Flood risk analysis is the instrument for local officials to create a sound strategy and adaptation plans for the impacts of inundation due to heavy rains, climate change and sea level rise. Hence, cities with aging i...Flood risk analysis is the instrument for local officials to create a sound strategy and adaptation plans for the impacts of inundation due to heavy rains, climate change and sea level rise. Hence, cities with aging infrastructure are retrofitting their stormwater management systems to mitigate the impacts. However determining the most at risk areas and the options for corrections is more challenging. As a result, there is an urgent need to develop a screening tool to analyze watersheds and identify the most at-risk areas. High-quality, open source data and sophisticated spatial analysis techniques allow engineers to create innovative ways to conduct watershed wide inundation analysis. In th</span><span style="font-family:Verdana;">is study, the investigators developed </span></span></span></span><span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">screening tool to identify at-ri</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">sk properties by combining readily available data on topography, groundwater, surface water, tidal information for coastal communities, soils, open space, and rainfall data. Once the screening tool is developed, the means to identify and prioritize improvements to be funded with scarce capital funds is the next step.</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">A tool box of solutions was developed to address flood risk and vulnerability. Testing of the screening tool was conducted in Browa</span><span style="font-family:Verdana;">rd County, Florida and shows encouraging results. Comparison wit</span><span style="font-family:Verdana;">h FEMA Flood maps and repetitive loss mapping indicates that the process works in展开更多
Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system.Axons in the central nervous system fail to regenerate,meaning that injurie...Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system.Axons in the central nervous system fail to regenerate,meaning that injuries or diseases that cause loss of axonal connectivity have life-changing consequences.In 2008,genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic nerve.PTEN is a phosphatase that opposes the actions of PI3-kinase,a family of enzymes that function to generate the membrane phospholipid PIP_(3) from PIP_(2)(phosphatidylinositol(3,4,5)-trisphosphate from phosphatidylinositol(4,5)-bisphosphate).Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase,and was initially demonstrated to promote axon regeneration by signaling through mTOR.More recently,additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative ability.This review describes neuronal signaling pathways downstream of PI3-kinase and PIP3,and considers them in relation to both developmental and regenerative axon growth.We briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability,and describe how these are affected by signaling through PI3-kinase.We highlight the recent finding of a developmental decline in the generation of PIP_(3) as a key reason for regenerative failure,and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous system.Finally,we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.展开更多
Background:Thymidine analogs,namely AZT(Zidovudine or Retrovir^(TM))and d4T(Stavudine or Zerit^(TM))are antiretroviral drugs still employed in over 75%of first line combination antiretroviral therapy(cART)in Kampala,U...Background:Thymidine analogs,namely AZT(Zidovudine or Retrovir^(TM))and d4T(Stavudine or Zerit^(TM))are antiretroviral drugs still employed in over 75%of first line combination antiretroviral therapy(cART)in Kampala,Uganda despite aversion to prescribing these drugs for cART in high income countries due in part to adverse events.For this study,we explored how the continued use of these thymidine analogs in cART could impact emergence of drug resistance and impact on future treatment success in Uganda,a low-income country.Methods:We examined the drug resistance genotypes by Sanger sequencing of 262 HIV-infected patients failing a first line combined antiretroviral treatment containing either AZT or d4T,which represents approximately 5%of the patients at the Joint Clinical Research Center receiving a AZT or d4T containing treatment.Next generation sequencing(DEEPGEN^(TM)HIV)and multiplex oligonucleotide ligation assays(AfriPOLA)were then performed on a subset of patient samples to detect low frequency drug resistant mutations.CD4 cell counts,viral RNA loads,and treatment changes were analyzed in a cohort of treatment success and failures.Results:Over 80%of patients failing first line AZT/d4T-containing cART had predicted drug resistance to 3TC(Lamivudine)and non-nucleoside RT inhibitors(NNRTIs)in the treatment regimen but only 45%had resistance AZT/d4T associated resistance mutations(TAMs).TAMs were however detected at low frequency within the patients HIV quasispecies(1-20%)in 21 of 34 individuals who were failing first-line AZT-containing cART and lacked TAMs by Sanger.Due to lack of TAMs by Sanger,AZT was typically maintained in second-line therapies and these patients had a low frequency of subsequent virologic success.Conclusions:Our findings suggest that continued use of AZT and d4T in first-line treatment in low-to-middle income countries may lead to misdiagnosis of HIV-1 drug resistance and possibly enhance a succession of second-and third-line treatment failures.展开更多
Spinal cord injury has devastating consequences because adult central nervous system （CNS） neurons do not regenerate their axons after injury. Two key reasons for axon regeneration fail- ure are extrinsic inhibitory...Spinal cord injury has devastating consequences because adult central nervous system （CNS） neurons do not regenerate their axons after injury. Two key reasons for axon regeneration fail- ure are extrinsic inhibitory factors and a low intrinsic capacity for axon regrowth. Research has therefore focused on overcom- ing extrinsic growth inhibition, and enhancing intrinsic regeneration capacity. Both of these issues will need to be addressed to enable optimal repair of the injured sp＋inal cord.展开更多
Background The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals,including universal health ...Background The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals,including universal health coverage(UHC).Current control strategies focus on school-aged children,systematically neglecting adults.We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC.Methods In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina,Tsiroanomandidy and Ankazomborona in Madagascar,we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants.Univariable and multivariable logistic regression were performed to evaluate odd ratios.Results The highest prevalence of S.mansoni,S.haematobium and co-infection of both species was 59.5%,61.3%and 3.3%,in Andina and Ankazomborona respectively.Higher prevalence was observed among males(52.4%)and main contributors to the family income(68.1%).Not working as a farmer and higher age were found to be protective factors for infection.Conclusions Our findings provide evidence that adults are a high-risk group for schistosomiasis.Our data suggests that,for ensuring basic health as a human right,current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific,holistic and integrated approaches.展开更多
文摘Flood risk analysis is the instrument for local officials to create a sound strategy and adaptation plans for the impacts of inundation due to heavy rains, climate change and sea level rise. Hence, cities with aging infrastructure are retrofitting their stormwater management systems to mitigate the impacts. However determining the most at risk areas and the options for corrections is more challenging. As a result, there is an urgent need to develop a screening tool to analyze watersheds and identify the most at-risk areas. High-quality, open source data and sophisticated spatial analysis techniques allow engineers to create innovative ways to conduct watershed wide inundation analysis. In th</span><span style="font-family:Verdana;">is study, the investigators developed </span></span></span></span><span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">screening tool to identify at-ri</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">sk properties by combining readily available data on topography, groundwater, surface water, tidal information for coastal communities, soils, open space, and rainfall data. Once the screening tool is developed, the means to identify and prioritize improvements to be funded with scarce capital funds is the next step.</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">A tool box of solutions was developed to address flood risk and vulnerability. Testing of the screening tool was conducted in Browa</span><span style="font-family:Verdana;">rd County, Florida and shows encouraging results. Comparison wit</span><span style="font-family:Verdana;">h FEMA Flood maps and repetitive loss mapping indicates that the process works in
基金the Medical Research Council(MR/R004544/1,MR/R004463/1,to RE)EU ERA-NET NEURON(AxonRepair grant,to BN)+1 种基金Fight for Sight(5119/5120,and 5065-5066,to RE)National Eye Research Centre(to RE).
文摘Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous system.Axons in the central nervous system fail to regenerate,meaning that injuries or diseases that cause loss of axonal connectivity have life-changing consequences.In 2008,genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic nerve.PTEN is a phosphatase that opposes the actions of PI3-kinase,a family of enzymes that function to generate the membrane phospholipid PIP_(3) from PIP_(2)(phosphatidylinositol(3,4,5)-trisphosphate from phosphatidylinositol(4,5)-bisphosphate).Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase,and was initially demonstrated to promote axon regeneration by signaling through mTOR.More recently,additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative ability.This review describes neuronal signaling pathways downstream of PI3-kinase and PIP3,and considers them in relation to both developmental and regenerative axon growth.We briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability,and describe how these are affected by signaling through PI3-kinase.We highlight the recent finding of a developmental decline in the generation of PIP_(3) as a key reason for regenerative failure,and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous system.Finally,we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.
基金F.K.was funded by a scholarship from the NIH Fogarty International Center grants D43-TW000011 and D43-TW009780.E.J.A.was funded by NIAID/NIH AI49170holds the Canada Research Chair in HIV-1 Pathogenesis and Viral Control.M.E.Q-M was partially supported by the CWRU/UH Center for AIDS Research(P30 AI036219)by funding from University Hospitals Cleveland Medical Center(UHCMC)for the University Hospitals Translational Laboratory(UHTL).
文摘Background:Thymidine analogs,namely AZT(Zidovudine or Retrovir^(TM))and d4T(Stavudine or Zerit^(TM))are antiretroviral drugs still employed in over 75%of first line combination antiretroviral therapy(cART)in Kampala,Uganda despite aversion to prescribing these drugs for cART in high income countries due in part to adverse events.For this study,we explored how the continued use of these thymidine analogs in cART could impact emergence of drug resistance and impact on future treatment success in Uganda,a low-income country.Methods:We examined the drug resistance genotypes by Sanger sequencing of 262 HIV-infected patients failing a first line combined antiretroviral treatment containing either AZT or d4T,which represents approximately 5%of the patients at the Joint Clinical Research Center receiving a AZT or d4T containing treatment.Next generation sequencing(DEEPGEN^(TM)HIV)and multiplex oligonucleotide ligation assays(AfriPOLA)were then performed on a subset of patient samples to detect low frequency drug resistant mutations.CD4 cell counts,viral RNA loads,and treatment changes were analyzed in a cohort of treatment success and failures.Results:Over 80%of patients failing first line AZT/d4T-containing cART had predicted drug resistance to 3TC(Lamivudine)and non-nucleoside RT inhibitors(NNRTIs)in the treatment regimen but only 45%had resistance AZT/d4T associated resistance mutations(TAMs).TAMs were however detected at low frequency within the patients HIV quasispecies(1-20%)in 21 of 34 individuals who were failing first-line AZT-containing cART and lacked TAMs by Sanger.Due to lack of TAMs by Sanger,AZT was typically maintained in second-line therapies and these patients had a low frequency of subsequent virologic success.Conclusions:Our findings suggest that continued use of AZT and d4T in first-line treatment in low-to-middle income countries may lead to misdiagnosis of HIV-1 drug resistance and possibly enhance a succession of second-and third-line treatment failures.
基金funded by grants from the Christopher and Dana Reeve Foundation[JFC-2013(3),JFC-2013(4)]the Medical Research Council(G1000864 018556)+1 种基金the International Spinal Research Trust(Nathalie Rose Barr studentship NRB110)ERANET NEURON grant Axon Repair(013-16-002)
文摘Spinal cord injury has devastating consequences because adult central nervous system （CNS） neurons do not regenerate their axons after injury. Two key reasons for axon regeneration fail- ure are extrinsic inhibitory factors and a low intrinsic capacity for axon regrowth. Research has therefore focused on overcom- ing extrinsic growth inhibition, and enhancing intrinsic regeneration capacity. Both of these issues will need to be addressed to enable optimal repair of the injured sp＋inal cord.
文摘Background The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals,including universal health coverage(UHC).Current control strategies focus on school-aged children,systematically neglecting adults.We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC.Methods In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina,Tsiroanomandidy and Ankazomborona in Madagascar,we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants.Univariable and multivariable logistic regression were performed to evaluate odd ratios.Results The highest prevalence of S.mansoni,S.haematobium and co-infection of both species was 59.5%,61.3%and 3.3%,in Andina and Ankazomborona respectively.Higher prevalence was observed among males(52.4%)and main contributors to the family income(68.1%).Not working as a farmer and higher age were found to be protective factors for infection.Conclusions Our findings provide evidence that adults are a high-risk group for schistosomiasis.Our data suggests that,for ensuring basic health as a human right,current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific,holistic and integrated approaches.
文摘背景：基线左心室重量增加可预测高血压的心血管并发症，但是高血压治疗期间，左心室重量降低与预后的关系尚未明确。
目的：确定抗高血压治疗期间，左心室重量降低是否能使主要心血管事件的危险性改善并独立于血压的变化。
设计、地点和参试者：于1995—2001年进行的氯沙坦干预降低高血压终点（Lasartan Intervention For Endpoint Reduction in Hypertension，LIFE）临床随机试验的前瞻性队列亚研究。LIFE试验共人选941例年龄55—80岁的原发性高血压且心电图提示左心室肥厚的患者。患者人选时接受超声心动图左心室重量测定，以后每年随访心血管事件，平均4．8±1．0年。
