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Objective: To examine factors associated with hospitalization among Mexican Americans aged 75 years and older with diabetes (with and without complications) and without diabetes over 12 years of follow up. Methods: Participants (N = 1454) were from the Hispanic Established Population for the Epidemiologic Study of the Elderly (2004/2005-2016) residing in Arizona, California, Colorado, New Mexico, and Texas. Measures included socio-demographics, medical conditions, falls, depressive symptoms, cognitive function, disability, physician visits, and hospitalizations. Participants were categorized as no diabetes (N = 1028), diabetes without complications (N = 180), and diabetes with complications (N = 246). Results: Participants with diabetes and complications had greater odds ratio (1.56, 95% Confidence Interval = 1.23-1.98) over time of being admitted to the hospital in the prior year versus those without diabetes. Participants with diabetes had greater odds of hospitalization if they had heart failure, falls, amputation, and insulin treatment. Conclusions: In Mexican American older adults, diabetes and diabetes-related complications increased the risk of hospitalization.

Abstract Introduction Early access to specialty palliative care is associated with better quality of life, less intensive end-of-life treatment and improved outcomes for patients with advanced cancer. However, significant variation exists in implementation and integration of palliative care. This study compares the organizational, sociocultural, and clinical factors that support or hinder palliative care integration across three U.S. cancer centers using an in-depth mixed methods case study design and proposes a middle range theory to further characterize specialty palliative care integration. Methods Mixed methods data collection included document review, semi-structured interviews, direct clinical observation, and context data related to site characteristics and patient demographics. A mixed inductive and deductive approach and triangulation was used to analyze and compare sites’ palliative care delivery models, organizational structures, social norms, and clinician beliefs and practices. Results Sites included an urban center in the Midwest and two in the Southeast. Data included 62 clinician and 27 leader interviews, observations of 410 inpatient and outpatient encounters and seven non-encounter-based meetings, and multiple documents. Two sites had high levels of “favorable” organizational influences for specialty palliative care integration, including screening, policies, and other structures facilitating integration of specialty palliative care into advanced cancer care. The third site lacked formal organizational policies and structures for specialty palliative care, had a small specialty palliative care team, espoused an organizational identity linked to treatment innovation, and demonstrated strong social norms for oncologist primacy in decision making. This combination led to low levels of specialty palliative care integration and greater reliance on individual clinicians to initiate palliative care. Conclusion Integration of specialty palliative care services in advanced cancer care was associated with a complex interaction of organization-level factors, social norms, and individual clinician orientation. The resulting middle range theory suggests that formal structures and policies for specialty palliative care combined with supportive social norms are associated with greater palliative care integration in advanced cancer care, and less influence of individual clinician preferences or tendencies to continue treatment. These results suggest multi-faceted efforts at different levels, including social norms, may be needed to improve specialty palliative care integration for advanced cancer patients.

Objectives To test associations between 11 caregiver aggressive and non-aggressive discipline behaviours and outcomes (aggression, distraction and prosocial peer relations) of children under 5 years in low-income and middle-income countries (LMICs).Participants Data came from the fourth (2009–2013) and fifth (2012–2017) rounds of the UNICEF Multiple Indicator Cluster Surveys. Analyses were restricted to households with children under 5 years, leaving a sample of 229 465 respondents across 60 LMICs. Data were analysed using Bayesian multilevel logistic regression.Results Verbal reasoning (80%) and shouting (66%) were the most common parental discipline behaviours towards young children. Psychological and physical aggression were associated with higher child aggression and distraction. Compared with not using verbal reasoning, verbal reasoning was associated with lower odds of aggression (OR)=0.92, 95% credible interval (CI)=0.86 to 0.99) and higher odds of prosocial peer relations (OR=1.30, 95% CI=1.20 to 1.42). Taking away privileges was associated with higher odds of distraction (OR=1.09, 95% CI=1.03 to 1.15) and lower odds of prosocial peer relations (OR=0.92, 95% CI=0.87 to 0.98). Giving the child something else to do was associated with higher odds of distraction (OR=1.06, 95% CI=1.01 to 1.12). The results indicated country-level variation in the associations between parenting behaviours and child socioemotional outcomes.Conclusions Psychological and physical aggression were disadvantageous for children’s socioemotional development across countries. Only verbal reasoning was associated with positive child socioemotional development. No form of psychological aggression or physical aggression benefited child socioemotional development in any country. Greater emphasis should be dedicated to reducing parental use of psychological and physical aggression across cultural contexts.

Abstract Background Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease. Results To address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state. Conclusions Altogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.

Wellbeing in buildings is often approached by practitioners and researchers as the aggregate result of individual interactions between building occupants and building features. This sum-of-the-parts approach, however, ignores the ways in which broader social ('i.e'. sense of ownership and belonging) and symbolic ('i.e'. what it means to be ‘well’ in a specific culture at a particular place and time) components of wellbeing influence occupant experience of the built environment. A social practice perspective on wellbeing in buildings is proposed that accounts for these elements. Beginning with discussions of how wellbeing has been assessed and the foundations of social practice theory, it is suggested that occupant wellbeing is emergent not just from individual interactions with building features but also from broader social and symbolic elements. 'Policy relevance' A social practice perspective on wellbeing in buildings has implications for both the assessment of wellbeing and the role of wellbeing in the building design process. Integrating social and symbolic elements into measures of wellbeing pushes assessment beyond the typical focus on comfort and spatial experience (indoor environmental quality). These more nuanced assessments may in turn shape how wellbeing is addressed in building design, construction, and management.

The current study applied a family systems approach to examine dyadic parental risk factors linked with mother–father co-involved physical abuse, neglect, sexual abuse, and emotional abuse. Parental substance use, mental health problems, disability and medical conditions, inadequate housing, economic insecurity, intimate partner violence, and prior maltreatment history were investigated as key risk factors at the dyadic parental level. Logistic regression analysis was conducted using national child welfare administrative data from the National Child Abuse and Neglect Data System. The results showed differential associations between risk factors and four child maltreatment types: physical abuse, neglect, emotional abuse, and sexual abuse. Intimate partner violence was associated with higher odds of mother–father co-involved neglect and emotional abuse. Parental substance use, inadequate housing, and prior maltreatment history were all associated with higher odds of mother–father co-involved neglect, but lower odds of physical abuse. Parental disability and medical conditions were associated with higher odds of mother-father co-involved sexual abuse, whereas parental substance use was associated with lower odds of sexual abuse. Implications include more nuanced ways of addressing multiple risk factors within the family to prevent future occurrences of child maltreatment involving both mothers and fathers.

Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human induced pluripotent stem cell-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC-related pathologies.

Abstract Background We calculated the performance of National Cancer Institute (NCI)/National Comprehensive Cancer Network (NCCN) cancer centers’ end‐of‐life (EOL) quality metrics among minority and white decedents to explore center‐attributable sources of EOL disparities. Methods We conducted a retrospective cohort study of Medicare beneficiaries with poor‐prognosis cancers who died between April 1, 2016 and December 31, 2016 and had any inpatient services in the last 6 months of life. We attributed patients’ EOL treatment to the center at which they received the preponderance of EOL inpatient services and calculated eight risk‐adjusted metrics of EOL quality (hospice admission ≤3 days before death; chemotherapy last 14 days of life; ≥2 emergency department (ED) visits; intensive care unit (ICU) admission; or life‐sustaining treatment last 30 days; hospice referral; palliative care; advance care planning last 6 months). We compared performance between patients across and within centers. Results Among 126,434 patients, 10,119 received treatment at one of 54 NCI/NCCN centers. In aggregate, performance was worse among minorities for ED visits (10.3% vs 7.4%, P

In the United States, childcare subsidies are available to low-income working parents to assist with the cost of childcare. The subsidies are provided as block grants to states, which allows for a great deal of flexibility in the specific policies guiding their distribution. Prior research has found a protective link between childcare subsidies and child maltreatment, but the variations in policies have been much less explored. The current study used longitudinal administrative child welfare data from 10 years (2009–2019) linked with state policies regarding the income eligibility requirements of states to examine the impact of these policies on child abuse and neglect among young children (0–5); early school-age children (6–12), and older children (13–17). Using multiple regression and controlling for state demographic characteristics, the study found that more generous policies surrounding income eligibility were related to lower rates of child abuse and neglect investigations at the state level.

Objective Ending violence against children is critical to promote the health and socioemotional development of children across the globe. To this end, the UNICEF and the WHO have called for the abolishment of spanking, which is the most pervasive form of physical violence against children worldwide. This study used an ecological perspective to examine micro-level and macro-level predictors of parental spanking across 65 countries.Participants Data came from the fourth and fifth rounds of the UNICEF Multiple Indicator Cluster Surveys, which were administered between 2009 and 2017 (N=613 861 households). We examined the predictors of spanking using multilevel logistic regression analysis.Results Micro-level factors (ie, those observed at the familial level) were stronger predictors of spanking in comparison to macro-level factors (ie, those observed at the community and country level). Caregiver belief that children need physical punishment in order to be raised properly was the largest risk factor for spanking (OR=2.55, p

Abstract Background Histopathology images of tumor biopsies present unique challenges for applying machine learning to the diagnosis and treatment of cancer. The pathology slides are high resolution, often exceeding 1GB, have non-uniform dimensions, and often contain multiple tissue slices of varying sizes surrounded by large empty regions. The locations of abnormal or cancerous cells, which may constitute a small portion of any given tissue sample, are not annotated. Cancer image datasets are also extremely imbalanced, with most slides being associated with relatively common cancers. Since deep representations trained on natural photographs are unlikely to be optimal for classifying pathology slide images, which have different spectral ranges and spatial structure, we here describe an approach for learning features and inferring representations of cancer pathology slides based on sparse coding. Results We show that conventional transfer learning using a state-of-the-art deep learning architecture pre-trained on ImageNet (RESNET) and fine tuned for a binary tumor/no-tumor classification task achieved between 85% and 86% accuracy. However, when all layers up to the last convolutional layer in RESNET are replaced with a single feature map inferred via a sparse coding using a dictionary optimized for sparse reconstruction of unlabeled pathology slides, classification performance improves to over 93%, corresponding to a 54% error reduction. Conclusions We conclude that a feature dictionary optimized for biomedical imagery may in general support better classification performance than does conventional transfer learning using a dictionary pre-trained on natural images.

This data set was collected over two years, 2012–2013, on maize under 12 irrigation treatments with varying levels of deficit during late-vegetative and grain-filling growth stages in semi-arid Northern Colorado supplied with surface drip irrigation. The data set, which can be found online at the USDA National Agricultural Library data repository (doi: 10.15482/USDA.ADC/1439968), includes hourly weather data; plant growth and canopy development over the season; final biomass, yield and harvest index; and daily water balance data including irrigation, precipitation, soil water content, and estimates of crop evapotranspiration. Soil parameters for the site, as well as data from a previous experiment on maize with different treatments can also be found online (doi: 10.15482/USDA.ADC/1254006). Here, we describe the synthesis of data collected from 2012 to 2013. These data can be used for modeling the relationship between maize yield and field-level water use under season water availability.

Clofarabine, an FDA approved purine analog, is used in the treatment of relapsed or refractory acute lymphoblastic leukemia. Clofarabine acts by inhibiting DNA synthesis. We demonstrated that clofarabine may have a novel function though inhibiting CD99, a transmembrane protein highly expressed on Ewing Sarcoma (ES) cells. CD99 is a validated target in ES whose inhibition may lead to a high therapeutic index for patients. Here we present additional data to support the hypothesis that clofarabine acts on CD99 and regulates key signaling pathways in ES. Cellular thermal shift assay indicated a direct interaction between clofarabine and CD99 in ES cell lysates. Clofarabine induced ES cell death does not require clofarabine's conversion to its active form by deoxycytidine kinase. A phosphokinase array screen with clofarabine and a CD99 blocking antibody identified alterations in signaling pathways. CD99 inhibition with clofarabine in ES cells caused rapid and sustained phosphorylation of ERK, MSK, and CREB. However, activation of this pathway did not correlate with clofarabine induced ES cell death. In summary, we demonstrated that clofarabine may activate ERK, MSK, and CREB phosphorylation through CD99 within minutes, however this paradoxical activation and subsequent ES cell death requires additional investigation.

Background: There are limited data and conflicting guideline recommendations regarding the role of neuroimaging in the pretreatment evaluation of non-small cell lung cancer (NSCLC). Methods: We performed a retrospective, pragmatic cohort study of patients with NSCLC diagnosed between January 1 and December 31, 2015. Eligible patients were identified from an institutional tumor registry. We collected all records of pretreatment neuroimaging within 12 weeks of diagnosis, including CT head (CT) and MRI brain (MRI). We abstracted the indication for neuroimaging, presence of central neurologic symptoms and cancer stage (with and without neuroimaging findings) from the tumor registry and the electronic health record. Results: We identified 216 evaluable patients with newly diagnosed NSCLC. 157 of 216 patients (72.7%) underwent neuroimaging as part of initial staging, and 41 (26%) were found to have brain metastases. Of 43 patients with central neurologic symptoms at the time of neuroimaging, 28 (67%) had brain metastasis. In patients without central neurologic symptoms, brain metastases were discovered in 0 of 33 patients with clinical stage I or II, 4 of 36 (11%) with clinical stage III and 9 of 45 (20%) with clinical stage IV disease. Conclusions: In patients with early stage NSCLC (i.e. clinical stage I and II) without central neurologic symptoms, brain metastases are unlikely. The continued use of neuroimaging in the pretreatment evaluation of clinical stage I patients without central neurologic symptoms is not needed.

Researchers have reported that participation in agricultural education reinforces STEM concepts. The use of projects is common in agricultural education. However, the foundational understanding of certain tenets of project use is not clear. A quasi-experimental study was conducted to test the effects of project authenticity on learning. AFNR students (N = 219) were sampled and assigned as a cohort to one of four treatments. Treatments were project types which varied in their degree of project authenticity. During analysis, it was apparent that the intended project variable of authenticity had less effect on the outcomes than other factors. An analysis of covariance was used to test the effects of perceived novelty on change scores in a pre-post quasi-experimental design. A test of project type groups, which varied on novelty, yielded statistically significant results (p < 0.05) with small effect size ([omega superscript 2] = 0.04). A Pearson Chi Square was calculated to determine if a relationship between novelty and project type existed and determined to be significant, X[superscript 2] (12, N=152) = 22.35, p = 0.034. A pairwise comparison was calculated to compare levels of novelty to determine where the variation existed. Students with novelty level 4 had statistically different change scores than those at novelty level 2 (p = 0.006) and students with novelty level 4 were different from those with a novelty level 5 (p = 0.012). Students with less familiarity with the project (a more novel project) showed more improvement on the science exam.

Noroviruses (NoVs) and Sapoviruses (SaVs) are enteric caliciviruses that have been detected in multiple mammalian species, including humans. Currently, efficient cell culture systems have been established only for murine NoVs and porcine SaV Cowden strain. Establishment of an efficient in vitro cell culture system for other NoVs and SaVs remains challenging; however, human NoV (HuNoV) replication in 3D cultured Caco-2 cells and a clone of Caco-2 cells, C2BBe1, human enteroids and in human B cells has been reported. In this study, we tested various cells and culture conditions to grow HuNoVs and a human SaV (HuSaV) to test the possibility of the propagation in different cells and culture conditions. We also attempted to grow a bovine NoV (BoNoV) in ex vivo organ cultures. We did not observe significant RNA level increases for HuSaV and BoNoV under our test conditions. HuNoV RNA levels increased to a maximum of ~600-fold in long-term Caco-2 cells that were cultured for 1-2 months in multi-well plates and inoculated with HuNoV-positive and bacteria-free human stool suspensions using serum-free medium supplemented with the bile acid, GCDCA. However, this positive result was inconsistent. Our results demonstrated that HuNoVs, BoNoV and HuSaV largely failed to grow in vitro under our test conditions. Our purpose is to share our findings with other researchers with the goal to develop efficient, reproducible simplified and cost-effective culture systems for human and animal NoVs and SaVs in the future.

During cortical network activity, recurrent synaptic excitation among pyramidal neurons is approximately balanced by synaptic inhibition, which is provided by a vast diversity of inhibitory interneurons. The relative contributions of different interneuron subtypes to inhibitory tone during cortical network activity is not well understood. We previously showed that many of the major interneuron subtypes in mouse barrel cortex are highly active during Up states (Neske et al., 2015); while fast-spiking (FS), parvalbumin (PV)-positive cells were the most active interneuron subtype, many non-fast-spiking (NFS), PV-negative interneurons were as active or more active than neighboring pyramidal cells. This suggests that the NFS cells could play a role in maintaining or modulating Up states. Here, using optogenetic techniques, we further dissected the functional roles during Up states of two major NFS, PV-negative interneuron subtypes: somatostatin (SOM)-positive cells and vasoactive intestinal peptide (VIP)-positive cells. We found that while pyramidal cell excitability during Up states significantly increased when SOM cells were optogenetically silenced, VIP cells did not influence pyramidal cell excitability either upon optogenetic silencing or activation. VIP cells failed to contribute to Up states despite their ability to inhibit SOM cells strongly. We suggest that the contribution of VIP cells to the excitability of pyramidal cells may vary with cortical state.

During even the most quiescent behavioral periods, the cortex and thalamus express rich spontaneous activity in the form of slow (

BackgroundAssociation of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease.ResultsTo address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state.ConclusionsAltogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.