Cholera hotspots and surveillance constraints contributing to recurrent epidemics in Tanzania

Objective: We described the dynamics of cholera in Tanzania between 2007 and 2017 and assessed the weaknesses of the current surveillance system in providing necessary data in achieving the global roadmap to 2030 for cholera control. Results: The Poisson-based spatial scan identifed cholera hotspots in mainland Tanzania. A zero-infated Poisson regression investigated the relationship between the incidence of cholera and available demographic, socio-economic and climatic exposure variables. Four cholera hotspots were detected covering 17 regions, home to 28 million people, including the central regions and those surrounding the Lakes Victoria, Tanganyika and Nyaza. The risk of experiencing cholera in these regions was up to 2.9 times higher than elsewhere in the country. Regression analyses revealed that every 100 km of water perimeter in a region increased the cholera incidence by 1.5%. Due to the compilation of surveillance data at regional level rather than at district, we were unable to reliably identify any other signifcant risk factors and specifc hotspots. Cholera high-risk populations in Tanzania include those living near lakes and central regions. Successful surveillance require disaggregated data available weekly and at district levels in order to serve as data for action to support the roadmap for cholera control.Published versio

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Predicting COVID-19 Incidence Using Wastewater Surveillance Data, Denmark, October 2021–June 2022

Analysis of wastewater is used in many settings for surveillance of SARS-CoV-2, but it remains unclear how well wastewater testing results reflect incidence. Denmark has had an extensive wastewater analysis system that conducts 3 weekly tests in ≈200 sites and has 85% population coverage; the country also offers free SARS-CoV-2 PCR tests to all residents. Using time series analysis for modeling, we found that wastewater data, combined with information on circulating variants and the number of human tests performed, closely fitted the incidence curve of persons testing positive. The results were consistent at a regional level and among a subpopulation of frequently tested healthcare personnel. We used wastewater analysis data to estimate incidence after testing was reduced to a minimum after March 2022. These results imply that data from a large-scale wastewater surveillance system can serve as a good proxy for COVID-19 incidence and for epidemic control

Accurate velocity measurements of boundary-layer flows using Doppler optical coherence tomography

Pulsed ultrasound Doppler velocimetry and nuclear magnetic resonance imaging are popular non-invasive measurement methods for flows of opaque fluids. The spatial and temporal resolution of these methods, however, is quite limited, and they lack accuracy, especially close to solid boundaries. In this paper, we show that solution to these problems is achieved by using Doppler optical coherence tomography (DOCT). DOCT provides simultaneous information about the fluid structure and velocity with very high spatial and temporal resolution. For benchmarking of the method we use water as the reference fluid. We show how DOCT gives a very good agreement with theory for the velocity profile, skin friction and viscosity directly from the measurement signal. The velocity profile extends from the turbulent region to viscous sublayer, and viscosity of the fluid can be calculated also from a turbulent flow with a good accuracy. Overall, DOCT is seen to be very well suited for providing new insight into boundary-layer flows, rheology and skin friction