Publisher Correction: Towards an ecosystem model of infectious disease

Correction to: Nature Ecology & Evolution https://doi.org/10.1038/s41559-021-01454-8, published online 17 May 2021

Towards an ecosystem model of infectious disease

Increasingly intimate associations between human society and the natural environment are driving the emergence of novel pathogens, with devastating consequences for humans and animals alike. Prior to emergence, these pathogens exist within complex ecological systems that are characterized by trophic interactions between parasites, their hosts and the environment. Predicting how disturbance to these ecological systems places people and animals at risk from emerging pathogens-and the best ways to manage this-remains a significant challenge. Predictive systems ecology models are powerful tools for the reconstruction of ecosystem function but have yet to be considered for modelling infectious disease. Part of this stems from a mistaken tendency to forget about the role that pathogens play in structuring the abundance and interactions of the free-living species favoured by systems ecologists. Here, we explore how developing and applying these more complete systems ecology models at a landscape scale would greatly enhance our understanding of the reciprocal interactions between parasites, pathogens and the environment, placing zoonoses in an ecological context, while identifying key variables and simplifying assumptions that underly pathogen host switching and animal-to-human spillover risk. As well as transforming our understanding of disease ecology, this would also allow us to better direct resources in preparation for future pandemics

Personalised therapy in follicular lymphoma - is the dial turning?

Follicular lymphoma is the most common indolent lymphoma accounting for approximately 20%–25% of all new non-Hodgkin lymphoma diagnoses in western countries. Whilst outcomes are mostly favorable, the spectrum of clinical phenotypes includes high-risk groups with significantly inferior outcomes. This review discusses recent updates in risk stratification and treatment approaches from upfront treatment for limited and advanced stage follicular lymphoma to the growing options for relapsed, refractory disease with perspectives on how to approach this from a personalized lens. Notable gaps remain on how one can precisely and prospectively select optimal treatment for patients based on varying risks, with an anticipation that an increased understanding of the biology of these different phenotypes and increasing refinement of imaging- and biomarker-based tools will, in time, allow these gaps to be closed

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Fractures are common within 18 months following first-line R-CHOP in older patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if <18 months; or at progression or death. Of 877 patients identified, 148 were excluded: 121 had progression or died before 6 months; 23 had follow-up <6 months. Across 729 remaining patients, the median age was 77 years, and 68% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Eighty-one fractures occurred within 18 months of follow-up; 42 were symptomatic, including 30 requiring hospital attendance or admission. The cumulative fracture incidence was 6.2% (95% confidence interval [CI], 4.7-8.2) at 6 months; 9.7% (95% CI, 7.8-12.1) at 12 months; and 11.4% (95% CI, 9.3-14.0) at 18 months. Multivariate analysis identified a predisposing history (osteoporosis, osteopenia, prior fracture, and rheumatoid arthritis [RhA]), DLBCL bone involvement at baseline, and receipt of prephase steroids as independent risk factors for fracture. There is a clinically relevant fracture risk and significant associated morbidity in older patients receiving R-CHOP. Careful attention to bone health is warranted in older patients receiving R-CHOP. Randomized studies are required to better define the most effective strategies to reduce fracture risk

Prognostic factors in non-surgically treated sciatica: A systematic review

<p>Abstract</p> <p>Background</p> <p>When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome.</p> <p>Methods</p> <p>A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment.</p> <p>Results</p> <p>Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated.</p> <p>Conclusions</p> <p>At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial factors alongside clinical and radiological findings are recommended to identify prognostic factors in this population.</p

Psychosocial factors and their predictive value in chiropractic patients with low back pain: a prospective inception cohort study

BACKGROUND: Being able to estimate the likelihood of poor recovery from episodes of back pain is important for care. Studies of psychosocial factors in inception cohorts in general practice and occupational populations have begun to make inroads to these problems. However, no studies have yet investigated this in chiropractic patients. METHODS: A prospective inception cohort study of patients presenting to a UK chiropractic practice for new episodes of non-specific low back pain (LBP) was conducted. Baseline questionnaires asked about age, gender, occupation, work status, duration of current episode, chronicity, aggravating features and bothersomeness using Deyo's 'Core Set'. Psychological factors (fear-avoidance beliefs, inevitability, anxiety/distress and coping, and co-morbidity were also assessed at baseline. Satisfaction with care, number of attendances and pain impact were determined at 6 weeks. Predictors of poor outcome were sought by the calculation of relative risk ratios. RESULTS: Most patients presented within 4 weeks of onset. Of 158 eligible and willing patients, 130 completed both baseline and 6-week follow-up questionnaires. Greatest improvements at 6 weeks were in interference with normal work (ES 1.12) and LBP bothersomeness (ES 1.37). Although most patients began with moderate-high back pain bothersomeness scores, few had high psychometric ones. Co-morbidity was a risk for high-moderate interference with normal work at 6 weeks (RR 2.37; 95% C.I. 1.15–4.74). An episode duration of >4 weeks was associated with moderate to high bothersomeness at 6 weeks (RR 2.07; 95% C.I. 1.19 – 3.38) and negative outlook (inevitability) with moderate to high interference with normal work (RR 2.56; 95% C.I. 1.08 – 5.08). CONCLUSION: Patients attending a private UK chiropractic clinic for new episodes of non-specific LBP exhibited few psychosocial predictors of poor outcome, unlike other patient populations that have been studied. Despite considerable bothersomeness at baseline, scores were low at follow-up. In this independent health sector back pain population, general health and duration of episode before consulting appeared more important to outcome than psychosocial factors

Gene Expression Profiles from Formalin Fixed Paraffin Embedded Breast Cancer Tissue Are Largely Comparable to Fresh Frozen Matched Tissue

BACKGROUND AND METHODS: Formalin Fixed Paraffin Embedded (FFPE) samples represent a valuable resource for cancer research. However, the discovery and development of new cancer biomarkers often requires fresh frozen (FF) samples. Recently, the Whole Genome (WG) DASL (cDNA-mediated Annealing, Selection, extension and Ligation) assay was specifically developed to profile FFPE tissue. However, a thorough comparison of data generated from FFPE RNA and Fresh Frozen (FF) RNA using this platform is lacking. To this end we profiled, in duplicate, 20 FFPE tissues and 20 matched FF tissues and evaluated the concordance of the DASL results from FFPE and matched FF material. METHODOLOGY AND PRINCIPAL FINDINGS: We show that after proper normalization, all FFPE and FF pairs exhibit a high level of similarity (Pearson correlation >0.7), significantly larger than the similarity between non-paired samples. Interestingly, the probes showing the highest correlation had a higher percentage G/C content and were enriched for cell cycle genes. Predictions of gene expression signatures developed on frozen material (Intrinsic subtype, Genomic Grade Index, 70 gene signature) showed a high level of concordance between FFPE and FF matched pairs. Interestingly, predictions based on a 60 gene DASL list (best match with the 70 gene signature) showed very high concordance with the MammaPrint® results. CONCLUSIONS AND SIGNIFICANCE: We demonstrate that data generated from FFPE material with the DASL assay, if properly processed, are comparable to data extracted from the FF counterpart. Specifically, gene expression profiles for a known set of prognostic genes for a specific disease are highly comparable between two conditions. This opens up the possibility of using both FFPE and FF material in gene expressions analyses, leading to a vast increase in the potential resources available for cancer research