The exhumation of the Indo-Burman Ranges, Myanmar

The Indo-Burman Ranges (IBR) are a mountain range comprised of Mesozoic-Cenozoic rocks which run the length of Western Myanmar, extending into India and Bangladesh; to the west lies the Indian Ocean, and to the east lies the Central Myanmar Basin (CMB) along which the Irrawaddy River flows. The IBR are considered to be an accretionary prism, developed at the juncture of the Indian and Sunda plates, and a number of hypotheses have been proposed for their evolution. However, in order for these hypotheses to be evaluated, the timing of IBR evolution needs to be determined. We undertook a two-pronged approach to determining the timing of uplift of the IBR. (1) We present the first low-temperature thermochronological age elevation profiles of the IBR using ZFT, AFT and ZHe techniques. Our data show: a major period of exhumation occurred around the time of the Oligo-Miocene boundary; we tentatively suggest, subject to further verification, an additional period of exhumation at or before the late Eocene. (2) We carried out a detailed multi-technique provenance study of the sedimentary rocks of the IBR and Arakan Coastal region to their west, and compared data to coeval rocks of the CMB. We determined that during Eocene times, rocks of the CMB and IBR were derived from similar local provenance, that of the Myanmar arc to the east. Therefore at this time there was an open connection from arc to ocean. By contrast, by Miocene times, provenance diverged. Rocks of the CMB were deposited by a through-flowing Irrawaddy River, with detritus derived from its upland source region of the Mogok Metamorphic Belt and Cretaceous-Paleogene granites to the north. Such a provenance is not recorded in coeval rocks of the IBR, indicating that the IBR had uplifted by this time, providing a barrier to transport of material to the west. To the previously published list of viable proposals to explain the exhumation of the range, we add a new suggestion: the period of exhumation around the time of the Oligo-Miocene boundary could have been governed by a change to wedge dynamics instigated by a major increase in the thickness of the incoming Bengal Fan sediment pile

The Binational/Crosscultural Health Enhancement Center

poster abstractThe Binational/Cross-Cultural Health Enhancement Center (BiCCHEC) fosters multidisciplinary research collaborations that address the biological, cultural, historical, legal, behavioral and demographic issues that impact the health status of communities where Latinos are born and where they live in Indiana. Since its inception, BiCCHEC projects have been multidisciplinary, 80% of the projects involve two or more IUPUI schools. BiCCHEC projects are also collaborative, 70% of the projects have one or more community partners. BiCCHEC researchers have also established a strong commitment to teaching and service, actively involving students in research (25% of current projects are student led) and servicelearning activities, developing exchange programs through our partnerships and providing direct health services in community organized events. Signature center funds have been utilized to fund internal pilot projects. The current poster will highlight four of those projects that have received pilot funding from signature center funds and have resulted in external grant applications or have already received funding, or have resulted in peer reviewed-publications. These projects are considered representative of BiCCHEC’s activities, because of their collaborative, multidisciplinary and community-based nature and include: • Study on oral health disparities using community-based participatory research • Study on the attitudes regarding children with disabilities, beliefs regarding death, coping skills and supports used during bereavement in communities in Indiana and rural Mexico • Building of a bi-national research partnership for healthful eating and diabetes prevention among Mexican and Mexican-American children • Study on emigration and return migration in 20th Century Mexico: Across the border and back again • Study on the effects of migrants' acculturation on oral health and diet in Indianapolis and Tala, Jaliscco using social network theor

Comparative genetic architectures of schizophrenia in East Asian and European populations

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations

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

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)