{\em Ab initio} Quantum Monte Carlo simulation of the warm dense electron gas in the thermodynamic limit

We perform \emph{ab initio} quantum Monte Carlo (QMC) simulations of the warm dense uniform electron gas in the thermodynamic limit. By combining QMC data with linear response theory we are able to remove finite-size errors from the potential energy over the entire warm dense regime, overcoming the deficiencies of the existing finite-size corrections by Brown \emph{et al.}~[PRL \textbf{110}, 146405 (2013)]. Extensive new QMC results for up to $N=1000$ electrons enable us to compute the potential energy $V$ and the exchange-correlation free energy $F_{xc}$ of the macroscopic electron gas with an unprecedented accuracy of $|\Delta V|/|V|, |\Delta F_{xc}|/|F|_{xc} \sim 10^{-3}$. A comparison of our new data to the recent parametrization of $F_{xc}$ by Karasiev {\em et al.} [PRL {\bf 112}, 076403 (2014)] reveals significant deviations to the latter

Stapling and Section of the Nasogastric Tube during Sleeve Gastrectomy: How to Prevent and Recover?

Bariatric surgery has become an integral part of morbid obesity treatment with well-defined indications. Some complications, specific or not, due to laparoscopic sleeve gastrectomy (LSG) procedure have recently been described. We report a rare complication unpublished to date: a nasogastric section during great gastric curve stapling. A 44-year-old woman suffered of severe obesity (BMI 36.6 kg/m2) with failure of medical treatments for years. According to already published technique, a LSG was performed. Six hours postoperatively, a nurse removed the nasogastric tube according to the local protocol and the nasogastric tube was abnormally short, with staples at its extremity. Surgery was performed with peroperative endoscopy. In conclusion, this is the first publication of a nasogastric section during LSG. Therefore we report this case and propose a solution to prevent its occurrence. To avoid this kind of accident, we now systematically insert the nasogastric tube by mouth through a Guedel cannula. Then, to insert the calibrating bougie, we entirely withdraw the nasogastric tube

СО́КА

In a recent Letter [T.~Dornheim \textit{et al.}, Phys. Rev. Lett. \textbf{117}, 156403 (2016)], we presented the first \textit{ab initio} quantum Monte-Carlo (QMC) results of the warm dense electron gas in the thermodynamic limit. However, a complete parametrization of the exchange-correlation free energy with respect to density, temperature, and spin polarization remained out of reach due to the absence of (i) accurate QMC results below $\theta=k_\text{B}T/E_\text{F}=0.5$ and (ii) of QMC results for spin polarizations different from the paramagnetic case. Here we overcome both remaining limitations. By closing the gap to the ground state and by performing extensive QMC simulations for different spin polarizations, we are able to obtain the first complete \textit{ab initio} exchange-correlation free energy functional; the accuracy achieved is an unprecedented $\sim 0.3\%$. This also allows us to quantify the accuracy and systematic errors of various previous approximate functionals

Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

AIMS: To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. METHODS: We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline. RESULTS: Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12‐week reductions in albuminuria compared with placebo: −33.2% [95% confidence interval (CI) −45.4, −18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: −23.5% (95% CI −37.6, −6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal‐related adverse events were observed in any group. CONCLUSIONS: Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin‐angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin‐induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long‐term renal and cardiovascular risk

Cost-Effectiveness of Surgically Induced Weight Loss for the Management of Type 2 Diabetes: Modeled Lifetime Analysis

OBJECTIVE--To estimate the cost-effectiveness of surgically induced weight loss relative to conventional therapy for the management of recently diagnosed type 2 diabetes in class VII obese patients. RESEARCH DESIGN AND METHODS--This study builds on a within-trial cost-efficacy analysis. The analysis compares the lifetime costs and quality-adjusted life-years (QALYs) between the two intervention groups. Intervention costs were extrapolated based on observed resource utilization during the trial. The proportion of patients in each intervention group with remission of diabetes at 2 years was the same as that observed in the trial. Health care costs for patients with type 2 diabetes and outcome variables required to derive estimates of QALYs were sourced from published literature. A health care system perspective was adopted. Costs and outcomes were discounted annually at 3%. Costs are presented in 2006 Australian dollars (AUD) (currency exchange: 1 AUD = 0.74 USD). RESULTS--The mean number of years in diabetes remission over a lifetime was 11.4 for surgical therapy patients and 2.1 for conventional therapy patients. Over the remainder of their lifetime, surgical and conventional therapy patients lived 15.7 and 14.5 discounted QALYs, respectively. The mean discounted lifetime costs were 98,900 AUD per surgical therapy patient and 101,400 AUD per conventional therapy patient. Relative to conventional therapy, surgically induced weight loss was associated with a mean health care saving of 2,400 AUD and 1.2 additional QALYs per patient. CONCLUSIONS--Surgically induced weight loss is a dominant intervention (it both saves health care costs and generates health benefits) for managing recently diagnosed type 2 diabetes in class IBI obese patients in Australia. <br /

Fragmentation of daily rhythms associates with obesity and cardiorespiratory fitness in adolescents: The HELENA study

Background & aims: Chronobiology studies periodic changes in living organisms and it has been proposed as a promising approach to investigate obesity. We analyze the association of the characteristics of the rest-activity rhythms with obesity, cardiorespiratory fitness and metabolic risk in adolescents from nine European countries. Methods: 1044 adolescents (12.5-17.5 y) were studied. Circadian health was evaluated by actigraphy with accelerometers (Actigraph GT1M). Characteristics of the daytime activity such as fragmentation (intradaily variability), estimated acrophase, and 10 h mean daytime activity index were obtained. Body composition was assessed using Bioelectrical-Impedance-Analysis, skinfold thickness, air-displacement-plethysmography and Dual-energy-X-ray-Absorptiometry. Cardiorespiratory fitness (VO2max) and metabolic risk were studied. Results: Highly fragmented activity rhythms were associated with obesity and central adiposity (P < 0.05). Obese adolescents had-3 times higher odds of having a high fragmentation of daytime activity compared to normal weight adolescents OR (95% CI) = 2.8 (1.170, 6.443). A highly fragmented rhythm was also related to lower cardiorespiratory fitness and higher metabolic risk (P < 0.05) so those adolescents classified as low fitness showed a significantly higher fragmentation of daytime activity than those included in the high fitness group (P < 0.0001). Other characteristics of the rhythms such as smaller 10 h daytime mean activity index and delayed estimated acrophase were also related to obesity and metabolic risk (P < 0.05). Conclusions: Our results indicate that the daily organization of the rest-activity cycle is more fragmented in obese and less fit adolescents and correlates with higher metabolic risk. This fact reinforces our hypothesis that disturbances in daily rhythms can be considered as sensitive markers of poorer adolescent's health

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

The Bone-Forming Effects of HIF-1α-Transduced BMSCs Promote Osseointegration with Dental Implant in Canine Mandible

The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore the oral function. Gene-transduced stem cells provide a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants with tissue engineering technology. Our previous studies have demonstrated that the hypoxia-inducible factor-1α (HIF-1α) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the function of HIF-1α was validated for the first time in a preclinical large animal canine model in term of its ability to promote new bone formation in defects around implants as well as the osseointegration between tissue-engineered bone and dental implants. A lentiviral vector was constructed with the constitutively active form of HIF-1α (cHIF). The ectopic bone formation was evaluated in nude mice. The therapeutic potential of HIF-1α-overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1α mediated canine BMSCs significantly promoted new bone formation both subcutaneously and in mesi-implant defects, including increased bone volume, bone mineral density, trabecular thickness, and trabecular bone volume fraction. Furthermore, osseointegration was significantly enhanced by HIF-1α-overexpressing canine BMSCs. This study provides an important experimental evidence in a preclinical large animal model concerning to the potential applications of HIF-1α in promoting new bone formation as well as the osseointegration of immediate implantation for oral function restoration

Adaptive and Phase Selective Spike Timing Dependent Plasticity in Synaptically Coupled Neuronal Oscillators

We consider and analyze the influence of spike-timing dependent plasticity (STDP) on homeostatic states in synaptically coupled neuronal oscillators. In contrast to conventional models of STDP in which spike-timing affects weights of synaptic connections, we consider a model of STDP in which the time lags between pre- and/or post-synaptic spikes change internal state of pre- and/or post-synaptic neurons respectively. The analysis reveals that STDP processes of this type, modeled by a single ordinary differential equation, may ensure efficient, yet coarse, phase-locking of spikes in the system to a given reference phase. Precision of the phase locking, i.e. the amplitude of relative phase deviations from the reference, depends on the values of natural frequencies of oscillators and, additionally, on parameters of the STDP law. These deviations can be optimized by appropriate tuning of gains (i.e. sensitivity to spike-timing mismatches) of the STDP mechanism. However, as we demonstrate, such deviations can not be made arbitrarily small neither by mere tuning of STDP gains nor by adjusting synaptic weights. Thus if accurate phase-locking in the system is required then an additional tuning mechanism is generally needed. We found that adding a very simple adaptation dynamics in the form of slow fluctuations of the base line in the STDP mechanism enables accurate phase tuning in the system with arbitrary high precision. Adaptation operating at a slow time scale may be associated with extracellular matter such as matrix and glia. Thus the findings may suggest a possible role of the latter in regulating synaptic transmission in neuronal circuits

Genetic variations in VEGF and VEGFR2 and glioblastoma outcome

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs significantly associated to survival, namely rs2071559 and rs12502008. However, these results are likely to be false positives due to multiple testing and could not be confirmed in a separate dataset. Overall, this study provides little evidence that VEGF and VEGFR2 polymorphisms are important for glioblastoma survival