Principles of Hand Fracture Management

The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner

Confocal microscopy 3D imaging of diesel particulate matter

To date, diesel particulate matter (DPM) has been described as aggregates of spherule particles with a smooth appearing surface. We have used a new colour confocal microscope imaging method to study the 3D shape of diesel particulate matter (DPM); we observed that the particles can have sharp jagged appearing edges and consistent with these findings, 2D light microscopy demonstrated that DPM adheres to human lung epithelial cells. Importantly, the slide preparation and confocal microscopy method applied avoids possible alteration to the particles' surfaces and enables colour 3D visualisation of the particles. From twenty-one PM particles, the mean (standard deviation) major axis length was 5.6 (2.25) μm with corresponding values for the minor axis length of 3.8 (1.25) μm. These new findings may help explain why air pollution particulate matter (PM) has the ability to infiltrate human airway cells, potentially leading to respiratory tract, cardiovascular and neurological disease

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Decisions on sick leave certifications for acute airways infections based on vignettes: A cross-sectional survey of GPs in Norway and Poland

Objective. To explore whether frequency and duration of sick-leave certifi cation for acute airway infections differ between general practitioners (GPs) in Poland and Norway. Design . Cross-sectional survey. Setting. Educational courses for GPs. Intervention. We used a questionnaire with four vignettes presenting patients with symptoms consistent with pneumonia, sinusitis, common cold, and exacerbation of chronic obstructive pulmonary disease (COPD), respectively. For each vignette GPs were asked whether they would offer a sick-leave note, and if so, for how many days. Subjects. Convenience samples of GPs in Poland (n 216) and Norway (n 171). Main outcome measures. Proportion of GPs offering a sick-leave certifi cate. Duration of sick-leave certifi cation. Results . In Poland 100%, 95%, 87%, and 94% of GPs would offer sick leave for pneumonia, sinusitis, common cold, and exacerbation of COPD, respectively. Corresponding fi gures in Norway were 97%, 83%, 60%, and 90%. Regression analysis adjusting for the GPs ’ sex, speciality, experience, and workload indicated that relative risks for offering sick leave (Poland versus Norway) were 1.16 (95% CI 1.07 – 1.26) for sinusitis and 1.50 (1.28 – 1.75) for common cold. Among GPs who offered sick leave for pneumonia, sinusitis, common cold, and exacerbation of COPD, mean duration was 8.9, 7.5, 5.1, and 6.9 days (Poland) versus 6.6, 4.3, 3.1, and 6.1 days (Norway), respectively. In regression analyses the differences between the Polish and Norwegian samples in duration of sick leave were statistically signifi cant for all vignettes. A pattern of offering sick leave for three, fi ve, seven, 10, or 14 days was observed in both countries. Conclusion . In the Polish sample GPs were more likely to offer sick-leave notes for sinusitis and common cold. GPs in Poland offered sick leaves of longer duration for pneumonia, sinusitis, common colds, and exacerbation of COPD compared with GPs in the Norwegian sample