Social Connection, Relationships and Older Lesbian and Gay People

This paper presents data from a small study exploring the impacts of homophobia on the lives of older lesbian and gay Australians. Eleven in-depth interviews were conducted with older lesbians (6) and gay men (5) ranging in age from 65 to 79 years. The study found that participants’ sense of self was shaped by the dominant medical, legal and religious institutions of their youth that defined them as sick, immoral or criminal. Participants described enforced “cure” therapies, being imprisoned, having employment terminated and being disowned and disinherited by family. In this context, intimate relationships and social networks provided refuge where trust was rebuilt and sexuality affirmed. Many created safe spaces for themselves. This equilibrium was threatened with increasing age, disability and the reliance on health and social services. Participants feared a return to institutional control and a need to “straighten up” or hide their sexuality. In response, partners stepped into the role of caregiver, at times beyond their capacity and at a cost to their relationship. The study describes the importance of understanding social connections in the lives of older lesbians and gay men. It highlights the need for inclusive services to ensure that social networks are supported and that health and well-being are promoted

Theoretical Evaluation of the Detectability of Random Lesions in Bayesian Emission Reconstruction

Detecting cancerous lesion is an important task in positron emission tomography (PET). Bayesian methods based on the maximum a posteriori principle (also called penalized maximum likelihood methods) have been developed to deal with the low signal to noise ratio in the emission data. Similar to the filter cut-off frequency in the filtered backprojection method, the prior parameters in Bayesian reconstruction control the resolution and noise trade-off and hence affect detectability of lesions in reconstructed images. Bayesian reconstructions are difficult to analyze because the resolution and noise properties are nonlinear and object-dependent. Most research has been based on Monte Carlo simulations, which are very time consuming. Building on the recent progress on the theoretical analysis of image properties of statistical reconstructions and the development of numerical observers, here we develop a theoretical approach for fast computation of lesion detectability in Bayesian reconstruction. The results can be used to choose the optimum hyperparameter for the maximum lesion detectability. New in this work is the use of theoretical expressions that explicitly model the statistical variation of the lesion and background without assuming that the object variation is (locally) stationary. The theoretical results are validated using Monte Carlo simulations. The comparisons show good agreement between the theoretical predications and the Monte Carlo results

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Governing Boards and Profound Organizational Change in Hospitals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69047/2/10.1177_107755878904600204.pd

Consensus standards of healthcare for adults and children with inflammatory bowel disease in the UK

Objective Symptoms and clinical course during inflammatory bowel disease (IBD) vary among individuals. Personalised care is therefore essential to effective management, delivered by a strong patient-centred multidisciplinary team, working within a well-designed service. This study aimed to fully rewrite the UK Standards for the healthcare of adults and children with IBD, and to develop an IBD Service Benchmarking Tool to support current and future personalised care models. Design Led by IBD UK, a national multidisciplinary alliance of patients and nominated representatives from all major stakeholders in IBD care, Standards requirements were defined by survey data collated from 689 patients and 151 healthcare professionals. Standards were drafted and refined over three rounds of modified electronic-Delphi. Results Consensus was achieved for 59 Standards covering seven clinical domains; (1) design and delivery of the multidisciplinary IBD service; (2) prediagnostic referral pathways, protocols and timeframes; (3) holistic care of the newly diagnosed patient; (4) flare management to support patient empowerment, self-management and access to specialists where required; (5) surgery including appropriate expertise, preoperative information, psychological support and postoperative care; (6) inpatient medical care delivery (7) and ongoing long-term care in the outpatient department and primary care setting including shared care. Using these patient-centred Standards and informed by the IBD Quality Improvement Project (IBDQIP), this paper presents a national benchmarking framework. Conclusions The Standards and Benchmarking Tool provide a framework for healthcare providers and patients to rate the quality of their service. This will recognise excellent care, and promote quality improvement, audit and service development in IBD

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Focal-plane detector system for the KATRIN experiment

The focal-plane detector system for the KArlsruhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high-vacuum system, a high-vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system. It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.Comment: 28 pages. Two figures revised for clarity. Final version published in Nucl. Inst. Meth.

Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants