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Contains fulltext : 251906.pdf (Publisher’s version ) (Open Access) BACKGROUND: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients. OBJECTIVES: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. METHODS: In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. RESULTS: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. CONCLUSIONS: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations.

Purpose Heterogeneity in work participation (WP) outcomes measurements hampers large scale evidence synthesis in systematic reviews of trials. In this survey we explore authors’ reasons for choosing specific WP outcomes and their measurement methods, including employment status, absence from work, at-work productivity loss, and employability. Methods We contacted authors of 260 trials and 69 systematic reviews and asked closed and open-ended questions about previously used WP outcomes and measurement methods as well as their opinion on the best way to measure WP. Results In total, 91 authors from a wide range of professional backgrounds completed the survey. The majority of authors (86%) chose WP outcomes based on their use in previous similar studies. In most studies (88%), patients had not been involved in the process of selecting the WP outcome. Authors judged feasibility to be an important factor for choosing a measurement instrument (67%). Additionally, valid measurement tools should be available, easy to administer and not too time consuming. Although authors preferred registry data for long term follow-up, the availability and validity of registries was seen as a barrier. Most of the reviewers (72%) struggled to pool data because of variation in follow-up times and cut off points and varying definitions of work outcomes. Almost all (92%) respondents support the use of a Core Outcome Set for Work. Conclusions There is strong support from authors of trials and systematic reviews to develop a core outcome set on work participation outcomes for the evaluation of interventions.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects of personal protective equipment, including donning and doffing procedures and individual hygienic behaviour, compared to no such equipment or alternative equipment, on asbestos exposure in workers exposed to asbestos in demolition and repair work.

Objective Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied. Design The study was a longitudinal validation study of serial NETest measurements – a blood-based gene expression signature – in 132 patients with GEPNETs on therapy or watch-and-wait strategy. Methods Serial samples were collected during 46 (range: 6–71) months of follow-up. NETest scores were compared with Response Evaluation Criteria in Solid Tumors version 1.1-defined treatment response (e.g. no evidence of disease (NED), stable disease (SD) or progressive disease (PD)). Results Consecutive NETest scores fluctuated substantially (range: 0–100) over time in individuals with SD (n = 28) and NED (n = 30). Follow-up samples were significantly higher in SD (samples 3–5) and NED subgroups (samples 2–5) compared with baseline results, without changes in imaging. In 82% of untreated patients with PD, consecutive NETest scores consistently remained high. In patients undergoing systemic treatment, the median pre-treatment NETest score in treatment-responders was 76.5 (n = 22) vs 33 (n = 12) in non-responders (P = 0.001). Patients with low pre-treatment scores had 21 months reduced progression-free survival (10 vs 31 months; P = 0.01). The accuracy of the NETest for treatment response prediction was 0.73 (P = 0.009). Conclusion In patients not undergoing treatment, consecutive low NETest scores are associated with indolent behavior. Patients who develop PD exhibit elevated scores. Elevated results have important predictive value for treatment responsiveness and could be used for individualizing decisions on systemic therapy. The clinical value of follow-up NETest scores for patients who choose to watch and wait requires further study.

Background: Although many people infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) experience no or mild symptoms, some individuals can develop severe illness and may die, particularly older people and those with underlying medical problems. Providing evidence-based interventions to prevent SARS-CoV-2 infection has become more urgent with the spread of more infectious SARS-CoV-2 variants of concern (VoC), and the potential psychological toll imposed by the coronavirus disease 2019 (COVID-19) pandemic. Controlling exposures to occupational hazards is the fundamental method of protecting workers. When it comes to the transmission of viruses, such as SARS-CoV-2, workplaces should first consider control measures that can potentially have the most significant impact. According to the hierarchy of controls, one should first consider elimination (and substitution), then engineering controls, administrative controls, and lastly, personal protective equipment (PPE). Objectives: To assess the benefits and harms of interventions in non-healthcare-related workplaces to reduce the risk of SARS-CoV-2 infection relative to other interventions, or no intervention. Search methods: We searched MEDLINE, Embase, Web of Science, Cochrane COVID-19 Study Register, the Canadian Centre for Occupational Health and Safety (CCOHS), Clinicaltrials.gov, and the International Clinical Trials Registry Platform to 14 September 2021. We will conduct an update of this review in six months. Selection criteria: We included randomised control trials (RCT) and planned to include non-randomised studies of interventions. We included adult workers, both those who come into close contact with clients or customers (e.g. public-facing employees, such as cashiers or taxi drivers), and those who do not, but who could be infected by co-workers. We excluded studies involving healthcare workers. We included any intervention to prevent or reduce workers' exposure to SARS-CoV-2 in the workplace, defining categories of intervention according to the hierarchy of hazard controls, i.e. elimination; engineering controls; administrative controls; personal protective equipment. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were incidence rate of SARS-CoV-2 infection (or other respiratory viruses), SARS-CoV-2-related mortality, adverse events, and absenteeism from work. Our secondary outcomes were all-cause mortality, quality of life, hospitalisation, and uptake, acceptability, or adherence to strategies. We used the Cochrane RoB 2 tool to assess the risk of bias, and GRADE methods to assess the certainty of evidence for each outcome. Main results: Elimination of exposure interventions. We included one study examining an intervention that focused on elimination of hazards. This study is an open-label, cluster-randomised, non-inferiority trial, conducted in England in 2021. The study compared standard 10-day self-isolation after contact with an infected person to a new strategy of daily rapid antigen testing and staying at work if the test is negative (test-based attendance). The trialists hypothesised that this would lead to a similar rate of infections, but lower COVID-related absence. Staff (N = 11,798) working at 76 schools were assigned to standard isolation, and staff (N = 12,229) at 86 schools to the test-based attendance strategy. The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of symptomatic PCR-positive SARS-COV-2 infection rate ratio ((RR) 1.28, 95% confidence interval (CI) 0.74 to 2.21; 1 study, very low-certainty evidence)). The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of any PCR-positive SARS-COV-2 infection (RR 1.35, 95% CI 0.82 to 2.21; 1 study, very low-certainty evidence). COVID-related absenteeism rates were 3704 absence days in 566,502 days-at-risk (6.5 per 1000 days at risk) in the control group and 2932 per 539,805 days-at-risk (5.4 per 1000 days at risk) in the intervention group (RR 0.83; 95% CI 0.55 to 1.25). The certainty of the evidence was downgraded to low, due to imprecision. Uptake of the intervention was 71 % in the intervention group, but not reported for the control intervention. The trial did not measure other outcomes, SARS-CoV-2-related mortality, adverse events, all-cause mortality, quality of life, and hospitalisation. We found one ongoing RCT about screening in schools, using elimination of hazard strategies. Personal protective equipment. We found one ongoing non-randomised study on the effects of closed face shields to prevent COVID-19 transmission. Other intervention categories. We did not find studies in the other intervention categories. Authors' conclusions: We are uncertain whether a test-based attendance policy affects rates of PCR-postive SARS-CoV-2 infection (any infection; symptomatic infection) compared to standard 10-day self-isolation amongst school and college staff. Test-based attendance policy may result in little to no difference in absence rates compared to standard 10-day self-isolation. As a large part of the population is exposed in the case of a pandemic, an apparently small relative effect that would not be worthwhile from the individual perspective may still affect many people, and thus, become an important absolute effect from the enterprise or societal perspective. The included study did not report on any other primary outcomes of our review, i.e. SARS-CoV-2-related mortality and adverse events. No completed studies were identified on any other interventions specified in this review, but two eligible studies are ongoing. More controlled studies are needed on testing and isolation strategies, and working from home, as these have important implications for work organisations.

Background: Work participation is important for health and can be considered as engagement in a major area of life which is of significance for most people, but it can also be thought of as fulfilling or discharging a role. Currently, academic research lacks a comprehensive classification of work participation outcomes. The International Classification of Functioning is the foremost model in defining work functioning and its counterpart work disability, but it does not provide a critical (core) set of outcomes. It is important to standardize the definitions and the nomenclature used in the research of work participation, so that the outcomes of studies are comparable, and practitioners and guideline developers can better decide what works best. As work participation is a broad umbrella term including outcome categories which need unambiguous differentiation, a framework needs to be developed first.Aim: To propose a framework which can be used to develop a generic core outcome set for work participation.Methods: First, we performed a systematic literature search on the concept of (work) participation, perspectives on how to measure it, and existing classifications for outcome measurements. Next, we derived criteria for the framework and proposed a framework based on the criteria. Last, we applied the framework to six case studies as a proof of concept. Results: Our literature search provided 2106 hits and we used 59 studies for full-text analysis. Based on the literature and the developed criteria we propose four overarching outcome categories: (1) initiating employment, (2) having employment, (3) increasing or maintaining productivity at work and (4) return to employment. These categories appeared feasible in our proof-of-concept assessment with six different case studies. Conclusion: We propose to use the framework for work participation outcomes to develop a core outcome set for intervention studies to improve work participation.

Background Work participation is important for health and can be considered as engagement in a major area of life which is of significance for most people, but it can also be thought of as fulfilling or discharging a role. Currently, academic research lacks a comprehensive classification of work participation outcomes. The International Classification of Functioning is the foremost model in defining work functioning and its counterpart work disability, but it does not provide a critical (core) set of outcomes. Standardizing the definitions and nomenclature used in the research of work participation would ensure that the outcomes of studies are comparable, and practitioners and guideline developers can better decide what works best. As work participation is a broad umbrella term including outcome categories which need unambiguous differentiation, a framework needs to be developed first. Aim To propose a framework which can be used to develop a generic core outcome set for work participation. Methods First, we performed a systematic literature search on the concept of (work) participation, views on how to measure it, and on existing classifications for outcome measurements. Next, we derived criteria for the framework and proposed a framework based on the criteria. Last, we applied the framework to six case studies as a proof of concept. Results Our literature search provided 2106 hits and we selected 59 studies for full-text analysis. Based on the literature and the developed criteria we propose four overarching outcome categories: (1) initiating employment, (2) having employment, (3) increasing or maintaining productivity at work, and (4) return to employment. These categories appeared feasible in our proof-of-concept assessment with six different case studies. Conclusion We propose to use the framework for work participation outcomes to develop a core outcome set for intervention studies to improve work participation.

Background Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability, and egg output of repeated exposure to hookworm larvae. Methods Twenty-four healthy volunteers were randomized, double-blindly, to 1, 2, or 3 doses of 50 Necator americanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20. Results There was no association between larval dose and number or severity of adverse events. Geometric mean egg loads stabilized at 697, 1668, and 1914 eggs per gram feces for the 1 × 50L3, 2 × 50L3, and 3 × 50L3 group, respectively. Bayesian statistical modeling showed that egg count variability relative to the mean was reduced with a second infectious dose; however, the third dose did not increase egg load or decrease variability. We therefore suggest 2 × 50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes the power of hypothetical vaccine trials. Conclusions Repeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events. Clinical Trials Registration NCT03257072.

Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas1. Novel medicines and vaccines are urgently needed2,3. An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3–10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4+ T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis. A new human challenge model of schistosomiasis, which affects more than 290 million people globally, will aid development of novel therapies and vaccines for this neglected tropical disease.

Vanadium dioxide (VO2) is a much-discussed material for oxide electronics and neuromorphic computing applications. Here, heteroepitaxy of VO2 is realized on top of oxide nanosheets that cover either the amorphous silicon dioxide surfaces of Si substrates or X-ray transparent silicon nitride membranes. The out-of-plane orientation of the VO2 thin films is controlled at will between (011)M1/(110)R and (−402)M1/(002)R by coating the bulk substrates with Ti0.87O2 and NbWO6 nanosheets, respectively, prior to VO2 growth. Temperature-dependent X-ray diffraction and automated crystal orientation mapping in microprobe transmission electron microscope mode (ACOM-TEM) characterize the high phase purity, the crystallographic and orientational properties of the VO2 films. Transport measurements and soft X-ray absorption in transmission are used to probe the VO2 metal–insulator transition, showing results of a quality equal to those from epitaxial films on bulk single-crystal substrates. Successful local manipulation of two different VO2 orientations on a single substrate is demonstrated using VO2 grown on lithographically patterned lines of Ti0.87O2 and NbWO6 nanosheets investigated by electron backscatter diffraction. Finally, the excellent suitability of these nanosheet-templated VO2 films for advanced lensless imaging of the metal–insulator transition using coherent soft X-rays is discussed.

Family inclusion in nursing homes is central to the provision of individualized care for people with dementia. Although, ideally, family and staff members in nursing homes for people with dementia are equal partners in caregiving, a wide variety of barriers have been identified that hamper family inclusion in nursing homes. The aim of this literature review was to provide insight into strategies and interventions that enable family members of people with dementia in nursing homes to participate actively in nursing homes. Systematically searching the databases PubMed, Cinahl, PsycInfo and Embase led to 841 potential relevant publications. After screening titles, abstracts and full-texts, 29 studies were included (11 qualitative, 17 quantitative and 1 mixed-method). Interventions and strategies assessed in the included studies reached from educating family members about dementia or facilitating contact with other families, to how to successfully communicate with staff members or being a resident’s advocate in the nursing home. Even in case interventions and strategies had no significant or promising effects, most family members were satisfied with them. At the same time, the preferences for and results of interventions and strategies often depended on characteristics of family members. For example, differences were seen between spouses and children. Based on the literature review, it can be concluded that an intervention consisting of different components (for example, education about dementia, provision of decision aids, peer support, and possibilities to discuss end-of-life care) might be most promising for enabling family members to act as equal partners in caregiving.

Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. Ketoconazole Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%. Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence). Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. Ciclopirox Ciclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungals Clotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies. Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms. Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar. Authors' conclusions Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis. Plain Language Summary Antifungal treatments applied to the skin to treat seborrhoeic dermatitis Background Seborrhoeic dermatitis is a chronic inflammatory skin condition found throughout the world, with rashes with varying degrees of redness, scaling and itching. It affects people of both sexes but is more common among men. The disease usually starts after puberty and can lead to personal discomfort and cosmetic concerns when rashes occur at prominent skin sites. Drugs that act against moulds, also called antifungal agents, have been commonly used on their own or in combination. Review question Do antifungal treatments applied to the skin clear up the rashes and itching of seborrhoeic dermatitis? Study characteristics We included 51 studies with 9052 participants. Trials typically were four weeks long, and very few trials were longer. In all, 24 studies had some involvement of pharmaceutical companies such as funding or employment of the researchers. Key results Particpants taking ketoconazole were 31% less likely than those given placebo to have symptoms that persisted at four weeks of follow-up. This was seen in eight studies with 2520 participants, but wide variation was noted between studies. Ketoconazole was as effective as steroids but had 44% fewer side effects. Without causing more side effects, ciclopirox was 21% more effective than placebo in achieving clinical clearance of rashes. Treatment effect on redness, itching or scaling symptoms of the skin was less clear. Evidence was insufficient to conclude that that one antifungal was superior to other antifungals, but this observation was based on few studies. Ketoconazole and ciclopirox are the most heavily investigated antifungals and are more effective than placebo. Other antifungals might have similar effects, but data are insufficient to underpin this. Common side effects were increased skin redness or itching, burning sensation and hair loss. No studies measured quality of life. Only one study reported on percentage of compliance in different treatment groups. Other studies used surrogates such as acceptability to represent compliance. We therefore could not assess the effect of compliance on treatment outcomes. One study on patients with HIV reported no clear effects of treatments. Quality of the evidence Evidence for the effects of ketoconazole compared with placebo or a steroid was assessed to be of low quality. Evidence derived from comparison of ciclopirox versus placebo was assessed to be of moderate quality. Better quality studies with longer follow-up and better reporting are needed to enlarge the evidence base for antifungals.

The fluxes and energy distributions of the charge exchange (CX) neutrals as measured at specific locations at the tokamak ASDEX Upgrade (AUG) and the stellarator W7-AS at Garching are discussed as a function of the discharge conditions. For the evaluation of the plasma-wall interaction, knowledge of the energetic neutral fluxes and their energy and angular distributions at all poloidal and toroidal locations are required. For AUG these are obtained from B2-EIRENE computer simulations, taking the experimental results into account. The CX fluxes and the shapes of the spectra vary greatly around a poloidal cross-section. This has a strong effect on the wall erosion by sputtering and hydrogen isotope implantation into the vessel walls. The sputtering of the actual carbon wall, and the effect on possible wall materials, such as tungsten, beryllium, TiC and SiC, are discussed. The depth distribution of the CX neutrals implanted into the walls is calculated for two cases using the TRIMSP code. Saturation, release by glow discharges and permanent retention of the implanted hydrogen isotopes are discussed. This is important for the expected tritium content of the vessel walls of a future D-T fusion device.

Quite a lot of key developments and innovations have occurred in the dynamic market of laundry detergents and cleaners in recent years. A detailed review on changes regarding the composition of powder and liquid laundry detergents and their manufacturing technology is presented. Also, differences and common characteristics between compact/super-compact detergents and conventional detergents are discussed. New developments with modern washing machines, changing consumer attitudes and washing habits as well as official directives regarding environmental compatibility have exerted quite a considerable influence on the composition of modern detergents and their ingredients such as surfactant combinations, bleach systems and enzyme cocktails. Ongoing trends regarding laundry detergents and cleaners as well as future prospects are discussed.

We analyzed the value in cervical cytology of a recently developed technique by which it is possible to remove thick tissue specimens, called microbiopsies, from cervical smears and to process them for histologic examination. In 12 (48%) of 25 cervical smears in which microbiopsies were found, the histologic sections from them confirmed the cytologic diagnosis. Most cases involved classification of lesions diagnosed as cervical intraepithelial neoplasia. In 13 (52%) of 25 smears, processing the microbiopsy allowed considerable modification of the cytologic diagnosis. In six of these cases, microbiopsies consisted of groups of columnar cells that were incorrectly classified as atypical on the basis of cytologic criteria. After histologic processing, the microbiopsies revealed nonatypical columnar cells in four cases and only mildly atypical columnar cells in two cases. In 3 of 13 smears, there were insufficient dispersed atypical cells for a conclusive diagnosis. Processing the microbiopsies in these cases allowed classification into one of the cervical intraepithelial neoplasia categories.

Edge plasma scenarios in island divertor configurations (‘natural’ magnetic islands intersected by targets) are studied by comparing data from moderate to high density NBI discharges with 3D code (EMC3/EIRENE) results. The data strongly indicate that high recycling with significant particle flux enhancement was achieved in this geometry. But, plasma pressure losses towards the targets are relatively strong, and high recycling sets in only at n e > 10 20 m −3 . The respective density enhancement in front of the targets is moderate (up to a factor of about three relative to the upstream density). These scenarios are also in basic agreement with B2/EIRENE code predictions. At n e > 1.5 × 10 20 m −3 detachment seems to develop. Improvements are expected from additional coils controlling the field line pitch inside the islands, and from optimized targets which will better focus recycling neutrals into the islands. Both are in preparation.

Basic topological features of the island divertor concept for low shear stellarators are discussed with emphasis on the differences to tokamak divertors. Extensive measurements of the edge structures by two-dimensional plasma spectroscopy and by target calorimetry are in excellent agreement with predicted vacuum and equilibrium configurations, which are available up to central β values of ∼ 1%. For this β value the calculated field-line pitch inside the islands is twice that of the corresponding vacuum case. Video observations of the strike points indicate stability of the island structures for central β values up to ∼ 3.7%. The interpretation of the complex island divertor physics of W7-AS has become possible by the development of the three-dimensional plasma transport code EMC3 (Edge Monte Carlo 3D), which has been coupled self-consistently to the EIRENE neutral gas code. Analysis of high density NBI discharges gives strong indications of stable high recycling conditions for n e ≥ 10 20 m −3 . The observations are reproduced by the EMC3/EIRENE code and supported by calculations with the B2/EIRENE code adapted to W7-AS. Improvement of recycling, pumping and target load distribution is expected from the new optimized target plates and baffles to be installed in W7-AS.

Institutional dementia care is increasingly directed towards small-scale and homelike care environments, in The Netherlands as well as abroad. In these facilities, a small number of residents, usually six to eight, live together, and normal daily household activities and social participation are emphasized. In a quasi-experimental study, we studied the effects of small-scale, homelike care environments on residents (n = 259), family caregivers (n = 206) and nursing staff (n = 305). We compared two types of institutional nursing care during a 1 year period (baseline assessment and follow-up measurements at 6 and 12 months): (28) small-scale, homelike care environments and (21) psychogeriatric wards in traditional nursing homes. A matching procedure was applied to increase comparability of residents at baseline regarding functional status and cognition. This study was unable to demonstrate convincing overall effects of small-scale, homelike care facilities. On our primary outcome measures, such as quality of life and behaviour of residents and job satisfaction and motivation of nursing staff, no differences were found with traditional nursing homes. We conclude that small-scale, homelike care environments are not necessarily a better care environment than regular nursing homes and other types of living arrangements should be considered carefully. This provides opportunities for residents and their family caregivers to make a choice which care facility suits their wishes and beliefs best.

Dampness and mould in buildings have been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture damage is a very common problem in private houses, workplaces and public buildings such as schools.To determine the effectiveness of remediating buildings damaged by dampness and mould in order to reduce or prevent respiratory tract symptoms, infections and symptoms of asthma.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1951 to June week 1, 2011), EMBASE (1974 to June 2011), CINAHL (1982 to June 2011), Science Citation Index (1973 to June 2011), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to November 2010) and CISDOC (1974 to November 2010).Randomised controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies and controlled before-after (CBA) studies of the effects of remediating dampness and mould in a building on respiratory symptoms, infections and asthma.Two authors independently extracted data and assessed the risk of bias in the included studies.We included eight studies (6538 participants); two RCTs (294 participants), one cRCT (4407 participants) and five CBA studies (1837 participants). The interventions varied from thorough renovation to cleaning only. We found moderate-quality evidence in adults that repairing houses decreased asthma-related symptoms (among others, wheezing (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66)). For children, we found moderate-quality evidence that the number of acute care visits (among others mean difference (MD) -0.45; 95% CI -0.76 to -0.14)) decreased in the group receiving thorough remediation. One CBA study showed very low-quality evidence that after repairing a mould-damaged office building, asthma-related and other respiratory symptoms decreased. For children and staff in schools, there was very low-quality evidence that asthma-related and other respiratory symptoms in mould-damaged schools were similar to those of children and staff in non-damaged schools, both before and after intervention. For children, respiratory infections might have decreased after the intervention.We found moderate to very low-quality evidence that repairing mould-damaged houses and offices decreases asthma-related symptoms and respiratory infections compared to no intervention in adults. There is very low-quality evidence that although repairing schools did not significantly change respiratory symptoms in staff or children, pupils' visits to physicians due to a common cold were less frequent after remediation of the school. Better research, preferably with a cRCT design and with more validated outcome measures, is needed.

OBJECTIVE: To describe a novel method by which small tissue fragments found in routine cytology specimens can be processed for histologic slides without destroying or damaging the cytologic specimen. STUDY DESIGN: To develop a method by which small tissue fragments (microbiopsies) are removed from cytologic slides and processed through paraffin or plastic, after which histologic slides can be prepared. RESULTS: In all cases described, the histologic sections from the microbiopsies were of excellent quality. Microscopic examination gave additional important information. Furthermore, immunochemistry could be performed on paraffin-processed microbiopsies. CONCLUSION: This method can be of great value in cytologic specimens in which microbiopsies are present, not only in those cases in which cytologic information is insufficient for diagnosis, but also in cases with conclusive diagnostic information. Routinely applied, this method could make biopsies unnecessary in some cases.

Electron cyclotron resonance heating (ECRH) at the W7-AS stellarator is performed two systems of comparable heating power at 70 GHz (0.8 MW, 3 s) and 140 GHz (0.9 MW, 0.4 s). Experiments with 140 GHz open a new parameter window with high density operation up to 1.1 × 1020 m−3. H mode transitions were observed in high density discharges at 2.5 T and at lower density at 1.25 T. The operational window for the stellarator H mode with emphasis on the density and power threshold and the influence of gas puffing on the H transitions are discussed. Perturbation experiments with modulated ECRH power were performed to determine the heat transport and the power deposition profile. Density control is achieved in combined heating with neutral beam injection (NBI) despite the beam particle fuelling, whereas with NBI alone a steady density rise is observed. The impact of combined heating on the impurity confinement was investigated. Electron cyclotron current drive (ECCD) was studied in different magnetic field configurations and the influence of trapped particles on the ECCD efficiency was examined experimentally and compared with theory.

The possibilities of fabricating integrated optical components on an InP substrate are demonstrated by a number of devices that have been made in recent years. These components can have a major impact on evolving communication networks by facilitating new techniques for increasing capacity such as wavelength division multiplexing and soliton transmission.

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Resonant optical amplification is studied both theoretically and experimentally. Coupled rate equations for the signal field and the spontaneous emission field, valid for input signals with bit rates up to 10 Gb/s are derived. A special weighing procedure based on a dwell-time analysis is used to account for bistable filter operation. The measured amplification characteristics of a /spl lambda//4 DFB laser injected with a 2.5 Gb/s signal show good agreement with theory. >

The paper describes the effect of the isotopic mass on plasma parameters as observed in the ASDEX tokamak. The paper comprises Ohmic as well as L mode, H mode and H* mode scenarios. The measurements reveal that the ion mass is a substantial and robust parameter, which affects all the confinement times (energy, particle and momentum) in the whole operational window. Both core properties such as the sawtooth repetition time and edge properties such as the separatrix density change with the isotopic mass. Specific emphasis is given to the edge parameters and changes of the edge plasma due to different types of wall conditioning, such as carbonization and boronization. The pronounced isotope dependences of the edge and divertor parameters are explained by the secondary effect of different power fluxes into the scrape-off layer plasma and onto the divertor plates. Finally, the observations serve to test different transport theories. With respect to the ion temperature gradient driven turbulence, the isotope effect is also studied in pellet refuelled discharges with peaked density profiles. The results from ASDEX are compared with the results from other experiments

A new instrument to measure the Wobbe index of natural gas has been developed and tested. The instrument detects the residual oxygen content of the flue gases after a known amount of gas is burned with a known amount of air. This residual oxygen content is a measure for the Wobbe index. The instrument has a fast response and a low noise level which makes it suitable for use in burner control systems. The measurement is hardly affected by external influences so an expensive conditioned room will not be required.

Functional capacity evaluation (FCE) has been widely used to assess workers' physical state of readiness to return to work (RTW) after an injury and to make recommendations for the time and capacity in which they might return. FCEs are also used to prevent re-injury after RTW. Despite being a commonly used tool, little is known about how effective FCE is in preventing occupational injuries.To assess the effectiveness of FCE-based return to work recommendations in preventing occupational re-injuries of injured workers compared with no intervention or alternative interventions.We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE (1966 to December 2009), EMBASE (1980 to December 2009), CINAHL (1980 to December 2009), PsycINFO (1983 to December 2009) and PEDro (1929 to December 2009). The searches were not restricted by date, language or type of publication.We included randomised controlled trials (RCTs) of FCE-based return to work recommendations for preventing occupational re-injuries in injured workers.Four authors (NM, ES, JV, ML), in pairs, independently selected studies for inclusion, extracted data and assessed risk of bias.We found no studies that compared FCE to no intervention. We found one RCT with 372 participants in which a short-form of one FCE was compared to the standard long-form FCE (Isernhagen Work Systems). Outcomes were recurrence rates of re-injuries. There was no significant difference between the two forms of FCE.We rated the overall quality of the evidence as low.There is no evidence for or against the effectiveness of FCE compared to no intervention. A short version of FCE showed similar effectiveness to a long version in preventing re-injury. More RCTs are needed.

The charge exchange (CX) neutral energy distributions from ASDEX measured with the conventional neutral particle analyzers (NPA) at energies >500 eV are combined with the low energy CX spectra from the low energy neutral analyzer (LENA). In the region of overlap their shapes fit each other very well. With the 3D EIRENE code the neutral gas was simulated and ion temperature ( T i ) profiles from the center to the edge are obtained. The T i values at the separatrix and the edge based on the LENA data are considerably lower than those suggested earlier from the NPA data. This is attributed to the different energy ranges—high energies for the NPA, low energies for LENA—that are used for the T i evaluation.

More than 400 km of high-resolution, partially digitally acquired seismic data were collected in a 30 × 60 km area offshore from the Dutch mesotidal barrier island shoreline, in order to analyze the Holocene transgressive sequence. The investigated area was subaerially exposed during the most recent (Weichselian) Pleistocene lowstand and glaciated during the previous (Saale/Illinoian) glacial period. Sea level was probably at a level comparable to that of the present during the intervening Eem/Sangamonian highstand. The area's seismic signature is characterized by several levels of channelization, separated by major, area-wide high-amplitude reflectors. The lowermost aerial reflector represents the Saale boulder clay. The largest channel system, which cuts this reflector, was incised during the Older Dryas cooling event and filled during the Allerod warming period. It was subsequently re-incised during the Younger Dryas and refilled during the early Holocene. The most pronounced and extensive reflector represents the base of the Holocene, and almost everywhere equals the planed-off top of the Eem highstand section. This reflector is overlain by aggradational facies, separated by one level of channelization and one planed-off (ravinement?) surface. The most prominent type of seismic facies above the lowermost level of channelization is a set of progradational clinoforms, which is interpreted as a preserved ebb-tidal delta system. This system is associated with the first Holocene shoreline of ca. 7500 yrs BP. The eastern part of the study area contains sand ridges with a complex pattern of internal cross-stratification. Ridge-crest sediments are very well-sorted with a mean grain size of 2.8-2.6 φ (ca. 0.15 mm), whereas sediments in the troughs are well-sorted with a mean grain size of 1.8-0.8 φ (0.25–0.5 mm). Origin of these ridges is tentatively thought to be related to reworking since 5000 yrs BP, when the dynamic regime was more or less similar to that of the present and sediment supply had decreased substantially.

BACKGROUND: Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. OBJECTIVES: To assess the effectiveness of non-pharmaceutical interventions for preventing occupational noise exposure or occupational hearing loss compared to no intervention or alternative interventions. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 4, 2008); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; NIOSHTIC, CISDOC and mRCT to 15 December 2008. SELECTION CRITERIA: Randomised controlled trials, controlled before-after studies and interrupted time series (ITS) of non-clinical hearing loss prevention interventions under field conditions among workers exposed to noise. DATA COLLECTION AND ANALYSIS: Two authors (EK, JV) independently assessed study eligibility and trial quality and extracted data. MAIN RESULTS: Twenty-one studies were included. One study evaluated a strategy to reduce noise exposure. Fourteen studies with 75,672 participants evaluated hearing loss prevention programmes (HLPPs), and six studies with 169 participants evaluated hearing protection. The overall quality of studies was low.One ITS study evaluated the effect of new legislation in reducing noise exposure. It found that the median noise level decreased by 27.7 dB(A) (95% confidence interval (CI) -36.1 to -19.3 dB) with a change in trend in time of -2.1 dB per year (95% CI -4.9 to 0.7).A hearing protection study in army recruits compared those exposed to impulse noise with non-exposed recruits. The odds ratio (OR) for hearing loss was 3.0 (95% CI 1.1 to 8.0) despite hearing protection. In four studies, workers in a HLPP had a 0.5 dB HL greater hearing loss at 4 kHz than non-noise exposed workers (95% CI -0.5 to 1.7). In one study, the hazard ratio of hearing loss was 3.8 (95% CI 2.7 to 5.3) for workers exposed to noise compared to non-exposed workers.In three studies, a high quality HLPP had a lower risk of hearing loss than lower quality programmes.Noise attenuation ratings of hearing protection under field conditions were consistently lower than the ratings provided by the manufacturers. AUTHORS' CONCLUSIONS: There is low quality evidence that legislation can reduce noise levels in workplaces.The effectiveness of hearing protection devices depends on their proper use. There is contradictory evidence that HLPPs are effective in the long-term. Even though case studies show that substantial reductions can be achieved, there is no evidence that this is realised in practice. Better implementation and reinforcement is needed.Better evaluations of technical interventions and long-term effects are needed. Audiometric and noise measurement data are potentially valuable for such studies