Markers of β-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes.

Objective: To assess whether clinical characteristics and simple biomarkers of β-cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes.

Research Design And Methods: We prospectively studied 620 participants with type 2 diabetes and HbA1c ≥58 mmol/mol (7.5%) commencing GLP-1RA therapy as part of their usual diabetes care and assessed response to therapy over 6 months.

Developmental improvements in reaching correction efficiency are associated with an increased ability to represent action mentally.

We investigated the purported association between developmental changes in the efficiency of online reaching corrections and improved action representation. Younger children (6-7 years), older children (8-12 years), adolescents (13-17 years), and young adults (18-24 years) completed a double-step reaching paradigm and a motor imagery task. Results showed similar nonlinear performance improvements across both tasks, typified by substantial changes in efficiency after 6 or 7 years followed by incremental improvements.

How well do health professionals interpret diagnostic information? A systematic review.

Objective: To evaluate whether clinicians differ in how they evaluate and interpret diagnostic test information.

Design: Systematic review.

Data Sources: MEDLINE, EMBASE and PsycINFO from inception to September 2013; bibliographies of retrieved studies, experts and citation search of key included studies.

Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients.

In animals, immunomodulatory dendritic cells (DCs) exposed to autoantigen can suppress experimental arthritis in an antigen-specific manner. In rheumatoid arthritis (RA), disease-specific anti-citrullinated peptide autoantibodies (ACPA or anti-CCP) are found in the serum of about 70% of RA patients and are strongly associated with HLA-DRB1 risk alleles. This study aimed to explore the safety and biological and clinical effects of autologous DCs modified with a nuclear factor κB (NF-κB) inhibitor exposed to four citrullinated peptide antigens, designated "Rheumavax," in a single-center, open-labeled, first-in-human phase 1 trial.

A crisis of visibility: The psychological consequences of false-positive screening mammograms, an interview study.

Objective: To understand the meaning of having a false-positive screening mammogram.

Design: Qualitative interview study.

Methods: Twenty-one women, who had experienced false-positive screening mammograms, took part in semi-structured interviews that were analysed with Interpretive Phenomenological Analysis.

A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients.

Background: Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK.

Exploring reasons for variation in ordering thyroid function tests in primary care: a qualitative study.

Background: The ordering of thyroid function tests (TFTs) is increasing but there is not a similar increase in thyroid disorders in the general population, leading some to query whether inappropriate testing is taking place. Inconsistent clinical practice is thought to be a cause of this, but there is little evidence of the views of general practitioners, practice nurses or practice managers on the reasons for variation in the ordering of TFTs.

Aim: To find out the reasons for variation in ordering of TFTs from the perspective of primary healthcare professionals Methods: Fifteen semi-structured interviews were carried out with primary healthcare professionals (general practitioners, practice nurses, practice managers) that used one laboratory of a general hospital in South West England for TFTs.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

Background: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy.

Methods: A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses.

Towards a resolution of the proton form factor problem: new electron and positron scattering data.

There is a significant discrepancy between the values of the proton electric form factor, G(E)(p), extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of G(E)(p) from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector.

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding.

Background: Trauma-induced coagulopathy (TIC) is a disorder of the blood clotting process that occurs soon after trauma injury. A diagnosis of TIC on admission is associated with increased mortality rates, increased burdens of transfusion, greater risks of complications and longer stays in critical care. Current diagnostic testing follows local hospital processes and normally involves conventional coagulation tests including prothrombin time ratio/international normalized ratio (PTr/INR), activated partial prothrombin time and full blood count.

Model-based iterative reconstruction in low-dose CT colonography-feasibility study in 65 patients for symptomatic investigation.

Rationale And Objectives: To compare image quality on computed tomographic colonography (CTC) acquired at standard dose (STD) and low dose (LD) using filtered-back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) techniques.

Materials And Methods: A total of 65 symptomatic patients were prospectively enrolled for the study and underwent STD and LD CTC with filtered-back projection, adaptive statistical iterative reconstruction, and MBIR to allow direct per-patient comparison. Objective image noise, subjective image analyses, and polyp detection were assessed.

Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis.

Objective: To obtain summary estimates of the accuracy of a single baseline measurement of the Elecsys Troponin T high-sensitive assay (Roche Diagnostics) for the diagnosis of acute myocardial infarction in patients presenting to the emergency department.

Design: Systematic review and meta-analysis of diagnostic test accuracy studies.

Data Sources: Medline, Embase, and other relevant electronic databases were searched for papers published between January 2006 and December 2013.

Dopamine transporter imaging for the diagnosis of dementia with Lewy bodies.

Background: Dementia with Lewy bodies (DLB) is a common cause of neurodegenerative dementia of old age. Its accurate recognition can be important in clinical management and is essential for the development of disease-modifying treatments. The current clinical diagnostic criteria are limited particularly by relatively poor sensitivity.

What is the clinical effectiveness and cost-effectiveness of conservative interventions for tendinopathy? An overview of systematic reviews of clinical effectiveness and systematic review of economic evaluations.

Background: Lateral elbow tendinopathy (LET) is a common complaint causing characteristic pain in the lateral elbow and upper forearm, and tenderness of the forearm extensor muscles. It is thought to be an overuse injury and can have a major impact on the patient's social and professional life. The condition is challenging to treat and prone to recurrent episodes.

¹⁸F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

Background: ¹⁸F-FDFG uptake by brain tissue as measured by positron emission tomography (PET) is a well-established method for assessment of brain function in people with dementia. Certain findings on brain PET scans can potentially predict the decline of mild cognitive Impairment (MCI) to Alzheimer's disease dementia or other dementias.

Objectives: To determine the diagnostic accuracy of the ¹⁸F-FDG PET index test for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease dementia or other forms of dementia at follow-up.

Improving screening recall services for women with false-positive mammograms: a comparison of qualitative evidence with UK guidelines.

Objectives: To gain an understanding of the views of women with false-positive screening mammograms of screening recall services, their ideas for service improvements and how these compare with current UK guidelines.

Methods: Inductive qualitative content analysis of semistructured interviews of 21 women who had false-positive screening mammograms. These were then compared with UK National Health Service (NHS) guidelines.

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer.

Background: In breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2-4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid amplification (OSNA); based on messenger RNA amplification to identify the cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using the CK19 and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND.

An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins.

DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls.

Rapid On-Line Control to Reaching Is Preserved in Children With Congenital Spastic Hemiplegia: Evidence From Double-Step Reaching Performance.

This study aimed to investigate the integrity of on-line control of reaching in congenital spastic hemiplegia in light of disparate evidence. Twelve children with and without spastic hemiplegia (11-17 years old) completed a double-step reaching task requiring them to reach and touch a target that remained stationary for most trials (viz nonjump trial) but unexpectedly displaced laterally at movement onset for a minority of trials (20%: known as jump trials). Although children with spastic hemiplegia were generally slower than age-matched controls, they could account for target perturbation at age-appropriate levels shown by a lack of interaction effect on movement time and nonsignificant group difference for time to reach trajectory correction on jump trials.

What is the test's accuracy in my practice population? Tailored meta-analysis provides a plausible estimate.

Objectives: Diagnostic test accuracy studies and meta-analyses may, in some cases, provide estimates that are highly improbable in practice; tailored meta-analysis provides a potential solution. To investigate the utility of tailored meta-analysis in synthesizing estimates of a test's accuracy compared with conventional meta-analysis for three case examples.

Study Design And Setting: MEDLINE, Embase, and CINAHL were searched for relevant studies, and routine data were collected on the test positive rate and disease prevalence from the case settings to define an applicable region for each setting.

Coupling online control and inhibitory systems in children with Developmental Coordination Disorder: Goal-directed reaching.

For children with Developmental Coordination Disorder (DCD), the real-time coupling between frontal executive function and online motor control has not been explored despite reported deficits in each domain. The aim of the present study was to investigate how children with DCD enlist online control under task constraints that compel the need for inhibitory control. A total of 129 school children were sampled from mainstream primary schools.

Risk of breast cancer in symptomatic women in primary care: a case-control study using electronic records.

Background: Breast cancer is the most common cancer in the UK. GPs are encouraged to refer all women whose symptoms may represent cancer, rather than selecting those at highest risk.

Aim: To identify and quantify features of breast cancer in primary care.

Strangeness suppression of qq creation observed in exclusive reactions.

We measured the ratios of electroproduction cross sections from a proton target for three exclusive meson-baryon final states: ΛK(+), pπ(0), and nπ(+), with the CLAS detector at Jefferson Lab. Using a simple model of quark hadronization, we extract qq creation probabilities for the first time in exclusive two-body production, in which only a single qq pair is created. We observe a sizable suppression of strange quark-antiquark pairs compared to nonstrange pairs, similar to that seen in high-energy production.