Course Manual - National Workshop on Effective Management of E-Resources in Research Libraries

The National Workshop on “Effective Management of EResources in Research Libraries" is the first of its kind organised by the Library & Documentation Centre of ICAR-Central Marine Fisheries Research Institute, Kochi. Periodic trainings on newer technologies developed in the field of Library & Information Sciences help library professionals to enhance their professional competencies that will contribute largely to the output of the parent organization. Digital repositories are the need of the hour where the Institute can showcase the research findings. ICAR-CMFRI is a pioneer in developing Institute repository and the open access repository of the Institute "eprints@cmfri" now stands 1st among ICAR Institute repositories, 3rd among Indian repositories and 343rd among the world repositories. Topics of current relevance towards development and modernisation of research libraries are included in the Workshop which is expected to help the participants to understand the possibilities and ways of supporting the research activities of the parent Institution more effectively

Evidence for models of diagnostic service provision in the community: literature mapping exercise and focused rapid reviews

Background Current NHS policy favours the expansion of diagnostic testing services in community and primary care settings. Objectives Our objectives were to identify current models of community diagnostic services in the UK and internationally and to assess the evidence for quality, safety and clinical effectiveness of such services. We were also interested in whether or not there is any evidence to support a broader range of diagnostic tests being provided in the community. Review methods We performed an initial broad literature mapping exercise to assess the quantity and nature of the published research evidence. The results were used to inform selection of three areas for investigation in more detail. We chose to perform focused reviews on logistics of diagnostic modalities in primary care (because the relevant issues differ widely between different types of test); diagnostic ultrasound (a key diagnostic technology affected by developments in equipment); and a diagnostic pathway (assessment of breathlessness) typically delivered wholly or partly in primary care/community settings. Databases and other sources searched, and search dates, were decided individually for each review. Quantitative and qualitative systematic reviews and primary studies of any design were eligible for inclusion. Results We identified seven main models of service that are delivered in primary care/community settings and in most cases with the possible involvement of community/primary care staff. Not all of these models are relevant to all types of diagnostic test. Overall, the evidence base for community- and primary care-based diagnostic services was limited, with very few controlled studies comparing different models of service. We found evidence from different settings that these services can reduce referrals to secondary care and allow more patients to be managed in primary care, but the quality of the research was generally poor. Evidence on the quality (including diagnostic accuracy and appropriateness of test ordering) and safety of such services was mixed. Conclusions In the absence of clear evidence of superior clinical effectiveness and cost-effectiveness, the expansion of community-based services appears to be driven by other factors. These include policies to encourage moving services out of hospitals; the promise of reduced waiting times for diagnosis; the availability of a wider range of suitable tests and/or cheaper, more user-friendly equipment; and the ability of commercial providers to bid for NHS contracts. However, service development also faces a number of barriers, including issues related to staffing, training, governance and quality control. Limitations We have not attempted to cover all types of diagnostic technology in equal depth. Time and staff resources constrained our ability to carry out review processes in duplicate. Research in this field is limited by the difficulty of obtaining, from publicly available sources, up-to-date information about what models of service are commissioned, where and from which providers. Future work There is a need for research to compare the outcomes of different service models using robust study designs. Comparisons of ‘true’ community-based services with secondary care-based open-access services and rapid access clinics would be particularly valuable. There are specific needs for economic evaluations and for studies that incorporate effects on the wider health system. There appears to be no easy way of identifying what services are being commissioned from whom and keeping up with local evaluations of new services, suggesting a need to improve the availability of information in this area. Funding The National Institute for Health Research Health Services and Delivery Research programme

"Transatlantic Magazines and the Rise of Environmental Journalism"

This chapter explores how a culture of transatlantic environmental journalism emerged during the early to middle decades of the nineteenth century. How did interest in science, travel and exploration during those years shape the ways in which North American and British magazines represented the natural environment? To what extent did articles in periodicals address readers’ demands for armchair tourism and the desire to experience, through reading, an encounter with nature that counterbalanced increasingly urban lifestyles? What difference did newspapers and magazines make to the way that people thought about the natural world? The chapter explores how environmental journalism provided a multi-medial network across different kinds of publication through which ideas about natural science, domestic landscapes, pastoralism, and wilderness were shared, consumed and discussed within a transatlantic context

Treatments for dry age-related macular degeneration and Stargardt disease : a systematic review

Background Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. Objective To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Design Systematic review. Methods We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. Results The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or government

High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD-negative women not known to be sensitised to the RhD antigen : a systematic review and economic evaluation

Background: High-throughput non-invasive prenatal testing (NIPT) for fetal rhesus (D antigen) (RhD) status could avoid unnecessary treatment with routine anti-D immunoglobulin for RhD-negative women carrying a RhD-negative fetus, although this may lead to an increased risk of RhD sensitisations. Objectives: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of high-throughput NIPT and to develop a cost-effectiveness model. Methods: We searched MEDLINE and other databases, from inception to February 2016, for studies of high-throughput NIPT free-cell fetal deoxyribonucleic acid (DNA) tests of maternal plasma to determine fetal RhD status in RhD-negative pregnant women who were not known to be sensitised to the RhD antigen. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and A Cochrane Risk of Bias Assessment Tool: for Non-Randomised Studies of Interventions (ACROBAT-NRSI). Summary estimates of false-positive rates (FPRs) and false-negative rates (FNRs) were calculated using bivariate models. Clinical effectiveness evidence was used to conduct a simulation study. We developed a de novo probabilistic decision tree-based cohort model that considered four alternative ways in which the results of NIPT could guide the use of anti-D immunoglobulin antenatally and post partum. Sensitivity analyses (SAs) were conducted to address key uncertainties and model assumptions. Results: Eight studies were included in the diagnostic accuracy review, seven studies were included in the clinical effectiveness review and 12 studies were included in the review of implementation. Meta-analyses included women mostly at or post 11 weeks’ gestation. The pooled FNR (women at risk of sensitisation) was 0.34% [95% confidence interval (CI) 0.15% to 0.76%] and the pooled FPR (women needlessly receiving anti-D) was 3.86% (95% CI 2.54% to 5.82%). SAs did not materially alter the overall results. Data on clinical outcomes, including sensitisation rates, were limited. Our simulation suggests that NIPT could substantially reduce unnecessary use of antenatal anti-D with only a small increase in the risk of sensitisation. All large implementation studies suggested that large-scale implementation of high-throughput NIPT was feasible. Seven cost-effectiveness studies were included in the review, which found that the potential for the use of NIPT to produce cost savings was dependent on the cost of the test. Our de novo model suggested that high-throughput NIPT is likely to be cost saving compared with the current practice of providing routine antenatal anti-D prophylaxis to all women who are RhD negative. The extent of the cost saving appeared to be sufficient to outweigh the small increase in sensitisations. However, the magnitude of the cost saving is highly sensitive to the cost of NIPT itself. Limitations: There was very limited evidence relating to the clinical effectiveness of high-throughput NIPT, with no evidence on potential adverse effects. The generalisability of the findings to non-white women and multiple pregnancies is unclear. Conclusions: High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women from 11 weeks’ gestation and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin, potentially resulting in cost savings of between £485,000 and £671,000 per 100,000 pregnancies if the cost of implementing NIPT is in line with that reflected in this evaluation

Accuracy of fundus autofluorescence imaging for the diagnosis and monitoring of retinal conditions: a systematic review

BackgroundNatural fluorescence in the eye may be increased or decreased by diseases that affect theretina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO) can detect this ‘fundusautofluorescence’ (FAF) by illuminating the retina using a specific light ‘excitation wavelength’. FAFimaging could assist the diagnosis or monitoring of retinal conditions. However, the accuracy of themethod for diagnosis or monitoring is unclear.ObjectiveTo conduct a systematic review to determine the accuracy of FAF imaging using cSLO for thediagnosis or monitoring of retinal conditions, including monitoring of response to therapy.Data sourcesElectronic bibliographic databases; scrutiny of reference lists of included studies andrelevant systematic reviews; and searches of internet pages of relevant organisations, meetings and trialregistries. Databases included MEDLINE, EMBASE, The Cochrane Library, Web of Science and the Mediondatabase of diagnostic accuracy studies. Searches covered 1990 to November 2014 and were limited tothe English language.Review methodsReferences were screened for relevance using prespecified inclusion criteria to capturea broad range of retinal conditions. Two reviewers assessed titles and abstracts independently. Full-textversions of relevant records were retrieved and screened by one reviewer and checked by a second. Datawere extracted and critically appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria(QUADAS) for assessing risk of bias in test accuracy studies by one reviewer and checked by a second.At all stages any reviewer disagreement was resolved through discussion or arbitration by a third reviewer.ResultsEight primary research studies have investigated the diagnostic accuracy of FAF imaging in retinalconditions: choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macularoedema (two studies) and diabetic macular oedema (two studies). Sensitivity of FAF imaging using anexcitation wavelength of 488 nm was generally high (range 81–100%), but was lower (55% and 32%) intwo studies using longer excitation wavelengths (514 nm and 790 nm, respectively). Specificity rangedfrom 34% to 100%. However, owing to limitations of the data, none of the studies provide conclusiveevidence of the diagnostic accuracy of FAF imaging.LimitationsNo studies on the accuracy of FAF imaging for monitoring the progression of retinalconditions or response to therapy were identified. Owing to study heterogeneity, pooling of diagnosticoutcomes in meta-analysis was not conducted. All included studies had high risk of bias. In most studiesthe patient spectrum was not reflective of those who would present in clinical practice and no studiesadequately reported how FAF images were interpreted.ConclusionsAlthough already in use in clinical practice, it is unclear whether or not FAF imaging isaccurate, and whether or not it is applied and interpreted consistently for the diagnosis and/or monitoringof retinal conditions. Well-designed prospective primary research studies, which conform to the paradigmof diagnostic test accuracy assessment, are required to investigate the accuracy of FAF imaging in diagnosisand monitoring of inherited retinal dystrophies, early age-related macular degeneration, geographicatrophy and central serous chorioretinopathy.Study registrationThis study is registered as PROSPERO CRD42014014997.FundingThe National Institute for Health Research Health Technology Assessment programme

Clonal dynamics and somatic evolution of haematopoiesis in mouse

Haematopoietic stem cells maintain blood production throughout life1. Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which they independently self-renew in parallel over life, evenly contributing to differentiated progenitors and peripheral blood. The stem cell pool grows steadily over the mouse lifespan to about 70,000 cells, self-renewing about every 6 weeks. Aged mice did not display the profound loss of clonal diversity characteristic of human haematopoietic ageing. However, targeted sequencing showed small, expanded clones in the context of murine ageing, which were larger and more numerous following haematological perturbations, exhibiting a selection landscape similar to humans. Our data illustrate both conserved features of population dynamics of blood and distinct patterns of age-associated somatic evolution in the short-lived mouse

A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) is a chronic, life-limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene leading to abnormal airway surface ion transport, chronic lung infections, inflammation and eventual respiratory failure. With the exception of the small-molecule potentiator, ivacaftor (Kalydeco®, Vertex Pharmaceuticals, Boston, MA, USA), which is suitable for a small proportion of patients, there are no licensed therapies targeting the basic defect. The UK Cystic Fibrosis Gene Therapy Consortium has taken a cationic lipid-mediated CFTR gene therapy formulation through preclinical and clinical development. OBJECTIVE: To determine clinical efficacy of the formulation delivered to the airways over a period of 1 year in patients with CF. DESIGN: This was a randomised, double-blind, placebo-controlled Phase IIb trial of the CFTR gene–liposome complex pGM169/GL67A. Randomisation was performed via InForm™ version 4.6 (Phase Forward Incorporated, Oracle, CA, USA) and was 1 : 1, except for patients in the mechanistic subgroups (2 : 1). Allocation was blinded by masking nebuliser chambers. SETTINGS: Data were collected in the clinical and scientific sites and entered onto a trial-specific InForm, version 4.6 database. PARTICIPANTS: Patients with CF aged ≥ 12 years with forced expiratory volume in the first second (FEV1) between 50% and 90% predicted and any combination of CFTR mutations. The per-protocol group (≥ 9 doses) consisted of 54 patients receiving placebo (62 randomised) and 62 patients receiving gene therapy (78 randomised). INTERVENTIONS: Subjects received 5 ml of nebulised pGM169/G67A (active) or 0.9% saline (placebo) at 28 (±5)-day intervals over 1 year. MAIN OUTCOME MEASURES: The primary end point was the relative change in percentage predicted FEV1 over the 12-month period. A number of secondary clinical outcomes were assessed alongside safety measures: other spirometric values; lung clearance index (LCI) assessed by multibreath washout; structural disease on computed tomography (CT) scan; the Cystic Fibrosis Questionnaire – Revised (CFQ-R), a validated quality-of-life questionnaire; exercise capacity and monitoring; systemic and sputum inflammatory markers; and adverse events (AEs). A mechanistic study was performed in a subgroup in whom transgene deoxyribonucleic acid (DNA) and messenger ribonucleic acid (mRNA) was measured alongside nasal and lower airway potential difference. RESULTS: There was a significant (p = 0.046) treatment effect (TE) of 3.7% [95% confidence interval (CI) 0.1% to 7.3%] in the primary end point at 12 months and in secondary end points, including forced vital capacity (FVC) (p = 0.031) and CT gas trapping (p = 0.048). Other outcomes, although not reaching statistical significance, favoured active treatment. Effects were noted by 1 month and were irrespective of sex, age or CFTR mutation class. Subjects with a more severe baseline FEV1 had a FEV1 TE of 6.4% (95% CI 0.8% to 12.1%) and greater changes in many other secondary outcomes. However, the more mildly affected group also demonstrated benefits, particularly in small airway disease markers such as LCI. The active group showed a significantly (p = 0.032) greater bronchial chloride secretory response. No difference in treatment-attributable AEs was seen between the placebo and active groups. CONCLUSIONS: Monthly application of the pGM169/GL67A gene therapy formulation was associated with an improvement in lung function, other clinically relevant parameters and bronchial CFTR function, compared with placebo. LIMITATIONS: Although encouraging, the improvement in FEV1 was modest and was not accompanied by detectable improvement in patients’ quality of life. FUTURE WORK: Future work will focus on attempts to increase efficacy by increasing dose or frequency, the coadministration of a CFTR potentiator, or the use of modified viral vectors capable of repeated administration. TRIAL REGISTRATION: ClinicalTrials.gov NCT01621867