Distorted TCR repertoires define multisystem inflammatory syndrome in children

While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with MIS-C (n = 12) and mild (n = 8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n = 8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of children with MIS-C are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines MIS-C in children

Drinking water quality governance: A comparative case study of Brazil, Ecuador, and Malawi

Human health is greatly affected by inadequate access to sufficient and safe drinking water, especially in low and middle-income countries. Drinking water governance improvements may be one way to better drinking water quality. Over the past decade, many projects and international organizations have been dedicated to water governance; however, water governance in the drinking water sector is understudied and how to improve water governance remains unclear. We analyze drinking water governance challenges in three countries—Brazil, Ecuador, and Malawi—as perceived by government, service providers, and civil society organizations. A mixed methods approach was used: a clustering model was used for country selection and qualitative semi-structured interviews were used with direct observation in data collection. The clustering model integrated political, economic, social and environmental variables that impact water sector performance, to group countries. Brazil, Ecuador and Malawi were selected with the model so as to enhance the generalizability of the results. This comparative case study is important because similar challenges are identified in the drinking water sectors of each country; while, the countries represent diverse socio-economic and political contexts, and the selection process provides generalizability to our results. We find that access to safe water could be improved if certain water governance challenges were addressed: coordination and data sharing between ministries that deal with drinking water services; monitoring and enforcement of water quality laws; and sufficient technical capacity to improve administrative and technical management of water services at the local level. From an analysis of our field research, we also developed a conceptual framework that identifies policy levers that could be used to influence governance of drinking water quality on national and sub-national levels, and the relationships between these levers

Do Aphid Colonies Amplify their Emission of Alarm Pheromone?

When aphids are attacked by natural enemies, they emit alarm pheromone to alert conspecifics. For most aphids tested, (E)-β-farnesene (EBF) is the main, or only, constituent of the alarm pheromone. In response to alarm pheromone, alerted aphids drop off the plant, walk away, or attempt to elude predators. However, under natural conditions, EBF concentration might be low due to the low amounts emitted, to rapid air movement, or to oxidative degradation. To ensure that conspecifics are warned, aphids might conceivably amplify the alarm signal by emitting EBF in response to EBF emitted by other aphids. To examine whether such amplification occurs, we synthesized deuterated EBF (DEBF), which allowed us to differentiate between applied and aphid-derived chemical. Colonies of Acyrthosiphon pisum were treated with DEBF, and headspace volatiles were collected and analyzed for evidence of aphid-derived EBF. No aphid-derived EBF was detected, suggesting that amplification of the alarm signal does not occur. We discuss the disadvantages of alarm signal reinforcement

Examining the effects of Lighting Effects on Peripheral Devices for Visual User Notifications

The ubiquitous and pervasive use of lighting effects embedded into peripheral hardware has gained popularity through it’s use in Triple-A video game titles such as Call of Duty and the availability of software development kits (SDK) from leading manufacturers. A preliminary NASA TLX experiment was performed to examine the effect that notifications displayed on a peripheral device has, in comparison to traditional dialog notifications. This research will prove useful to create notification design guidance for these devices

Geographical inequalities in drinking water in the Solomon Islands

Sustainable Development Goal 6.1 seeks to “by 2030, achieve universal and equitable access to safe and affordable drinking water”, which is challenging particularly in Small Island Developing States (SIDS) and Pacific Island Countries (PIC). We report drinking water sources and services in the Solomon Islands and examine geographical inequalities. Based on two quantitative baseline datasets of n = 1,598 rural and n = 1,068 urban households, we analyzed different drinking water variables (source type, collection time, amount, use, perceived quality, storage, treatment) and a composite index, drinking water service level. We stratified data by urban and rural areas and by province, mapped, and contextualized them. There are substantive rural–urban drinking water inequalities in the Solomon Islands. Overall, urban households are more likely to: use improved drinking water sources, need less time to collect water, collect more water, store their water more safely, treat water prior to consumption, perceive their water quality as better and have an at least basic drinking water service than rural households. There are also provincial and center-periphery inequalities in drinking water access, with more centrally located provinces using piped water supplies and more distant and remote provinces using rainwater and surface water as their primary source. There are also inter-national inequalities. Out of all PICs, the Solomon Islands have among the lowest access to basic drinking water services: 92% of urban and 55% of rural households. Of all SIDS, PICs are least serviced. This study shows that drinking water inequality is a critical issue, and highlights that all identified dimensions of inequality - rural–urban, provincial, center-periphery and inter-national - need to be explicitly recognized and addressed and included in pro-equity monitoring, policy and programming efforts by the Solomon Islands Government and stakeholders to reduce inequalities as per the Agenda 2030

The transition into veterinary practice: Opinions of recent graduates and final year students

Background The transition from veterinary student to member of the veterinary profession is known to be challenging. This study aimed to determine and compare the opinions of final year veterinary students and recent graduates on graduate attributes that ease this transition. Methods The study was carried out across 3 veterinary schools in the United Kingdom. Paper based or electronic surveys were used. Final year students in the 3 schools were surveyed either electronically (school A) or on paper (schools B and C). Student cohort sizes were 112, 227 and 102 respectively. Recent graduates were contacted either at a reunion event (school A) or electronically from database records (school B and school C). Cohort sizes of contacted graduates were 80, 175 and 91 respectively. Respondents were asked to rate 42 individual attributes on a 5 point Likert scale. Focus groups with final year students and recent graduates and telephone interviews with recent graduates were carried out. Data were analysed by two researchers through a combination of manual coding and thematic analysis. Data were grouped into broad themes then sorted into narrower themes. Data were then searched for counter examples. Results Response rates for final year students were 34% (school A), 36% (school B) and 40% (school C). Response rates for recent graduates were 56% (school A), 20% (school B) and 11% (school C). There was a high level of agreement between the cohorts with respect to communication skills, problem solving and decision making skills, recognition of own limitations and the ability to cope with pressure all rated unanimously important or very important. Business acumen, knowledge of veterinary practice management and research skills were the 3 attributes ranked at the bottom of the list. Nine attributes were identified with a significantly different (p < 0.05) ranking between the cohorts. Final year students ranked veterinary clinical knowledge, knowledge of veterinary public health and zoonotic issues, veterinary legislation and veterinary practice management, commitment to continuing professional development and ability to evaluate information higher than recent graduates. Recent graduates ranked the attributes of integrity, friendliness and compassion higher than final year students. Conclusions Recent graduates and final year students rate highly the attributes which help foster the client/veterinarian relationship. Recent graduates reflect that a focus on knowledge based attributes is less important once in practice when compared to final year. The study confirms the importance to recent graduates and final year students of attributes considered as non-technical in the transition to working in the veterinary profession

The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A

Genome-wide association studies (GWAS) have provided strong evidence for inherited predisposition to childhood acute lymphoblastic leukaemia (ALL) identifying a number of risk loci. We have previously shown common SNPs at 9p21.3 influence ALL risk. These SNP associations are generally not themselves candidates for causality, but simply act as markers for functional variants. By means of imputation of GWAS data and subsequent validation SNP genotyping totalling 2,177 ALL cases and 8,240 controls, we have shown that the 9p21.3 association can be ascribed to the rare highimpact CDKN2A p.Ala148Thr variant (rs3731249; Odds ratio=2.42, P=3.45×10−19). The association between rs3731249 genotype and risk was not specific to particular subtype of B-cell ALL. The rs3731249 variant is associated with predominant nuclear localisation of the CDKN2A transcript suggesting the functional effect of p.Ala148Thr on ALL risk may be through compromised ability to inhibit cyclin D within the cytoplasm