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Background: The life expectancy of people with intellectual disabilities has increased. The implications of ageing have resulted in changes in their support needs and challenges to support staff. Access to evidence based strategies for support staff providing care to elderly with intellectual disabilities remains scarce. A systematic review was conducted to provide an overview of available psychosocial interventions. Methods: Four databases were searched and assessed according to the PRISMA guidelines. A narrative, integrative method of analysis was conducted to synthesise quantitative and qualitative data. Results: The 36 studies included in the review reported on interventions aimed at either identifying and meeting the needs or perceptions of older individuals or at improving their behaviour and skills. Furthermore, the role of support staff in the implementation of interventions was either active, assisting or undefined. Conclusions: This overview of studies could contribute to the existing body of knowledge and help to optimise psychosocial support for a growing population.

The COVID‐19 pandemic has changed the face of many practices throughout the world. Through necessity to minimize spread and provide clinical care to those with severe disease, focus has been on limiting face‐to‐face contact. Research in many areas has been put on hold. We sought to determine the impact of the COVID‐19 pandemic on epilepsy research from international basic science and clinical researchers. Responses to five questions were solicited through a convenience sample by direct email and through postings on the ILAE social media accounts and an ILAE online platform (utilizing Slack). Information was collected from 15 respondents in 11 countries by email or via Zoom interviews between May 19, 2020, and June 4, 2020. Several themes emerged including a move to virtual working, project delays with laboratory work halted and clinical work reduced, funding concerns, a worry about false data with regard to COVID research and concern about research time lost. However, a number of positive outcomes were highlighted, not least the efficiency of online working and other adaptations that could be sustained in the future.

The World Health Organization (WHO) has recognized epilepsy as a public health imperative due to its occurrence at all ages in all regions of the world, its high impact on disability-adjusted life years and psychosocial aspects, and the accompanying stigma. The International League Against Epilepsy and the International Bureau for Epilepsy have established crucial collaborations with regional and global organizations to promote epilepsy as a treatable disease, close the treatment gap in care, education, and research, and eradicate stigma. In November 2020, the efforts of these three organizations-with support from WHO member states, the World Federation of Neurology, and the European Federation of Neurological Associations-culminated in the unanimous approval of a WHO resolution to create and implement an Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders. This unique achievement is built on more than 2 decades of collaboration and effort, and heralds extraordinary opportunities to work toward a world where no person's life is limited by epilepsy.

Background: Professional support for people with intellectual disabilities is increasingly delivered remotely. Understanding what support workers do to support people with intellectual disabilities remotely, and how they do this, is therefore important. The purpose of this study was to gain insight into the remote support practice of the support staff of the Dutch service DigiContact. Methods: A qualitative study was performed in which we followed an inductive-iterative process and used different sources of information: documents, interviews with people who are supported by DigiContact and their caseworkers, and interviews with DigiContact support workers. Findings: Seven themes were constructed and described. Four themes reflected the support activities of DigiContact support workers, and three themes reflected qualities that guide how the support is provided. Conclusions: A remote support context can bring both challenges and opportunities to the practice of supporting people with intellectual disabilities. The findings can be useful for service organisations who are contemplating the adoption of remote support initiatives for people with intellectual disabilities.

Background During the COVID‐19 outbreak, service providers in the Netherlands had to switch towards providing remote support for people with intellectual disabilities living independently. This study aims to provide insight into the use of online support during the outbreak. Methods We analysed quantitative data on planned and unplanned contacts between the online support service DigiContact and its service users. Results The results indicate that the COVID‐19 outbreak and the related containment measures had a strong impact on online support use, specifically on the unplanned use of online support. Conclusion Offering online support as a standard component of services for independently living people with intellectual disability enables service providers to be flexible and responsive towards fluctuations in both support needs and onsite support availability during a social crisis such as COVID‐19.

Service organizations for people with intellectual disabilities (ID) increasingly look for technological applications to improve their services. DigiContact is an online support service developed by Philadelphia Care Foundation in the Netherlands which enables independently living people with ID to contact specially trained support workers 24/7. The purpose of this study was to explore the support needs for which people with ID use online support. We first conducted interviews with 21 individuals with ID who use the online support service. Transcriptions of the interviews were analyzed using inductive thematic analysis. Second, online support workers registered items regarding the support needs when in contact with support users. These data were analyzed to assess which and how often the support needs were present. Online support is used for a broad variety of issues. Four themes emerged during analysis of the interviews: mental health, social contacts (conflicts with others as well as lack of contacts), practical issues, and physical health. Analysis of the support workers' data showed that making a connection with someone and talking about worries and stress are the two most frequent support needs. Most support needs did not differ across the time of day or across the week. The results suggest that 24/7 online support is a useful way of providing services to independently living people with ID. Unlimited access to support has multiple advantages. It appears to have a signaling and a preventive function with regard to emotional and behavioral problems.

Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Relatively few SCN1A mutations associated with genetic epilepsy with febrile seizures-plus (GEFS+) and Dravet syndrome (DS) have been functionally characterized. In contrast to GEFS+, many mutations detected in DS patients are predicted to have complete loss of function. However, functional consequences are not immediately apparent for DS missense mutations. Therefore, we performed a biophysical analysis of three SCN1A missense mutations (R865G, R946C and R946H) we detected in six patients with DS. Furthermore, we compared the functionality of the R865G DS mutation with that of a R859H mutation detected in a GEFS+ patient; the two mutations reside in the same voltage sensor domain of Na(v) 1.1. The four mutations were co-expressed with β1 and β2 subunits in tsA201 cells, and characterized using the whole-cell patch clamp technique. The two DS mutations, R946C and R946H, were nonfunctional. However, the novel voltage sensor mutants R859H (GEFS+) and R865G (DS) produced sodium current densities similar to those in wild-type channels. Both mutants had negative shifts in the voltage dependence of activation, slower recovery from inactivation, and increased persistent current. Only the GEFS+ mutant exhibited a loss of function in voltage-dependent channel availability. Our results suggest that the R859H mutation causes GEFS+ by a mixture of biophysical defects in Na(v) 1.1 gating. Interestingly, while loss of Na(v) 1.1 function is common in DS, the R865G mutation may cause DS by overall gain-of-function defects.

Background and Objectives National guidelines for monitoring bacterial contamination of blood components were introduced in Germany in 1997. Between 1998 and 2002, numerous measures were implemented to prevent bacterial contamination. This study investigates their impact on contamination rates. Materials and Methods Culture-based testing for bacterial detection on a random sample of blood components is part of routine quality control in German blood establishments. Using standardized questionnaires, data from the production periods 1998, 2001 and 2005/2006 were collected and analysed. Results The bacterial contamination rate of RBCs was reduced from 0·157% in 1998 to 0·029% in 2005/2006 (P

Summary Ubiquitous noxious hydrophobic substances, such as hydrocarbons, pesticides and diverse industrial chemicals, stress biological systems and thereby affect their ability to mediate biosphere functions like element and energy cycling vital to biosphere health. Such chemically diverse compounds may have distinct toxic activities for cellular systems; they may also share a common mechanism of stress induction mediated by their hydrophobicity. We hypothesized that the stressful effects of, and cellular adaptations to, hydrophobic stressors operate at the level of water : macromolecule interactions. Here, we present evidence that: (i) hydrocarbons reduce structural interactions within and between cellular macromolecules, (ii) organic compatible solutes – metabolites that protect against osmotic and chaotrope-induced stresses – ameliorate this effect, (iii) toxic hydrophobic substances induce a potent form of water stress in macromolecular and cellular systems, and (iv) the stress mechanism of, and cellular responses to, hydrophobic substances are remarkably similar to those associated with chaotrope-induced water stress. These findings suggest that it may be possible to devise new interventions for microbial processes in both natural environments and industrial reactors to expand microbial tolerance of hydrophobic substances, and hence the biotic windows for such processes.

Pseudomonas putida S12.49, a mutant stain of P. putida S12 that tolerates up to 20 mM benzene, was obtained by evolutionary selection. The genetic basis for the strongly enhanced benzene tolerance was investigated by proteome and transcriptome analysis. Indications were found that the highly benzene-tolerant phenotype is the resultant of multilevel systemic changes. The solvent extrusion pump SrpABC was constitutively expressed in P. putida S12.49, which could be attributed to the disruption of the srpS regulator gene by the indigenous mutator element ISS12. The occurrence of this and two additional transposition events was in good agreement with the increased transcriptional activity of transposase-encoding genes in strain S12.49. These observations suggested that transposition events are an important force driving the generation of the genetic diversity apparently required to obtain highly solvent-tolerant phenotypes. In addition, various expression responses relating to energy generation indicated system changes that accommodated the energy demand associated with the high-level expression of the proton-driven solvent extrusion pump. The relatively modest effect of a respiratory chain uncoupler on benzene tolerance in P. putida S12.49 indicated the involvement of an alternative, non-respiratory mechanism to maintain the proton gradient. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

The first transition-metal complexes bearing the natural product dihydroasparagusic acid, (HSCH2)2CHCO2H, as a ligand are reported. Various coordination modes and nuclearities are demonstrated for the chelating ligand by a series of iron and nickel complexes. Fe2[(SCH2)2CHCO2H](CO)6 retains carbonyl substitution reactivity typical of Fe2(SR)2(CO)6 complexes, yet carboxy coordination to FeI was unobserved. Coupling of the carboxylic acid with amines yields the corresponding amides Fe2[(SCH2)2CHC(O)NHR](CO)6 (R = Et, gly–O–tBu). Fe2[(SCH2)2CHCO2H](CO)4(PMe3)2 catalyzes H2 production, but no better than unfunctionalized alkyl dithiolate analogs. Reactions of the ligand with NiCl2(dppe) afforded mono-, di-, and trinuclear complexes. Noteworthy is Ni3[(SCH2)2CHCO2]2(dppe)2, which features an octahedrally coordinated NiII center linked to a pair of square-planar NiII centers. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

BACKGROUND: A study was conducted to assess the diagnostic sensitivity of neopterin screening of blood donors with regard to the detection of window-phase specimens of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In total, 1002 diagnostic window-phase specimens from 98 seroconversion panels (29 HIV-1, 52 HCV, and 17 HBV) were analyzed with viral antigen detection, viral nucleic acid amplification testing (NAT), and neopterin quantitation assays. The study was completed by the analysis of 92 anti-hepatitis B core antigen (HBc)-reactive and 103 alanine aminotransferase (ALT)-elevated blood donor specimens. RESULTS: A significant association between elevated neopterin concentrations and the very early phase of HIV-1 infection was found. No significant correlation could be observed between neopterin levels and the early phase of HCV or HBV infection. Neopterin concentration was not increased in specimens from blood donors with anti-HBc reactivity or ALT elevation. CONCLUSIONS: Neopterin screening of blood donors may identify window-phase cases of HIV, but not of HCV or HBV infection. The diagnostic sensitivity of neopterin screening during the HIV window phase is similar to that of the p24 antigen test. With the introduction of viral NATs in blood screening, there is no additional benefit of neopterin screening with regard to the three blood-borne viruses HIV, HCV, and HBV. Acute phases of other infectious agents, however, have been reported to be detected by neopterin enzyme-linked immunosorbent assays.

The aim of this study was to assess the cellular response of the solvent-tolerant Pseudomonas putida S12 to toluene as the single effector. Proteomic analysis (two-dimensional difference-in-gel-electrophoresis) was used to assess the response of P. putida S12 cultured in chemostats. This approach ensures constant growth conditions, both in the presence and absence of toluene. A considerable negative effect of toluene on the cell yield was found. The need for energy in the defence against toluene was reflected by differentially expressed proteins for cell energy management. In toluene-stressed cells the balance between proton motive force (PMF) enforcing and dissipating systems was shifted. NAD(P)H generating systems were upregulated whereas the major proton-driven system, ATP synthase, was downregulated. Other differentially expressed proteins were identified: outer membrane proteins, transport proteins, stress-related proteins and translation-related proteins. In addition, a protein with no assigned function was found. This study yielded a more detailed view of the effect of toluene on the intracellular energy management of P. putida S12 and several novel leads have been obtained for further targeted investigations. © 2006 The Authors.

A field experiment with maize for silage was conducted to assess the effects of mineral nitrogen (N) fertilizer application rates (0, 50, 100, 150 kg ha⁻¹), slurry application rates (0, 20, 40 m³ ha⁻¹) and the use of an understorey with perennial ryegrass on nitrate (NO₃)-leaching losses. Leachate was collected using ceramic suction cups. Soil mineral N (SMN) was determined to a depth of 90 cm at the end of the growing season. Higher levels of N supply with mineral fertilizer or slurry resulted in higher leaching losses. The grass understorey significantly reduced the losses. The amount of N lost to the groundwater was positively related to SMN at the end of the growing season, with leaching losses representing less than 0·45 of SMN on average. Leaching losses were positively related to the N surplus, which was calculated from the difference between N input (N from fertilizer, slurry and atmospheric deposition) and N output (N removed with maize herbage mass and bound in the understorey biomass in spring). In view of the large variation in weather conditions between the experimental years, it is suggested that for the sandy soils in this experiment N-leaching losses under maize can be estimated satisfactorily from SMN and the calculated N surplus.

A field experiment was conducted from 1998 to 2001 to measure the performance and environmental effects of a maize crop (Zea mais L.) in a continuous production system with and without a grass understorey (Lolium perenne L.), with varied N inputs. The experiment was located on a sandy soil in northern Germany and comprised all combinations of slurry application rate (0, 20, 40 m 3 ha )1 ) and mineral N fertilizer (0, 50, 100, 150 kg N ha )1 ). Understorey treatments included maize with and without perennial ryegrass. Net energy (NEL) yield of maize increased with mineral N application rate but reached a plateau at high rates. Increase in yield of dry matter because of mineral N fertilizer was lower with increased slurry application rate. Neither slurry and mineral N application nor a grass understorey affected NEL concentration of maize, whereas crude protein (CP) concentration increased with increase in application of slurry and mineral N fertilizer. Nitrogen supply by slurry or mineral fertilizer had no effect on the amount of N in the grass understorey after the harvest of maize. The average amount of N bound annually in the understorey was 60 kg N ha )1 . The reduced biomass of the understorey because of enhanced maize competition was compensated for by an increased CP concentration in the grass. The grass understorey affected the NEL yield of maize negatively only at very low levels of N input but increased the N surplus at all levels.

Background and Objectives National guidelines for monitoring the bacterial contamination rate of blood components were introduced in Germany in 1997. The objective of this study was to present and evaluate the results of sterility testing of platelet concentrates (PCs) prepared by different methods. Materials and Methods The analysis of results of sterility testing of blood component production from transfusion medicine centres in Germany in 1998 and 2001 was based on information collected using standardized questionnaires. Results The bacterial contamination rates for single-donor PCs derived from whole blood and apheresis (0·210% vs. 0·156%) were comparable and showed no significant difference. However, pooled PCs produced from four buffy coats using the sterile docking procedure showed a significantly higher bacterial contamination rate compared with single-donor PCs derived from whole blood and apheresis (0·184% vs. 0·604%). Conclusions Use of standardized methods for sterility monitoring is sufficient to assess collection and production processes in terms of hygiene and yields reliable data on bacterial contamination rates of blood components. The methods described are suitable for using to analyse the efficiency of newly introduced methods to reduce bacterial contamination rates of blood components (e.g. diversion, bacteria screening and pathogen inactivation).

The Committee on Medical Products for Human Use (CHMP) has recently issued two new guidance documents that are of particular note to statisticians. The purpose of this short note is to give a little background to the origins of these documents and a flavour of some of their most important features. The two guidelines are reproduced as the next two papers in the journal.

No-carrier-added 31Si was produced by 31P(n,p)31Si in the nuclear reactor of the Delft University of Technology. Several methods were investigated to remove the side product 32P, and the chemical form of 31Si was investigated. All methods except one gave good results. Anion exchange with Dowex resin gave the best results in activity concentration (3.8 × 106 Bq/ml, with only 3.2 × 103 Bq/ml 32P as by-product) and specific activity (As>17 TBq/g). The product is suitable for biological systems. Copyright © 2006 John Wiley & Sons, Ltd.

Based on experimental data gathered in a research project on nitrogen fluxes in intensive dairy farming in Northern Germany, an analysis of fossil energy input and energy efficiency in forage production from permanent grassland and maize for silage was conducted. Field experiments comprised different defoliation systems and different rates of mineral N fertilizer and slurry application. Each change from grazing to cutting in grassland systems reduced the energy efficiency. Energy efficiency consistently decreased with increasing rates of mineral N application. In the production of maize for silage, maximum energy efficiency was obtained with an application of 50 kg N ha−1 from slurry only. Net energy yields of maize for silage were much higher than that of grassland when compared at the same level of fossil energy and nitrogen fertilizer input. Considering both nitrate-leaching losses and a necessary minimum quantity of grass herbage in a well-balanced ration, it is suggested that a high proportion of maize for silage in combination with N-unfertilized grass/clover swards used in a mixed cutting/grazing system represents a good trade-off between the leaching of nitrates and energy efficiency.

Verhave JC, Balje-Volkers CP, Hillege HL, de Zeeuw D, de Jong PE (University Medical Center Groningen, Groningen University, Institute of Drug Exploration, Groningen, the Netherlands). The reliability of different formulae to predict creatinine clearance. J Intern Med 2003; 253: 563–573. Objectives. Creatinine clearance (CCR) is a commonly used tool to measure glomerular filtration rate (GFR) in clinical practice. This tool requires collection of 24-h urine, which is quite bothersome. Several different formulae have been used to estimate GFR using plasma creatinine and other easy formulae to obtain biometrical data. We examined 10 formulae and compared them with actually measured CCR in a large sample of the general population. Design. Cross-sectional cohort study. Setting. University hospital outpatient clinic, a population based study. Subjects. A total of 8592 inhabitants of the city of Groningen, 28–75 years of age. The cohort is enriched for microalbuminuria. Results. In general, the formulae did not give an accurate estimation of CCR, particularly not in male and in obese subjects. Six formulae, including the Cockcroft–Gault gave a fairly good estimation of CCR in the overall population and in subgroups of specific gender, body mass index and age. All formulae however, gave an underestimation of the measured CCR in higher ranges of CCR and an overestimation in the lower ranges. Moreover, the age-related decline of CCR is hard to approximate with a formula. Conclusions. We conclude that formulae to estimate CCR in the general population, although giving a fairly good estimate of mean CCR, do not offer reliable data on CCR in the upper and lower ranges and do not adequately estimate the age–related decline in CCR.

Introduction: Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV), The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV. Methods and Results: Ninety-seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given, Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF, Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively. Conclusion: Stand-alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome.

Tricyclo[5.2.1.02,6]deca-2(6),8-dien-3-one contains a highly strained central double bond due to geometrical constraints imposed by the tricyclic skeleton which does not allow optimal sp2 hybridization at the C2 and C6 bridgehead positions. Michael addition of various nucleophiles (alkoxides, cyanide, and malonate) under protic conditions resulted in an exclusive exo-facial selectivity. This preference can be explained by steric and electronic factors. Michael additions using lithium dialkylcuprates resulted in predominant formation of endo-products, but also some exo-products were obtained. These exo-products arising from endo-approach may be the result of coordination of the cuprate with both the enone moiety and the olefinic C8–C9 bond. Michael additions to tricyclo[5.2.1.02,6]dec-2(6)-en-3-one, which lacks this C8–C9 double bond showed exclusive exo-facial selectivity to give exo-products. Besides these additions were all considerably slower than those to tricyclo[5.2.1.02,6]deca-2(6),8-dien-3-one proving significant electronic participation of the C8–C9 double bond in reactions with this substrate.