Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial

The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity

Temporal Controls of the Asymmetric Cell Division Cycle in Caulobacter crescentus

The asymmetric cell division cycle of Caulobacter crescentus is orchestrated by an elaborate gene-protein regulatory network, centered on three major control proteins, DnaA, GcrA and CtrA. The regulatory network is cast into a quantitative computational model to investigate in a systematic fashion how these three proteins control the relevant genetic, biochemical and physiological properties of proliferating bacteria. Different controls for both swarmer and stalked cell cycles are represented in the mathematical scheme. The model is validated against observed phenotypes of wild-type cells and relevant mutants, and it predicts the phenotypes of novel mutants and of known mutants under novel experimental conditions. Because the cell cycle control proteins of Caulobacter are conserved across many species of alpha-proteobacteria, the model we are proposing here may be applicable to other genera of importance to agriculture and medicine (e.g., Rhizobium, Brucella)

A manufacturable platform for photonic quantum computing

Whilst holding great promise for low noise, ease of operation and networking, useful photonic quantum computing has been precluded by the need for beyond-state-of-the-art components, manufactured by the millions. Here we introduce a manufacturable platform for quantum computing with photons. We benchmark a set of monolithically-integrated silicon photonics-based modules to generate, manipulate, network, and detect photonic qubits, demonstrating dual-rail photonic qubits with $99.98\% \pm 0.01\%$ state preparation and measurement fidelity, Hong-Ou-Mandel quantum interference between independent photon sources with $99.50\%\pm0.25\%$ visibility, two-qubit fusion with $99.22\%\pm0.12\%$ fidelity, and a chip-to-chip qubit interconnect with $99.72\%\pm0.04\%$ fidelity, not accounting for loss. In addition, we preview a selection of next generation technologies, demonstrating low-loss silicon nitride waveguides and components, fabrication-tolerant photon sources, high-efficiency photon-number-resolving detectors, low-loss chip-to-fiber coupling, and barium titanate electro-optic phase shifters.Comment: 8 pages, 5 figure

Improved oxygenation following methylprednisolone therapy and survival in paediatric acute respiratory distress syndrome.

BackgroundMethylprednisolone remains a commonly used ancillary therapy for paediatric acute respiratory distress syndrome (PARDS), despite a lack of level 1 evidence to justify its use. When planning prospective trials it is useful to define response to therapy and to identify if there is differential response in certain patients, i.e. existence of 'responders' and 'non responders' to therapy. This retrospective, observational study carried out in 2 tertiary referral paediatric intensive care units aims to characterize the change in Oxygen Saturation Index, following the administration of low dose methylprednisolone in a cohort of patients with PARDS, to identify what proportion of children treated demonstrated response, whether any particular characteristics predict response to therapy, and to determine if a positive response to corticosteroids is associated with reduced Paediatric Intensive Care Unit mortality.MethodsAll patients who received prolonged, low dose, IV methylprednisolone for the specific indication of PARDS over a 5-year period (2011-2016) who met the PALICC criteria for PARDS at the time of commencement of steroid were included (n = 78).OSI was calculated four times per day from admission until discharge from PICU (or death). Patients with ≥20% improvement in their mean daily OSI within 72 hours of commencement of methylprednisolone were classified as 'responders'. Primary outcome measure was survival to PICU discharge.ResultsMean OSI of the cohort increased until the day of steroid commencement then improved thereafter. 59% of patients demonstrated a response to steroids. Baseline characteristics were similar between responders and non-responders. Survival to PICU discharge was significantly higher in 'responders' (74% vs 41% OR 4.14(1.57-10.87) p = 0.004). On multivariable analysis using likely confounders, response to steroid was an independent predictor of survival to PICU discharge (p = 0.002). Non-responders died earlier after steroid administration than responders (p = 0.003).ConclusionsAn improvement in OSI was observed in 60% of patients following initiation of low dose methylprednisolone therapy in this cohort of patients with PARDS. Baseline characteristics fail to demonstrate a difference between responders and non-responders. A 20% improvement in OSI after commencement of methylprednisolone was independently predictive of survival, Prospective trials are needed to establish if there is a benefit from this therapy

Characteristics of paediatric acute respiratory distress syndrome patients by paediatric intensive care unit survival status.

Characteristics of paediatric acute respiratory distress syndrome patients by paediatric intensive care unit survival status.</p

Characteristics of paediatric intensive care unit patients by oxygenation response to intravenous methylprednisolone.

Characteristics of paediatric intensive care unit patients by oxygenation response to intravenous methylprednisolone.</p

Kaplan-Meier plot of all-cause mortality in days after commencement of steroids and 95% confidence interval (shaded areas) by responder / non-responder to steroid status.

The analysis was adjusted for age, PIM-3 score, PELOD, admitting unit, prior steroid use, immune compromise, prematurity, direct/indirect PARDS phenotype (direct/indirect) and infection/non-infection as independent variables in a Cox proportional hazard model, and demonstrates that death occurred earlier in ‘non-responders to steroid therapy (p = 0.003).</p

Multivariable logistic regression testing response to steroid and likely con-founders as independent predictors of PICU mortality.

Multivariable logistic regression testing response to steroid and likely con-founders as independent predictors of PICU mortality.</p