The complete costs of genome sequencing: a microcosting study in cancer and rare diseases from a single center in the United Kingdom

Abstract: Purpose: The translation of genome sequencing into routine health care has been slow, partly because of concerns about affordability. The aspirational cost of sequencing a genome is $1000, but there is little evidence to support this estimate. We estimate the cost of using genome sequencing in routine clinical care in patients with cancer or rare diseases. Methods: We performed a microcosting study of Illumina-based genome sequencing in a UK National Health Service laboratory processing 399 samples/year. Cost data were collected for all steps in the sequencing pathway, including bioinformatics analysis and reporting of results. Sensitivity analysis identified key cost drivers. Results: Genome sequencing costs £6841 per cancer case (comprising matched tumor and germline samples) and £7050 per rare disease case (three samples). The consumables used during sequencing are the most expensive component of testing (68–72$1000/genome in a single laboratory. This aspirational sequencing cost will likely only be achieved if consumable costs are considerably reduced and sequencing is performed at scale

Methods for environment: productivity trade-off analysis in agricultural systems

Trade-off analysis has become an increasingly important approach for evaluating system level outcomes of agricultural production and for prioritising and targeting management interventions in multi-functional agricultural landscapes. We review the strengths and weakness of different techniques available for performing trade-off analysis. These techniques, including mathematical programming and participatory approaches, have developed substantially in recent years aided by mathematical advancement, increased computing power, and emerging insights into systems behaviour. The strengths and weaknesses of the different approaches are identified and discussed, and we make suggestions for a tiered approach for situations with different data availability. This chapter is a modified and extended version of Klapwijk et al. (2014)

The capability set for work - correlates of sustainable employability in workers with multiple sclerosis

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014

Dispatch from the field: ecology of ground-web-building spiders with description of a new species (Araneae, Symphytognathidae).

Crassignathadanaugirangensis sp. n. (Araneae: Symphytognathidae) was discovered during a tropical ecology field course held at the Danau Girang Field Centre in Sabah, Malaysia. A taxonomic description and accompanying ecological study were completed as course activities. To assess the ecology of this species, which belongs to the ground-web-building spider community, three habitat types were surveyed: riparian forest, recently inundated riverine forest, and oil palm plantation. Crassignathadanaugirangensis sp. n. is the most abundant ground-web-building spider species in riparian forest; it is rare or absent from the recently inundated forest and was not found in a nearby oil palm plantation. The availability of this taxonomic description may help facilitate the accumulation of data about this species and the role of inundated riverine forest in shaping invertebrate communities

Mind the (yield) gap(s)

This paper explores the origin of the notion of “yield gap” and its use as a framing device for agricultural policy in sub-Saharan Africa. The argument is that while the yield gap of policy discourse provides a simple and powerful framing device, it is most often used without the discipline or caveats associated with the best examples of its use in crop production ecology and microeconomics. This argument is developed by examining how yield gap is used in a selection of recent and influential agricultural policy documents. The message for policy makers and others is clear: “mind the (yield) gap(s)”, for they are seldom what they appear

Aplicação de deficientes físicos nas atividades da Polícia Militar do Paraná

Orientador: Ivan Santa MariaMonografia (Especialização) - Universidade Federal do Paraná,Setor de Ciências Sociais Aplicadas, Departamento de Contabilidade, Curso de Especialização em Administração PolicialResumo: O presente trabalho monográfico abordou o problema da aplicabilidade de policiais-militares em atividades consideradas meio na Organização, sendo que os mesmos poderiam ser substituídos por deficientes físicos em algumas funções básicas, como telefonista, recepcionista, digitador e outros, redundando num maior emprego de policiaismilitares nas ruas. Para tanto, buscou primeiramente retratar a realidade na PMPR; caracterizar atividades de cunho civil e de cunho militar na atividade meio; além de onde e como aplicar a pessoa portadora de deficiência física. Na parte do desenvolvimento, foram abordadas conceituações básicas, como atividade Policial Militar, atividades-meio e atividades-fim da Polícia Militar, cunho civil e militar na atividade-meio. Na seqüência, abordaram-se aspectos da pessoa portadora de deficiência, sendo navegado em assuntos a respeito da antigüidade, do renascimento, a política demográfica, deficiência em si, Programa Nacional de Direitos Humanos, a realidade social do deficiente e sua situação atual. Tratou-se também dos deficientes físicos e a Polícia Militar, em que buscou-se evidenciar o que existe em legislação peculiar e cargos privativos de militares. Quanto aos direitos dos deficientes, relatou-se a respeito dos tratados internacionais e a legislação brasileira. Ainda no capítulo referente ao desenvolvimento retratou-se a respeito do PSAV - Prestador de Serviço Auxiliar Voluntário (Deficientes Físicos); APR - Associação Paranaense de Reabilitação; ADFP -Associação dos Deficientes Físicos do Paraná; empresas que abrem caminhos para deficientes; uma importante matéria veiculada na Gazeta do Povo com o título "700 Deficientes podem Perder o Emprego", postura esta defendida pelo Estado como sendo o serviço prestado de grande importância econômica e social. Um capítulo tratou sobre a presença de pessoal civil na Polícia Militar, com seus fundamentos legais e doutrinários. Chegou-se ao final do desenvolvimento retratando como seria uma possível implantação da alocação de deficientes físicos em certas atividades-meio da Polícia Militar do Paraná Finalizou o presente estudo tratando das considerações finais, em que algumas propostas foram colocadas, ressaltando-se a importância de primeiramente serem readequadas as instalações físicas das Unidades Policiais-Militares para o ideal recebimento destes funcionário

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be “all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty”. The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios