Effectiveness of a simple lymphoedema treatment regimen in podoconiosis management in southern Ethiopia: one year follow-up

Background: Podoconiosis is a non-filarial elephantiasis caused by long-term barefoot exposure to volcanic soils in endemic areas. Irritant silicate particles penetrate the skin, causing a progressive, debilitating lymphoedema of the lower leg, often starting in the second decade of life. A simple patient-led treatment approach appropriate for resource poor settings has been developed, comprising (1) education on aetiology and prevention of podoconiosis, (2) foot hygiene (daily washing with soap, water and an antiseptic), (3) the regular use of emollient, (4) elevation of the limb at night, and (5) emphasis on the consistent use of shoes and socks. Methodology/Principal Findings: We did a 12-month, non-comparative, longitudinal evaluation of 33 patients newly presenting to one clinic site of a non-government organization (the Mossy Foot Treatment & Prevention Association, MFTPA) in southern Ethiopia. Outcome measures used for the monitoring of disease progress were (1) the clinical staging system for podoconiosis, and (2) the Amharic Dermatology Life Quality Index (DLQI), both of which have been recently validated for use in this setting. Digital photographs were also taken at each visit. Twenty-seven patients completed follow up. Characteristics of patients completing follow-up were not significantly different to those not. Mean clinical stage and lower leg circumference decreased significantly (mean difference -0.67 (95% CI -0.38 to -0.96) and -2.00 (95% CI -1.26 to -2.74), respectively, p<0.001 for both changes). Mean DLQI diminished from 21 (out of a maximum of 30) to 6 (p<0.001). There was a non-significant change in proportion of patients with mossy lesions (p = 0.375). Conclusions/Significance: This simple, resource-appropriate regimen has a considerable impact both on clinical progression and self-reported quality of life of affected individuals. The regimen appears ideal for scaling up to other endemic regions in Ethiopia and internationally. We recommend that further research in the area include analysis of cost-effectiveness of the regimen

The Sister-Chromatid Exchange Assay in Human Cells

The semiconservative nature of DNA replication allows the differential labeling of sister chromatids that isthe fundamental requirement to perform the sister-chromatid exchange (SCE) assay. SCE assay is apowerful technique to visually detect the physical exchange of DNA between sister chromatids. SCEscould result as a consequence of DNA damage repair by homologous recombination (HR) during DNAreplication. Here, we provide the detailed protocol to perform the SCE assay in cultured human cells. Cellsare exposed to the thymidine analog 5-bromo-20-deoxyuridine (BrdU) during two cell cycles, resulting inthe two sister chromatids having differential incorporation of the analog. After metaphase spreads prepara-tion and further processing, SCEs are nicely visualized under the microscope

Lithium isotope evidence for enhanced weathering and erosion during the Paleocene-Eocene Thermal Maximum

The Paleocene-Eocene Thermal Maximum (PETM; ~55.9 Ma) was a geologically rapid warming period associated with carbon release, which caused a marked increase in the hydrological cycle. Here, we use lithium (Li) isotopes to assess the global change in weathering regime, a critical carbon drawdown mechanism, across the PETM. We find a negative Li isotope excursion of ~3‰ in both global seawater (marine carbonates) and in local weathering inputs (detrital shales). This is consistent with a very large delivery of clays to the oceans or a shift in the weathering regime toward higher physical erosion rates and sediment fluxes. Our seawater records are best explained by increases in global erosion rates of ~2× to 3× over 100 ka, combined with model-derived weathering increases of 50 to 60% compared to prewarming values. Such increases in weathering and erosion would have supported enhanced carbon burial, as both carbonate and organic carbon, thereby stabilizing climate

Need Polynomial Systems Be Doubly-Exponential?

Polynomial Systems, or at least their algorithms, have the reputation of being doubly-exponential in the number of variables [Mayr and Mayer, 1982], [Davenport and Heintz, 1988]. Nevertheless, the Bezout bound tells us that that number of zeros of a zero-dimensional system is singly-exponential in the number of variables. How should this contradiction be reconciled? We first note that [Mayr and Ritscher, 2013] shows that the doubly exponential nature of Gr\"{o}bner bases is with respect to the dimension of the ideal, not the number of variables. This inspires us to consider what can be done for Cylindrical Algebraic Decomposition which produces a doubly-exponential number of polynomials of doubly-exponential degree. We review work from ISSAC 2015 which showed the number of polynomials could be restricted to doubly-exponential in the (complex) dimension using McCallum's theory of reduced projection in the presence of equational constraints. We then discuss preliminary results showing the same for the degree of those polynomials. The results are under primitivity assumptions whose importance we illustrate.Comment: Extended Abstract for ICMS 2016 Presentation. arXiv admin note: text overlap with arXiv:1605.0249

Decarbonising the critical sectors of aviation, shipping, road freight and industry to limit warming to 1.5–2°C

Limiting warming to well below 2°C requires rapid and complete decarbonisation of energy systems. We compare economy-wide modelling of 1.5°C and 2°C scenarios with sector-focused analyses of four critical sectors that are difficult to decarbonise: aviation, shipping, road freight transport, and industry. We develop and apply a novel framework to analyse and track mitigation progress in these sectors. We find that emission reductions in the 1.5°C and 2°C scenarios of the IMAGE model come from deep cuts in CO2 intensities and lower energy intensities, with minimal demand reductions in these sectors’ activity. We identify a range of additional measures and policy levers that are not explicitly captured in modelled scenarios but could contribute significant emission reductions. These are demand reduction options, and include less air travel (aviation), reduced transportation of fossil fuels (shipping), more locally produced goods combined with high load factors (road freight), and a shift to a circular economy (industry). We discuss the challenges of reducing demand both for economy-wide modelling and for policy. Based on our sectoral analysis framework, we suggest modelling improvements and policy recommendations, calling on the relevant UN agencies to start tracking mitigation progress through monitoring key elements of the framework (CO2 intensity, energy efficiency, and demand for sectoral activity, as well as the underlying drivers), as a matter of urgency

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

Mortality Risk Prediction by an Insurance Company and Long-Term Follow-Up of 62,000 Men

Background: Insurance companies use medical information to classify the mortality risk of applicants. Adding genetic tests to this assessment is currently being debated. This debate would be more meaningful, if results of present-day risk prediction were known. Therefore, we compared the predicted with the observed mortality of men who applied for life insurance, and determined the prognostic value of the risk assessment. Methods: Long-term follow-up was available for 62,334 male applicants whose mortality risk was predicted with medical evaluation and they were assigned to five groups with increasing risk from 1 to 5. We calculated all cause standardized mortality ratios relative to the Dutch population and compared groups with Cox's regression. We compared the discriminative ability of risk assessments as indicated by a concordance index (c). Results: In 844,815 person years we observed 3,433 deaths. The standardized mortality relative to the Dutch male population was 0.76 (95 percent confidence interval, 0.73 to 0.78). The standardized mortality ratios ranged from 0.54 in risk group 1 to 2.37 in group 5. A large number of risk factors and diseases were significantly associated with increased mortality. The algorithm of prediction was significantly, but only slightly better than summation of the number of disorders and risk factors (c-index, 0.64 versus 0.60, P,0.001). Conclusions: Men applying for insurance clearly had better survival relative to the general population. Readily available medical evaluation enabled accurate prediction of the mortality risk of large groups, but the deceased men could not have been identified with the applied prediction method

Extended Cognition Hypothesis Applied to Computational Thinking in Computer Science Education

Computational thinking is a much-used concept in computer science education. Here we examine the concept from the viewpoint of the extended cognition hypothesis. The analysis reveals that the extent of the concept is limited by its strong historical roots in computer science and software engineering. According to the extended cognition hypothesis, there is no meaningful distinction between human cognitive functions and the technology. This standpoint promotes a broader interpretation of the human-technology interaction. Human cognitive processes spontaneously adapt available technology enhanced skills when technology is used in cognitively relevant levels and modalities. A new concept technology synchronized thinking is presented to denote this conclusion. More diverse and practical approach is suggested for the computer scienceeducation.Peer reviewe