4,848 research outputs found
Investigating Multiple Household Water Sources and Uses with a Computer-Assisted Personal Interviewing (CAPI) Survey
The investigation of multiple sources in household water management is considered overly complicated and time consuming using paper and pen interviewing (PAPI). We assess the advantages of computer-assisted personal interviewing (CAPI) in Pacific Island Countries (PICs). We adapted an existing PAPI survey on multiple water sources and expanded it to incorporate location of water use and the impacts of extreme weather events using SurveyCTO on Android tablets. We then compared the efficiency and accuracy of data collection using the PAPI version (n = 44) with the CAPI version (n = 291), including interview duration, error rate and trends in interview duration with enumerator experience. CAPI surveys facilitated high-quality data collection and were an average of 15.2 min faster than PAPI. CAPI survey duration decreased by 0.55% per survey delivered (p < 0.0001), whilst embedded skip patterns and answer lists lowered data entry error rates, relative to PAPI (p < 0.0001). Large-scale household surveys commonly used in global monitoring and evaluation do not differentiate multiple water sources and uses. CAPI equips water researchers with a quick and reliable tool to address these knowledge gaps and advance our understanding of development research priorities
Uncertainty assessment in river flow projections for Ethiopia’s Upper Awash Basin using multiple GCMs and hydrological models
Uncertainty in climate change impacts on river discharge in the Upper Awash Basin, Ethiopia, is assessed using five MIKE SHE hydrological models, six CMIP5 general circulation models (GCMs) and two representative concentration pathways (RCP) scenarios for the period 2071–2100. Hydrological models vary in their spatial distribution and process representations of unsaturated and saturated zones. Very good performance is achieved for 1975–1999 (NSE: 0.65–0.8; r: 0.79–0.93). GCM-related uncertainty dominates variability in projections of high and mean discharges (mean: –34% to +55% for RCP4.5,–2% to +195% for RCP8.5). Although GCMs dominate uncertainty in projected low flows, inter-hydrological model uncertainty is considerable (RCP4.5: –60% to +228%, RCP8.5: –86% to +337%). Analysis of variance uncertainty attribution reveals that GCM-related uncertainty occupies, on average, 68% of total uncertainty for median and high flows and hydrological models no more than 1%. For low flows, hydrological model uncertainty occupies, on average, 18% of total uncertainty; GCM-related uncertainty remains substantial (average: 28%)
Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy.
Neocortical epilepsy is frequently drug-resistant. Surgery to remove the epileptogenic zone is only feasible in a minority of cases, leaving many patients without an effective treatment. We report the potential efficacy of gene therapy in focal neocortical epilepsy using a rodent model in which epilepsy is induced by tetanus toxin injection in the motor cortex. By applying several complementary methods that use continuous wireless electroencephalographic monitoring to quantify epileptic activity, we observed increases in high frequency activity and in the occurrence of epileptiform events. Pyramidal neurons in the epileptic focus showed enhanced intrinsic excitability consistent with seizure generation. Optogenetic inhibition of a subset of principal neurons transduced with halorhodopsin targeted to the epileptic focus by lentiviral delivery was sufficient to attenuate electroencephalographic seizures. Local lentiviral overexpression of the potassium channel Kv1.1 reduced the intrinsic excitability of transduced pyramidal neurons. Coinjection of this Kv1.1 lentivirus with tetanus toxin fully prevented the occurrence of electroencephalographic seizures. Finally, administration of the Kv1.1 lentivirus to an established epileptic focus progressively suppressed epileptic activity over several weeks without detectable behavioral side effects. Thus, gene therapy in a rodent model can be used to suppress seizures acutely, prevent their occurrence after an epileptogenic stimulus, and successfully treat established focal epilepsy
Decreased STARD10 expression is associated with defective insulin secretion in humans and mice
Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in β cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult β cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the β cell
Choroidal metastases in testicular choriocarcinoma, successful treatment with chemo- and radiotherapy: a case report
<p>Abstract</p> <p>Background</p> <p>Choriocarcinoma is a very rare cause of ocular metastasis. Only 18 male patients have been reported on, 4 of whom survived, but with significant loss of vision.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man, suffering from testicular choriocarcinoma with pulmonary, cerebral, renal, hepatic and osseous metastases, underwent left radical orchiectomy. While being treated with chemotherapy, he presented with loss of vision in the left eye. Ophthalmoscopy revealed bilateral non-pigmented, hemorrhagic choroidal tumours, compatible with secondary lesions. Continued chemotherapy and stereotactic radiotherapy of the skull and spine lead to full remission with excellent vision, after more than 4 years of follow up.</p> <p>Conclusion</p> <p>Testicular choriocarcinoma is an exceptional cause of choroidal metastasis, potentially asymptomatic and with specific clinical features. Radiotherapy can complement radical orchiectomy and chemotherapy, to achieve full remission and maintain good vision.</p
Comparing microfluidic performance of three-dimensional (3D) printing platforms
Three-dimensional (3D) printing has emerged as a potential revolutionary technology for the fabrication of microfluidic devices. A direct experimental comparison of the three 3D printing technologies dominating microfluidics was conducted using a Y-junction microfluidic device, the design of which was optimized for each printer: fused deposition molding (FDM), Polyjet, and digital light processing stereolithography (DLP-SLA). Printer performance was evaluated in terms of feature size, accuracy, and suitability for mass manufacturing; laminar flow was studied to assess their suitability for microfluidics. FDM was suitable for microfabrication with minimum features of 321 ± 5 μm, and rough surfaces of 10.97 μm. Microfluidic devices >500 μm, rapid mixing (71% ± 12% after 5 mm, 100 μL/min) was observed, indicating a strength in fabricating micromixers. Polyjet fabricated channels with a minimum size of 205 ± 13 μm, and a surface roughness of 0.99 μm. Compared with FDM, mixing decreased (27% ± 10%), but Polyjet printing is more suited for microfluidic applications where flow splitting is not required, such as cell culture or droplet generators. DLP-SLA fabricated a minimum channel size of 154 ± 10 μm, and 94 ± 7 μm for positive structures such as soft lithography templates, with a roughness of 0.35 μm. These results, in addition to low mixing (8% ± 1%), showed suitability for microfabrication, and microfluidic applications requiring precise control of flow. Through further discussion of the capabilities (and limitations) of these printers, we intend to provide guidance toward the selection of the 3D printing technology most suitable for specific microfluidic applications
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