Searching for real-world effectiveness versus efficacy of healthcare innovations: the case of social prescribing for diabetes

Background: Social prescribing is a process whereby primary care patients are linked or referred to nonmedical sources of support in the community and voluntary sector. It is a concept that has arisen in practice and implemented widely in the United Kingdom and has been evaluated by various organizations. Objective: The aim of our study was to characterize, collate, and analyze the evidence from evaluation of social prescribing for type 2 diabetes in the United Kingdom and Ireland, comparing information available on publicly available websites with the published literature. Methods: We used a broad, pragmatic definition of social prescribing and conducted Web-based searches for websites of organizations providing potentially relevant services. We also explored linked information. In parallel, we searched Medline, PubMed, Cochrane Library, Google Scholar, and reference lists for relevant studies published in peer-reviewed journals. We extracted the data systematically on the characteristics, any reported evaluation, outcomes measured and results, and terminology used to describe each service. Results: We identified 40 UK- or Ireland-based projects that referred people with type 2 diabetes and prediabetes to nonmedical interventions or services provided in the community. We located evaluations of 24 projects; 11 as published papers, 12 as Web-based reports, and 1 as both a paper and a Web-based report. The interventions and services identified included structured group educational programs, exercise referral schemes, and individualized advice and support with signposting of health-related activities in the community. Although specific interventions such as community-based group educational programs and exercise referral have been evaluated in randomized controlled trials, evaluation of individualized social prescribing services involving people with type 2 diabetes has, in most cases, used pre-post and mixed methods approaches. These evaluations report generic improvement in a broad range of outcomes and provide an insight into the criteria for the success of social prescribing services. Conclusions: Our study revealed the varied models of social prescribing and nonmedical, community-based services available to people with type 2 diabetes and the extent of evaluation of these, which would not have been achieved by searching databases alone. The findings of this scoping study do not prove that social prescribing is an effective measure for people with type 2 diabetes in the United Kingdom, but can be used to inform future evaluation and contribute to the development of the evidence base for social prescribing. Accessing Web-based information provides a potential method for investigating how specific innovative health concepts, such as social prescribing, have been translated, implemented, and evaluated in practice. Several challenges were encountered including defining the concept, focusing on process plus intervention, and searching diverse, evolving Web-based sources. Further exploration of this approach will inform future research on the application of innovative health care concepts into practice

Serial optical coherence microscopy for label-free volumetric histopathology

The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents

Geminate and Nongeminate Pathways for Triplet Exciton Formation in Organic Solar Cells

Abstract: Organic solar cells (OSCs) have recently shown a rapid improvement in their performance, bringing power conversion efficiencies to above 18%. However, the open‐circuit voltage of OSCs remains low relative to their optical gap and this currently limits efficiency. Recombination to spin‐triplet excitons is a key contributing factor, and is widely, but not universally, observed in donor–acceptor blends using both fullerene and nonfullerenes as electron acceptors. Here, an experimental framework that combines time‐resolved optical and magnetic resonance spectroscopies to detect triplet excitons and identify their formation mechanisms, is reported. The methodology is applied to two well‐studied polymer:fullerene systems, PM6:PC60BM and PTB7‐Th:PC60BM. In contrast to the more efficient nonfullerene acceptor systems that show only triplet states formed via nongeminate recombination, the fullerene systems also show significant triplet formation via geminate processes. This requires that geminate electron–hole pairs be trapped long enough to allow intersystem crossing. It is proposed that this is a general feature of fullerene acceptor systems, where isolated fullerenes are known to intercalate within the alkyl sidechains of the donor polymers. Thus, the study demonstrates that engineering good donor and acceptor domain purity is key for suppressing losses via triplet excitons in OSCs

Detecting sulphate aerosol geoengineering with different methods

Sulphate aerosol injection has been widely discussed as a possible way to engineer future climate. Monitoring it would require detecting its effects amidst internal variability and in the presence of other external forcings. We investigate how the use of different detection methods and filtering techniques affects the detectability of sulphate aerosol geoengineering in annual-mean global-mean near-surface air temperature. This is done by assuming a future scenario that injects 5 Tg yr−1 of sulphur dioxide into the stratosphere and cross-comparing simulations from 5 climate models. 64% of the studied comparisons would require 25 years or more for detection when no filter and the multi-variate method that has been extensively used for attributing climate change are used, while 66% of the same comparisons would require fewer than 10 years for detection using a trend-based filter. This highlights the high sensitivity of sulphate aerosol geoengineering detectability to the choice of filter. With the same trend-based filter but a non-stationary method, 80% of the comparisons would require fewer than 10 years for detection. This does not imply sulphate aerosol geoengineering should be deployed, but suggests that both detection methods could be used for monitoring geoengineering in global, annual mean temperature should it be needed

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro

Abstract Introduction Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines. Methods Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response. Results Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450 differentially expressed genes between sensitive and resistant cells. pRb and cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2-amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade. Conclusions These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991

Assessing recent trends in high-latitude Southern Hemisphere surface climate

Understanding the causes of recent climatic trends and variability in the high-latitude Southern Hemisphere is hampered by a short instrumental record. Here, we analyse recent atmosphere, surface ocean and sea-ice observations in this region and assess their trends in the context of palaeoclimate records and climate model simulations. Over the 36-year satellite era, significant linear trends in annual mean sea-ice extent, surface temperature and sea-level pressure are superimposed on large interannual to decadal variability. However, most observed trends are not unusual when compared with Antarctic paleoclimate records of the past two centuries. With the exception of the positive trend in the Southern Annular Mode, climate model simulations that include anthropogenic forcing are not compatible with the observed trends. This suggests that natural variability likely overwhelms the forced response in the observations, but the models may not fully represent this natural variability or may overestimate the magnitude of the forced response

Next-generation mitogenomics: A comparison of approaches applied to caecilian amphibian phylogeny

Mitochondrial genome (mitogenome) sequences are being generated with increasing speed due to the advances of next-generation sequencing (NGS) technology and associated analytical tools. However, detailed comparisons to explore the utility of alternative NGS approaches applied to the same taxa have not been undertaken. We compared a 'traditional' Sanger sequencing method with two NGS approaches (shotgun sequencing and non-indexed, multiplex amplicon sequencing) on four different sequencing platforms (Illumina's HiSeq and MiSeq, Roche's 454 GS FLX, and Life Technologies' Ion Torrent) to produce seven (near-) complete mitogenomes from six species that form a small radiation of caecilian amphibians from the Seychelles. The fastest, most accurate method of obtaining mitogenome sequences that we tested was direct sequencing of genomic DNA (shotgun sequencing) using the MiSeq platform. Bayesian inference and maximum likelihood analyses using seven different partitioning strategies were unable to resolve compellingly all phylogenetic relationships among the Seychelles caecilian species, indicating the need for additional data in this case

Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies

The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was determined by immunohistochemistry on tissue microarrays. Association with progression-free survival (PFS) and overall survival (OS) was analysed by univariate and multivariate Cox regression analysis. Aberrant p53 overexpression was significantly associated with PFS in the Dutch and Scottish cohorts (P=0.001 and 0.038, respectively), but not with OS in univariate analysis. In multivariate analysis, when the two groups were combined and account taken of clinical factors and country of origin of the cohort, p53 expression was not an independent prognostic predictor of PFS or OS. In this well-powered study with minimal methodological variability, p53 immunostaining is not an independent prognostic marker of clinical outcome in epithelial ovarian cancer. The data demonstrate the importance of methodological standardisation, particularly defining patient characteristics and survival end-point data, if biomarker data from multicentre studies are to be combined