Long-term passive acoustic recordings track the changing distribution of North Atlantic right whales (Eubalaena glacialis) from 2004 to 2014

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 13460, doi:10.1038/s41598-017-13359-3.Given new distribution patterns of the endangered North Atlantic right whale (NARW; Eubalaena glacialis) population in recent years, an improved understanding of spatio-temporal movements are imperative for the conservation of this species. While so far visual data have provided most information on NARW movements, passive acoustic monitoring (PAM) was used in this study in order to better capture year-round NARW presence. This project used PAM data from 2004 to 2014 collected by 19 organizations throughout the western North Atlantic Ocean. Overall, data from 324 recorders (35,600 days) were processed and analyzed using a classification and detection system. Results highlight almost year-round habitat use of the western North Atlantic Ocean, with a decrease in detections in waters off Cape Hatteras, North Carolina in summer and fall. Data collected post 2010 showed an increased NARW presence in the mid-Atlantic region and a simultaneous decrease in the northern Gulf of Maine. In addition, NARWs were widely distributed across most regions throughout winter months. This study demonstrates that a large-scale analysis of PAM data provides significant value to understanding and tracking shifts in large whale movements over long time scales.This research was funded and supported by many organizations, specified by projects as follows: Data recordings from region 1 were provided by K. Stafford and this research effort was funded by the National Science Foundation #NSF-ARC 0532611. Region 2 data were provided by D. K. Mellinger and S. Nieukirk, funded by National Oceanic and Atmospheric Agency (NOAA) and the Office of Naval Research (ONR) #N00014–03–1–0099, NOAA #NA06OAR4600100, US Navy #N00244-08-1-0029, N00244-09-1-0079, and N00244-10-1-0047

The cGMP-Dependent Protein Kinase II Is an Inhibitory Modulator of the Hyperpolarization-Activated HCN2 Channel

Opening of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is facilitated by direct binding of cyclic nucleotides to a cyclic nucleotide-binding domain (CNBD) in the C-terminus. Here, we show for the first time that in the HCN2 channel cGMP can also exert an inhibitory effect on gating via cGMP-dependent protein kinase II (cGKII)-mediated phosphorylation. Using coimmunoprecipitation and immunohistochemistry we demonstrate that cGKII and HCN2 interact and colocalize with each other upon heterologous expression as well as in native mouse brain. We identify the proximal C-terminus of HCN2 as binding region of cGKII and show that cGKII phosphorylates HCN2 at a specific serine residue (S641) in the C-terminal end of the CNBD. The cGKII shifts the voltage-dependence of HCN2 activation to 2–5 mV more negative voltages and, hence, counteracts the stimulatory effect of cGMP on gating. The inhibitory cGMP effect can be either abolished by mutation of the phosphorylation site in HCN2 or by impairing the catalytic domain of cGKII. By contrast, the inhibitory effect is preserved in a HCN2 mutant carrying a CNBD deficient for cGMP binding. Our data suggest that bidirectional regulation of HCN2 gating by cGMP contributes to cellular fine-tuning of HCN channel activity

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and

Chemische evenwichtsmodellering van metaalpartitie in bodems

In dit rapport wordt de toepassing beschreven van speciatiemodellering voor het voorspellen van de partitie van Ni, Cu, Zn, Cd en Pb tussen de vaste en de vloeibare fase in bodems die afkomstig zijn van tien verschillende locaties in Nederland. Bij de modellering is rekening gehouden met complexatie-, redox-, precipitatie- en adsorptieprocessen van de zware metalen. Amorf ijzeroxide is als modelverbinding gebruikt voor de vaste adsorptiefase. Berekende concentraties in de vloeibare fase zijn vergeleken met gemeten concentraties in het poriewater van de bemonsterde bodems. In het algemeen blijkt dat voor Cu en Pb de overeenkomst tussen berekende en gemeten concentraties redelijk is. Voor Cd en Zn wordt alleen een goede overeenkomst gevonden voor monsters met een hoge pH. Tenslotte blijken gemeten en berekende Ni-concentraties slecht met elkaar overeen te komen. Geconcludeerd wordt dan ook dat op dit moment, modelleringsresultaten op een kwalitatieve manier kunnen bijdragen aan het vergroten van het inzicht in de processen die het lot van zware metalen in bodems bepalen. Vooralsnog kan speciatiemodellering van de vaste fase nog niet als kwantitatief instrument worden ingezet. Dit wordt onder andere veroorzaakt door het gebrek aan geschikte adsorptie-data. Additionele adsorptiefases, zoals bijvoorbeeld MnOx, dienen meegenomen te worden om een betere beschrijving van de speciatieprocessen in de bodems te verkrijgen.The application of chemical equilibrium modelling to predict the partitioning of Ni, Cu, Zn, Cd and Pb between the solid and solution phase in soils from ten different locations in the Netherlands, is described. Complexation, redox, precipitation and adsorption processes are accounted for. Hydrous Ferric Oxide serves as a model compound for the soil adsorption phase. Calculated solution phase concentrations are compared with those measured in soil pore waters. Agreement between calculated and measured concentrations for Cu and Pb is reasonable in all samples. For Cd and Zn, good agreement is observed only for samples with high pH. Poor agreement is observed for Ni. It is concluded that modelling results may be used in a qualitative manner to obtain a better understanding (or formulate new ideas) about processes affecting the fate of metals in soil systems. However, with the present knowledge available, chemical equilibrium modelling can not yet be used as a quantitative instrument for the prediction of metal partitioning in soil systems. This is partly due to the lack of adequate adsorption data. In general, results suggest that additional adsorption phases, such as MnOx, should be included in the model.DGM/BoDGM/SV

Bepaling van de relatie tussen bodemkarakteristieken en veldgemeten partitiecoefficienten van zware metalen in Nederlandse bodems

Twintig met zware metalen verontreinigde bodems zijn bemonsterd. Veldgemeten partitiecoefficienten (Kp) voor As, Cd, Cr, Cu, Ni, Pb en Zn zijn bepaald als de verhouding tussen de metaalgehalten geextraheerd met 0,01M CaCl2 of geconcentreerd HNO3 en de metaal concentraties in het poriewater. De gemeten Kp waarden varieerden sterk per metaal en bodemtype. De Kp waarden gebaseerd op de CaCl2 extracten, zijn slecht gerelateerd aan poriewater- en bodemkarakteristieken. Daarentegen bleken de Kp waarden, gebaseerd op de HNO3 destructies, sterk gerelateerd te zijn aan dezelfde karakteristieken. Vooral pH, lutum gehalte, amorf Fe- en Al gehalte, CEC en de Ca concentratie in het poriewater bleken van grote invloed op de variatie in de Kp waarden. Tenslotte zijn per metaal regressiemodellen opgesteld, waarin met een combinatie van twee van bovengenoemde bodemkarakteristieken de variatie in Kp waarden goed kon worden voorspeld.Twenty Dutch soils were sampled at sites which were polluted with heavy metals. Field-based partition coefficients (Kp) for As, Cd, Cr, Cu, Ni, Pb and Zn were determined by calculating the ratio of the content of metal extracted by 0.01M CaCl2 or concentrated HNO3, to the total metal concentration in the pore water. Kp values varied greatly with metal and soil type. Kp values based on the CaCl2 extract were poorly correlated to soil and pore water characteristics. Kp values based on the HNO3 destruate were well correlated to the same characteristics. It was concluded that especially pH, clay content, amorphous Fe and Al content, CEC and Ca concentration in the pore water explained the high percentage of variation in Kp values. Finally, for every studied metal, regression equations, including a combination of two of above mentioned soil characteristics, were derived, explaining most of the variation in Kp.DGM/Bo/SV

Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end‐stage liver disease

BackgroundThe effect of anti-viral treatment on downstream costs for hepatitis C virus (HCV)-infected patients is unknown.AimTo evaluate follow-up costs in patients with chronic HCV, stratified by liver disease severity.MethodsUsing a US private insurance database, mean all-cause per-patient-per-month (PPPM) US (2010) medical costs were calculated for HCV-infected persons who did and did not receive anti-HCV treatment between January 2002 and August 2010. Analysis was stratified by liver disease severity [noncirrhotic disease (NCD), compensated cirrhosis (CC) or end-stage liver disease (ESLD)] defined by ICD-9 and CPT codes.ResultsA total of 33 309 patients were included (78% NCD, 7% CC and 15% ESLD); 4111 individuals (12%) received anti-HCV treatment during the 2-year baseline period. Mean PPPM follow-up health care costs were significantly lower among treated patients with NCD ($900 vs.$1378 in untreated patients, P < 0.001) and ESLD ($3634 vs.$5071, P < 0.001) groups but not in the CC group ($1404 vs.$1795, P < 0.071; t-test). In a multivariable model adjusted for demographic characteristics, comorbidities, index date and geographical region, incremental cost ratios for total health care costs differed significantly (P < 0.001) between treated and untreated patients in the NCD and ESLD groups but not in the CC group. From this model, mean PPPM total health care costs between treated and untreated patients were $885 and$1370 in the NCD, $1369 and$1802 in the CC, and $3547 and$5137 in the ESLD groups, respectively.ConclusionsAnti-HCV therapy was associated with lower follow-up US health care costs, and these savings were independent of baseline patient comorbidities and stage of disease