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Dermatomyositis is an uncommon autoimmune disorder with distinctive cutaneous manifestations that are frequently challenging to manage. Although a number of therapies including hydroxychloroquine, methotrexate, mycophenolate mofetil, and intravenous immunoglobulin have demonstrated efficacy, few alternative treatments are available when these agents fail. Recently, tofacitinib, an oral Janus kinase (JAK)-1/3 inhibitor, was approved for use in rheumatoid arthritis and has demonstrated efficacy for treating inflammatory skin diseases including psoriasis, alopecia areata, vitiligo, and atopic dermatitis. 1,2 Studies suggest that tofacitinib suppresses interferon signaling, 3 a pathway that has been found to be abnormally upregulated in dermatomyositis. 4 With this context in mind, we sought to evaluate the utility of tofacitinib for treating cutaneous dermatomyositis.

Drs Hubiche and Valério had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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Objectives To determine the impact of obtaining housing on geriatric conditions and acute care utilization among older homeless adults. Methods We conducted a 12-month prospective cohort study of 250 older homeless adults recruited from shelters in Boston, Massachusetts between January and June 2010. We determined housing status as reported at the follow-up interview. We examined 4 measures of geriatric conditions at baseline and 12 months: independence in activities of daily living and instrumental activities of daily living, depressive symptoms, and symptoms of urinary incontinence. We determined number of emergency department visits and hospitalizations over 12 months by medical record review. We used multivariate regression models to evaluate the association between obtaining housing and our outcomes of interest. Results At 12 months, 41% of participants had obtained housing. Compared to participants who remained homeless at follow-up, those with housing had fewer depressive symptoms. Other measures of health status at follow-up did not differ by housing status. Participants who obtained housing had a lower rate of acute care utilization over the follow-up period (IRR, 0.5; 95% CI, 0.4–0.6), with an adjusted annualized rate of acute care visits of 2.5 per year (95% CI, 1.7–3.3) among participants who obtained housed and 5.3 per year (95% CI, 3.8–6.7) among participants who remained homeless. Conclusions Older homeless adults who obtained housing experienced improved depressive symptoms and reduced acute care utilization compared to those who remained homeless.

Prepared in cooperation with the Indiana Department of Transportation and Federal Highway Administration. AbstractThe presence of organics in soils is generally associated with high compressibility, significant secondary compression, often unsatisfactory strength characteristics, and low unit weight. As a result of the above, many state DOTs (Departments of Transportation) in the United States have strict limits on the maximum value of the organic content (2-7%) that can be present in soils to be used as subgrades and backfills. The loss on ignition test is the most widely used technique for measuring organic content. However, especially for low organic content soils, this method can lead to significantly overestimate the true organic content. As a result, certain soils may be incorrectly classified and erroneously considered unviable for certain applications; in other cases unnecessary costly treatments may be requested, even if not required. These are the issues motivating the research presented in this report, which addressed the classification of organic soils and the quantification of organic matter in soils.The research reviewed existing classification systems for organic soils, the effects of organic matter on the geotechnical properties of soils, and the methods for determination of organic content. In addition to the review of the existing literature, this research also included experimental work conducted on natural soils with varying organic content, as well as on laboratory prepared ("artificial") organic soils. The experiments performed included loss on ignition tests, Atterberg limits, colorimetric tests, dry combustion tests, thermal analyses, and X-ray diffraction analyses.The work led to propose a system for classifying organic soils which is based on the percentage of organic matter present: soils with organic content <3% are termed mineral soils; if the organic content is >3% and < 15%, soils are classified as mineral soils with organics; when the organic content exceeds 15% but is <30%, the term organic soil is employed. Finally, soils with organic content higher than 30% are termed highly organic soils or peats. Given the potential errors associated with measuring organic content using the LOI method, this research proposes an approach based on the combined use of the LOI test, the liquid limit test conducted both before. Key WordsOrganic soils, classification, LOI, Atterberg limits, liquid limit ratio, colorimetric test. Distribution StatementNo restrictions. This document is available to the public through the National Technical Information Service, Springfield, VA 22161 A variety of methods are available to identify organic matter in soils. In general, these methods can be divided into two categories: qualitative assessments and quantitative measurements. In civil engineering practice, a commonly used qualitative approach to determine whether a soil can be considered organic is the use of the Atterberg limits tests. As outlined in ASTM D2487, the Unified Soil Classification Syst...

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