Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems. ...Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales. Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.
Detecting blood vessels in retinal images with the presence of bright and dark lesions is a challenging unsolved problem. In this paper, a novel multiconcavity modeling approach is proposed to handle ...both healthy and unhealthy retinas simultaneously. The differentiable concavity measure is proposed to handle bright lesions in a perceptive space. The line-shape concavity measure is proposed to remove dark lesions which have an intensity structure different from the line-shaped vessels in a retina. The locally normalized concavity measure is designed to deal with unevenly distributed noise due to the spherical intensity variation in a retinal image. These concavity measures are combined together according to their statistical distributions to detect vessels in general retinal images. Very encouraging experimental results demonstrate that the proposed method consistently yields the best performance over existing state-of-the-art methods on the abnormal retinas and its accuracy outperforms the human observer, which has not been achieved by any of the state-of-the-art benchmark methods. Most importantly, unlike existing methods, the proposed method shows very attractive performances not only on healthy retinas but also on a mixture of healthy and pathological retinas.
The therapeutic role of 6-mercaptopurine (6-MP) and azathioprine (AZA) remains controversial due to their perceived relatively slow-acting effect and adverse effects. An updated meta-analysis was ...performed to evaluate the efficacy of these agents for the maintenance of remission in quiescent Crohn's disease.
To assess the efficacy of AZA and 6-MP for maintenance of remission in quiescent Crohn's disease.
We searched MEDLINE, EMBASE, and the Cochrane Library from inception to June 30, 2015.
Randomized controlled trials of oral azathioprine or 6-mercaptopurine compared to placebo or active therapy involving adult patients (> 18 years) with quiescent Crohn's disease were considered for inclusion. Patients with surgically-induced remission were excluded.
At least two authors independently extracted data and assessed study quality using the Cochrane risk of bias tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (CI). The primary outcomes was maintenance of remission. Secondary outcomes included steroid sparing, adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria.
Eleven studies (881 participants) were included. Comparisons included AZA versus placebo (7 studies, 532 participants), AZA or 6-MP versus mesalazine or sulfasalazine (2 studies, 166 participants), AZA versus budesonide (1 study, 77 participants), AZA and infliximab versus infliximab (1 study, 36 patients), 6-MP versus methotrexate (1 study, 31 patients), and early AZA versus conventional management (1 study, 147 participants). Two studies were rated as low risk of bias. Three studies were rated as high risk of bias for being non-blinded. Six studies were rated as unclear risk of bias. A pooled analysis of six studies (489 participants) showed that AZA (1.0 to 2.5 mg/kg/day) was significantly superior to placebo for maintenance of remission over a 6 to 18 month period. Seventy-three per cent of patients in the AZA group maintained remission compared to 62% of placebo patients (RR 1.19, 95% CI 1.05 to 1.34). The number needed to treat for an additional beneficial outcome was nine. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (327 events) and unclear risk of bias. A pooled analysis of two studies (166 participants) showed no statistically significant difference in the proportion of patients who maintained remission between AZA (1.0 to 2.5 mg/kg/day) or 6-MP (1.0 mg/day) and mesalazine (3 g/day) sulphasalazine (0.5 g/15 kg) therapy. Sixty-nine per cent of patients in the AZA/6-MP group maintained remission compared to 67% of mesalazine/sulphasalazine patients (RR 1.09, 95% CI 0.88 to 1.34). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (113 events) and high or unclear risk of bias. One small study found AZA (2.0 to 2.5 mg/kg/day) to be superior to budesonide (6 to 9 mg/day) for maintenance of remission at one year. Seventy-six per cent (29/38) of AZA patients maintained remission compared to 46% (18/39) of budesonide patients (RR 1.65, 95% CI 1.13 to 2.42). GRADE indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (47 events) and high risk of bias. One small study found no difference in maintenance of remission rates at one year between combination therapy with AZA (2.5 mg/kg) and infliximab (5 mg/kg every 8 weeks) compared to infliximab monotherapy. Eighty-one per cent (13/16) of patients in the combination therapy group maintained remission compared to 80% (16/20) of patients in the infliximab group (RR 1.02, 95% CI 0.74 to 1.40). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (29 events) and unclear risk of bias. One small study found no difference in maintenance of remission rates at one year between 6-MP (1 mg/day) and methotrexate (10 mg/week). Fifty per cent (8/16) of 6-MP patients maintained remission at one year compared to 53% (8/15) of methotrexate patients (RR 0.94, 95% CI 0.47 to 1.85). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (16 events) and high risk of bias. One study (147 participants) failed to show any significant benefit for early azathioprine treatment over a conventional management strategy. In the early azathioprine treatment group 67% (11-85%) of the trimesters were spent in remission compared to 56% (29-73%) in the conventional management group. AZA when compared to placebo had significantly increased risk of adverse events (RR 1.29, 95% CI 1.02 to 1.64), withdrawal due to adverse events (3.12, 95% CI 1.59 to 6.09) and serious adverse events (RR 2.45, 95% CI 1.22 to 4.90). AZA/6-MP also demonstrated a significantly higher risk of serious adverse events when compared to mesalazine or sulphasalazine (RR 9.37, 95% CI 1.84 to 47.7). AZA/6-MP did not differ significantly from other active therapies with respect to adverse event data. Common adverse events included pancreatitis, leukopenia, nausea, allergic reaction and infection.
Low quality evidence suggests that AZA is more effective than placebo for maintenance of remission in Crohn's disease. Although AZA may be effective for maintenance of remission its use is limited by adverse effects. Low quality evidence suggests that AZA may be superior to budesonide for maintenance of remission but because of small study size and high risk of bias, this result should be interpreted with caution. No conclusions can be drawn from the other active comparator studies because of low and very low quality evidence. Adequately powered trials are needed to determine the comparative efficacy and safety of AZA and 6-MP compared to other active maintenance therapies. Further research is needed to assess the efficacy and safety of the use of AZA with infliximab and other biologics and to determine the optimal management strategy for patients quiescent Crohn's disease.
The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS ...distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations.
We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants.
Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL
(asthma, 22 studies); 200-400 cells·µL
(severe asthma, eight studies); 150-183 cells·µL
(COPD, six studies); and 100-160 cells·µL
(controls, three studies); and 100-200 cells·µL
(general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity.
EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.
Recent years have witnessed growing interest in the role of the social environment in the development and outcomes of schizophrenia. We investigated whether neighborhood characteristics are ...associated with two important prognostic factors in early-course psychosis, age at onset of psychosis (AOP) and duration of untreated psychosis (DUP).
Data were collected from patients admitted to the hospital for first-episode schizophrenia-spectrum disorder. We collected data on perceived neighborhood disorder during childhood/adolescence and extracted data on 13 neighborhood characteristics from the American Community Survey based upon individual addresses. Four neighborhood-level factors were derived from factor analysis. Multiple logistic regression analyses assessed the association between specific neighborhood characteristics and the two prognostic factors (earlier AOP and longer DUP) in early-course psychosis.
143 participants had valid addresses geo-coded. Neighborhood-level residential instability was associated with an earlier AOP (OR = 1.760; p = 0.022) even after controlling for known risk factors (OR = 2.026; p = 0.020) and also after controlling for individual-level residential instability (OR = 1.917; p = 0.037). The general socioeconomic status neighborhood factor (OR = 1.119; p = 0.019) and perceived neighborhood disorder (OR = 1.075; p = 0.005) were associated with a longer DUP. But only perceived neighborhood disorder (OR = 1.146; p = 0.011) remained significant, and general socioeconomic status was close to significant (OR = 1.215; p = 0.062), after controlling for individual-level predictors and socioeconomic status.
This study found evidence that neighborhood-level characteristics (in this case, residential instability) may be associated with earlier AOP, and perceptions of neighborhood disorder are associated with a longer treatment delay. Socioenvironmental factors should be more consistently considered going forward in research on early psychotic disorders.
Summary
Background
The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically ...evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder.
Objectives
To develop and assess a comprehensive, yet clinically practicable, sensitive diagnostic scoring system for PG.
Methods
Clinical history and images of a total of 60 participants with previously confirmed PG located on the lower extremity and a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of 10 criteria.
Results
The three major diagnostic criteria are rapidly progressing disease, assessment of relevant differential diagnoses and a reddish‐violaceous wound border (prevalent in 98% of patients with PG). Minor criteria (evident in 61–95% of patients with PG) include amelioration by immunosuppressant drugs, characteristically irregular shape of ulceration, extreme pain > 4/10 on a visual analogue scale and localization of lesion at the site of the trauma. Three additional criteria (observed in up to 60% of patients with PG) encompass suppurative inflammation in histopathology, undermined wound borders and systemic disease associated. A total score value of 10 points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers. The initial letters of the above‐listed criteria form the acronym PARACELSUS.
Conclusions
The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.
What's already known about this topic?
Pyoderma gangrenosum (PG) represents a diagnosis of exclusion.
Objective and systematically evaluated diagnostic approaches for patients with suspected PG are lacking.
What does this study add?
A comprehensive and practicable diagnostic scoring system for PG was developed and evaluated by expert teams at two leading tertiary dermatological centres specializing in wound care. The initial letters of the score criteria form the acronym PARACELSUS.
A total score of 10 points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers.
The PARACELSUS score is an effective and easily implementable diagnostic tool for PG.
Respond to this article
Linked Editorial: Schreml. Br J Dermatol 2019; 180:438–439.
Plain language summary available online
Leber hereditary optic neuropathy (LHON) is a rare, maternally inherited mitochondrial disorder that presents with severe bilateral sequential vision loss, due to the selective degeneration of ...retinal ganglion cells (RGCs). Since the mitochondrial genetic basis for LHON was uncovered in 1988, considerable progress has been made in understanding the pathogenetic mechanisms driving RGC loss, which has enabled the development of therapeutic approaches aimed at mitigating the underlying mitochondrial dysfunction. In this review, we explore the genetics of LHON, from bench to bedside, focusing on the pathogenetic mechanisms and how these have informed the development of different gene therapy approaches, in particular the technique of allotopic expression with adeno-associated viral vectors. Finally, we provide an overview of the recent gene therapy clinical trials and consider the unanswered questions, challenges, and future prospects.
An understanding of risks to biodiversity is needed for planning action to slow current rates of decline and secure ecosystem services for future human use. Although the IUCN Red List criteria ...provide an effective assessment protocol for species, a standard global assessment of risks to higher levels of biodiversity is currently limited. In 2008, IUCN initiated development of risk assessment criteria to support a global Red List of ecosystems. We present a new conceptual model for ecosystem risk assessment founded on a synthesis of relevant ecological theories. To support the model, we review key elements of ecosystem definition and introduce the concept of ecosystem collapse, an analogue of species extinction. The model identifies four distributional and functional symptoms of ecosystem risk as a basis for assessment criteria: A) rates of decline in ecosystem distribution; B) restricted distributions with continuing declines or threats; C) rates of environmental (abiotic) degradation; and D) rates of disruption to biotic processes. A fifth criterion, E) quantitative estimates of the risk of ecosystem collapse, enables integrated assessment of multiple processes and provides a conceptual anchor for the other criteria. We present the theoretical rationale for the construction and interpretation of each criterion. The assessment protocol and threat categories mirror those of the IUCN Red List of species. A trial of the protocol on terrestrial, subterranean, freshwater and marine ecosystems from around the world shows that its concepts are workable and its outcomes are robust, that required data are available, and that results are consistent with assessments carried out by local experts and authorities. The new protocol provides a consistent, practical and theoretically grounded framework for establishing a systematic Red List of the world's ecosystems. This will complement the Red List of species and strengthen global capacity to report on and monitor the status of biodiversity.
PDF
