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Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia.

Graphical abstract:

Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies.

The calibration and training of a neural network is a complex and time-consuming procedure that requires significant computational resources to achieve satisfactory results. Key obstacles are a large number of hyperparameters to select and the onset of overfitting in the face of a small amount of data. In this framework, we propose an innovative training strategy for feed-forward architectures - called split-boost - that improves performance and automatically includes a regularizing behaviour without modeling it explicitly. Such a novel approach ultimately allows us to avoid explicitly modeling the regularization term, decreasing the total number of hyperparameters and speeding up the tuning phase. The proposed strategy is tested on a real-world (anonymized) dataset within a benchmark medical insurance design problem.

Regularization aims to shrink model parameters, reducing complexity and overfitting risk. Traditional methods like LASSO and Ridge regression, limited by a single regularization hyperparameter, can restrict bias-variance trade-off adaptability. This paper addresses system identification in a multi-ridge regression framework, where an l2-penalty on the model coefficients is introduced, and a different regularization hyperparameter is assigned to each model parameter. To compute the optimal hyperparameters, a cross-validation-based criterion is optimized through gradient descent. Autoregressive and Output Error models are considered. The former requires formulating a regularized least-squares problem. The identification of the latter class is more challenging and is addressed by adopting regularized instrumental variable methods to ensure a consistent parameter estimation.

Enzymatic electrocatalysis holds promise for new biotechnological approaches to produce chemical commodities such as molecular hydrogen (H2). However, typical inhibitory limitations include low stability and/or low electrocatalytic currents (low product yields). Here we report a facile single-step electrode preparation procedure using indium–tin oxide nanoparticles on carbon electrodes. The subsequent immobilization of a model [FeFe]-hydrogenase from Clostridium pasteurianum(“CpI”) on the functionalized carbon electrode permits comparatively large quantities of H2to be produced in a stable manner. Specifically, we observe current densities of >8 mA/cm2at −0.8 V vs the standard hydrogen electrode (SHE) by direct electron transfer (DET) from cyclic voltammetry, with an onset potential for H2production close to its standard potential at pH 7 (approximately −0.4 V vs. SHE). Importantly, hydrogenase-modified electrodes show high stability retaining ∼92% of their electrocatalytic current after 120 h of continuous potentiostatic H2production at −0.6 V vs. SHE; gas chromatography confirmed ∼100% Faradaic efficiency. As the bioelectrode preparation method balances simplicity, performance, and stability, it paves the way for DET on other electroenzymatic reactions as well as semiartificial photosynthesis.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open‐label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft‐related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p= .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p= .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p= .03, log‐rank test). In addition, patients in the SCS group had a higher re‐admission and overall complication rate at six months, in particular cardio‐vascular adverse events (p= .04 and p= .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival. A single‐center randomized study shows that hypothermic oxygenated perfusion is associated with lower graft dysfunction rates and better graft survival in extended criteria donor liver transplantation.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p= .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p= .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p= .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at si months, in particular cardio-vascular adverse events (p= .04 and p= .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Graphical abstract:

To evaluate a workshop using a low-fidelity simulator for training vascular surgery residents in vascular anastomosis during the COVID-19 pandemic.

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open‐label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third‐party bone marrow–derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1‐year follow‐up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion‐related complications. The incidence of serious and non‐serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56brightNK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC‐treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance‐associated transcripts in 1‐year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375. This randomized controlled trial shows that pretransplant infusion of third‐party bone marrow–derived mesenchymal stromal cells in liver transplant recipients is safe and induces modest increases in circulating regulatory T and natural killer cells.

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third-party bone marrow–derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56brightNK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.govidentifier: NCT02260375.

Participation in the two most recent screening mammography appointments before a breast cancer diagnosis confers a higher protection against breast cancer death than participation in neither or only one examination.

The sodium mixed-phosphate polyanionic compound Na7V4(P2O7)4PO4(NVPP) is an attractive high-potential cathode material for sodium-ion batteries. In this study, a water-soluble binder, namely polyacrylic acid (PAA), was used to successfully process NVPP-based electrodes. In the absence of toxic and expensive organic solvents, the fabrication scenario of our NVPP-PAA electrode appears as a more sustainable and cost-effective approach for slurry processing and electrode production. Supported by detailed electrochemical investigations, we highlight the excellent electrochemical performance of the NVPP-PAA electrodes, which show capacity retention of ∼97% after 200 cycles at a high current density (3 C) in addition to its attractive rate capability with minimal electrode polarization up to 5 C rate.

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2‐3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in‐situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy. Left lateral segment liver transplantation into the splenic fossa (after splenectomy) followed by native hepatectomy 2 weeks later is feasible, providing good short‐term outcomes to a patient with metastatic disease secondary to colorectal cancer.

BackgroundDyspnoea is the most common sign of heart failure (HF). Patients accessing the ED for HF-related symptoms require fast diagnosis and early treatment. Transthoracic echocardiography has a crucial role in HF diagnosis, but requires qualified staff and adequate time for execution. The measurement of inferior vena cava (IVC) diameter has been recently proposed as a rapid, simple and reliable marker of volume overload. The aim of this systematic review was to assess the accuracy of IVC-ultrasound as a stand-alone test for HF diagnosis in patients presenting to the ED with acute dyspnoea.MethodsStudies evaluating the diagnostic accuracy of the inferior vena cava collapsibility index (IVC-CIx) for HF diagnosis were systematically searched in the EMBASE and MEDLINE databases (up to January 2018). Quality Assessment of Diagnostic Accuracy Studies 2 tool was used for the quality assessment of the primary studies. A bivariate random-effects regression approach was used for summary estimates of both sensitivity and specificity.ResultsSeven studies, for a total of 591 patients, were included. Three studies were at low-risk of bias. All studies used a proper reference test. Weighted mean prevalence of HF was 49.3% at random-effect model (I2index for heterogeneity=74.7%). IVC-CIx bivariate weighted mean sensitivity was 79.1% (95% CI 68.5% to 86.8%) and bivariate weighted mean specificity was 81.8% (95% CI 75.0% to 87.0%).ConclusionsOur findings suggest that the sensitivity and specificity of IVC-CIx are suboptimal to rule in or rule out HF diagnosis in patients with acute dyspnoea in the ED setting. Therefore, IVC-CIx is not advisable as a stand-alone test, but may be useful when integrated in a specific diagnostic algorithm for the differential diagnosis of acute dyspnoea.

Introduction:Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. Methods:Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. Results:CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, pvalue = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12–0.60; pvalue = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14–0.94; pvalue = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. Discussion/Conclusion:Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

It is well known that the Al2O3coating of the LiMn2O4cathodes leads to improvement of the performance of these electrodes. However, the effect of the coating on the fundamental processes occurring on the interface with the active material which results in the formation of the solid permeable interphase is yet to be investigated. These effects should be more pronounced in the first cycle when a dynamic interaction of the active material at high voltage with the electrolyte and binder leads to the formation of this passivation layer. Here, we present a detailed investigation of the solid permeable interphase formation in alumina-coated and uncoated LiMn2O4electrodes using X-ray absorption spectroscopy and analysis on the electrodes at the predesigned charging/discharging states. We demonstrate that the alumina coating leads to modification of the solid permeable layer and its dynamics. We also discuss the possible influences of interface modifications via coating on the battery performance.

Direct force measurements between negatively charged silica microparticles are carried out in suspensions of like-charged nanoparticles with atomic force microscopy (AFM). In agreement with previous studies, oscillatory force profiles are observed at larger separation distances. At smaller distances, however, soft and strongly repulsive forces are present. These forces are caused by double layer repulsion between the like-charged surfaces and can be quantitatively interpreted with the Poisson–Boltzmann (PB) model. However, the PB model must be adapted to a strongly asymmetric electrolyte to capture the nonexponential nature of these forces. Thereby, the nanoparticles are modeled as highly charged co-ions, while the counter ions are monovalent. This model permits extraction of the effective charge of the nanoparticles, which is well comparable to the one obtained from electrophoresis. The PB model also explains the presence of a particle-free layer close to the interface.

Treatment of dysplastic Barrett's oesophagus prevents progression to adenocarcinoma; however, the optimal diagnostic strategy for Barrett's oesophagus is unclear. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett's oesophagus. The aim of this study was to investigate whether offering this test to patients on medication for gastro-oesophageal reflux would increase the detection of Barrett's oesophagus compared with standard management.

In this study, self-cross-linked chitosan/alginate dialdehyde multilayer films, capped with either alginate dialdehyde (6 layers) or chitosan (7 layers), were fabricated using the layer-by-layer method. The disruption of the electrostatic equilibrium when exposing the fabricated layers to acidic and alkaline conditions causes swelling within the film and independently in the outermost layer, showing dependence on the ionic strength. Spectroscopic ellipsometry and quartz crystal microbalance with dissipation monitoring were employed to examine the swelling behavior. Atomic force microscopy colloidal probe measurements were conducted to assess the surface forces between the multilayer films at different pH and ionic strengths. Finally, the electrostatic properties of the multilayer films were examined at different pH and ionic strengths using zeta potential measurements. The results suggest that stimuli-responsiveness and overall swelling behavior of the polysaccharide multilayer films significantly depend on the outermost layer, an effect that should expectedly become more pronounced the thinner the film becomes.

ABSTRACTThe purpose of this study was to compare the separate and combined effects of two practical cooling methods (hand and torso) used prior to exercise on subsequent high-intensity cycling performance in heat. Ten trained male cyclists (V̇O2peak: 65.7 ± 10.7 ml.kg−1.min−1) performed four experimental trials (randomised within-subjects design) involving 30-min of pre-cooling (20-min seated; PRE-COOL, 10 min warm-up; PRE-COOL+WUP), while using a: (1) hand-cooling glove (CG); (2) cooling jacket (CJ); (3) both CG and CJ (CG+J); or (4) no-cooling (NC) control, followed by a cycling race simulation protocol (all performed in 35.0 ± 0.6°C and 56.6 ± 4.5% RH). During the 30-min of pre-cooling, no reductions in core (Tc) or mean skin temperature (Tsk) occurred; however, Tsk remained lower in the CJ and CG+J trials compared to NC and CG (p = 0.002–0.040, d= 0.55–1.01). Thermal sensation ratings also indicated that participants felt “hotter” during NC compared to all other trials during both PRE-COOL and PRE-COOL+WUP (p = 0.001–0.015, d= 1.0–2.19), plus the early stages of exercise (sets 1–2; p = 0.005–0.050, d= 0.56–1.22). Following cooling, no differences were found for absolute Tc and Tsk responses between trials over the entire exercise protocol (p > 0.05). Exercise and cognitive (working memory) performance also did not differ between trials (p = 0.843); however, cognitive performance improved over time in all trials (p < 0.001). In summary, pre-cooling (20-min seated and 10-min warm-up) in heat did not improve subsequent high-intensity cycling performance, cognitive responses and associated thermoregulatory strain (Tc and Tsk) compared to control.

Modification of solid substrates by poly-l-lysine (PLL) layers has been widely employed in order to improve their biocompatibility, for promoting protein and cell immobilization for fabrication of biosensor arrays and antibacterial coatings. However, despite many studies conducted in the literature, there is a deficiency in a quantitative description of PLL adsorption processes. It is postulated that this becomes feasible by applying direct experimental techniques combined with thorough theoretical modeling. In this work, the kinetics of PLL adsorption on silica for various ionic strengths was determined in situunder controlled flow conditions using the optical reflectometry and the streaming potential methods. Both the initial adsorption rates and longer time kinetic runs were acquired and quantitatively interpreted in terms of the convective diffusion and the random sequential adsorption theoretical modeling based on the coarse-grained Monte Carlo approach. This unique combination of experimental and theoretical approaches enabled us to gain new insight into the mechanism of macroion adsorption controlled by the electrostatic interactions, which affect both the molecule conformations and the blocking effects. Besides significance for basic science, the results obtained in this work can be exploited for developing reliable procedures for preparing stable PLL monolayers of well-controlled coverage and electrokinetic properties.

Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline.

The prevalence of blood group antigens and phenotypes varies significantly in Brazil. To ensure a proper rare blood supply, it is essential to establish a local and regional database of rare donors connected to the national registry. The objective of this study was to create a database of rare blood donors in the northern region of southern Brazil. From November 2011 to December 2018, red blood cell (RBC) phenotyping and genotyping were performed on common and high-prevalence antigens in donors and patients in southern Brazil. During this study period, 17 patients and 33 blood donors with rare phenotypes were identified. Six patients had already been alloimmunized to clinically significant antigens. Patients with the following phenotypes (i.e., negative for high-prevalence antigens) were found: Yt(a–), Jk(a–b–), Lu(a–b–), Oh(Bombay), Tc(a–), k–, and Fy(a–b–). Among the donors, Kp(a+b–), Fy(a–b–), Lu(a–b–), and k– phenotypes were identified. We also found four donors with the weak D type 18 phenotype. In conclusion, we observed that the prevalence of rare blood phenotypes in our region corresponds more to the prevalence found in the Caucasian population when compared with other regions in Brazil. Our results show the importance of continuous screening for rare donors in different regions of the country and the creation of a local database to support RBC transfusions in patients who need rare blood.

RPLND for low-volume, clinical stage II (CSII) testicular seminoma may provide an alternative to radiation therapy or chemotherapy for local control, preserving the high rate of cure while reducing exposure to long-term side effects. The objective of this study was to determine the willingness of patients and providers to participate in a clinical trial with this approach.

Direct force measurements between negatively charged colloidal latex particles of a diameter of 1 μm were carried out in aqueous solutions of various inorganic monovalent and multivalent cations with the multiparticle colloidal probe technique based on the atomic force microscope (AFM). The observed force profiles were rationalized within the theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO). In the presence of monovalent and divalent cations, this theory was capable to describe the force profiles correctly down to distances of few nm. At shorter distances, however, a strong non-DLVO attraction was identified. For more highly charged cations, an additional and more long-ranged non-DLVO attractive force is observed, and it was interpreted by surface charge heterogeneities. Based on these force profiles, the aggregation rates, which were independently measured by light scattering, can be predicted relatively well. The main conclusion of this study is that in the present system, direct force measurements do capture the principal interactions driving aggregation in colloidal suspensions.

In this study, we propose an effective strategy to improve the electrochemical performance of a P2-Na0.67Mn0.75Ni0.25O2(P2-MNO) cathode material for Na-ion batteries based on MgO surface coating. The MgO coating, with a thickness of ∼20–50 nm, is obtained by means of a facile wet-chemistry approach followed by heat treatment carried out at comparatively low temperatures (400–500 °C) in order to avoid possible Mg doping in the bulk of the P2-MNO. Detailed electrochemical investigations demonstrate improved electrochemical performance of the MgO-coated material (M-P2-MNO) in comparison to pristine bare one at both room and elevated (40 °C) temperatures. Operandodifferential electrochemical mass spectroscopy (DEMS) demonstrate that the MgO coating is effective in suppressing unwanted gas evolution due to side reactions thus stabilizing the cathode/electrolyte interface.

Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate-to-severe asthma for up to 3 years.

Double-layer forces acting between micron-sized silica particles are measured with the atomic force microscope in solutions of symmetric, multivalent electrolytes. In particular, the 2:2 electrolytes, CuSO4and MgSO4, and the 3:3 electrolyte LaFe(CN)6were investigated. For the multivalent electrolytes, the measured decay lengths are substantially larger than the ones expected on the basis of simple Debye–Hückel (DH) theory. These deviations can be explained quantitatively by the formation of neutral ion pairs. The measured surface charge density decreases in magnitude with increasing valence. Both effects are caused by ion–ion correlations, which are not included in the classical DH theory. However, this theory remains applicable, provided one considers the formation of ion pairs in solution and an effective surface charge density. This effective charge is substantially smaller in magnitude than the one of the bare surface. This reduction results from adsorption of counterions, which becomes stronger with increasing valence. These observations reveal that DH theory is applicable even in the presence of multivalent ions, provided the effective parameters are chosen appropriately.

All solid-state lithium batteries (ASLB) are paving the attention of the battery community due to the possibility of improving safety at good energy level. Their future development requires the investigation of new electrodes chemistries both based on intercalation or conversion mechanism. In this work we report on the synthesis and characterization of a V2O5 cryogel electrode and its application in ASLB. The combination of V2O5 cryogel and a solid-state electrolyte shows appealing properties of high capacity and enhanced safety.

Previously, anthropogenic ecological overshoot has been identified as a fundamental cause of the myriad symptoms we see around the globe today from biodiversity loss and ocean acidification to the disturbing rise in novel entities and climate change. In the present paper, we have examined this more deeply, and explore the behavioural drivers of overshoot, providing evidence that overshoot is itself a symptom of a deeper, more subversive modern crisis of human behaviour. We work to name and frame this crisis as ‘the Human Behavioural Crisis’ and propose the crisis be recognised globally as a critical intervention point for tackling ecological overshoot. We demonstrate how current interventions are largely physical, resource intensive, slow-moving and focused on addressing the symptoms of ecological overshoot (such as climate change) rather than the distal cause (maladaptive behaviours). We argue that even in the best-case scenarios, symptom-level interventions are unlikely to avoid catastrophe or achieve more than ephemeral progress. We explore three drivers of the behavioural crisis in depth: economic growth; marketing; and pronatalism. These three drivers directly impact the three ‘levers’ of overshoot: consumption, waste and population. We demonstrate how the maladaptive behaviours of overshoot stemming from these three drivers have been catalysed and perpetuated by the intentional exploitation of previously adaptive human impulses. In the final sections of this paper, we propose an interdisciplinary emergency response to the behavioural crisis by, amongst other things, the shifting of social norms relating to reproduction, consumption and waste. We seek to highlight a critical disconnect that is an ongoing societal gulf in communication between those that know such as scientists working within limits to growth, and those members of the citizenry, largely influenced by social scientists and industry, that must act.

Purpose: Prolonged Postoperative Ileus (PPOI) after abdominal surgery may affect unfavourably the patient recovery. The aim of this study was to estimate the incidence of PPOI in patients elective for colorectal resection and investigate perioperative variables associated with PPOI. Methods: A consecutive series of 428 patients undergoing colorectal resection (median age 72, range 24-92, years; men/women ratio 1.14) were analyzed. Data were extracted retrospectively throughout a five-year period from an electronic prospectively maintained database. PPOI was defined as the need for postoperative insertion of a nasogastric tube in a patient experiencing nausea and two episodes of vomiting and further showing absence of adequate bowel function (absence of flatus/stool) with lack of bowel sounds and abdominal distension. Results: Incidence of PPOI was 7% [95% confidence interval (95%CI), 4.8-9.9%]. Mean hospital stay was 8 days longer in patients with PPOI. Male gender, cancer, cardiac and respiratory co-morbidity, rectal resection, open/converted access, duration of operation, stoma formation and body mass index were associated with PPOI at univariate analysis (0.001< P< 0.048). PPOI was independently associated with male gender [adjusted odds ratio (OR), 4.2; 95%CI, 1.5-11.5], stoma formation (OR, 2.8; 95%CI, 1.2-6.8) and obesity (OR of obese vs. normal weight patients, 3.8, 95%CI, 1.2-12.0). Conclusion: After colorectal resection, PPOI leads to a prolonged hospital stay and slower patient's recovery. An international standardized definition of PPOI is strongly needed to make comparable results from researches and to reliably identify patients with increased risk, also to improve the therapeutic preventive policies in these patients.

The short-term desorption induced by changes of aqueous chemistry of predeposited polyelectrolyte layers on solid surfaces was studied with reflectometry. The behavior of a strong polycation, polydiallydimethylammonium chloride (PDADMAC), interacting with flat silica was investigated in detail. Results showed that partial desorption of preadsorbed polymer chains can be quickly triggered by changes in ionic strength and pH. When lowering these parameters in the PDADMAC–silica system, the increased lateral repulsive potential of neighboring chains drove the desorption of some of the polymer. Furthermore, layer desorption was favored when electrostatic interactions between a polyelectrolyte and the underlying surface became less attractive or switched to being repulsive. At the investigated timescales (<1 h), adlayer desorption was always partial and often incomplete. When initiating desorption from a condition of large adsorbed mass, desorption effects did not result in the plateau mass obtained by adsorption on a clean surface: an excess mass remained deposited. The results thus suggest that a relatively large energy barrier needs to be overcome to induce redissolution of predeposited chains and that this barrier may be a function of the number of polymer–surface interactions, which are in turn correlated with polymer molecular mass. These mechanisms have important implications for environmental processes and colloidal systems because they imply that, once adsorbed, polymeric chains may be redissolved but only to a limited degree at typical engineering timescales.

Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters.

Amorphous silicon thin films having various thicknesses were investigated as a negative electrode material for lithium-ion batteries. Electrochemical characterization of the 20 nm thick thin silicon film revealed a very low first cycle Coulombic efficiency, which can be attributed to the silicon oxide layer formed on both the surface of the as-deposited Si thin film and the interface between the Si and the substrate. Among the investigated films, the 100 nm Si thin film demonstrated the best performance in terms of first cycle efficiency and cycle life. Observations from scanning electron microscopy demonstrated that the generation of cracks was inevitable in the cycled Si thin films, even as the thickness of the film was as little as 20 nm, which was not predicted by previous modeling work. However, the cycling performance of the 20 and 100 nm silicon thin films was not detrimentally affected by these cracks. The poor capacity retention of the 1 μm silicon thin film was attributed to the delamination.

An accounting of the lithium-inventory associated with Si-graphite composite anode cycling in a full cell is reported. The evaluation makes use of a Si-graphite/LiFePO4 diagnostic cell couple whereby Li supply is available from a capacity over-sized LiFePO4 cathode. Electrochemical results indicate that the irreversible capacity per cycle is progressive and cumulative, dependent on the lithiation capacity, but independent of Li-inventory. Under a capacity limited cycling protocol, however, capacity fade is delayed until the lithium reserve is consumed. Our analysis suggests a link between the total exchanged charge and the duration of the silicon particle degradation process, after which the Coulombic efficiency is improved. However, due to the large amounts of Li consumed in this long "formation" process, capitalizing on this could be difficult to achieve in practice. Results from Raman spectroscopy and scanning electron microscopy (SEM) of focused-ion beam (FIB) cross-sectioned samples indicate a dramatic increase to the Si-graphite electrode thickness and loss of Si domain microstructure after cycling, although the large voids present in the pristine electrode remain.

The Small Hive Beetle (SHB), Aethina tumida, is an invasive pest of honey bee colonies that causes significant damage to the beekeeping sector. SHB was detected in southern Italy (EU) in 2014 and despite adopted eradication measures, is still present there. After three years of observations of SHB in Calabria (2014-2016), we provide here some practical tips for improving control measures. A new time-saving colony examination method, including the use of an internal divider reduced the time needed for hive inspections by 31.86 % on average. Prioritizating the inspection of pollen and honey combs rather than brood combs is advised. Sentinel apiaries with no more than five colonies without supers are suggested for each beekeeping location in order to attract and to monitor the early appearance of SHB. The use of these methods will enable early detection and prompt control measures application before this destructive pest can spread in the region.

Residence at higher altitude has been associated with improved anemia parameters and lower mortality rates among end-stage renal disease (ESRD) patients. However, these associations were observed prior to the 2011 shift in erythropoiesis-stimulating agent (ESA) dosing. To determine the impact of altitude on contemporary ESRD patients, a retrospective observational analysis was conducted in which patients were ascribed to one of four altitude categories as of 1 Jan 2012 and outcomes were assessed during 2012. Associations between altitude category and outcomes were estimated using generalized linear mixed models, adjusted for covariates that differed at baseline. Patients at higher altitude were less likely to receive ESA treatment, and dose was 723 U/treatment (95 % confidence interval [CI]: 544, 834) lower in the highest altitude category compared to the lowest category. The proportion of patients using IV iron decreased with increasing altitude category. Patients in the highest two categories had greater mean hemoglobin values (+0.15 and +0.23 g/dL) than the lowest. Mortality was lower for patients in the highest altitude category compared to those in the lowest (incidence rate ratio 0.73; 95 % CI: 0.63, 0.88), although their rate of missed dialysis treatments was slightly higher. This study confirms that, in the context of current anemia management practices, high altitude is associated with higher hemoglobin and lower mortality, despite lower utilization of ESA and IV iron.

In this paper, a modification of the standard particle filter algorithm is applied to face the fault detection issue, on an electro-mechanical actuator. The variant, based on a hybrid system interpretation of the health monitoring problem, is known as OTPF (Observation and Transition Particle Filter). By modeling each fault condition as a hybrid system mode, the method is able to assess the most likely regime for each time stamp. Following this approach, data were acquired from an electro-mechanical actuator, used in aerospace environment, under various fault conditions. The injected mechanical defects consisted in damages undergone by steel spheres, inside a ballscrew transmission system. Then, a model for each condition was identified and the proposed methodology applied. Simulation results show the superiority of the method with respect to the EKF (Extended Kalman Filter), especially because the distribution of the disturbances which affect the system is usually not gaussian.

Following the discovery of the small hive beetle (Aethina tumida) (SHB) in the Calabria region of Italy in 2014, and similar finds in the region in the following years, it seems appropriate to evaluate measures that could allow the movement of supers full of honey from SHB non-infested but at risk areas, to extraction and processing facilities located in SHB non-infested areas. Freezing is appropriate as a sanitary measure for hive products such as pollen, but honey has a low thermal conductivity, so long periods of time are necessary to freeze whole supers. Supers containing two different honey crops (chestnut and eucalyptus) were placed in a freezing facility to determine the optimum times for SHB control. We found that supers full of honey should be stored in a −20 °C freezer for at least 71 (chestnut honey) and 83 (eucalyptus honey) hours respectively, to fulfil OIE recommendations for sanitization, but considering eucalyptus honey the worst scenario, we would recommend an 83-h-treatment generally.

Microbial products are thought to influence the progression of cholangiopathies, in particular primary sclerosing cholangitis (PSC). Inflammasomes are molecular platforms that respond to microbial products through the synthesis of proinflammatory cytokines. We investigated the role of inflammasome activation in cholangiocyte response to injury. Nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing protein 3 (Nlrp3) expression was tested in cholangiocytes of normal and cholestatic livers. Effects of Nlrp3 activation induced by incubation with lipopolysaccharide and ATP was studied in vitroin normal and siRNA-Nlrp3 knocked-down cholangiocytes. Wild-type and Nlrp3 knockout (Nlrp3−/−) mice were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; a model of sclerosing cholangitis) for 4 weeks. Nlrp3 and its components were overexpressed in cholangiocytes of mice subjected to DDC and in patients affected by PSC. In vitro, Nlrp3 activation stimulated expression of Il-18 but not of Il-1β and Il-6. Nlrp3 activation had no effect on cholangiocyte proliferation but significantly decreased the expression of Zonulin-1 and E-cadherin, whereas Nlrp3 knockdown increased the permeability of cholangiocyte monolayers. In vivo, the DDC-stimulated number of cytokeratin-19–positive cells in the liver of wild-type animals was slightly reduced in Nlrp3−/−mice, and expression of E-cadherin was reestablished. In conclusion, Nlrp3 is expressed in reactive cholangiocytes, in both murine models and patients with PSC. Activation of Nlrp3 leads to synthesis of proinflammatory cytokines and influences epithelial integrity of cholangiocytes.

Materials with the general composition LiMO2, where M is a mix of nickel, cobalt, and manganese, have been studied extensively as cathodes for lithium-based batteries. Some compositions, like LiNi0.5Co0.2Mn0.3O2 (NCM523), are already being employed in commercial lithium-ion batteries. The study reported here focuses on Raman spectroscopic investigations of NCM523 in the laminate form typically used to fabricate lithium battery cathodes. One of the problems encountered in such studies is that the scattering from LiMO2-type phases gets progressively weaker as the nickel content increases. NCM523 exhibits this behavior due to the fact that half of the transition metal content is nickel. In this study we show that the intensity of the Raman scattering from the NCM523 phonons can be significantly increased by electroplating sub-micron gold clusters on NCM523 laminates. The gold tends to plate preferentially on the NCM523 particles in randomly sized clusters. These clusters stimulate the NCM523 Raman scattering to varying extents approaching 100 times the scattering intensity from uncoated laminates. Intensity enhancement variations created by heterogeneities associated with the multi-phase nature of the NCM523 laminate, the random character of the sub-micron gold deposits, and the induced preferential orientation of NCM523 grains during laminate fabrication are addressed.