138 research outputs found
Comparing men's and womens' experiences of multiple exclusion homelessness
This article explores gender as a variable in multiple exclusion homelessness in England. Much past research has taken insufficient account of the gender of homeless people, especially the predominance of men in the single homeless population and of women heading homeless households with dependent children. Drawing on qualitative data generated in a study of multiple exclusion homelessness in London and Nottingham, the article considers three ways in which gender may act as a homelessness variable: in people's susceptibility to homelessness, in their experiences of homelessness and in their encounters with accommodation services. By comparing the accounts of homeless men and women with complex support needs with evidence from staff working for support agencies, the overall aim of the article is to offer a critical examination of the gendered assumptions of homelessness policy and practice
Supervisor trainees' and their supervisors' perceptions of attainment of knowledge and skills. An empirical evaluation of a psychotherapy supervisor training programme
Objectives. This study aimed to evaluate the success of a two-year, part-time training programme for psychotherapy supervisors. A second aim was to examine factors that might contribute to perceived knowledge and skills attainment during the training course. Design. This is a naturalistic, longitudinal study where several measures are used to examine group process and outcome. Methods. Supervisor trainees’ (n=21) and their facilitators’ (n=6) ratings of learning (knowledge and skills), relations to the supervisor and supervision group, usage of the group, and supervisor style were completed at three time points. Results. The findings suggested that both trainees and their supervisors perceived that the trainees attained a substantial amount of knowledge and skills during the course. In accordance with the literature and expectations, the regression analysis suggested a strong negative association between a strong focus on group processes in the initial and middle phases of the training and perceived knowledge and skills attainment in the final phase of the training. The expected, positive role of relations among trainees in the supervision group in the first half of the training and perceived knowledge and skills attainment in the final part of the training was obtained, whilst the hypothesized significance of the relationship between trainee and supervisor did not receive support. Conclusions The supervisory course seemed to provide a training that allowed trainees to attain knowledge and skills that are necessary for psychotherapy supervisors. The results of this pilot study also emphasize the need of more research on learning in the context of group supervision in psychotherapy
Aglycone specificity of Thermotoga neapolitana β-glucosidase 1A modified by mutagenesis, leading to increased catalytic efficiency in quercetin-3-glucoside hydrolysis
Background: The thermostable beta-glucosidase (TnBgl1A) from Thermotoga neapolitana is a promising biocatalyst for hydrolysis of glucosylated flavonoids and can be coupled to extraction methods using pressurized hot water. Hydrolysis has however been shown to be dependent on the position of the glucosylation on the flavonoid, and e. g. quercetin-3-glucoside (Q3) was hydrolysed slowly. A set of mutants of TnBgl1A were thus created to analyse the influence on the kinetic parameters using the model substrate para-nitrophenyl-beta-D-glucopyranoside (pNPGlc), and screened for hydrolysis of Q3. Results: Structural analysis pinpointed an area in the active site pocket with non-conserved residues between specificity groups in glycoside hydrolase family 1 (GH1). Three residues in this area located on beta-strand 5 (F219, N221, and G222) close to sugar binding sub-site +2 were selected for mutagenesis and amplified in a protocol that introduced a few spontaneous mutations. Eight mutants (four triple: F219L/P165L/M278I, N221S/P165L/M278I, G222Q/P165L/M278I, G222Q/V203M/K214R, two double: F219L/K214R, N221S/P342L and two single: G222M and N221S) were produced in E. coli, and purified to apparent homogeneity. Thermostability, measured as T-m by differential scanning calorimetry (101.9 degrees C for wt), was kept in the mutated variants and significant decrease (Delta T of 5 -10 degrees C) was only observed for the triple mutants. The exchanged residue(s) in the respective mutant resulted in variations in K-M and turnover. The K-M-value was only changed in variants mutated at position 221 (N221S) and was in all cases monitored as a 2-3 x increase for pNPGlc, while the K-M decreased a corresponding extent for Q3. Turnover was only significantly changed using pNPGlc, and was decreased 2-3 x in variants mutated at position 222, while the single, double and triple mutated variants carrying a mutation at position 221 (N221S) increased turnover up to 3.5 x compared to the wild type. Modelling showed that the mutation at position 221, may alter the position of N291 resulting in increased hydrogen bonding of Q3 (at a position corresponding to the +1 subsite) which may explain the decrease in K-M for this substrate. Conclusion: These results show that residues at the +2 subsite are interesting targets for mutagenesis and mutations at these positions can directly or indirectly affect both K-M and turnover. An affinity change, leading to a decreased K-M, can be explained by an altered position of N291, while the changes in turnover are more difficult to explain and may be the result of smaller conformational changes in the active site
Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids
This is an expert consensus from the European Neuroendocrine Tumor Society recommending best practice for the management of pulmonary neuroendocrine tumors including typical and atypical carcinoids. It emphasizes the latest discussion on nomenclature, advances and utility of new diagnostic techniques as well as the limited evidence and difficulties in determining the optimal therapeutic strateg
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Human Bone Marrow Mesenchymal Stromal Cell-Derived CXCL12, IL-6 and GDF-15 and Their Capacity to Support IgG-Secreting Cells in Culture Are Divergently Affected by Doxorubicin
Various subsets of bone marrow mesenchymal stromal cells (BM MSCs), including fibroblasts, endothelial, fat and reticular cells, are implicated in the regulation of the hematopoietic microenvironment and the survival of long-lived antibody-secreting cells (ASCs). Nowadays it is widely acknowledged that vaccine-induced protective antibody levels are diminished in adults and children that are treated for hematological cancers. A reason behind this could be damage to the BM MSC niche leading to a diminished pool of ASCs. To this end, we asked whether cell cytotoxic treatment alters the capacity of human BM MSCs to support the survival of ASCs. To investigate how chemotherapy affects soluble factors related to the ASC niche, we profiled a large number of cytokines and chemokines from in vitro-expanded MSCs from healthy donors or children who were undergoing therapy for acute lymphoblastic leukemia (ALL), following exposure to a widely used anthracycline called doxorubicin (Doxo). In addition, we asked if the observed changes in the measured soluble factors after Doxo exposure impacted the ability of the BM niche to support humoral immunity by co-culturing Doxo-exposed BM MSCs with in vitro-differentiated ASCs from healthy blood donors, and selective neutralization of cytokines. Our in vitro results imply that Doxo-induced alterations in BM MSC-derived interleukin 6 (IL-6), CXCL12 and growth and differentiation factor 15 (GDF-15) are not sufficient to disintegrate the support of IgG-producing ASCs by the BM MSC niche, and that serological memory loss may arise during later stages of ALL therapy.</jats:p
REPORT OF THE JOINT EIFAAC/ICES/GFCM WORKING GROUP ON EELS (WGEEL)
The Joint EIFAAC/ICES/GFCM Working group on eels (WGEEL) met in a split meeting from 4–8 September (online) and 25 September–02 October 2023 (hybrid meeting) in Helsinki, Finland, to provide the scientific basis for the ICES advice on fishing opportunities and conservation as-pects for the European eel and address requests from EIFAAC and GFCM. WGEEL assessed the state of the European eel and its fisheries, collated and analysed biometric data, reviewed the implementation of the WKFEA (Workshop on the future of eel advice) roadmap, examined available recruitment data from coastal and marine habitats, reported on any updates to the scientific basis of the advice, new and emerging threats or opportunities, in-cluding developments in the Mediterranean region. After high levels in the late 1970s, the recruitment declined dramatically in the 1980s and remains low. Compared to 1960–1979, the recruitment in the “North Sea” was 0.4% in 2023 (provisional) and 0.7 % in 2022 (final). In the “Elsewhere Europe” index series was 8.8 % in 2023 (provisional) and 11.3% in 2022 (final). For the yellow eel data series, recruitment for 2022 was 9% (final). Time-series from 1980 to 2023 show that glass eel recruitment remains at a very low level, with an historical minimum value in the North Sea. Silver eel time series have been analysed to identify patterns in abundance trends. These analyses are exploratory and have enabled us to test certain statistical methods and their limitations for analysing temporal series on silver eels. Although they give us an initial idea of trends in silver eel abundance, their results should be treated with caution. In fact, several problems have been identified and these points need to be improved in order to be able to interpret the results. The trend of reported commercial landings shows a long-term continuing decline, from a level of around 10,000 t in the 1960s, reported commercial landings have now dropped to 2028 (glass eel + yellow eel + silver eel) in 2022. The commercial glass eel fishery in 2022 was 60.1 t and 53.6 t in 2023. Reported landings from yellow and silver eel commercial fisheries (Y, S, YS) add up to 2914 t in 2021 and 2437 t in 2022. Spain was the only country allowing a recreational catch of glass eel, with landings estimated at 0.72 t in 2022 and 1.32 t in 2023. Reported recreational land-ings for yellow and silver eel combined were 240 t for 2021 (11 countries reporting) and 249 t for 2022. Progress with regards to the ‘road map’ developed within WKFEA was evaluated. The returns from the three questionnaires distributed by WKSMEEL to WGEEL members were summarised. In relation to the progress of the WKFEA roadmap, item 1; the inclusion of biological data is advanced with biometry data included in the annual data call. Item 2 relates to the reconstruction of the landings data and a workshop will take place in December 2023. Items 3 and 4 are also in progress, the Spatial database and Model for Eel (WKSMEEL) workshop was held in June 2023 with a follow up workshop planned for October 2023. A questionnaire for 3 topics (electrofish-ing, hydrographic network, and river obstructions & hydropower) was circulated to WGEEL members in August 2023. Of the 21 countries who responded, a large majority carry out electro-fishing, have available hydrographic networks and hold some information of obstructions to migration. However, it was recognised that considerable effort and resources will be required before the available data could be collated.publishedVersio
An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: The BOOSTB4 trial protocol
Introduction Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. Methods and analysis BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial. Each subject receives four intravenous doses of 3×10 6 /kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally. The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. Ethics and dissemination The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. Trial registration numbers EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482
The Mental Vitality @ Work study: design of a randomized controlled trial on the effect of a workers' health surveillance mental module for nurses and allied health professionals
Employees in health care service are at high risk for developing mental health complaints. The effects of mental health complaints on work can have serious consequences for the quality of care provided by these workers. To help health service workers remain healthy and productive, preventive actions are necessary. A Workers' Health Surveillance (WHS) mental module may be an effective strategy to monitor and promote good (mental) health and work performance. The objective of this paper is to describe the design of a three arm cluster randomized controlled trial on the effectiveness of a WHS mental module for nurses and allied health professionals. Two strategies for this WHS mental module will be compared along with data from a control group. Additionally, the cost effectiveness of the approaches will be evaluated from a societal perspective. The study is designed as a cluster randomized controlled trial consisting of three arms (two intervention groups, 1 control group) with randomization at ward level. The study population consists of 86 departments in one Dutch academic medical center with a total of 1731 nurses and allied health professionals. At baseline, after three months and after six months of follow-up, outcomes will be assessed by online questionnaires. In both intervention arms, participants will complete a screening to detect problems in mental health and work functioning and receive feedback on their screening results. In cases of impairments in mental health or work functioning in the first intervention arm, a consultation with an occupational physician will be offered. The second intervention arm offers a choice of self-help e-mental health interventions, which will be tailored based on each individual's mental health state and work functioning. The primary outcomes will be help-seeking behavior and work functioning. Secondary outcomes will be mental health and wellbeing. Furthermore, cost-effectiveness in both intervention arms will be assessed, and a process evaluation will be performed. When it is proven effective compared to a control group, a WHS mental module for nurses and allied health professionals could be implemented and used on a regular basis by occupational health services in hospitals to improve employees' mental health and work functioning. NTR278
The mbo Operon Is Specific and Essential for Biosynthesis of Mangotoxin in Pseudomonas syringae
Mangotoxin is an antimetabolite toxin produced by certain Pseudomonas syringae pv. syringae strains. This toxin is an oligopeptide that inhibits ornithine N-acetyl transferase, a key enzyme in the biosynthesis of ornithine and arginine. Previous studies have reported the involvement of the putative nonribosomal peptide synthetase MgoA in virulence and mangotoxin production. In this study, we analyse a new chromosomal region of P. syringae pv. syringae UMAF0158, which contains six coding sequences arranged as an operon (mbo operon). The mbo operon was detected in only mangotoxin-producing strains, and it was shown to be essential for the biosynthesis of this toxin. Mutants in each of the six ORFs of the mbo operon were partially or completely impaired in the production of the toxin. In addition, Pseudomonas spp. mangotoxin non-producer strains transformed with the mbo operon gained the ability to produce mangotoxin, indicating that this operon contains all the genetic information necessary for mangotoxin biosynthesis. The generation of a single transcript for the mbo operon was confirmed and supported by the allocation of a unique promoter and Rho-independent terminator. The phylogenetic analysis of the P. syringae strains harbouring the mbo operon revealed that these strains clustered together
Toxic iron species in lower-risk myelodysplastic syndrome patients:course of disease and effects on outcome
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