A manual and an automatic TERS based virus discrimination

Rapid techniques for virus identification are more relevant today than ever. Conventional virus detection and identification strategies generally rest upon various microbiological methods and genomic approaches, which are not suited for the analysis of single virus particles. In contrast, the highly sensitive spectroscopic technique tip-enhanced Raman spectroscopy (TERS) allows the characterisation of biological nano-structures like virions on a single-particle level. In this study, the feasibility of TERS in combination with chemometrics to discriminate two pathogenic viruses, Varicella-zoster virus (VZV) and Porcine teschovirus (PTV), was investigated. In a first step, chemometric methods transformed the spectral data in such a way that a rapid visual discrimination of the two examined viruses was enabled. In a further step, these methods were utilised to perform an automatic quality rating of the measured spectra. Spectra that passed this test were eventually used to calculate a classification model, through which a successful discrimination of the two viral species based on TERS spectra of single virus particles was also realised with a classification accuracy of 91%

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Factors related to and economic implications of inhospital death in German lung cancer patients - results of a Nationwide health insurance claims data based study

Abstract Background When patients die in a hospital their quality of life is lower than when they die at home or in a hospice. Despite efforts to improve palliative care supply structures, still about 60% of lung cancer patients die in a hospital. Studies have examined factors related to inhospital death in lung cancer patients, yet none used data of a representative German population, additionally including economic aspects. This study aimed to identify factors related to inhospital death in German lung cancer patients and analysed resulting costs. Methods We analysed a dataset of health insurance claims of 17,478 lung cancer patients (incident 2009) with 3 year individual follow-up. We grouped patients into inhospital death and death elsewhere. Studied factors were indicators of healthcare utilization, palliative care, comorbidities and disease spread. We used logistic regression models with LASSO selection method to identify relevant factors. We compared all-cause healthcare expenditures for the last 30 days of life between both groups using generalized linear models with gamma distribution. Results Twelve thousand four hundred fifty-seven patients died in the observation period, thereof 6965 (55.9%) in a hospital. The key factors for increased likelihood of inhospital death were receipt of inpatient palliative care (OR = 1.85), chemotherapeutic treatments in the last 30 days of life (OR = 1.61) and comorbid Congestive Heart Failure (OR = 1.21), and Renal Disease (OR = 1.19). In contrast, higher care level (OR = 0.16), nursing home residency (OR = 0.25) and receipt of outpatient palliative care (OR = 0.25) were associated with a reduced likelihood. All OR were significant (p-values< 0.05). Expenditures in the last 30 days of life were significantly higher for patients with inhospital death (€ 6852 vs. € 33,254, p-value< 0.0001). Conclusion Findings suggest that factors associated with inhospital death often relate to previous contact with hospitals like prior hospitalizations, and treatment of the tumour or comorbidities. Additionally, factors associated with dying elsewhere relate to access to care settings which are more focused on palliation than hospitals. From these results, we can derive that implementing tools like palliative care into tumour-directed therapy might help patients make self-determined decisions about their place of death. This can possibly be achieved at reduced economic burden for SHIs

Anti-CD20 therapeutic antibody rituximab modifies the functional organization of rafts/microdomains of B lymphoma cells

Incubation of Burkitt lymphoma-derived Raji cells at physiological temperature with submicromolar concentrations of humanized anti-CD20 antibody rituximab (RTX) redistributes CD20 to liquid-ordered, plasma membrane rafts. This accumulation of the CD20 tetraspan protein in rafts does not change the existing lipid and phosphoprotein composition but makes sphingolipids and the Src regulator Cbp/PAG (Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomain) transmembrane phosphoprotein more resistant to n-octyl-beta-pyranoside, a detergent that dissociates sphingolipid clusters. On the contrary, sphingolipids and Cbp/PAG are not protected by the presence of CD20 against the disruptive effects of methyl-beta-cyclodextrin, a cyclic carbohydrate that removes membrane cholesterol. After accumulation of CD20, the activity of the raft-associated Lyn kinase is down-regulated without apparent alteration of its relationship to substrates. Moreover, in rafts of lymphoblastoid cells that express lower amounts of Cbp/PAG, RTX redistributes CD20 to rafts but does not modulate the raft-associated protein tyrosine kinase activity, suggesting that the presence of Cbp/PAG protein in rafts is necessary for RTX to exert its transmembrane "signaling effects." Lastly, redistribution of CD20 in rafts renders the glycosylphosphatidyl inositol (GPI)-linked CD55 C'-defense protein hypersensitive to glycosylphosphatidyl inositol-specific phospholipases. By redistributing CD20 to rafts, RTX modifies their stability and organization and modulates the associated signaling pathways and C' defense capacity

Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

Abstract Background Squamous cell carcinoma (SCC) is a common skin cancer that poses a risk of metastasis. Clinical investigations into SCC treatment are common, but the outcomes reported are highly variable, omitted, or clinically irrelevant. The outcome heterogeneity and reporting bias of these studies leave clinicians unable to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set of outcomes recommended to be measured and reported in all clinical trials of a given condition or disease. Although COSs are under development for several dermatologic conditions, work has yet to be done to identify core outcomes specific for SCC. Methods/design Outcome extraction for COS generation will occur via four methods: (1) systematic literature review; (2) patient interviews; (3) other published sources; and (4) input from stakeholders in medicine, pharmacy, and other relevant industries. The list of outcomes will be revaluated by the Measuring PRiority Outcome Variables via Excellence in Dermatologic surgery (IMPROVED) Steering Committee. Delphi processes will be performed separately by expert clinicians and patients to condense the list of outcomes generated. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. At the end of the meeting, members will vote and decide on a final recommended set of core outcomes. The Core Outcome Measures in Effectiveness Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation process. Discussion Comparison of clinical trials via systematic reviews and meta-analyses is facilitated when investigators study outcomes that are relevant and similar. The aim of this project is to develop a COS to guide use for future clinical trials

Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative

Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG-COUSIN) supports the development of core outcomes in dermatology. In the second CSG-COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers

Additional file 1: of Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

SPIRIT checklist. Completed checklist of the study protocol for the development of a core outcome set. (DOCX 48 kb

Development of a core outcome set for clinical trials in basal cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

Abstract Background Basal cell carcinoma is the most common skin cancer worldwide. Treatment options include both surgical and topical modalities. Although risk of metastasis is low, basal cell carcinoma can be invasive and infiltrate important underlying structures such as bone or cartilage. While many clinical trials examining therapies for basal cell carcinoma exist, the lack of consensus in outcome reporting across all trials poses a concern. Proper evaluation and comparison of treatment modalities is challenging. In order to address the inconsistencies present, this project aims to determine a core set of outcomes which should be evaluated in all clinical trials of basal cell carcinoma. Methods/design Outcomes will be extracted over four phases: (1) a systematic literature review, (2) patient interviews, (3) other published sources, and (4) stakeholder involvement. Potential outcomes will then be examined by the Steering Committee, who may add or remove outcomes. The Delphi process will then be performed to condense the list of outcomes generated. Two rounds of Delphi surveys will be performed with two groups of participants – physicians and patients. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. By the end of the meeting, members will vote and decide on a final recommended set of core outcomes. For the duration of the study, we will be in collaboration with both the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN). Discussion This study aims to develop a core outcome set to guide assessment in clinical trials on basal cell carcinoma. The end-goal is to improve the consistency of outcome reporting and allow proper evaluation of treatment effectiveness

Additional file 1: of Development of a core outcome set for clinical trials in facial aging: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

SPIRIT checklist. Completed checklist of the study protocol for the development of a core outcome set. (DOCX 52 kb