Amino acid sequence of retinal transducin at the site ADP-ribosylated by cholera toxin

Transducin was [32P]ADP-ribosylated by cholera toxin in bovine retinal rod outer segments and then partially purified on ω-amino octyl agarose to remove other ADP-ribosylated proteins. Trypsin digestion of the ADP-ribosylated transducin and further purification using boronate-polyacrylamide beads and high performance liquid chromatography yielded a single radiolabeled tetrapeptide, Ser-Arg-Val-Lys. The ADP-ribose is linked to the guanidinium group of arginine

Mass-Flux Characteristics of Reactive Scalars in the Convective Boundary Layer

The transport of nonreactive and reactive bottom-up and top-down diffusing scalars in a solid-lid convective boundary layer is studied using large-eddy simulation (LES). The chemistry considered consists of an irreversible, binary reaction involving the bottom-up and top-down diffusing scalars. The mass-flux or top-hat characteristics of the reactive flow are determined. Also, several mass-flux schemes are run in an off-line mode, that is, with prescribed profiles of the mass flux and the updraft area fraction, and are compared to the LES. Top-hat approximations are found to capture about 25% of the covariance between two arbitrary (nonreacting or reacting) scalars and about 65% of the flux. Subplume fluxes are located either in the updraft for bottom-up diffusing scalars or in the downdraft for top-down diffusing scalars. The mass-flux scheme that is nearly identical to the exact plume-budget equations gives the best performance. For the parameterization of lateral exchange this mass-flux scheme includes gross exchange across the interface between updrafts and downdrafts, that is, includes also subinterface-scale exchange processes (like the other dynamical quantities also prescribed in an off-line mode using LES data). A simpler mass-flux scheme, which does not include the more sophisticated parameterizations of subplume fluxes and subinterface-scale lateral exchange, is found to perform only slightly worse. The results of this paper are also valid for the surface layer and lower mixed layer of the entraining convective boundary layer but not for the entrainment zone

Comparing palliative care in care homes across Europe (PACE) : protocol of a cross-sectional study of deceased residents in 6 EU countries

Objectives: Although a growing number of older people are dying in care homes, palliative care has developed in these settings only recently. Cross-country representative comparative research hardly exists in this area. As part of a large EU-funded project, we aim to undertake representative comparative research in care homes in Europe, to describe and compare 6 countries in terms of (1) resident outcomes, quality and costs of palliative and end-of-life care; and (2) palliative care structures and staff knowledge and attitudes toward palliative care. We also aim to explore country, facility, staff, patient, and care characteristics related to better outcomes at resident level. Design and Methods: To obtain a representative nationwide sample, we will conduct a large-scale cross-sectional study of deceased residents in care homes in Belgium, Finland, Italy, the Netherlands, Poland, and the United Kingdom, using proportional stratified random sampling (taking into account region, facility type and bed capacity). In each country, all participating care homes retrospectively report all deaths of residents in and outside the facilities over the previous 3-month period. For each case, structured questionnaires, including validated instruments, are sent to (1) the administrator/manager, (2) staff member most involved in care, (3) treating physician (general practitioner or elderly care physician), and (4) a closely involved relative. It is estimated that, per country, 50 care homes are needed on average to obtain a minimum of 200 deceased residents. Collected data include clinical and socio-demographic characteristics, quality of dying, quality and costs of palliative care and end-of-life care, and palliative care structures at the facility level and country level. To obtain a representative view of staff knowledge and attitudes regarding palliative care, PACE will conduct a cross-sectional study of staff working in the participating care homes. Conclusion: Considering the growing challenges associated with aging in all European countries, there is an urgent need to build a robust international comparative evidence base that can inform the development of policies to target improved palliative care in care homes. By describing this research protocol, we hope to inform international research in care homes on how to perform representative end-of-life care research in these settings and better understand which systems are associated with better outcomes

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA):long-term outcomes of a multicentre, double-blind, randomised controlled trial

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p &lt; 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.</p

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA):long-term outcomes of a multicentre, double-blind, randomised controlled trial

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p &lt; 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.</p

Detection of child abuse in emergency departments: a multi-centre study

Objective: This study examines the detection rates of suspected child abuse in the emergency departments of seven Dutch hospitals complying and not complying with screening guidelines for child abuse. Design: Data on demographics, diagnosis and suspected child abuse were collected for all children aged ≤18 years who visited the emergency departments over a 6-month period. The completion of a checklist of warning signs of child abuse in at least 10% of the emergency department visits was considered to be compliance with screening guidelines. Results: A total of 24 472 visits were analysed, 54% of which took place in an emergency department complying with screening guidelines. Child abuse was suspected in 52 children (0.2%). In 40 (77%) of these 52 cases, a checklist of warning signs had been completed compared with a completion rate of 19% in the total sample. In hospitals complying with screening guidelines for child abuse, the detection rate was higher (0.3%) than in those not complying (0.1%, p<0.001). Conclusion: During a 6-month period, emergency department staff suspected child abuse in 0.2% of all children visiting the emergency department of seven Dutch hospitals. The numbers of suspected abuse cases detected were low, but an increase is likely if uniform screening guidelines are widely implemented

Capacity building for sustainable aquaculture and fisheries development in Myanmar

This report presents the results of a Dutch public-private capacity building (Knowledge to Knowledge or K2K) mission for fostering sustainable aquaculture and fisheries development in Myanmar. The objectives of the K2K mission were to: 1) analyse Myanmar’s aquaculture and fisheries knowledge infrastructure including a gap analysis; 2) identify future stakeholder needs and recommend improvements in terms of capacity building; 3) provide basic practical knowledge in support of a sustainable aquaculture and fisheries sector to Myanmar stakeholders; and 4) develop a Terms of Reference for a possible future programme aiming at building capacity for a sustainable fisheries and aquaculture sector in Myanmar through Dutch knowledge infrastructure (public and private)

Five-Year Follow-Up of a Slowly Resorbable Biosynthetic P4HB Mesh (Phasix) in VHWG Grade 3 Incisional Hernia Repair

OBJECTIVE: To assess the 5-year recurrence rate of incisional hernia repair in Ventral Hernia Working Group (VHWG) 3 hernia with a slowly resorbable mesh.SUMMARY BACKGROUND DATA: Incisional hernia recurs frequently after initial repair. In potentially contaminated hernia, recurrences rise to 40%. Recently, the biosynthetic Phasix mesh has been developed that is resorbed in 12-18 months. Resorbable meshes might be a solution for incisional hernia repair to decrease short- and long-term (mesh) complications. However, long-term outcomes after resorption are scarce.METHODS: Patients with VHWG grade 3 incisional midline hernia, who participated in the Phasix trial (Clinilcaltrials.gov: NCT02720042) were included by means of physical examination and computed tomography (CT). Primary outcome was hernia recurrence; secondary outcomes comprised of long-term mesh complications, reoperations, and abdominal wall pain [visual analogue score (VAS): 0-10].RESULTS: In total, 61/84 (72.6%) patients were seen. Median follow-up time was 60.0 [interquartile range (IQR): 55-64] months. CT scan was made in 39 patients (68.4%). A recurrence rate of 15.9% (95% confidence interval: 6.9-24.8) was calculated after 5 years. Four new recurrences (6.6%) were found between 2 and 5 years. Two were asymptomatic. In total, 13/84 recurrences were found. No long-term mesh complications and/or interventions occurred. VAS scores were 0 (IQR: 0-2).CONCLUSIONS: Hernia repair with Phasix mesh in high-risk patients (VHWG 3, body mass index &gt;28) demonstrated a recurrence rate of 15.9%, low pain scores, no mesh-related complications or reoperations for chronic pain between the 2- and 5-year follow-up. Four new recurrences occurred, 2 were asymptomatic. The poly-4-hydroxybutyrate mesh is a safe mesh for hernia repair in VHWG 3 patients, which avoids long-term mesh complications like pain and mesh infection.</p

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study

Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients