Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.

Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.

Characterization and assessment of the potential toxicity/pathogenicity of fibrous glaucophane.

In California, the metamorphic blueschist occurrences within the Franciscan Complex are commonly composed of glaucophane, which can be found with a fibrous habit. Fibrous glaucophane's potential toxicity/pathogenicity has never been determined and it has not been considered by the International Agency for Research on Cancer (IARC) as a potential carcinogen to date. Notwithstanding, outcrops hosting fibrous glaucophane are being excavated today in California for building/construction purposes (see for example the Calaveras Dam Replacement Project - CDRP). Dust generated by these excavation activities may expose workforces and the general population to this potential natural hazard. In this work, the potential toxicity/pathogenicity of fibrous glaucophane has been determined using the fibre potential toxicity index (FPTI). This model has been applied to a representative glaucophane-rich sample collected at San Anselmo, Marin County (CA, USA), characterized using a suite of experimental techniques to determine morphometric, crystal-chemical parameters, surface reactivity, biodurability and related parameters. With respect to the asbestos minerals, the FPTI of fibrous glaucophane is remarkably higher than that of chrysotile, and comparable to that of tremolite, thus supporting the application of the precautionary approach when excavating fibrous glaucophane-rich blueschist rocks. Because fibrous glaucophane can be considered a potential health hazard, just like amphibole asbestos, it should be taken into consideration in the standard procedures for the identification and assessment of minerals fibres in soil and air samples.

Comparison of long-read sequencing technologies in the hybrid assembly of complex bacterial genomes.

Illumina sequencing allows rapid, cheap and accurate whole genome bacterial analyses, but short reads (<300 bp) do not usually enable complete genome assembly. Long-read sequencing greatly assists with resolving complex bacterial genomes, particularly when combined with short-read Illumina data (hybrid assembly). However, it is not clear how different long-read sequencing methods affect hybrid assembly accuracy. Relative automation of the assembly process is also crucial to facilitating high-throughput complete bacterial genome reconstruction, avoiding multiple bespoke filtering and data manipulation steps. In this study, we compared hybrid assemblies for 20 bacterial isolates, including two reference strains, using Illumina sequencing and long reads from either Oxford Nanopore Technologies (ONT) or SMRT Pacific Biosciences (PacBio) sequencing platforms. We chose isolates from the family Enterobacteriaceae, as these frequently have highly plastic, repetitive genetic structures, and complete genome reconstruction for these species is relevant for a precise understanding of the epidemiology of antimicrobial resistance. We de novo assembled genomes using the hybrid assembler Unicycler and compared different read processing strategies, as well as comparing to long-read-only assembly with Flye followed by short-read polishing with Pilon. Hybrid assembly with either PacBio or ONT reads facilitated high-quality genome reconstruction, and was superior to the long-read assembly and polishing approach evaluated with respect to accuracy and completeness. Combining ONT and Illumina reads fully resolved most genomes without additional manual steps, and at a lower consumables cost per isolate in our setting. Automated hybrid assembly is a powerful tool for complete and accurate bacterial genome assembly.

Forty years of reform and opening up: China's progress toward a sustainable path.

After 40 years of reform and "opening up," China has made remarkable economic progress. Such economic prosperity, however, has been coupled with environmental degradation. We analyze diverse long-term data to determine whether China is experiencing a decoupling of economic growth and environmental impacts, and where China stands with respect to the Sustainable Development Goals (SDGs) in terms of reducing regional division, urban-rural gap, social inequality, and land-based impacts on oceans. The results highlight that China's desire to achieve "ecological civilization" has resulted in a decoupling trend for major pollutants since 2015, while strong coupling remains with CO2 emissions. Progress has been made in health care provision, poverty reduction, and gender equity in education, while income disparity continues between regions and with rural-urban populations. There is a considerable way to go toward achieving delivery of the SDGs; however, China's progress toward economic prosperity and concomitant sustainability provides important insights for other countries.

Assessment of the bimodality in the distribution of bacterial genome sizes.

Bacterial genome sizes have previously been shown to exhibit a bimodal distribution. This phenomenon has prompted discussion regarding the evolutionary forces driving genome size in bacteria and its ecological significance. We investigated the level of inherent redundancy in the public database and the effect it has on the shape of the apparent bimodal distribution. Our study reveals that there is a significant bias in the genome sequencing efforts towards a certain group of species, and that correcting the bias using species nomenclature and clustering of the 16S rRNA gene, results in a unimodal rather than the previously published bimodal distribution. The true genome size distribution and its wider ecological implications will soon emerge as we are currently witnessing rapid growth in the number of sequenced genomes from diverse environmental niches across a range of habitats at an unprecedented rate.

Building a laboratory workforce to meet the future: ASCP Task Force on the Laboratory Professionals Workforce.

OBJECTIVES: To analyze the demand for services from the nation's medical laboratories, which is predicted to dramatically increase as our citizens age and millions receive insurance coverage through the Affordable Care Act. METHODS: A systematic review of relevant publications and databases was conducted to assess the current state of the nation's medical laboratory workforce and to examine the impact of population demographics and health reform on workforce development to address the future demand for laboratory services. RESULTS: Building a Laboratory Workforce to Meet the Future, a new report from the American Society for Clinical Pathology (ASCP), provides a comprehensive strategy to address the future workforce needs of the nation's medical laboratories to meet this demand to provide timely, accurate, and safe patient care and to fully realize the benefits of personalized medicine. CONCLUSIONS: The report, from the ASCP Task Force on the Laboratory Professionals Workforce, is a comprehensive review of the myriad of factors affecting recruitment and retention of qualified laboratory professionals and provides a set of thoughtful recommendations outlining a multifaceted approach to bolster the pipeline of potential candidates for the profession as well as leadership in health care.

Ambulance triage and treatment zones at major rugby events in Wellington, New Zealand: a sobering experience.

AIMS: A prospective analysis was undertaken of the workload of prehospital triage and treatment facilities established in Wellington for the 2011 and 2012 International Rugby Sevens, and the Rugby World Cup 2011 (RWC). The introduction of an alcohol intoxication pathway, the impact of the initiative on ambulance and Emergency Department (ED) workload, and its cost effectiveness were assessed. METHODS: A log of patients seen and their diagnoses and treatment was maintained. An alcohol questionnaire was completed when applicable. Patients intoxicated with alcohol were managed in accordance with a flowchart designed for paramedic use. Costs and savings were calculated. RESULTS: Half the patients were New Zealanders. The average age was 25 years with a slight female preponderance (52.9% female). 30% were students. Alcohol was a contributory or causative factor for the patient's attendance in 80-90% of cases. Approximately 60% of the 121 patients seen at the last two events would have had to be transferred to the ED in the absence of the treatment centre. Cost savings for the ambulance service and ED for the RWC and 2012 Sevens are estimated to be NZ$70,000. No adverse clinical event was identified. CONCLUSIONS: With minimal supervision, event medics and paramedics can safely care for the majority of patients attending large rugby events in New Zealand, easing the pressure on ambulances and the ED, and generating significant cost savings for those services.

Non-price competition in NHS secondary care contracting: empirical results.

PURPOSE: The purpose of this paper is, for English acute NHS hospitals, to investigate how they operate their governance systems in the area of secondary care contracting and identify the key determinants of relationship building within the contacting/commissioning of secondary care focusing upon non-price competitive behaviour. DESIGN/METHODOLOGY/APPROACH: A survey instrument was designed and mailed to a sample of all acute NHS hospitals in England of whom 35 per cent responded. This survey was then analysed using logit techniques. FINDINGS: The analysis suggests that: those NHS Trusts offering volume discounts, non-price competitive incentives or having a strong belief in performance being by "payment by results" criteria are significantly more likely to offer augmented services to secondary care purchasers over and above contractual minima; those NHS Trusts strongly believing in the importance of non-price factors (such as contract augmentation or quality) in the contracting process are more likely to offer customisation of generic services; and those NHS Trusts using cost-sharing agreements to realign contracts when negotiating contracts or who strongly believe in the importance of service augmentation in strengthening relationships, or that increased hospital efficiency is the most important aspect of recent NHS reform are more likely to utilise default measures to help realign contracts. ORIGINALITY/VALUE: This paper fills a gap in the area of non-price competition in English NHS acute secondary care contracting.

Normal-flow virus filtration: detection and assessment of the endpoint in bio-processing.

The breakthrough of a model virus, bacteriophage PhiX-174, through normal-flow virus filters was studied using both commercial process fluids and model feed streams. The results indicate that (i) PhiX-174 is a reasonable model for a mammalian parvovirus [MMV (murine minute virus)] in virus filtration studies; (ii) PhiX-174 LRV [log(reduction value)] shows a better correlation with percentage flow decline compared with volume processed under a variety of conditions; (iii) although the extent of decline in virus LRV is dependent on the mechanism of filter fouling, the fouling mechanisms operative in a viral validation study are representative of those likely to be found under actual production conditions. The mechanism of LRV decline by many process streams was proposed to be due to selective plugging of small pores. A theoretical model as well as a predictive equation for LRV decline versus flow decay was derived; experimental results from filtration studies using pore-plugging feed stocks were consistent with the equation. As protein solutions may vary in their adsorptive versus plugging behaviour during filtration, an evaluation of the LRV-versus-flow-decay relationship on a biopharmaceutical-product-specific basis may be warranted.