Searching for galaxy clusters in the VST-KiDS Survey

We present the methods and first results of the search for galaxy clusters in the Kilo Degree Survey (KiDS). The adopted algorithm and the criterium for selecting the member galaxies are illustrated. Here we report the preliminary results obtained over a small area (7 sq. degrees), and the comparison of our cluster candidates with those found in the RedMapper and SZ Planck catalogues; the analysis to a larger area (148 sq. degrees) is currently in progress. By the KiDS cluster search, we expect to increase the completeness of the clusters catalogue to z = 0.6-0.7 compared to RedMapper.Comment: 5 pages, 4 figures, to be published in the Proceedings of the Conference "The Universe of Digital Sky Surveys", Naples, November 25-28 201

String Thermalization at a Black Hole Horizon

Susskind has recently shown that a relativistic string approaching the event horizon of a black hole spreads in both the transverse and longitudinal directions in the reference frame of an outside observer. The transverse spreading can be described as a branching diffusion of wee string bits. This stochastic process provides a mechanism for thermalizing the quantum state of the string as it spreads across the stretched horizon.Comment: 14 pages, latex, SU-ITP-94-4, NSF-ITP-94-1

Noncompliance to guidelines in head and neck cancer treatment; associated factors for both patient and physician

Background: Decisions on head and neck squamous cell carcinoma (HNSCC) treatment are widely recognized as being difficult, due to high morbidity, often involving vital functions. Some patients may therefore decline standard, curative treatment. In addition doctors may propose alternative, nonstandard treatments. Little attention is devoted, both in literature and in daily practice, to understanding why and when HNSCC patients or their physicians decline standard, curative treatment modalities. Our objective is to determine factors associated with noncompliance in head and neck cancer treatment for both patients and physicians and to assess the influence of patient compliance on prognosis. Methods: We did a retrospective study based on the medical records of 829 patients with primary HNSCC, who were eligible for curative treatment and referred to our hospital between 2010 and 2012. We analyzed treatment choice and reasons for nonstandard treatment decisions, survival, age, gender, social network, tumor site, cTNM classification, and comorbidity (ACE27). Multivariate analysis using logistic regression methods was performed to determine predictive factors associated with non-standard treatment following physician or patient decision. To gain insight in survival of the different groups of patients, we applied a Cox regression analysis. After checking the proportional hazards assumption for each variable, we adjusted the survival analysis for gender, age, tumor site, tumor stage, comorbidity and a history of having a prior tumor. Results: 17 % of all patients with a primary HNSCC did not receive standard curative treatment, either due to nonstandard treatment advice (10 %) or due to the patient choosing an alternative (7 %). A further 3 % of all patients refused any type of therapy, even though they were considered eligible for curative treatment. Elderliness, single marital status, female gender, high tumor stage and severe comorbidity are predictive factors. Patients declining standard treatment have a lower overall 3-year survival (34 % vs. 70 %). Conclusions: Predictive factors for nonstandard treatment decisions in head and neck cancer treatment differed between the treating physician and the patient. Patients who received nonstandard treatment had a lower overall 3-year survival. These findings should be taken into account when counselling patients in whom nonstandard treatment is considered

Visually Impaired OLder people's Exercise programme for falls prevenTion (VIOLET): a feasibility study

This study aims to conduct a mixed methods feasibility study to inform the design and conduct of a future definitive RCT of an adapted exercise programme to prevent falls by reducing fear of falling among older people with visual impairment (OPVI). The research questions are: can an existing exercise programme be adapted for OPVI and successfully delivered in the community; is it feasible to conduct an RCT of this intervention and what are the features of a future definitive trial? We propose to: (i) Adapt an existing exercise programme with the full involvement of OPVI and practitioners; (ii) Run a feasibility study in 2 sites to test our proposed measures, trial processes and recruitment; explore acceptability of the intervention; fidelity of and compliance with the intervention. Two stakeholder panels will be established including OPVI aged 60 and over from Newcastle Society for Blind People (NSBP) and Visibility in Glasgow, practitioners and researchers. They will work together to adapt the FaME programme, which is known to be effective in reducing falls in frequent fallers, so that the methods are acceptable for OPVI, whilst retaining the effective components of the exercise. The panels will meet 4 times to adapt the intervention and contribute to decisions on outcome measures and data collection. During this time we will identify OPVI wishing to act as expert stakeholders in the subsequent WPs. OPVI aged 60+ will be recruited from low vision clinics and voluntary organisations and randomised into the intervention or comparator arm. Those in the comparator arm will receive no intervention, but will be offered it after final data collection. The core components of the adapted exercise programme aim to strengthen leg muscles and retrain balance. However, the detail of the methods and timing will be decided by the stakeholder panel. The programme is likely to run once a week over 12 weeks, with each session lasting up to one hour. The final form of delivery will be one of the outcomes of the PPI work in WP1. Participants will be provided with instructions and equipment to do the exercises at home if they wish. The intervention will be delivered by exercise instructors engaged by Health Works, Newcastle and Visibility, Glasgow, in venues agreed with participants. The final primary outcome of the future RCT will be decided by the responsiveness to change, participant burden and participant feedback from this study. The likely candidate primary outcome is fear of falling (Short FES-I scale). The main secondary outcomes will be: activity avoidance; balance/falls risk; number of falls; quality of life; loneliness; depression; adherence to exercise programme; self-reported home exercising. An estimate of cost effectiveness and cost utility of the intervention will be undertaken. In-depth interviews with a sample of OPVI will be conducted to explore their reasons for taking part/not taking part; factors that facilitate/hinder them from participating in exercise groups; their experiences of the recruitment and randomisation process and views on the outcome measures; their experience of the adapted intervention. The interviews will highlight site specific issues to consider for the definitive RCT. Structured interviews will be undertaken with commissioners and practitioners to explore their perspectives on the application of the intervention

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Liposomes loaded with vitamin D3 induce regulatory circuits in human dendritic cells

Biopharmaceutic

Uptake kinetics of liposomal formulations of differing charge influences development of in vivo dendritic cell immunotherapy

Dendritic cells (DCs) control adaptive immunity and are therefore attractive for in vivo targeting to either induce immune activation or tolerance, depending on disease. Liposomes, nanoparticles comprised of a lipid bi-layer, provide a nanoplatform for loading disease-relevant antigen, adjuvant and DC-targeting molecules simultaneously. However, it is yet not fully understood how liposomal formulations affect uptake by DCs and DC function. Here, we examined monocyte-derived DC (moDC) and skin DC uptake of six different liposomal formulations, together with their DC-modulating effect. Contrary to literature, we show using imaging flow cytometry that anionic or neutral liposomes are taken up more efficiently than cationic liposomes by moDCs, or by skin DCs after intradermal injection. None of the formulations yielded significant modulation of DC function as determined by the upregulation of maturation markers and cytokine production. These results suggest that anionic liposomes would be more suitable as vaccine carriers for a dermal application.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Drug Delivery Technolog

Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273

BACKGROUND: Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants. METHODS: The dynamics of cellular immune reactivation upon vaccination of SARS-CoV-2 experienced MS patients treated with the humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) and RA patients treated with methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry of whole blood samples upon vaccination with the SARS-CoV-2 mRNA-1273 (Moderna) vaccine. Longitudinal B and T cell immune responses were compared to SARS-CoV-2 experienced healthy controls (HCs) before and 7 days after the first and second vaccination. RESULTS: OCR-treated MS patients exhibit a preserved recall response of CD8(+) T central memory cells following first vaccination compared to HCs and a similar CD4(+) circulating T follicular helper 1 and T helper 1 dynamics, whereas humoral and B cell responses were strongly impaired resulting in absence of SARS-CoV-2-specific humoral immunity. MTX treatment significantly delayed antibody levels and B reactivation following the first vaccination, including sustained inhibition of overall reactivation marker dynamics of the responding CD4(+) and CD8(+) T cells. CONCLUSIONS: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients may still benefit from vaccination by inducing a broad CD8(+) T cell response which has been associated with milder disease outcome. The delayed vaccine-induced IgG kinetics in RA-MTX patients indicate an increased risk after the first vaccination, which might require additional shielding or alternative strategies such as treatment interruptions in vulnerable patients. FUNDING: This research project was supported by ZonMw (The Netherlands Organization for Health Research and Development, #10430072010007), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (#792532 and #860003), the European Commission (SUPPORT-E, #101015756) and by PPOC (#20_21 L2506), the NHMRC Leadership Investigator Grant (#1173871)

Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV

We present a search for the production of neutral Higgs bosons decaying into tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the 95% C.L. on the product of production cross section and branching ratio for a scalar resonance decaying into tautau pairs, and we then interpret these limits as limits on the production of Higgs bosons in the minimal supersymmetric standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL