“Users United”: The Civil Justice Reform Act of 1990

The implementation of the Civil Justice Reform Act of 1990, a law designed to improve the management of the civil justice system, is discussed. The substantive components of the law and the process that led to its enactment are addressed

Cell wall protection by the Candida albicans class I chitin synthases

Open Access funded by Medical Research Council Acknowledgments We thank Kevin Mackenzie in the Microscopy and Histology Core Facility (Institute of Medical Sciences, University of Aberdeen), and Donna MacCallum for helpful statistical advice. This work was supported by grants from the Wellcome Trust (0868827 and 080088) including a Wellcome Trust Strategic Award (097377) and an Investigator Award to NG (101873), an MRC New Investigator Award to ML (MR/J008230/1) and a PhD scholarship awarded to KP from the Ministry of Sciences and Technology and Chiang Mai University, Thailand. Author contributions are as follows: KP constructed strains, performed the majority of the experiments, analyzed the data and contributed to the preparation of the manuscript. JA produced Fig. S1 using the data from the phosphoproteomic analysis conducted by SP and AB. NG conceived and designed experiments, analyzed data and commented on drafts of the manuscript. ML constructed strains, conceived, designed and performed experiments, analyzed data and wrote the manuscript.Peer reviewedPublisher PD

A Comparative Study of the ReCell® Device and Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries.

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG

Evaluation of Average and Maximum Heart Rate of Wrist-worn Wearable Technology Devices During Trail Running

It has been estimated that there are 20 million people who participate in trail running, and these numbers are expected to increase by 15% each year. Our laboratory group has conducted studies on the validity of wearable technology watches and heart rate (HR) during trail running. The previous generation devices were mostly inaccurate, and a limitation was that reliability was not measured. PURPOSE: To determine both validity and reliability in newer models of wearable devices during trail running. METHODS: Seventeen participants (F = 7) ran on the Thunderbird Gardens Lightning Switch trail in Cedar City, UT. Demographic characteristics: Age = 25 (9) years (mean [standard deviation]), ht = 168 (9) cm, mass = 72 (14) kg. Two Garmin Instincts and two Polar Vantage M2s were evaluated, along with the Polar H10 chest strap as the criterion measure. Participants ran out on the trail for 10-minutes, and then returned to the trailhead. Maximum HR and average HR were measured during the run. Data were analyzed for validity (Mean Absolute Percent Error [MAPE] and Lin’s Concordance [CCC]) and reliability (Coefficient of Variation [CV] and Intraclass Correlation Coefficient [ICC]). Predetermined thresholds were: MAPE0.70, CV0.70. RESULTS: The Garmin Instinct met the threshold for both reliability tests for average and maximum HR (see table). The Garmin Instinct and Polar Vantage met the threshold for both validity tests for maximum HR. CONCLUSION: In order for a device to be considered valid, it must meet the predetermined thresholds for both validity and reliability. These results indicate that only the Garmin Instinct is valid and reliable, but only for measuring maximum HR. This is challenging for those who wish to track their HR while trail running, because neither of the studied devices were valid and reliable for maximum and average HR

Selection of Optimal Quantile Protein Biomarkers Based on Cell-Level Immunohistochemistry Data

BACKGROUND: Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited. Instead, it is reduced to a single mean across the cells of interest or converted into a simple proportion of binary biomarker-positive or -negative cells. RESULTS: We investigated the utility of retaining all quantitative information at the single-cell level by considering the values of the quantile function (inverse of the cumulative distribution function) estimated from a sample of cell signal intensity levels in a tumor tissue. An algorithm was developed for selecting optimal cutoffs for dichotomizing cell signal intensity distribution quantiles as predictors of continuous, categorical or survival outcomes. The proposed algorithm was used to select optimal quantile biomarkers of breast cancer progression based on cancer cells\u27 cell signal intensity levels of nuclear protein Ki-67, Proliferating cell nuclear antigen, Programmed cell death 1 ligand 2, and Progesterone receptor. The performance of the resulting optimal quantile biomarkers was validated and compared to the standard cancer compartment mean signal intensity markers using an independent external validation cohort. For Ki-67, the optimal quantile biomarker was also compared to established biomarkers based on percentages of Ki67-positive cells. For proteins significantly associated with PFS in the external validation cohort, the optimal quantile biomarkers yielded either larger or similar effect size (hazard ratio for progression-free survival) as compared to cancer compartment mean signal intensity biomarkers. CONCLUSION: The optimal quantile protein biomarkers yield generally improved prognostic value as compared to the standard protein expression markers. The proposed methodology has a broad application to single-cell data from genomics, transcriptomics, proteomics, or metabolomics studies at the single cell level

Global hepatitis C elimination: an investment framework

WHO has set global targets for the elimination of hepatitis B and hepatitis C as a public health threat by 2030. However, investment in elimination programmes remains low. To help drive political commitment and catalyse domestic and international financing, we have developed a global investment framework for the elimination of hepatitis B and hepatitis C. The global investment framework presented in this Health Policy paper outlines national and international activities that will enable reductions in hepatitis C incidence and mortality, and identifies potential sources of funding and tools to help countries build the economic case for investing in national elimination activities. The goal of this framework is to provide a way for countries, particularly those with minimal resources, to gain the substantial economic benefit and cost savings that come from investing in hepatitis C elimination

Environmental cues and constraints affecting the seasonality of dominant calanoid copepods in brackish, coastal waters: a case study of Acartia, Temora and Eurytemora species in the south-west Baltic

Information on physiological rates and tolerances helps one gain a cause-and-effect understanding of the role that some environmental (bottom–up) factors play in regulating the seasonality and productivity of key species. We combined the results of laboratory experiments on reproductive success and field time series data on adult abundance to explore factors controlling the seasonality of Acartia spp., Eurytemora affinis and Temora longicornis, key copepods of brackish, coastal and temperate environments. Patterns in laboratory and field data were discussed using a metabolic framework that included the effects of ‘controlling’, ‘masking’ and ‘directive’ environmental factors. Over a 5-year period, changes in adult abundance within two south-west Baltic field sites (Kiel Fjord Pier, 54°19′89N, 10°09′06E, 12–21 psu, and North/Baltic Sea Canal NOK, 54°20′45N, 9°57′02E, 4–10 psu) were evaluated with respect to changes in temperature, salinity, day length and chlorophyll a concentration. Acartia spp. dominated the copepod assemblage at both sites (up to 16,764 and 21,771 females m−3 at NOK and Pier) and was 4 to 10 times more abundant than E. affinis (to 2,939 m−3 at NOK) and T. longicornis (to 1,959 m−3 at Pier), respectively. Species-specific salinity tolerance explains differences in adult abundance between sampling sites whereas phenological differences among species are best explained by the influence of species-specific thermal windows and prey requirements supporting survival and egg production. Multiple intrinsic and extrinsic (environmental) factors influence the production of different egg types (normal and resting), regulate life-history strategies and influence match–mismatch dynamics

Regional Climate Response Collaboratives: Multi-Institutional Support for Climate Resilience

Federal investments by U.S. agencies to enhance climate resilience at regional scales grew over the past decade (2010s). To maximize efficiency and effectiveness in serving multiple sectors and scales, it has become critical to leverage existing agency-specific research, infrastructure, and capacity while avoiding redundancy. We discuss lessons learned from a multi-institutional "regional climate response collaborative" that comprises three different federally supported climate service entities in the Rocky Mountain west and northern plains region. These lessons include leveraging different strengths of each partner, creating deliberate mechanisms to increase cross-entity communication and joint ownership of projects, and placing a common priority on stakeholder-relevant research and outcomes. We share the conditions that fostered successful collaboration, which can be transferred elsewhere, and suggest mechanisms for overcoming potential barriers. Synergies are essential for producing actionable research that informs climate-related decisions for stakeholders and ultimately enhances climate resilience at regional scales.</p

Innovative strategies for the elimination of viral hepatitis at a national level: a country case series

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints