Integrated photo-responsive metal oxide semiconductor circuit

An infrared photoresponsive element (RD) is monolithically integrated into a source follower circuit of a metal oxide semiconductor device by depositing a layer of a lead chalcogenide as a photoresistive element forming an ohmic bridge between two metallization strips serving as electrodes of the circuit. Voltage from the circuit varies in response to illumination of the layer by infrared radiation

Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM) inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based switch motifs (ITSMs) in genes and protein domains that have not been previously reported in any species. This checkpoint molecule analysis and review of salient features for each of the molecules presented here can serve as road map for the development of a Tasmanian devil facial tumor disease immunotherapy. Finally, the strategies can be used as a guide for veterinarians, ecologists, and other researchers willing to venture into the nascent field of wild immunology

Hypothermia: an unusual indication for gastric lavage.

BACKGROUND: Previous reports suggest that gastric lavage holds many risks and is not routinely indicated for decontamination of the overdose patient. OBJECTIVE: To present a case of overdose with concurrent accidental hypothermia where gastric decontamination was utilized. CASE REPORT: A 50-year-old hypothermic, comatose patient was transported to the Emergency Department with a concurrent, massive medication ingestion diagnosed incidentally on a routine abdominal computed tomography scan. Both active and passive rewarming measures, in conjunction with gastric lavage and retrieval of multiple pill fragments, were performed, and the patient survived to hospital discharge without sequelae. Interestingly, the patient admitted to an intentional ingestion of both labetalol and lorazepam. CONCLUSION: Due to hypothermia-mediated changes in metabolism, including gastric atony and decreased hepatic metabolism, gastric lavage may provide additional benefit in the management of severely hypothermic patients with potentially lethal, massive pill ingestions

Genetic alterations and cancer formation in a European flatfish at sites of different contamination burdens

Fish diseases are an indicator for marine ecosystem health since they provide a biological end-point of historical exposure to stressors. Liver cancer has been used to monitor the effects of exposure to anthropogenic pollution in flatfish for many years. The prevalence of liver cancer can exceed 20%. Despite the high prevalence and the opportunity of using flatfish to study environmentally induced cancer, the genetic and environmental factors driving tumor prevalence across sites are poorly understood. This study aims to define the link between genetic deterioration, liver disease progression, and anthropogenic contaminant exposures in the flatfish dab (Limanda limanda). We assessed genetic changes in a conserved cancer gene, Retinoblastoma (Rb), in association with histological diagnosis of normal, pretumor, and tumor pathologies in the livers of 165 fish from six sites in the North Sea and English Channel. The highest concentrations of metals (especially cadmium) and organic chemicals correlated with the presence of tumor pathology and with defined genetic profiles of the Rb gene, from these sites. Different Rb genetic profiles were found in liver tissue near each tumor phenotype, giving insight into the mechanistic molecular-level cause of the liver pathologies. Different Rb profiles were also found at sampling sites of differing contaminant burdens. Additionally, profiles indicated that histological “normal” fish from Dogger sampling locations possessed Rb profiles associated with pretumor disease. This study highlights an association between Rb and specific contaminants (especially cadmium) in the molecular etiology of dab liver tumorigenesis

Effects of national housing quality standards on hospital emergency admissions: a quasi-experiment using data-linkage

Background National housing quality standards are now being applied throughout the UK. The Welsh Government has introduced the Welsh Housing Quality Standards. A housing improvement programme in Wales has been delivered through one local authority to bring 9500 homes up to standard. Homes received multiple elements, including new kitchens, bathrooms, windows and doors, boilers, insulation, and wiring, through an 8 year rolling work programme. The study aimed to determine the impacts of the different housing improvements on hospital emergency admissions for residents over 60 years of age. Methods Intervention homes (council homes that received at least one element of work) were data linked to individual health records of residents. Counts of admissions for respiratory and cardiovascular conditions, and for falls and burns, were obtained retrospectively for each individual in a dynamic housing cohort (Jan 1, 2005, to March 31, 2015). The criterion for the intervention cohort was for someone to have lived in any one of the 9500 intervention homes for at least 3 months within the intervention period. Counts were captured for up to 123 consecutive months for 7054 individuals in the intervention cohort and analysed in a multilevel approach to account for repeated observations for individuals, nested within geographical areas. Negative binomial regression models were constructed to determine the effect on emergency admissions for those living in homes compliant for each element of work compared with those living in homes that were non-compliant at that time. We adjusted for background trends in the regional general population, and for other confounding factors. Findings For residents 60 years old and over there was a reduction in admissions for people with compliant boilers (rate ratio 0·71, 95% CI 0·67–0·76), loft insulation (0·87, 0·80–0·95), wall insulation (0·74, 0·69–0·80), and windows and doors (0·56, 0·52–0·61) compared with those living in homes that were non-compliant for those work elements. Interpretation Improving housing to national standards reduces the number of emergency admissions to hospital for older residents. Strengths of the data-linkage approach included the retrospective collection of complete baseline and follow-up data using routine data for a long-term intervention, and large scale regional adjustment

Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study

Objectives Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years. Study design The study design used in the study is a population-based electronic cohort study. Methods We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors. Results There were 107,479 and 43,648 children included in the analysis, with follow-up to 6–7 years (KS1) and 10–11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09–1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10–1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37–1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04–1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84–2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment. Conclusion The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation