Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A statistical analysis of climate variability and ecosystem response in the German Bight

We compiled homogeneous long-term time series comprising 39 variables representing the German Bight and for the period 1975-2004. A diverse set of variables was selected to cover multiple trophic levels and different environmental forcing thus to examine long-term changes in this coastal region. Previous studies have hypothesised the presence of regime shifts in observations extending over the entire North Sea. Focusing on a smaller spatial scale, and closer to the coast, we investigated the major modes of variability in the compiled time series using principal component analysis. The results obtained confirm a previously identified regime shift in the North Sea in 1987/1988 and suggest that the German Bight is dominantly characterised by long-term modes of variability. In the German Bight, the shift of 1987/1988 is driven primarily by temperature, Gulf Stream index, frost days and Secchi depth. Changes in some of the ecosystem variables (plankton and fish) appear to be related to changes in these driving variables. In particular, we documented strong positive correlations between the long-term trend showed by the first principal component and herring, Noctiluca scintillans, and, to a lesser extent, Pleurobrachia pileus. Two gadoids, namely cod and saithe, showed negative correlations with the observed long-term mode of variability. Changes in the sum of five small calanoid copepods were, however, less marked. Phosphate and ammonium exhibited a decreasing trend over the last 30 years. Diatoms and Calanus helgolandicus did not show evidence of changes in concert to this trend. Specific analyses of the data divided into three different subsets (biological, climatic and chemical) characterise the climate of the German Bight as highly dynamic also on short timescales (a few years) as compared to much smoother biological and chemical components. The dynamic regime of the German Bight taken together with a low correlation between the major mode of variability and phytoplankton and zooplankton data suggests that the lower trophic levels of this ecosystem are remarkably resilient