Thickness dependence of unidirectional spin-Hall magnetoresistance in metallic bilayers

A nonlinear magnetoresistance - called unidirectional spin-Hall magnetoresistance - is recently experimentally discovered in metallic bilayers consisting of a heavy metal and a ferromagnetic metal. To study the fundamental mechanism of the USMR, both ferromagnetic and heavy metallic layer thickness dependence of the USMR are presented in a Pt/Co/AlOx trilayer at room temperature. To avoid ambiguities, second harmonic Hall measurements are used for separating spin-Hall and thermal contributions to the non-linear magnetoresistance. The experimental results are fitted by using a drift-diffusion theory, with parameters extracted from an analysis of longitudinal resistivity of the Co layer within the framework of the Fuchs-Sondheimer model. A good agreement with the theory is found, demonstrating that the USMR is governed by both the spin-Hall effect in the heavy metallic layer and the metallic diffusion process in the ferromagnetic layer

Controlling magnetic skyrmion nucleation with Ga+ ion irradiation

In this paper, we show that magnetic skyrmion nucleation can be controlled using Ga+ ion irradiation, which manipulates the magnetic interface effects (in particular the magnetic anisotropy and Dzyaloshinskii-Moriya interaction) that govern the stability and energy cost of skyrmions in thin film systems. We systematically and quantitatively investigated what effect these changes have on the nucleation of magnetic skyrmions. Our results indicate that the energy cost of skyrmion nucleation can be reduced up to 26% in the studied dose range and that it scales approximately linearly with the square root of the domain-wall energy density. Moreover, the total number of nucleated skyrmions in irradiated devices after nucleation was found to depend linearly on the ion dose and could be doubled compared to nonirradiated devices. These results show that ion irradiation cannot only be used to enable local nucleation of skyrmions, but that it also allows for fine control of the threshold and efficiency of the nucleation process.Comment: Main: 17 pages, 3 figures; Supplemental Material: 7 pages, 5 figure

Development of a multi-layered psychosocial care system for children in areas of political violence

Few psychosocial and mental health care systems have been reported for children affected by political violence in low- and middle income settings and there is a paucity of research-supported recommendations. This paper describes a field tested multi-layered psychosocial care system for children (focus age between 8-14 years), aiming to translate common principles and guidelines into a comprehensive support package. This community-based approach includes different overlapping levels of interventions to address varying needs for support. These levels provide assessment and management of problems that range from the social-pedagogic domain to the psychosocial, the psychological and the psychiatric domains. Specific intervention methodologies and their rationale are described within the context of a four-country program (Burundi, Sri Lanka, Indonesia and Sudan). The paper aims to contribute to bridge the divide in the literature between guidelines, consensus & research and clinical practice in the field of psychosocial and mental health care in low- and middle-income countries

Stabilizing chiral spin-structures via an alternating Dzyaloshinskii-Moriya interaction

The stabilization of chiral magnetic spin-structures in thin films is often attributed to the interfacial Dzyaloshinskii-Moriya interaction (DMI). Very recently, however, it has been reported that the chirality induced by the DMI can be affected by dipolar interactions. These dipolar fields tend to form N\'eel caps, which entails the formation of a clockwise chirality at the top of the film and a counterclockwise chirality at the bottom. Here, we show that engineering an alternating DMI that changes sign across the film thickness, together with the tendency to form N\'eel caps, leads to an enhanced stability of chiral spin-structures. Micromagnetic simulations for skyrmions demonstrate that this can increase the effective DMI in a prototypical [Pt/Co/Ir] multilayer system by at least \SI{0.6}{mJ.m^{-2}}. These gains are comparable to what has been achieved using additive DMI, but more flexible as we are not limited to a select set of material combinations. We also present experimental results: by measuring equilibrium domain widths we quantify the effective DMI in [Pt/Co/Ir] multilayer systems typically used for skyrmion stabilization. Upon introducing an alternating DMI we demonstrate changes in the effective DMI that agree with our simulations. Our results provide a route towards enhancing the stability of chiral spin-structures that does not rely on enlarging the chiral interactions.Comment: Includes supplementar

Epidemiology of combined clavicle and rib fractures:a systematic review

Purpose The aim of this systematic review was to provide an overview of the incidence of combined clavicle and rib fractures and the association between these two injuries. Methods A systematic literature search was performed in the MEDLINE, EMBASE, and CENTRAL databases on the 14(th) of August 2020. Outcome measures were incidence, hospital length of stay (HLOS), intensive care unit admission and length of stay (ILOS), duration of mechanical ventilation (DMV), mortality, chest tube duration, Constant-Murley score, union and complications. Results Seven studies with a total of 71,572 patients were included, comprising five studies on epidemiology and two studies on treatment. Among blunt chest trauma patients, 18.6% had concomitant clavicle and rib fractures. The incidence of rib fractures in polytrauma patients with clavicle fractures was 56-60.6% versus 29% in patients without clavicle fractures. Vice versa, 14-18.8% of patients with multiple rib fractures had concomitant clavicle fractures compared to 7.1% in patients without multiple rib fractures. One study reported no complications after fixation of both injuries. Another study on treatment, reported shorter ILOS and less complications among operatively versus conservatively treated patients (5.4 +/- 1.5 versus 21 +/- 13.6 days). Conclusion Clavicle fractures and rib fractures are closely related in polytrauma patients and almost a fifth of all blunt chest trauma patients sustain both injuries. Definitive conclusions could not be drawn on treatment of the combined injury. Future research should further investigate indications and benefits of operative treatment of this injury

The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction

We investigated the effect of trastuzumab on cardiac function in a real‐world historic cohort of patients with HER2‐positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty‐seven patients with HER2‐positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%‐48%) and median follow‐up was 18 months (IQR 9‐34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF 5%‐points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase 5%‐points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio‐protective medications (CPM), including ACE‐inhibitors, beta‐blockers and angiotensine‐2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty‐five percent of patients who received trastuzumab for HER2‐positive MBC did not develop severe cardiotoxicity during a median follow‐up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two‐thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population

Petri Nets with Fuzzy Logic (PNFL): Reverse Engineering and Parametrization

Background: The recent DREAM4 blind assessment provided a particularly realistic and challenging setting for network reverse engineering methods. The in silico part of DREAM4 solicited the inference of cycle-rich gene regulatory networks from heterogeneous, noisy expression data including time courses as well as knockout, knockdown and multifactorial perturbations. Methodology and Principal Findings: We inferred and parametrized simulation models based on Petri Nets with Fuzzy Logic (PNFL). This completely automated approach correctly reconstructed networks with cycles as well as oscillating network motifs. PNFL was evaluated as the best performer on DREAM4 in silico networks of size 10 with an area under the precision-recall curve (AUPR) of 81%. Besides topology, we inferred a range of additional mechanistic details with good reliability, e.g. distinguishing activation from inhibition as well as dependent from independent regulation. Our models also performed well on new experimental conditions such as double knockout mutations that were not included in the provided datasets. Conclusions: The inference of biological networks substantially benefits from methods that are expressive enough to deal with diverse datasets in a unified way. At the same time, overly complex approaches could generate multiple different models that explain the data equally well. PNFL appears to strike the balance between expressive power and complexity. This also applies to the intuitive representation of PNFL models combining a straightforward graphical notation with colloquial fuzzy parameters

Environmental factors contributing to the spread of H5N1 avian influenza in mainland China

Background: Since late 2003, highly pathogenic avian influenza (HPAI) outbreaks caused by infection with H5N1 virus has led to the deaths of millions of poultry and more than 10 thousands of wild birds, and as of 18-March 2008, at least 373 laboratory-confirmed human infections with 236 fatalities, have occurred. The unrestrained worldwide spread of this disease has caused great anxiety about the potential of another global pandemic. However, the effect of environmental factors influencing the spread of HPAI H5N1 virus is unclear. Methodology/Principal Findings: A database including incident dates and locations was developed for 128 confirmed HPAI H5N1 outbreaks in poultry and wild birds, as well as 21 human cases in mainland China during 2004-2006. These data, together with information on wild bird migration, poultry densities, and environmental variables (water bodies, wetlands, transportation routes, main cities, precipitation and elevation), were integrated into a Geographical Information System (GIS). A case-control design was used to identify the environmental factors associated with the incidence of the disease. Multivariate logistic regression analysis indicated that minimal distance to the nearest national highway, annual precipitation and the interaction between minimal distance to the nearest lake and wetland, were important predictive environmental variables for the risk of HPAI. A risk map was constructed based on these factors. Conclusions/Significance: Our study indicates that environmental factors contribute to the spread of the disease. The risk map can be used to target countermeasures to stop further spread of the HPAI H5N1 at its source

Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours

Purpose: Peptide receptor radionuclide therapy using β-emitting radiolabelled somatostatin analogues like DOTA,Tyr3-octreotate shows beneficial results in patients suffering from somatostatin receptor overexpressing tumours. However, after high-dose therapy partial renal reabsorption of radiopeptides may lead to nephrotoxicity. Co-infusion of lysine/arginine lowers renal retention of these radiopeptides without affecting tumour uptake. Recently co-administration of Gelofusine has been described to have a comparable kidney-protecting effect in rats. In the present study optimal dosing of Gelofusine co-administration was studied in tumour-bearing rats. Methods: Doses of 40, 80, 120 or 160 mg/kg Gelofusine were co-injected with 15 μg DOTA,Tyr3-octreotate, labelled with 3 MBq111In for biodistribution (24 h post-injection, n=4 per group) and with 60 MBq111In for microSPECT imaging experiments at 3, 24 and 48 h post-injection. An additional group of rats received 80 mg/kg Gelofusine plus 400 mg/kg lysine co-injection. Biodistribution studies were performed both in older (475 g) and younger (300 g) rats, the latter bearing CA20948 tumours. Results: Co-injection of 40 mg/kg Gelofusine resulted in 40-50% reduction of renal uptake and retention of111In-DOTA,Tyr3-octreotate, whereas higher doses further increased the reduction to 50-60% in both groups of rats. Combining Gelofusine and lysine caused 70% reduction of renal uptake. The uptake of radiolabelled octreotate both in somatostatin receptor-expressing normal tissues and tumours was not affected by Gelofusine co-injection. Conclusion: In rats co-injection of 80 mg/kg Gelofusine resulted in maximum reduction of renal retention of111In-DOTA,Tyr3- octreotate, which was further improved when combined with lysine. Tumour uptake of radiolabelled octreotate was not affected, resulting in an increased tumour to kidney ratio

Tofacitinib for ulcerative colitis:results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice. Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. Conclusion: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients