the β-lactam antibiotics cefsulodin and ceftazidime, which inhibited integrin β-subunit cytoplasmic domain binding to the tandem SH2 domains of Syk (IC50 range, 1.02–4.9 µM). Modeling suggested antagonist binding to Syk outside the pITAM binding site. Ceftazidime inhibited integrin signaling via Syk, including inhibition of adhesion-dependent upregulation of interleukin-1β and monocyte chemoattractant protein-1, but did not inhibit ITAM-dependent phosphorylation of Syk mediated by FcγRI signaling. Our results demonstrate a novel means to target Syk independent of its kinase and pITAM binding sites such that integrin signaling via this kinase is abrogated but ITAM-dependent signaling remains intact. As integrin signaling through Syk is essential for leukocyte activation, this may represent a novel approach to target inflammation.

Fibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue engineering. Previous studies have sought to slow the degradation rate of fibrin with the addition of proteolysis inhibitors or synthetic crosslinkers that require multiple functionalization or polymerization steps. These strategies are difficult to implement in vivo and introduce increased complexity, both of which hinder the use of fibrin in research and medicine. Previously, we demonstrated that additional crosslinking of fibrin gels using bifunctionalized poly(ethylene glycol)-n-hydroxysuccinimide (PEG-NHS) slows the degradation rate of fibrin. In this study, we aimed to further improve the longevity of these PEG-fibrin gels such that they could be used for tissue engineering in vitro or in situ without the need for proteolysis inhibitors. It is well documented that increasing the salinity of fibrin precursor solutions affects the resulting gel morphology. Here, we investigated whether this altered morphology influences the fibrin degradation rate. Increasing the final sodium chloride (NaCl) concentration from 145 mM (physiologic level) to 250 mM resulted in fine, transparent high-salt (HS) fibrin gels that degrade 2-3 times slower than coarse, opaque physiologic-salt (PS) fibrin gels both in vitro (when treated with proteases and when seeded with amniotic fluid stem cells) and in vivo (when injected subcutaneously into mice). Increased salt concentrations did not affect the viability of encapsulated cells, the ability of encapsulated endothelial cells to form rudimentary capillary networks, or the ability of the gels to maintain induced pluripotent stem cells. Finally, when implanted subcutaneously, PS gels degraded completely within one week while HS gels remained stable and maintained viability of seeded dermal fibroblasts. To our knowledge, this is the simplest method reported for the fabrication of fibrin gels with tunable degradation properties and will be useful for implementing fibrin gels in a wide range of research and clinical applications.

Heart disease is the leading cause of death in the United States among both adults and infants. In adults, 5-year survival after a heart attack is

Small intestinal neuroendocrine tumors (SINT) are rare with incidence increasing over the past 40 years. The purpose of this work is to examine the role of environmental exposures in the rise of SINT incidence using the Utah Population Database, a resource of linked records including life events, cancer diagnoses and residential histories. SINT cases born in Utah were identified through the Utah Cancer Registry with: diagnosis years of 1948 to 2014 and age at diagnosis of 23 to 88 years. Controls were matched to cases 10:1 based on sex, birth year and residence time in Utah. Cases and controls were geocoded to their birth locale. An isotonic spatial scan statistic was used to test for the occurrence and location(s) of SINT clusters. Potential environmental exposures and economic conditions in the birth locales at the time of the birth (1883-1982) were generated using historical references. Conditional logistic regression was used to estimate odd ratios. We report a spatial cluster central to historic coal mining communities, associated with a 2.86 relative risk (p = 0.016) of SINT. Aspatial analyses of industry and mining exposures further suggest elevated risk for early life exposure near areas involved in the construction industry (OR 1.98 p = 0.024). Other exposures approached significance including coal, uranium and hard rock mining during the earliest period (1883-1929) when safety from exposures was not considered. We do observe a lower risk (OR 0.58 p = 0.033) associated with individuals born in rural areas in the most recent period (1945-1982). Environmental exposures early in life, especially those from industries such as mining, may confer an elevated risk of SINT.

[Display omitted] Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework to elucidate the fiber-level remodeling mechanisms that drive tissue-level adaptation for each subject. We found that a progressively diffused collagen fiber structure combined with similarly disorganized myofiber architecture in the healthy region leads to the loss of LVFW anisotropy post-MI, offering an important tissue-level hallmark for LV maladaptation. In contrast, our results suggest that reductions in collagen undulation are an adaptive mechanism competing against LVFW thinning. Additionally, we show that the inclusion of subject-specific geometry when modeling myocardial tissue is essential for accurate prediction of tissue kinematics. Our approach serves as an essential step toward identifying fiber-level remodeling indices that govern the transition of MI to systolic heart failure. These indices complement the traditional, organ-level measures of LV anatomy and function that often fall short of early prognostication of heart failure in MI. In addition, our approach offers an integrated methodology to advance the design of personalized interventions, such as hydrogel injection, to reinforce and suppress native adaptive and maladaptive mechanisms, respectively, to prevent the transition of MI to heart failure. Biomechanical and architectural adaptation of the LVFW remains a central, yet overlooked, remodeling process post-MI. Our study indicates the biomechanical adaptation of the LVFW post-MI is highly individual and driven by altered fiber network architecture and collective changes in collagen fiber content, undulation, and stiffness. Our findings demonstrate the possibility of using cardiac strains to infer such fiber-level remodeling events through in-silico modeling, paving the way for in-vivo characterization of multiscale biomechanical indices in humans. Such indices will complement the traditional, organ-level measures of LV anatomy and function that often fall short of early prognostication of heart failure in MI. [ABSTRACT FROM AUTHOR]

Introduction Effects of early life conditions on Alzheimer’s disease (AD) and related dementia (RD) risk have been hypothesized. However, prospective study is potentially cost prohibitive. Retrospective studies using routinely collected health records in large cohorts may be a feasible way to carry out such research, but diagnostic accuracy should be determined. Objectives and Approach We aim to determine accuracy of AD/RD diagnoses in electronic health records (EHR) (inpatient, ambulatory surgery, and Medicare) and death certificates (DC) compared to gold standard. The Cache County Study on Memory in Aging (CACHE, 1995–2008) enrolled 90% of the county’s residents age ≥ 65 years (N=5092). Over the course of 12 years/4 triennial waves of thorough dementia ascertainment, 942 persons (18.5%) were identified with dementia. Prevalence of AD or AD comorbid with other dementia (AD mixed) was 12.8% and for RD alone, 5.7%. We used the Utah Population Database, linking EMR/DCs (1995–2008) to CACHE participants (98% linkage). Results The prevalence of AD/AD mixed and RD in EHR/DCs was 12.2% and 35.8%. Among linked CACHE participants diagnosed with AD or AD mixed (n=628), 505 (80%) were captured by EHR/DCs as having some form of dementia (AD, AD mixed, or RD) with 301 (60%) correctly classified as having AD or AD mixed. Among those with RD (n=399), 275 (69%) were captured by EHR/DCs as having some form of dementia, with 163 (60%) correctly classified as having RD. Sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) were 48%, 93%, 49%, 93%, and 0.70 for AD or AD mixed; and 67%, 67%, 15%, 96%, and 0.67 for RD. Overall dementia agreement between CACHE diagnoses and EHR/DCs was fair (Cohen's κ = 0.34). Conclusion/Implications In this will characterized cohort, routinely collected health record diagnoses of AD/AD mixed and RD have only fair correlation with carefully phenotyped diagnoses. Determining additional features of a person’s medical record that may be predictive of AD/RD via formal classification modeling is warranted.

Eve teasing was identified as a significant community problem through a community-based participatory process with nine villages in Punjab, India. Eve teasing is a common euphemism in South Asia for sexual harassment of women in public areas by men. The purpose of this study was to characterize the meaning of eve teasing in the rural context, especially among female youth, and to develop a means to measure its occurrence. Mixed methods were utilized including focus group discussions (FGDs), semistructured interviews, and direct observation of questionnaire administration. Thirty-four people participated in six FGDs; two with adolescent boys ( n = 10), two with adolescent girls ( n = 15), and two with women ages 20 to 26 years ( n = 9). Eighty-nine females, ages 14 to 26 years, were recruited through purposive sampling for face-to-face interviews in homes and schools. Twenty-four interviews were observed directly to aid questionnaire development. Eve teasing was described as staring, stalking, passing comments, and inappropriate physical touch. Perceived consequences of eve teasing included tight restrictions on girls’ mobility, inability to attend school or work, girls being blamed, and causing family problems. FGD participants suggested that eve teasing can lead to depression and suicide. Among the 36 (40.4%) interview participants who reported eve teasing, 61.1% reported feelings of anger, 47.2% reported feelings of shame or humiliation, and more than one third reported feelings of fear, worry, or tension. The questionnaire offers a means to assess the occurrence of eve teasing that is culturally relevant and age appropriate for female youth in India.

The purpose of this paper is to describe a Centrifugal Pump Experiment that provided an experiential learning experience to chemical engineering undergraduates at the University of Missouri in the spring of 2010 in the Unit Operations Laboratory course. Lab equipment was used by senior students with computer-based data and control technology. In addition to pump performance results, lab reports included paragraphs on: educational assessment, applicability to chemical engineering practice, and students' opinion of the new pump experiment. This experiential learning experience is encouraging for the continued use of the Centrifugal Pump Experiment in the Unit Operations Lab.

The primary purpose of this study is to identify predictors of complete household enrollment into the National Health Insurance Scheme (NHIS) among inhabitants of the Barekese sub-district in the Ashanti Region of Ghana. Heads of households in 20 communities from the Barekuma Collaborative Community Project site were interviewed to gather data on demographic, socioeconomic status (SES) indicators and complete household subscription in the NHIS. Logistic regression model was used to predict enrollment in the NHIS. Of the 3228 heads of households interviewed, 60 percent reported having all members of their respective households enrolled in the NHIS. Residents in the classified Middle and High SES brackets had 1.47 (95% CI: 1.21-1.77) and 1.66 (95% CI: 1.27- 2.16) times higher odds, respectively, of complete household enrollment compared to their counterparts in the Low SES category. The odds of enrolling in the program tend to increase progressively with the highest level of education attained by the head of the family unit. Eight years after the introduction of the national health insurance policy in Ghana, the reported subscription rate for complete households was about 60 percent in the 20 rural communities that participated in the study. This finding calls for the need to step up further national strategies that will help increase enrollment coverage, especially among the poor and less educated in the rural communities.

The use of health insurance schemes in financing healthcare delivery and to minimize the poverty gap is gaining considerable recognition among the least developed and resource challenged countries around the world. With the implementation of the socialized health insurance scheme, Ghana has taken the lead in Sub-Saharan Africa and now working out further strategies to gain universal coverage among her citizenry. The primary goal of this study is to explore the spatial relationship between the residential homes and demographic features of the people in the Barekese subdistrict in Ghana on the probability to enroll the entire household unit in the National Health Insurance Scheme (NHIS). Household level data were gathered from 20 communities on the enrollment status into the NHIS alongside demographic and socioeconomic indicators and the spatial location of every household that participated in the study. Kulldorff’s purely spatial scan statistic was used to detect geographic clusters of areas with participatory households that have either higher or lower enrollment patterns in the insurance program. Logistic regression models on selected demographic and socioeconomic indicators were built to predict the effect on the odds of enrolling an entire household membership in the NHIS. Three clusters significantly stood out to have either high or low enrollment patterns in the health insurance program taking into accounts the number of households in those sub-zones of the study region. Households in the Cluster 1 insurance group have very high travel expenses compared to their counterparts in the other idenfied clusters. Travel cost and time to the NHIS registration center to enroll in the program were both significant predictors to participation in the program when controlling for cluster effect. Residents in the High socioeconomic group have about 1.66 [95% CI: 1.27-2.17] times the odds to enroll complete households in the insurance program compared to their counterparts in the Low socioeconomic group. The study demonstrated the use of spatial analytical tools to identify clusters of household enrollment pattern in the NHIS among residents in rural Ghana. In the face of limited resources, policy makers can therefore use the findings as guideline to strategically channel interventions to areas of most need. Furthermore, these analyses can be repeated annually to assess progress on improving insurance coverage.

Human adults in diverse cultures, children, infants, and non-human primates relate number to space, but it is not clear whether this ability reflects a specific and privileged number-space mapping. To investigate this possibility, we tested preschool children in matching tasks where the dimensions of number and length were mapped both to one another and to a third dimension, brightness. Children detected variation on all three dimensions, and they reliably performed mappings between number and length, and partially between brightness and length, but not between number and brightness. Moreover, children showed reliably better mapping of number onto the dimension of length than onto the dimension of brightness. These findings suggest that number establishes a privileged mapping with the dimension of length, and that other dimensions, including brightness, can be mapped onto length, although less efficiently. Children's adeptness at number-length mappings suggests that these two dimensions are intuitively related by the end of the preschool years.

BACKGROUND: Cell-based therapy shows promise in treating peripheral arterial disease (PAD); however, the optimal cell type and long-term efficacy are unknown. In this study, we identified a novel subpopulation of adult progenitor cells positive for CD34 and M-cadherin (CD34⁺/M-cad⁺ BMCs) in mouse and human bone marrow. We also examined the long-lasting therapeutic efficacy of mouse CD34⁺/M-cad⁺ BMCs in restoring blood flow and promoting vascularization in an atherosclerotic mouse model of PAD. METHODS AND FINDINGS: Colony-forming cell assays and flow cytometry analysis showed that CD34⁺/M-cad⁺ BMCs have hematopoietic progenitor properties. When delivered intra-arterially into the ischemic hindlimbs of ApoE⁻/⁻ mice, CD34⁺/M-cad⁺ BMCs alleviated ischemia and significantly improved blood flow compared with CD34⁺/M-cad⁻ BMCs, CD34⁻/M-cad⁺ BMCs, or unselected BMCs. Significantly more arterioles were seen in CD34⁺/M-cad⁺ cell-treated limbs than in any other treatment group 60 days after cell therapy. Furthermore, histologic assessment and morphometric analyses of hindlimbs treated with GFP⁺ CD34⁺/M-cad⁺ cells showed that injected cells incorporated into solid tissue structures at 21 days. Confocal microscopic examination of GFP⁺ CD34⁺/M-cad⁺ cell-treated ischemic legs followed by immunostaining indicated the vascular differentiation of CD34⁺/M-cad⁺ progenitor cells. A cytokine antibody array revealed that CD34⁺/M-cad⁺ cell-conditioned medium contained higher levels of cytokines in a unique pattern, including bFGF, CRG-2, EGF, Flt-3 ligand, IGF-1, SDF-1, and VEGFR-3, than did CD34⁺/M-cad⁻ cell-conditioned medium. The proangiogenic cytokines secreted by CD34⁺/M-cad⁺ cells induced oxygen- and nutrient-depleted endothelial cell sprouting significantly better than CD34⁺/M-cad⁻ cells during hypoxia. CONCLUSION: CD34⁺/M-cad⁺ BMCs represent a new progenitor cell type that effectively alleviates hindlimb ischemia in ApoE⁻/⁻ mice by consistently improving blood flow and promoting arteriogenesis. Additionally, CD34⁺/M-cad⁺ BMCs contribute to microvascular remodeling by differentiating into vascular cells and releasing proangiogenic cytokines and growth factors.

Introduction: Epileptic spasms (ES) are the ictal manifestation of West syndrome. Due to poor interrater reliability in diagnosing hypsarrhythmia, identification of ES - ideally on video EEG monitoring - is important to start proper treatment.Methods: We retrospectively analyzed inpatient video EEG recordings of 42 patients with new onset ES and calculated the time needed to capture the first ES, along with time to first sleep epoch, among other data.Results: The average time to capture ES was 188.36 min with a 95 percent confidence interval from 116.95 to 259.76 min. The average onset of sleep occurred at 30.8 min with 95% Confidence interval between 19.9 and 41.9 min. There was no significant correlation between duration of symptoms and etiology and the time needed to detect first spasm on EEG.Conclusions: Routine or short duration EEGs are not sufficient to capture ES in most patients. 4-5-hour VEEG monitoring duration should be considered to capture ictal data in patients suspected of having ES. [ABSTRACT FROM AUTHOR]

Background: Air pollution is a carcinogen and causes pulmonary and cardiac complications. We examined the association of fine particulate matter pollution (PM2.5) and mortality from cancer and all causes among pediatric, adolescent, and young adult (AYA) patients with cancer in Utah, a state with considerable variation in PM2.5. Methods: We followed 2,444 pediatric (diagnosed ages 0-14) and 13,459 AYA (diagnosed ages 15-39) patients diagnosed in 1986-2015 from diagnosis to 5 and 10 years postdiagnosis, death, or emigration. We measured average monthly PM2.5 by ZIP code during follow-up. Separate pediatric and AYA multivariable Cox models estimated the association of PM2.5 and mortality. Among AYAs, we examined effect modification of PM2.5 and mortality by stage while controlling for cancer type. Results: Increases in PM2.5 per 5 μg/m³ were associated with cancer mortality in pediatric lymphomas and central nervous system (CNS) tumors at both time points, and all cause mortality in lymphoid leukemias [HR5-year = 1.32 (1.02-1.71)]. Among AYAs, PM2.5 per 5 μg/m³ was associated with cancer mortality in CNS tumors and carcinomas at both time points, and all cause mortality for all AYA cancer types [HR5-year = 1.06 (1.01-1.13)]. PM2.5 ≥12 μg/m³ was associated with cancer mortality among breast [HR5-year = 1.50 (1.29-1.74); HR10-year = 1.30 (1.13-1.50)] and colorectal cancers [HR5-year = 1.74 (1.29-2.35); HR10-year = 1.67 (1.20-2.31)] at both time points. Effect modification by stage was significant, with local tumors at highest risk. Conclusions: PM2.5 was associated with mortality in pediatric and AYA patients with specific cancers. Impact: Limiting PM2.5 exposure may be important for young cancer patients with certain cancers [ABSTRACT FROM AUTHOR]

Background: Incidence of small-intestine neuroendocrine tumors (SINT) has been increasing in the United States over the past 40 years, with higher incidence in Utah than elsewhere. As information about how these tumors arise is limited, elucidating lifestyle factors associated with SINT in a statewide cohort could potentially identify those at risk to help mitigate their effects. Methods: Cases of SINT with a carcinoid histology (8240 or 8241) diagnosed in Utah from 1996 to 2014 with no prior history of cancer within 5 years (n = 433) were matched to population controls (1:10 ratio). Tobacco and alcohol exposures before case diagnosis were identified from International Classification of Diseases codes in statewide medical records and from self-reported data captured at patient encounters beginning in 1996. Multivariate logistic regression was used to estimate risk of SINT associated with tobacco and alcohol in cases compared with controls. Results: An increased risk of SINT was observed in tobacco-exposed individuals compared with unexposed [OR, 1.44; 95% confidence interval (CI), 1.11-1.86; P = 0.006]. Those who were exposed to alcohol exhibited an increased risk of SINT (OR, 1.62; 95% CI, 1.05-2.49; P = 0.03). Conclusions: This study supports tobacco and alcohol use as risk factors for SINT, independent of family history. However, low rates of smoking and alcohol use in Utah coupled with higher rates of SINT suggest other factors may contribute to development of these tumors. Impact: Although tobacco and alcohol modestly contribute to risk, our study suggests in addition to greater detection of tumors, other as-of-yet undefined exposures may drive rising SINT incidence. [ABSTRACT FROM AUTHOR]

Despite increasing evidence that particulate air pollution has adverse effects on human semen quality, few studies examine the impact of air pollution on clinically relevant thresholds used to diagnose male fertility problems. Furthermore, exposure is often assessed using average air pollution levels in a geographic area rather than individualized estimates. Finally, physiologically-informed exposure windows are inconsistent. We sought to test the hypothesis that airborne particulate exposures during early-phase spermatogenesis will have a differential impact on spermatogenic formation compared to late-phase exposures, using an individualized model of exposure to particulate matter ≤ 2.5 µm and ≤ 10 µm (PM 2.5 and PM 10 , respectively). From an original cohort of 183 couples, we conducted a retrospective analysis of 130 healthy males seeking to become parents, using spermatogenesis-relevant exposure windows of 77–34 days and 37–0 days prior to semen collection to encompass sperm development stages of mitosis/meiosis and spermiogenesis, respectively. Individualized residential exposure to PM 2.5 and PM 10 was estimated by selecting multiple air pollution sensors within the same geographic air basin as participants and employing inverse distance weighting to calculate mean daily exposure levels. We used multiple logistic regression to assess the association between pollution, temperature, and dichotomized World Health Organization semen parameters. During the early phase of spermatogenesis, air pollution exposure is associated with 1.52 (95% CI: 1.04–2.32) times greater odds of < 30% normal heads per 1-unit increase in IQR for PM 2.5. In the late phase of spermatogenesis, air pollution exposure is associated with 0.35 (95% CI: 0.10–0.74) times greater odds of semen concentration < 15 million/mL per 1-unit increase in IQR for PM 2.5 , and 0.28 (95% CI: 0.07–0.72) for PM 10. Particulate exposure has a differential and more deleterious impact on sperm during early-phase spermatogenesis than late-phase. [Display omitted] • Exposure to particulate air pollution is associated with sperm head malformation. • Exposure in early spermatogenesis differs from exposure in late spermatogenesis. • Effects can be seen in healthy, offspring-seeking males. • Pollution-related sperm malformation has a clinically relevant impact on fertility. • Harm occurs at pollution levels lower than U.S. federal guidelines. [ABSTRACT FROM AUTHOR]

Human adults in diverse cultures, children, infants, and non-human primates relate number to space, but it is not clear whether this ability reflects a specific and privileged number-space mapping. To investigate this possibility, we tested preschool children in matching tasks where the dimensions of number and length were mapped both to one another and to a third dimension, brightness. Children detected variation on all three dimensions, and they reliably performed mappings between number and length, and partially between brightness and length, but not between number and brightness. Moreover, children showed reliably better mapping of number onto the dimension of length than onto the dimension of brightness. These findings suggest that number establishes a privileged mapping with the dimension of length, and that other dimensions, including brightness, can be mapped onto length, although less efficiently. Children's adeptness at number-length mappings suggests that these two dimensions are intuitively related by the end of the preschool years., Psychology