Weyl-van-der-Waerden formalism for helicity amplitudes of massive particles

The Weyl-van-der-Waerden spinor technique for calculating helicity amplitudes of massive and massless particles is presented in a form that is particularly well suited to a direct implementation in computer algebra. Moreover, we explain how to exploit discrete symmetries and how to avoid unphysical poles in amplitudes in practice. The efficiency of the formalism is demonstrated by giving explicit compact results for the helicity amplitudes of the processes gamma gamma -> f fbar, f fbar -> gamma gamma gamma, mu^- mu^+ -> f fbar gamma.Comment: 24 pages, late

Side effects and treatment initiation barriers of sodium-glucose cotransporter 2 inhibitors in heart failure: a systematic review and meta-analysis

Aims Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium–glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. Methods and results We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91–1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95–1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51–0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. Conclusion Sodium–glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors

The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice

Campylobacter jejuni infections have a high prevalence worldwide and represent a significant socioeconomic burden. C. jejuni can cross the intestinal epithelial barrier as visualized in biopsies derived from human patients and animal models, however, the underlying molecular mechanisms and associated immunopathology are still not well understood. We have recently shown that the secreted serine protease HtrA (high temperature requirement A) plays a key role in C. jejuni cellular invasion and transmigration across polarized epithelial cells in vitro. In the present in vivo study we investigated the role of HtrA during C. jejuni infection of mice. We used the gnotobiotic IL-10−/− mouse model to study campylobacteriosis following peroral infection with the C. jejuni wild-type (WT) strain NCTC11168 and the isogenic, non-polar NCTC11168ΔhtrA deletion mutant. Six days post infection (p.i.) with either strain mice harbored comparable intestinal C. jejuni loads, whereas ulcerative enterocolitis was less pronounced in mice infected with the ΔhtrA mutant strain. Moreover, ΔhtrA mutant infected mice displayed lower apoptotic cell numbers in the large intestinal mucosa, less colonic accumulation of neutrophils, macrophages and monocytes, lower large intestinal nitric oxide, IFN-γ, and IL-6 as well as lower TNF-α and IL-6 serum concentrations as compared to WT strain infected mice at day 6 p.i. Notably, immunopathological responses were not restricted to the intestinal tract given that liver and kidneys exhibited mild histopathological changes 6 days p.i. with either C. jejuni strain. We also found that hepatic and renal nitric oxide levels or renal TNF-α concentrations were lower in the ΔhtrA mutant as compared to WT strain infected mice. In conclusion, we show here that the C. jejuni HtrA protein plays a pivotal role in inducing host cell apoptosis and immunopathology during murine campylobacteriosis in the gut in vivo

Movement and ranging patterns of the Common Chaffinch in heterogeneous forest landscapes

The partitioning of production forests into discretely managed forest stands confronts animals with diversity in forest attributes at scales from point-level tree assemblages to distinct forest patches and range-level forest cover. We have investigated the movement and ranging patterns of male Common Chaffinches, Fringilla coelebs, in heterogeneous forest production landscapes during spring and summer in south-western Germany. We radio-tracked a total of 15 adult males, each for up to six days, recording locations at 10-min intervals. We then performed point-level tree surveys at all tracking locations and classified forest stand attributes for the areal covering of birds’ ranges. Movement distances were shortest in beech forest stands and longer in spruce-mixed and non-spruce conifer stands. Movement distances increased with stand age in beech stands but not in others, an effect that was only detectable in a multilevel hierarchical model. We found negligible effects of point-level tree assemblages and temperature on movement distances. Daily range estimates were from 0.01 to 8.0 hectare (median of 0.86 ha) with no evident impact of forest attributes on ranging patterns but considerable intra-individual variation in range sizes over consecutive days. Most daily ranges covered more than one forest stand type. Our results show that forest management impacts the movement behaviour of chaffinches in heterogeneous production forest. Although point-level effects of movement distances are weak compared with stand-level effects in this study, the hierarchical organization of forest is an important aspect to consider when analysing fine-scale movement and might exert more differentiated effects on bird species that are more sensitive to habitat changes than the chaffinch

N=2 Supersymmetric Scalar-Tensor Couplings

We determine the general coupling of a system of scalars and antisymmetric tensors, with at most two derivatives and undeformed gauge transformations, for both rigid and local N=2 supersymmetry in four-dimensional spacetime. Our results cover interactions of hyper, tensor and double-tensor multiplets and apply among others to Calabi-Yau threefold compactifications of Type II supergravities. As an example, we give the complete Lagrangian and supersymmetry transformation rules of the double-tensor multiplet dual to the universal hypermultiplet.Comment: 23 pages, LaTeX2e with amsmath.sty; v2: corrected typos and added referenc

Self-organized density patterns of molecular motors in arrays of cytoskeletal filaments

The stationary states of systems with many molecular motors are studied theoretically for uniaxial and centered (aster-like) arrangements of cytoskeletal filaments using Monte Carlo simulations and a two-state model. Mutual exclusion of motors from binding sites of the filaments is taken into account. For small overall motor concentration, the density profiles are exponential and algebraic in uniaxial and centered filament systems, respectively. For uniaxial systems, exclusion leads to the coexistence of regions of high and low densities of bound motors corresponding to motor traffic jams, which grow upon increasing the overall motor concentration. These jams are insensitive to the motor behavior at the end of the filament. In centered systems, traffic jams remain small and an increase in the motor concentration leads to a flattening of the profile, if the motors move inwards, and to the build-up of a concentration maximum in the center of the aster if motors move outwards. In addition to motors density patterns, we also determine the corresponding patterns of the motor current.Comment: 48 pages, 8 figure

Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study

Background In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. Methods In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. Results Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. Conclusions While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. Trial registration Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien

Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring

Aims Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Methods and results The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan-treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non-loop diuretics (P = 0.21). Conclusions In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes

Predicting a small molecule-kinase interaction map: A machine learning approach

<p>Abstract</p> <p>Background</p> <p>We present a machine learning approach to the problem of protein ligand interaction prediction. We focus on a set of binding data obtained from 113 different protein kinases and 20 inhibitors. It was attained through ATP site-dependent binding competition assays and constitutes the first available dataset of this kind. We extract information about the investigated molecules from various data sources to obtain an informative set of features.</p> <p>Results</p> <p>A Support Vector Machine (SVM) as well as a decision tree algorithm (C5/See5) is used to learn models based on the available features which in turn can be used for the classification of new kinase-inhibitor pair test instances. We evaluate our approach using different feature sets and parameter settings for the employed classifiers. Moreover, the paper introduces a new way of evaluating predictions in such a setting, where different amounts of information about the binding partners can be assumed to be available for training. Results on an external test set are also provided.</p> <p>Conclusions</p> <p>In most of the cases, the presented approach clearly outperforms the baseline methods used for comparison. Experimental results indicate that the applied machine learning methods are able to detect a signal in the data and predict binding affinity to some extent. For SVMs, the binding prediction can be improved significantly by using features that describe the active site of a kinase. For C5, besides diversity in the feature set, alignment scores of conserved regions turned out to be very useful.</p