Biomarkers in Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)

PURPOSE OF REVIEW: Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis, a rare autoimmune disease characterised by fibrosis and vasculopathy. The variety of phenotypes in SSc-ILD have inspired multiple studies aimed at the identification of biomarkers which can provide disease-specific information but due to the complex pathogenesis of SSc-ILD, it has been challenging to validate such markers. We provide a comprehensive update on those most studied along with emerging biomarkers. RECENT FINDINGS: We review the up-to-date findings with regard to the use of well-studied molecular biomarkers in SSc-ILD along with novel biomarkers offering promise as prognostic markers such as IGFBP-2 and IGFBP-7, the adipokine CTRP9, endothelial progenitor cells, and cellular markers such as CD21lo/neg B cells. Expression profiling data is being used in SSc patients to determine genetic and epigenetic clusters which shed further light on mechanisms involved in the pathogenesis of SSc-ILD and are likely to uncover novel biomarkers. SUMMARY: With the exception of autoantibodies, there are no routinely measured biomarkers in SSc-ILD and reliable validation of the many potential biomarkers is lacking. Identifying biomarkers which can offer diagnostic and prognostic certainty may help patients to receive preventative treatment as part of a personalised medicine approach

Funeral Practices in Ghana and the United States: A Cultural Comparison

Across the life course, culture is never more evident than at the end of life. Due to the great variability of end-of-life practices and observed customs across the world, it is important to understand cultural differences from a variety of perspectives. This study provides a comparative analysis of death and funeral practices in three cultures: (1) Akan culture in Ghana, West Africa; (2) African-Americans born in the U.S.; and (3) European Americans in the United States. Two frameworks are used: (1) the biopsychosocial, spiritual, cultural framework; and (2) a framework of independent/interdependent cultural values, to compare the three cultural groups in a qualitative exploratory study with 20 participants from each group. The purpose is to explore whether African-American end-of-life traditions are more similar to the majority culture’s (European American) customs in the United States or to customs still practiced in Ghana today. This study also considers how the findings might be used to enhance culturally sensitive services in the provision of end-of-life care. Findings suggest that, although African-Americans have lived in the United States for over a century, their culture retains aspects reflective of African culture and traditions related to end-of-life activities. This study offers unique findings that address issues of cultural humility, sensitivity, and competency. An understanding of these issues is crucial for anyone working in human services and for practitioners supporting dying and bereaved families

Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies

Percutaneous Endoscopic Gastrostomy Tube Insertion in Neurodegenerative Disease:a Retrospective Study and Literature Review

Background/Aims With the notable exceptions of dementia, stroke, and motor neuron disease, relatively little is known about the safety and utility of percutaneous endoscopic gastrostomy (PEG) tube insertion in patients with neurodegenerative disease. We aimed to determine the safety and utility of PEG feeding in the context of neurodegenerative disease and to complete a literature review in order to identify whether particular factors need to be considered to improve safety and outcome. Methods A retrospective case note review of patients referred for PEG insertion by neurologists in a single neuroscience center was conducted according to a pre-determined set of standards. For the literature review, we identified references from searches of PubMed, mainly with the search items “percutaneous endoscopic gastrostomy” and “neurology” or “neurodegenerative disease.” Results Short-term mortality and morbidity associated with PEG in patients with neurological disease were significant. Age greater than 75 years was associated with poor outcome, and a trend toward adverse outcome was observed in patients with low serum albumin. Conclusions This study highlights the relatively high risk of PEG in patients with neurodegenerative disease. We present points for consideration to improve outcome in this particularly vulnerable group of patients

Understanding the national performance of flood forecasting models to guide incident management and investment

The preparation of routine flood guidance statements and formulation of incident management strategies requires national operating agencies to have a firm understanding of the performance of flood forecasting models. Studies of flood forecasting model performance are commonly evaluated on a groupedcatchment or local basis and can lack the analytical consistency required for integration into coherent national assessments. Here, the first nationally consistent analysis of flood forecasting model performance across England and Wales is presented. Application of the assessment framework, accounting for regional and model-type differences, yields a national overview of relative forecasting capability for models in current operational use. To achieve extensive site coverage, information from many existing local performance studies are pooled into a single structure for analysis under a national framework. The performance information spanning a variety of local models is also compared against the area-wide national G2G (Grid-to-Grid) distributed model. An integrated national assessment gives an evidence base of model performance useful for guiding strategic planning and investment in flood forecasting models. A concise single-page Performance Summary has been created for each site model that contains performance statistics, forecast hydrographs and catchment properties to aid operational use. A prototype web portal has been developed to make information on forecasting model performance more accessible and understandable for end-users

Diffuse cutaneous systemic sclerosis following SARS-Co V-2 vaccination

The largest world-wide vaccination rollout ever is currently underway to tackle the covid-19 pandemic. We report a case of diffuse cutaneous systemic sclerosis (SSc) in a 70-year-old male with rapidly progressive skin thickening which developed two weeks after receiving the first dose of the ChAdOx1 nCOV-19 vaccine. As the onset of SSc skin was in close temporal proximity to the administration of the first dose vaccine with no other triggers, we suspected a possible adverse reaction to the ChAdOx1 nCOV-19 vaccine. We hypothesise that the recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 triggered an unexpected immune activation resulting in an atypical presentation of late-onset SSc, within the well-recognised ANA positive, ENA negative subgroup of patients.We review the possible mechanisms underlying autoimmunity when provoked by vaccination and other published rheumatological phenomenon occurring shortly after COVID vaccination

Harmonic Force Constants for Molecular Mechanics Force Fields via Hessian Matrix Projection.

A modification to the Seminario method [ Int. J. Quantum Chem. 1996 , 60 , 1271 - 1277 ] is proposed, which derives accurate harmonic bond and angle molecular mechanics force field parameters directly from the quantum mechanical Hessian matrix. The new method reduces the average error in the reproduction of quantum mechanical normal-mode frequencies of a benchmark set of 70 molecules from 12.3% using the original method, to 6.3%. The modified Seminario method is fully automated, and all parameters are computed directly from quantum mechanical data, thereby avoiding interdependency between bond and angle parameters and other components of the force field. A complete set of bond and angle force field parameters for the 20 naturally occurring amino acids is also provided for use in the future development of protein force fields

Sociodemographic disparities in survival from colorectal cancer in South Australia: a population-wide data linkage study

Copyright © Beckmann et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Inequalities in survival from colorectal cancer (CRC) across socioeconomic groups and by area of residence have been described in various health care settings. Few population-wide datasets which include clinical and treatment information are available in Australia to investigate disparities. This study examines socio-demographic differences in survival for CRC patients in South Australia (SA), using a population-wide database derived via linkage of administrative and surveillance datasets. Methods: The study population comprised all cases of CRC diagnosed in 2003-2008 among SA residents aged 50-79 yrs in the SA Central Cancer Registry. Measures of socioeconomic status (area level), geographical remoteness, clinical characteristics, comorbid conditions, treatments and outcomes were derived through record linkage of central cancer registry, hospital-based clinical registries, hospital separations, and radiotherapy services data sources. Socio-demographic disparities in CRC survival were examined using competing risk regression analysis. Results: Four thousand six hundred and forty one eligible cases were followed for an average of 4.7 yrs, during which time 1525 died from CRC and 416 died from other causes. Results of competing risk regression indicated higher risk of CRC death with higher grade (HR high v low =2.25, 95 % CI 1.32-3.84), later stage (HR C v A = 7.74, 95 % CI 5.75-10.4), severe comorbidity (HR severe v none =1.21, 95 % CI 1.02-1.44) and receiving radiotherapy (HR = 1.41, 95 % CI 1.18-1.68). Patients from the most socioeconomically advantaged areas had significantly better outcomes than those from the least advantaged areas (HR =0.75, 95 % 0.62-0.91). Patients residing in remote locations had significantly worse outcomes than metropolitan residents, though this was only evident for stages A-C (HR = 1.35, 95 % CI 1.01-1.80). These disparities were not explained by differences in stage at diagnosis between socioeconomic groups or area of residence. Nor were they explained by differences in patient factors, other tumour characteristics, comorbidity, or treatment modalities. Conclusions: Socio-economic and regional disparities in survival following CRC are evident in SA, despite having a universal health care system. Of particular concern is the poorer survival for patients from remote areas with potentially curable CRC. Reasons for thes