Validation of a fully autonomous phosphate analyser based on a microfluidic lab-on-a-chip

This work describes the design of a phosphate analyser that utilises a microfluidic lab-on-a-chip. The analyser contains all the required chemical storage, pumping and electronic components to carry out a complete phosphate assay. The system is self-calibrating and self-cleaning, thus capable of long-term operation. This was proven by a bench top calibration of the analyser using standard solutions and also by comparing the analyser's performance to a commercially available phosphate monitor installed at a waste water treatment plant. The output of the microfluidic lab-on-a-chip analyser was shown to have sensitivity and linear range equivalent to the commercially available monitor and also the ability to operate over an extended period of time

Deep Convolutional LSTM for improved flash flood prediction

Flooding remains one of the most devastating and costly natural disasters. As flooding events grow in frequency and intensity, it has become increasingly important to improve flood monitoring, prediction, and early warning systems. Recent efforts to improve flash flood forecasts using deep learning have shown promise, yet commonly-used techniques such as long short term memory (LSTM) models are unable to extract potentially significant spatial relationships among input datasets. Here we propose a hybrid approach using a Convolutional LSTM (ConvLSTM) network to predict stream stage heights using multi-modal hydrometeorological remote sensing and in-situ inputs. Results suggest the hybrid network can more effectively capture the specific spatiotemporal landscape dynamics of a flash flood-prone catchment relative to the current state-of-the-art, leading to a roughly 26% improvement in model error when predicting elevated stream conditions. Furthermore, the methodology shows promise for improving prediction accuracy and warning times for supporting local decision making

Haptoglobin Genotype and the Rate of Renal Function Decline in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Many patients with type 1 diabetes develop renal disease despite moderately good metabolic control, suggesting other risk factors may play a role. Recent evidence suggests that the haptoglobin (HP) 2-2 genotype, which codes for a protein with reduced antioxidant activity, may predict renal function decline in type 1 diabetes. We examined this hypothesis in 1,303 Caucasian participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. HP genotype was determined by polyacrylamide gel electrophoresis. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albumin excretion based on timed urine samples. Participants were followed up for a mean of 22 years. HP genotype was significantly associated with the development of sustained estimated glomerular filtration rate (GFR) \u3c60 mL/min/1.73 m2and with end-stage renal disease (ESRD), with HP 2-2 having greater risk than HP 2-1 and 1-1. No association was seen with albuminuria. Although there was no treatment group interaction, the associations were only significant in the conventional treatment group, where events rates were much higher. We conclude that the HP genotype is significantly associated with the development of reduced GFR and ESRD in the DCCT/EDIC study

Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study.

Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously \u3c30 mg/d), sustained microalbuminuria (AER, 30–299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER\u3c30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (\u3c60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease. Results At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification. Conclusions In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes

Autonomous reagent-based microfluidic pH sensor platform

A portable sensor has been developed for in situ measurements of pH within aqueous environments. The sensor design incorporates microfluidic technology, allowing for the use of low volume of samples and reagents, and an integrated low cost detection system that uses a light emitting diode as light source and a photodiode as the detector. Different combination of dyes has been studied in order to allow for a broader pH detection range, than can be obtained using a single dye. The optimum pH range for this particular dye combination was found to be between pH 4 and pH 9. The reagents developed for pH measurement were first tested using bench-top instrumentation and once optimised, the selected formulation was then implemented in the microfluidic system. The prototype system has been characterised in terms of pH response, linear range, reproducibility and stability. Results obtained using the prototype system are in good agreement with those obtained using reference instrumentation, i.e. a glass electrode/pH meter and analysis via spectrophotometer based assays. The reagent (mixture #3) is shown to be stable for over 8 months, which is important for long term deployments. A high reproducibility is reported with a global RSD of ≤1.8% across measurements of 90 samples, i.e. with respect to concentrations reported by a calibrated pH meter. A series of real water samples from multiple sources were also analysed using the portable sensor system, of which the global error found was 3.84% showing its feasibility for real-world applications

The Atacama Cosmology Telescope: Extragalactic Sources at 148 GHz in the 2008 Survey

We report on extragalactic sources detected in a 455 square-degree map of the southern sky made with data at a frequency of 148 GHz from the Atacama Cosmology Telescope 2008 observing season. We provide a catalog of 157 sources with flux densities spanning two orders of magnitude: from 15 to 1500 mJy. Comparison to other catalogs shows that 98% of the ACT detections correspond to sources detected at lower radio frequencies. Three of the sources appear to be associated with the brightest cluster galaxies of low redshift X-ray selected galaxy clusters. Estimates of the radio to mm-wave spectral indices and differential counts of the sources further bolster the hypothesis that they are nearly all radio sources, and that their emission is not dominated by re-emission from warm dust. In a bright (>50 mJy) 148 GHz-selected sample with complete cross-identifications from the Australia Telescope 20 GHz survey, we observe an average steepening of the spectra between 5, 20, and 148 GHz with median spectral indices of $\alpha_{\rm 5-20} = -0.07 \pm 0.06$, $\alpha_{\rm 20-148} = -0.39 \pm0.04$, and $\alpha_{\rm 5-148} = -0.20 \pm 0.03$. When the measured spectral indices are taken into account, the 148 GHz differential source counts are consistent with previous measurements at 30 GHz in the context of a source count model dominated by radio sources. Extrapolating with an appropriately rescaled model for the radio source counts, the Poisson contribution to the spatial power spectrum from synchrotron-dominated sources with flux density less than 20 mJy is C^{\rm Sync} = (2.8 \pm 0.3) \times 10^{-6} \micro\kelvin^2.Comment: Accepted to Ap

Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression.

Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen was a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen, where IL-3 induced their differentiation into megakaryocytes (MKs). In the spleen, immune-skewed MKs produced a CD40 ligandhi platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.NHS Blood and Transplant European Union's Horizon 2020 (ERC-2014-CoG-648765) MRC-AMED (MR/V005421/1

Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal

Background: The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies. Methods/design: A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods. Discussion: The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation. Trial registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974

The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review

Background: Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. Methods: Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. Results: We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14–.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. Conclusions: Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection