The pathophysiology of distal renal tubular acidosis

The kidneys have a central role in the control of acid-base homeostasis owing to bicarbonate reabsorption and production of ammonia and ammonium in the proximal tubule and active acid secretion along the collecting duct. Impaired acid excretion by the collecting duct system causes distal renal tubular acidosis (dRTA), which is characterized by the failure to acidify urine below pH 5.5. This defect originates from reduced function of acid-secretory type A intercalated cells. Inherited forms of dRTA are caused by variants in SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, WDR72 and probably in other genes that are yet to be discovered. Inheritance of dRTA follows autosomal-dominant and -recessive patterns. Acquired forms of dRTA are caused by various types of autoimmune diseases or adverse effects of some drugs. Incomplete dRTA is frequently found in patients with and without kidney stone disease. These patients fail to appropriately acidify their urine when challenged, suggesting that incomplete dRTA may represent an intermediate state in the spectrum of the ability to excrete acids. Unrecognized or insufficiently treated dRTA can cause rickets and failure to thrive in children, osteomalacia in adults, nephrolithiasis and nephrocalcinosis. Electrolyte disorders are also often present and poorly controlled dRTA can increase the risk of developing chronic kidney disease

Investing in Maine Research Infrastructure: Sustainable Forest Bioproducts

The University of Maine, the University of Southern Maine, several baccalaureate institutions in the state, along with other federal, state and local public, private, and non-profit institutions will collaborate to create the Forest Bioproducts Research Institute (FBRI) at the University of Maine. The vision of the FBRI is to advance understanding about the scientific underpinnings, system behavior, and policy implications for the production of forest-based bioproducts that meet societal needs for materials, chemicals, and fuels in an economically and ecologically sustainable manner.The research plans Integrate three themes. They are (1) forest sustainability modeling of life cycle assessment, (2) integrated biopolymer separations and residual solids modifications, and (3) biological and chemical platform conversion technologies.The research capitalizes upon Maine\u27s unique position of having a large natural resource base, existing research capacities in pulp and paper, forestry, and wood products, along with a strong industrial presence. State, national, and global collaborations, including those with Rensselaer Polytechnic Institute and the University of Tennessee-Knoxville, will contribute broader benefits to society as a result of this investment in forestry research.The FBRI will serve as the forest-based carbohydrate economy center of excellence for the region, with a primary goal of transitioning developed science and technology to the state\u27s industrial arena. State, national, and global impacts will be realized as a result of the investment in this research. In addition, a cadre of future engineers and scientists in multidisciplinary disciplines as well as policy-makers will result from the expected collaborations. Support is provided through the NSF Experimental Program To Stimulate Competitive Research (EPSCoR)

Barriers to colonoscopy in UK colorectal cancer screening programmes: Qualitative interviews with ethnic minority groups

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom. METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African(n=5), Black-Caribbean(n=5), South Asian(n=10) and White British(n=10) descent. Participants were eligible for screening, but had not necessarily been invited for colonoscopy. All interviews were conducted in the participant's first language and were assessed using Framework-analysis, in line with a conceptual framework developed from previous interviews with healthcare professionals. RESULTS: Five thematic groups of barriers and facilitators were developed: 'Locus of control', 'Cultural attitudes and beliefs', 'Individual beliefs, knowledge and personal experiences with colonoscopy and cancer', 'Reliance on family and friends' and 'Health concerns'. Differences were observed, between ethnic groups, for: 'Locus of control', 'Cultural attitudes and beliefs' and 'Reliance on family and friends'. Black and South Asian participants frequently described the decision to attend colonoscopy as lying with 'God' (Muslims, specifically), 'the doctor', or 'family' (Locus of control). Black and South Asian participants also reported relying on friends and family for 'language, transport and emotional support' (Reliance on family and friends). Black-African participants, specifically, described cancer as 'socially taboo' (Cultural attitudes and beliefs). CONCLUSIONS: The results highlight several targets for culturally-tailored interventions to make colonoscopy more equitable. This article is protected by copyright. All rights reserved

AACAP 2006 Research Forum--Advancing research in early-onset bipolar disorder: barriers and suggestions

OBJECTIVE: The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity. METHOD: Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy. RESULTS: There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP\u27s developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind. CONCLUSIONS: EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace

Enhancement-mode Ga2O3 wrap-gate fin field-effect transistors on native (100) β-Ga2O3 substrate with high breakdown voltage

Sn-doped gallium oxide (Ga2O3) wrap-gate fin-array field-effect transistors (finFETs) were formed by top-down BCl3 plasma etching on a native semi-insulating Mg-doped (100) β-Ga2O3 substrate. The fin channels have a triangular cross-section and are approximately 300 nm wide and 200 nm tall. FinFETs, with 20 nm Al2O3 gate dielectric and ∼2 μm wrap-gate, demonstrate normally-off operation with a threshold voltage between 0 and +1 V during high-voltage operation. The ION/IOFF ratio is greater than 105 and is mainly limited by high on-resistance that can be significantly improved. At VG = 0, a finFET with 21 μm gate-drain spacing achieved a three-terminal breakdown voltage exceeding 600 V without a field-plate

Tanzania's reptile biodiversity : Distribution, threats and climate change vulnerability

Assessments of biodiversity patterns and threats among African reptiles have lagged behind those of other vertebrate groups and regions. We report the first systematic assessment of the distribution, threat status, and climate change vulnerability for the reptiles of Tanzania. A total of 321 reptile species (including 90 Tanzanian endemics) were assessed using the global standard IUCN Red List methodology and 274 species were also assessed using the IUCN guidelines for climate change vulnerability. Patterns of species richness and threat assessment confirm the conservation importance of the Eastern Arc Mountains, as previously demonstrated for birds, mammals and amphibians. Lowland forests and savannah-woodland habitats also support important reptile assemblages. Protected area gap analysis shows that 116 species have less than 20% of their distribution ranges protected, among which 12 are unprotected, eight species are threatened and 54 are vulnerable to climate change. Tanzania's northern margins and drier central corridor support high numbers of climate vulnerable reptile species, together with the eastern African coastal forests and the region between Lake Victoria and Rwanda. This paper fills a major gap in our understanding of the distribution and threats facing Tanzania's reptiles, and demonstrates more broadly that the explicit integration of climate change vulnerability in Red Listing criteria may revise spatial priorities for conservation

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved