Additional file 1: of Exploring musculoskeletal injuries in the podiatry profession: an international cross sectional study

FLEXAR survey consent and questions. (PDF 434 kb

Additional file 1: of What is the impact of rerouting a cancer diagnosis from emergency presentation to GP referral on resource use and survival? Evidence from a population-based study

Technical Appendix. Description of the Basu-Manning estimator used in the statistical analysis. (DOCX 23 kb

Association between high ambient temperature and acute work-related injury: a case-crossover analysis using workers’ compensation claims data

Objectives: The aim of this study was to investigate the association between high ambient temperature and acute work-related injury, expanding on previous research in this area. Specifically we examined the relationship between both daytime and overnight temperatures and injury risk and disentangled physically demanding occupational exposures from exposure to outdoor working conditions. Methods: A time-stratified case-crossover study design was used to examine the association between ambient temperatures and acute work-related injuries in Melbourne, Australia, 2002–2012, using workers’ compensation claims to identify work-related injuries. The relationship was assessed for both daily maximum and daily minimum temperatures using conditional logistic regression. Results: Significant positive associations between temperature and acute work-related injury were seen for younger workers (<25 years), with the odds of injury increasing by 1% for each 1 °C increase in daily minimum temperature, and by 0.8% for each 1 °C increase in daily maximum temperature. Statistically significant associations were also observed between daily maximum temperature and risk of injury for workers employed in the highest strength occupations and for male workers, and between daily minimum temperature and injury for all cases combined, female workers, workers aged 25–35 and ≥55 years, "light" and "limited" physical demand groups, and "in vehicle or cab" and "regulated indoor climate" workplace exposure groups. Conclusions: Young workers, male workers and workers engaged in heavy physical work are at increased risk of injury on hot days, and a wider range of worker subgroups are vulnerable to injury following a warm night. In light of climate change projections, this information is important for informing injury prevention strategies.</p

The baseline characteristics of the enrolled cohort.

1<p>CD4-counts were collected from the clinical record. We recorded the last CD4-count prior to study enrolment.</p>2<p>Viral load measurements were collected from the clinical record. We recorded the last viral load prior to study enrolment that was done within 6 months of tuberculosis diagnosis and treatment.</p>3<p>One patient was started on LPV/r-based ART and tuberculosis treatment on the same day in the double dose LPV/r group.</p

The profile of the study cohort.

<p>The profile of the study cohort.</p

Lopinavir concentrations of individual patients during the study period.

<p>The circles indicate lopinavir concentrations measured while patients were receiving tuberculosis treatment, while the squares indicate lopinavir concentrations once tuberculosis treatment has been completed.</p

Additional file 1: Table S1. of Validation of an NGS mutation detection panel for melanoma

Complete mutation hotspot list included in Custom Ampliseq gene panel for melanoma, including common driver mutations in BRAF, NRAS, KRAS, MEK, GNAQ, and GNA11. (DOCX 125 kb

Sample level gene expression changes in MSI-H STAD samples with a <i>JAK1</i> frameshift.

<p>(A) Heatmap of MSI-H, STAD tumors (columns). Marker rows: 1) Samples with a <i>JAK1</i> frameshift are denoted in green. 2) IFN Response, after <i>JAK1</i> frameshift samples are ordered by IFN Response. 3) Log10 of <i>JAK1</i> expression. 4) <i>JAK1</i> frameshift (FS) MAF. Gene expression was scaled by Z scoring and the order of genes (rows) is determined by the signal to noise metric for GSEA analysis (t). Negative t indicated decreased expression in <i>JAK1</i> frameshift samples. Only genes in the HALLMARK IFN GAMMA RESPONSE are shown. (B) Histogram of IFN Gamma Response in arbitrary units (AU). (C) Scatter plot of samples for <i>JAK1</i> expression and IFN Gamma Response. Pearson’s r and associated P values are shown. (D) Scatter plot of samples for <i>JAK1</i> expression and <i>JAK1</i> FS MAF. Pearson’s r and associated P values are shown. (E) Scatter plot of <i>JAK1</i> frameshift samples for <i>JAK1</i> FS MAF and IFN Gamma Response. Pearson’s r and associated P value is shown.</p

GSEA of MSI WT vs. JAK1 frameshift STAD.

<p>GSEA of MSI WT vs. JAK1 frameshift STAD.</p

Loss of function <i>JAK1</i> mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion

<div><p>Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (<i>JAK1/2/3</i>, <i>TYK2</i>). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in <i>JAK1</i> were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a <i>JAK1</i> frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) <i>JAK1</i> frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which <i>JAK1</i> loss of function contributes to tumor immune evasion is likely associated with loss of the <i>JAK1</i>-mediated interferon response.</p></div