From A to Z: Wearable technology explained

Wearable technology (WT) has become a viable means to provide low-cost clinically sensitive data for more informed patient assessment. The benefit of WT seems obvious: small, worn discreetly in any environment, personalised data and possible integration into communication networks, facilitating remote monitoring. Yet, WT remains poorly understood and technology innovation often exceeds pragmatic clinical demand and use. Here, we provide an overview of the common challenges facing WT if it is to transition from novel gadget to an efficient, valid and reliable clinical tool for modern medicine. For simplicity, an A–Z guide is presented, focusing on key terms, aiming to provide a grounded and broad understanding of current WT developments in healthcare

Mobility impairment is associated with reduced microstructural integrity of the inferior and superior cerebellar peduncles in elderly with no clinical signs of cerebellar dysfunction☆

While the cerebellum plays a critical role in motor coordination and control no studies have investigated its involvement in idiopathic mobility impairment in community-dwelling elderly. In this study we tested the hypothesis that structural changes in the cerebellar peduncles not detected by conventional magnetic resonance imaging are associated with reduced mobility performance. The analysis involved eighty-five subjects (age range: 75–90 years) who had no clinical signs of cerebellar dysfunction. Based on the short physical performance battery (SPPB) score, we defined mobility status of the subjects in the study as normal (score 11–12, n = 26), intermediate (score 9–10, n = 27) or impaired (score < 9, n = 32). We acquired diffusion tensor imaging data to obtain indices of white matter integrity: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Using a parcellation atlas, regional indices within the superior, middle, and inferior cerebellar peduncles (ICP, MCP, SCP) were calculated and their associations with mobility performance were analyzed. Subjects with impaired mobility showed reduced FA and AD values in the ICP and SCP but not in the MCP. The ICP-FA, ICP-AD and SCP-FA indices showed a significant association with the SPPB score. We also observed significant correlation between ICP-FA and walk time (r = − 0.311, p = 0.004), as well as between SCP-AD and self-paced maximum walking velocity (r = 0.385, p = 0.003) and usual walking velocity (r = 0.400, p = 0.002). In logistic regression analysis ICP-FA and ICP-AD together explained 51% of the variability in the mobility status of a sample comprising the normal and impaired subgroups, and correctly classified more than three-quarters of those subjects. Our findings suggest that presence of microstructural damage, likely axonal, in afferent and efferent connections of the cerebellum contributes to the deterioration of motor performance in older people

Stability of β-catenin as a potential mechanism of glucocorticoid dependant expansion of human erythroid progenitors

Introduction: Cooperative signalling between the glucocorticoid nuclear receptor and the cytokine receptors was proven to be central for proper balance between progenitor proliferation and differentiation. The glucocorticoid, Dexamethasone (Dex) has been identified as an essential requirement for the generation of mass cultures of erythroblasts. The production of massive cultures of human red blood cells in vitro would possibly lead to ex vivo transfusions. Although many signalling pathways have been unravelled, transcription regulation induced by glucocorticoids in haematopoietic progenitors is still unclear.peer-reviewe

Development of in vitro erythroblast cultures for transfusion purposes

Introduction: The demand for Red Blood Cell (RBC) transfusion is continuously increasing while the supply is not always sufficient. As there is no appropriate alternative to RBC transfusion, the in vitro manufacture of RBCs is a potential means to ensure an adequate and safe supply of blood products. Our previous studies developed an erythropoiesis model to culture human erythroblasts in vitro using media supplemented with Erythropoietin (Epo), Stem Cell Factor (SCF) and Dexamethasone (Dex) to allow survival, proliferation and self renewal capacity. Aim: To enhance erythroblast growth capacity in vitro by constitutive activation of SCF and Epo signaling and investigating the cooperative mechanisms with Dex resulting in induced self renewal potential. Methodology: Haematopoietic progenitors were isolated using Magnetic cell sorting. The CD34+ fraction was cultured in specific media and characterised by flow cytometry. The CD34- fraction was also kept in culture for erythroblast commitment and proliferation. The growth curves were calculated using the CASY cell counter and analyser. Cells were factor deprived for 4 hours and stimulated for 2 hours with Epo, SCF, Dex alone or selected combinations. Cells were harvested and the nuclear cell lysates isolated. The activation of the transcription factors NFkB, AP-1, CREB, NFAT and GR were investigated using Luminex technology. In addition, an electroporation protocol was optimised for expression studies. Currently Jak2 and cKit coding sequences are being amplified from cDNA samples. Results: The erythroblast culture originating from the CD34- fraction was improved by a co-culture of a stromal cell layer. This co-culture showed enhanced proliferation and retained a mean erythroblast diameter of 9.5µm. In the absence of the stromal layer an erythroblast diameter of 8.5µm was obtained, with continuous cell purification. The transcription factor multiplex profile of cultured erythroblasts showed a specific transcription activation upon the addition of Epo and Dex inducing CREB and NFAT activity. The CD34+ cell culture retained an immature cell morphology and the capacity to differentiate into erythroblasts upon culturing in a selective media (ESD). Conclusion: The identification of the co-culture system merits further investigation. Studying the mechanism of self renewal of erythroblasts and expression of Jak2 and cKit will assess the possibility of factor-independent growth of the blasts. The outcome could provide key insights into mass production of erythrocytes in culture which would eventually allow additional research for production of transfusion compatible erythrocyte units.peer-reviewe

Cohort profile: prescriptions dispensed in the community linked to the national cancer registry in England.

PURPOSE: The linked prescriptions cancer registry data resource was set up to extend our understanding of the pathway for patients with cancer past secondary care into the community, to ultimately improve patient outcomes. PARTICIPANTS: The linked prescriptions cancer registry data resource is currently available for April to July 2015, for all patients diagnosed with cancer in England with a dispensed prescription in that time frame.The dispensed prescriptions data are collected by National Health Service (NHS) Prescription Services, and the cancer registry data are processed by Public Health England. All data are routine healthcare data, used for secondary purposes, linked using a pseudonymised version of the patient's NHS number and date of birth.Detailed demographic and clinical information on the type of cancer diagnosed and treatment is collected by the cancer registry. The dispensed prescriptions data contain basic demographic information, geography measures of the dispensed prescription, drug information (quantity, strength and presentation), cost of the drug and the date that the dispensed prescription was submitted to NHS Business Services Authority. FINDINGS TO DATE: Findings include a study of end of life prescribing in the community among patients with cancer, an investigation of repeat prescriptions to derive measures of prior morbidity status in patients with cancer and studies of prescription activity surrounding the date of cancer diagnosis. FUTURE PLANS: This English linked resource could be used for cancer epidemiological studies of diagnostic pathways, health outcomes and inequalities; to establish primary care comorbidity indices and for guideline concordance studies of treatment, particularly hormonal therapy, as a major treatment modality for breast and prostate cancer which has been largely delivered in the community setting for a number of years

Multiple impact therapy : evaluation and design for future study

The theoretical underpinnings of Washington County Children\u27s Services Division (CSD) Immediate Conflict-Resolution Family Treatment Program include the systems theory of family therapy with a focus on communication and roles. One of the many approaches to helping families in crisis, it incorporates theories regarding assessment of and intervention in families in crisis. Finally, while it draws upon several different approaches to family therapy, the Washington County program is most closely related to Multiple Impact Therapy (MIT). Thus, a review of relevant literature must address portions of the above enumerated theories that illuminate the thinking behind the Immediate Conflict- Resolution Family Treatment Program. While each of the four components of the literature review (systems theory, family crisis theory, assessment of families in crisis, and Multiple Impact Therapy) represents a topic area of breadth and complexity, the aspects of each topic area which seem most relevant to Washington County\u27s MIT project have been reviewed

Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial.

BACKGROUND: In sub-Saharan Africa, 20%-25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and timing of different causes of mortality/morbidity. METHODS: Participants started ART with a CD4 count .3); and reduced nonfatal/fatal tuberculosis and cryptococcosis (P .2). CONCLUSIONS: Enhanced prophylaxis reduced mortality from cryptococcosis and unknown causes and nonfatal tuberculosis and cryptococcosis. High early incidence of fatal/nonfatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease. CLINICAL TRIALS REGISTRATION: ISRCTN43622374

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis