Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome

Background: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). Objective: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. Methods: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. Results: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad TH1/TH2/TH17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by TH1 effector T cells. Conclusions: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS

The FAIR Guiding Principles for scientific data management and stewardship

There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community

DES Y3 + KiDS-1000: Consistent cosmology combining cosmic shear surveys

We present a joint cosmic shear analysis of the Dark Energy Survey (DES Y3) and the Kilo-Degree Survey (KiDS-1000) in a collaborative effort between the two survey teams. We find consistent cosmological parameter constraints between DES Y3 and KiDS-1000 which, when combined in a joint-survey analysis, constrain the parameter $S_8 = \sigma_8 \sqrt{\Omega_{\rm m}/0.3}$ with a mean value of $0.790^{+0.018}_{-0.014}$. The mean marginal is lower than the maximum a posteriori estimate, $S_8=0.801$, owing to skewness in the marginal distribution and projection effects in the multi-dimensional parameter space. Our results are consistent with $S_8$ constraints from observations of the cosmic microwave background by Planck, with agreement at the $1.7\sigma$ level. We use a Hybrid analysis pipeline, defined from a mock survey study quantifying the impact of the different analysis choices originally adopted by each survey team. We review intrinsic alignment models, baryon feedback mitigation strategies, priors, samplers and models of the non-linear matter power spectrum.Comment: 38 pages, 21 figures, 15 tables, submitted to the Open Journal of Astrophysics. Watch the core team discuss this analysis at https://cosmologytalks.com/2023/05/26/des-kid

Validation of flexible goniometry as a measure of joint kinematics

The Biometrics Flexible electrogoniometer has the potential to allow physiotherapists to record the motion of joints during dynamic functional activities. In order to make full and appropriate use of this device it is necessary to comprehend the design, attachment and measurement properties of this instrument. The results of these studies indicate that the electrogoniometers are stable, precise, accurate and repeatable in performance. Little variation exists between electrogoniometers or between the performance of an electrogoniometer at different times, on different days or in different environmental conditions. Small hysteretic effects and inaccuracies are present in the devices but these are of the order of 1 or 2 degrees. The system is not affected by environmental pollutants such as heat, electrical interference, convection currents or noise and therefore can be used in a variety of hospital settings. The device is however affected by abduction/adduction angle with angles of 40° or more giving substantial errors when associated with simultaneous flexion or extension. The electrogoniometer should be attached firmly and securely across the joint in an essentially planar configuration. Provided care is taken to handle and mount the electrogoniometers appropriately they appear to record knee movement faithfully and accurately and the system is capable of giving valid and meaningful clinical data

Experimental investigation of the post-buckling behaviour of curved aluminium alloy panels under axial compression

SIGLEAvailable from British Library Document Supply Centre- DSC:6015.42F(N--87-19781)(microfiche) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Experimental investigation of the post-buckling behaviour of curved aluminium alloy panels under axial compression

SIGLEAvailable from British Library Document Supply Centre- DSC:6015.42F(N--87-19781)(microfiche) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery

Background: Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. Methods: We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004–13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs <65 years old) and the timing of BP measurement. Results: A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01–1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03–1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. Conclusions: In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality