Multi-seasonal systematic camera-trapping reveals fluctuating densities and high turnover rates of Carpathian lynx on the western edge of its native range

Camera-trapping and capture-recapture models are the most widely used tools for estimating densities of wild felids that have unique coat patterns, such as Eurasian lynx. However, studies dealing with this species are predominantly on a short-term basis and our knowledge of temporal trends and population persistence is still scarce. By using systematic camera-trapping and spatial capture-recapture models, we estimated lynx densities and evaluated density fluctuations, apparent survival, transition rate and individual's turnover during five consecutive seasons at three different sites situated in the Czech–Slovak–Polish borderland at the periphery of the Western Carpathians. Our density estimates vary between 0.26 and 1.85 lynx/100 km2 suitable habitat and represent the lowest and the highest lynx densities reported from the Carpathians. We recorded 1.5–4.1-fold changes in asynchronous fluctuated densities among all study sites and seasons. Furthermore, we detected high individual’s turnover (on average 46.3 ± 8.06% in all independent lynx and 37.6 ± 4.22% in adults) as well as low persistence of adults (only 3 out of 29 individuals detected in all seasons). The overall apparent survival rate was 0.63 ± 0.055 and overall transition rate between sites was 0.03 ± 0.019. Transition rate of males was significantly higher than in females, suggesting male-biased dispersal and female philopatry. Fluctuating densities and high turnover rates, in combination with documented lynx mortality, indicate that the population in our region faces several human-induced mortalities, such as poaching or lynx-vehicle collisions. These factors might restrict population growth and limit the dispersion of lynx to other subsequent areas, thus undermining the favourable conservation status of the Carpathian population. Moreover, our study demonstrates that long-term camera-trapping surveys are needed for evaluation of population trends and for reliable estimates of demographic parameters of wild territorial felids, and can be further used for establishing successful management and conservation measures

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett’s esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett’s Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%–88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Numerical modeling of transport and accumulation of DNA on electronically active biochips

Transport and accumulation of biomolecules, particularly DNA, in active electronic chips are investigated through numerical modeling and experimental verification. Various geometric and design configurations of electronically active DNA chips are considered. Further, we investigate the effect of electric field distribution on practical design of flow cells and chips. Particular attention is focused on the geometric effects on current and electric field distribution which are well captured by a finite element method-based model. We demonstrate that these geometric effects are observed only in buffers of very low conductivity. We also demonstrate that numerical models which do not include the charge transfer mechanism between electrodes and the buffer solution will fail to predict the reduction of these geometric effects with increased buffer conductivity. The review of the technology is based on computer simulation using a finite element-based computational model and experimental results of electric field distribution, DNA transport and accumulation. Comparison of theoretical results for electrophoretic DNA accumulation with those obtained from experiments and a simple analytical model is presented.close313