Updates on the antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by venous or arterial thrombosis, and/or pregnancy loss or complications in the presence of persistently positive antiphospholipid antibodies. Organ involvement, referred to as non-criteria manifestations, includes livedo reticularis, thrombocytopenia and nephropathy. Non-thrombotic inflammatory mechanisms are increasingly identified in the pathogenesis of APS, alongside a recognition that obstetric APS might be a specific subset of APS. Treatment remains focused on life-long anticoagulation and prevention of further thrombosis or obstetric complications. Identification of novel mechanisms is, however, leading the development of diagnostic tests and more targeted therapies to improve disease management

Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients

Downer cows: a reanalysis of an old data set.

CAUL Read and Publish Agreement.AIMS: To compare the performance of two predictive models for the survival of downer cows. METHODS: The first model had been developed in 1987 using a dataset containing missing values, while the second, new model was developed on the same dataset but using modern data imputation and analytical methods. Missing data were imputed using multiple imputation by chained equations and a logistic regression model fitted to the imputed data, with survival or not as the outcome variable. The predictive ability of the model built on the imputed data was contrasted with the original prognostic model by testing them both on a second smaller but complete data set, collected contemporaneously with the development of the original model but from a different region of New Zealand. Sensitivity, specificity, accuracy, and cut point for the two models were calculated. RESULTS: The original 1987 model had a slightly higher accuracy than that of the new one with a sensitivity of 0.85 (95% CI = 0.72-0.94) and a specificity of 0.82 (95% CI = 0.7-0.91), using a cut point for the probability of survival = 0.313. CONCLUSIONS: The original prognostic formula published by Clark et al. in 1987 performed as well as a modern model built on an imputed data set. CLINICAL RELEVANCE: The use of a prognostic test based on the Clark model should remain an important part of the clinical examination of downer cows by New Zealand veterinarians.Abbreviations: AUC: Area under the curve; AST: Aspartate transaminase activity; CK: Creatine phosphokinase activity; GAM: Generalised additive model; NSAID: Non-steroidal-anti-inflammatory drugs; PCV: Packed cell volume.Publishe

AlH3 between 65-110 GPa: implications of electronic band and phonon structures

A first-principles density-functional-theory method has been used to reinvestigate the mechanical and dynamical stability of the metallic phase of AlH3 between 65-110 GPa. The electronic properties and phonon dynamics as a function of pressure are also explored. We find electron-phonon superconductivity in the cubic Pm-3n structure with critical temperature Tc = 37 K at 70 GPa which decreases rapidly with the increase of pressure. Further unlike a previously calculated Tc value of 24 K at 110 GPa, we do not find any superconductivity of significance at this pressure which is consistent with experimental observation.Comment: 6 pages, 4 figures Keywords: AlH3, Electronic structure, Phonon dynamics, Superconductivity PACS number(s): 62.50.-p, 63.20.kd, 74.10.+v, 74.20.P

Synoptic-scale and mesoscale controls for tornadogenesis on cold fronts: Shear-zone vortex-genesis in a developing frontal wave

High-resolution model simulations and radar observations are used to investigate the onset of vortex-genesis in a tornadic narrow cold-frontal rain band (NCFR). The timing and location of vortex-genesis was strongly constrained by a developing frontal wave, which tracked northeast across the United Kingdom and Ireland on 17 October 2011. In the simulations, vortices occurred preferentially during the early stages of wave development and just down-front of the wave centre, where large increases in vertical vorticity occurred in concert with decreases in the cross-frontal confluence. Vortex-genesis ceased as the frontal wave matured, due to the onset of frontal fracture. Two distinct scales of vortex-genesis are documented: primary vortex-genesis on the meso-γ-scale, and secondary vortex-genesis on the miso-scale. We show that horizontal shearing instability is the most likely vortex-genesis mechanism, consistent with previous theoretical work on the stability of vertical vortex strips in the presence of horizontal stretching deformation. Secondary vortices occurred along the braid regions between primary vortices where the shear zone became particularly narrow and intense. In the model, these vortices developed extremely rapidly (from small perturbations to maximum vertical vorticity in 5–15 min) and the strongest exhibited near-surface vertical vorticity maxima approaching 10−1 s−1. Vortices of both scales were associated with characteristic local perturbations in the NCFR and we show, by comparison with radar reflectivity data, that primary and secondary vortices were likely present in the real NCFR. Tornado reports were associated with small NCFR perturbations like those associated with the secondary vortices in the model simulations. Analysis of the sub-structure of individual simulated vortices suggests that tornado-genesis is most likely within a region of intense near-surface vertical vorticity stretching at the north or northwest flank of the secondary vortices

Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease that is generally considered to be T cell-driven. Accordingly, most strategies of immunotherapy for T1D prevention and treatment in the clinic have targeted the T cell compartment. To date, however, immunotherapy has had only limited clinical success. Although certain immunotherapies have promoted a protective effect, efficacy is often short-term and acquired immunity may be impacted. This has led to the consideration of combining different approaches with the goal of achieving a synergistic therapeutic response. In this review, we will discuss the status of various T1D therapeutic strategies tested in the clinic, as well as possible combinatorial approaches to restore β cell tolerance