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Temperature and crime is one of the most extreme relationships between the atmospheric environment and human behaviour, yet our knowledge about it is primarily based on Northern Hemisphere research. This study used both temporal and spatial models to investigate the relationship between temperature and crime in New South Wales (NSW), Australia, using an 11-year data set. Results suggested that assault and theft counts were significantly higher in summer than winter (17.8 and 3.7%, respectively), while fraud counts were not significantly different. Using linear and quadratic terms for maximum daily temperature, a linear regression model indicated that daily assault counts significantly increased with rising temperature and the rate of increase slowed as temperatures exceeded 30 °C. Theft counts significantly increased with rising temperature then declined as temperatures exceeded 30°C. Again, there was no evidence of a relationship between temperature and frequency of fraud count. Spatial modelling revealed that 96% of local government areas (LGAs) in NSW had a higher summer assault rate than winter. The findings of this study provide an empirical foundation for understanding crime-temperature relationships in Australia.

There are more incidents of violence in summer and on hot days, a trend likely to be exacerbated by climate change. Urban areas experience additional temperature modulation due to the urban form, however, to date, no studies have considered the effect of the urban heat island (UHI) or green space with respect to the temperature–violence relationship. This study modelled the relationship between the number of daily violent crime incidents that occurred inside or outside between July 2013 and June 2018, and the average surface UHI or percentage greencover (including grasses, shrubs and trees) within each local government area in Greater Sydney, Australia. Panelised negative binomial time series regression models indicated that the violent crime rate was associated with higher surface UHI for crimes committed outside (p = 0.006) but not inside (p = 0.072). Greater percentage of all vegetation was associated with significantly lower rates of violent crime committed outside (p = 0.011) but was not associated with violent crimes committed inside (p = 0.430). More socio-economic disadvantage was associated with higher rates of violent crime committed inside (p = 0.002) but not outside (p = 0.145). Greater temperature was non-linearly associated with higher rates of violent crime committed both inside and outside (p < 0.001). The findings of this study are important because both violence and heat exposure are critical health issues and will be stressed by urbanisation and climate change. The expansion of green space and/or reduction in UHI may mitigate these effects.

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia’s strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 ( C4 ) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A . Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia. WebSchizophrenia is associated with genetic variation at the major histocompatibility complex locus; this study reveals that alleles at this locus associate with schizophrenia in proportion to their tendency to generate greater expression of complement component 4 ( C4A ) genes and that C4 promotes the elimination of synpases. The genetics of schizophrenia The strongest genetic association found in schizophrenia is its association to genetic markers across the major histocompatibility complex (MHC) locus, first described in three Nature papers in 2009. The association signal at the MHC is extremely complex. Here Steven McCarroll and colleagues report a dissection of the MHC association to schizophrenia. They find a strong contribution from many structurally diverse alleles of the complement component 4 ( C4 ) genes. The linkage was higher for C4 alleles that promoted greater expression of C4A , measured in the brain tissues of adult post-mortem donors with or without schizophrenia. The authors suggest that C4 may work with other components of the classical complement cascade to promote synaptic pruning, and demonstrate that C4 mediates synaptic refinement in a mouse model.

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors.

The facets of host control during Plasmodium liver infection remain largely unknown. We find that the SLC7a11-GPX4 pathway, which has been associated with the production of reactive oxygen species, lipid peroxidation, and a form of cell death called ferroptosis, plays a critical role in control of Plasmodium liver stage infection. Specifically, blocking GPX4 or SLC7a11 dramatically reduces Plasmodium liver stage parasite infection. In contrast, blocking negative regulators of this pathway, NOX1 and TFR1, leads to an increase in liver stage infection. We have shown previously that increased levels of P53 reduces Plasmodium LS burden in an apoptosis-independent manner. Here, we demonstrate that increased P53 is unable to control parasite burden during NOX1 or TFR1 knockdown, or in the presence of ROS scavenging or when lipid peroxidation is blocked. Additionally, SLC7a11 inhibitors Erastin and Sorafenib reduce infection. Thus, blocking the host SLC7a11-GPX4 pathway serves to selectively elevate lipid peroxides in infected cells, which localize within the parasite and lead to the elimination of liver stage parasites.

The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.

Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies. Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify treatment failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended treatment failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes. This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml treatment failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.

Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to \"Cafeteria diets\" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome.

Objective To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention.Design Systematic review and meta-analysis.Data sources Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases.Eligibility criteria Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible.Results 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups.Conclusions Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.

In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted. To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics. This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site. In-hospital death adjusted for exposures for 4 periods in 2020. The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73). In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.