Critical current of YBa2Cu3O7-delta low-angle grain boundaries

Transport critical current measurements have been performed on 5degrees [001]-tilt thin film YBa2Cu3O7-delta single grain boundaries with the magnetic field rotated in the plane of the film, phi. The variation of the critical current has been determined as a function of the angle between the magnetic field and the grain boundary plane. In applied fields above 1 T the critical current j(c) is found to be strongly suppressed only when the magnetic field is within an angle phi(k) of the grain boundary. Outside this angular range the behavior of the artificial grain boundary is dominated by the critical current of the grains. We show that the phi dependence of j(c) in the suppressed region is well described by a flux cutting model.EPSR

Impact of the COVID-19 pandemic on the research activities of UK ophthalmologists

BACKGROUND: The COVID-19 pandemic has impacted negatively on many areas of biomedical research and there is concern that academic recovery will take several years. This survey aimed to define the impact of the COVID-19 pandemic on UK ophthalmologists' research activities and understand the implications for recovery. METHODS: An online survey comprising multiple choice and free-text questions was designed, piloted and then distributed to Royal College of Ophthalmologists (RCOphth) members in January 2021. Respondent characteristics, research expectations and experiences through the pandemic were captured. Descriptive and comparative statistics were applied to quantitative data alongside content analysis of qualitative data. RESULTS: In total, 148 respondents (3.7% of RCOphth membership) comprised 46 trainees (31.1%), 97 consultants (65.5%) and 5 SAS doctors (3.4%); 54 had clinical-academic roles (36.5%) and 65/94 (69.1%) ophthalmologists with fully clinical posts identified as research-active. Of 114 research-active respondents, 104 (91.2%) reported an impact on their research from COVID-19; negative impacts included loss of research time (n = 69), research delays (n = 96) and funding shortfalls (n = 63). Content analysis identified five common themes; type of research activity, clinical demands, institutional challenges, COVID-19 alignment and work-life balance. CONCLUSIONS: UK ophthalmology research has been adversely impacted by the pandemic. A substantial proportion of UK ophthalmologists are research active, but 20.4% of those surveyed felt that the pandemic had made research less attractive. Strategic steps must be taken to nurture UK ophthalmologists' engagement with research, especially for those who currently do no research, if the profession is to align itself with the Government vision of 'Research for All'

The formation of professional identity in medical students: considerations for educators

<b>Context</b> Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.<p></p> <b>Objectives</b> This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.<p></p> <b>Implications</b> A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.<p></p> <b>Conclusions</b> Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education

Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis

Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study.

Background: Spinal manipulation for nonspecific neck pain is thought to work in part by improving inter-vertebral range of motion (IV-RoM), but it is difficult to measure this or determine whether it is related to clinical outcomes. Objectives: This study undertook to determine whether cervical spine flexion and extension IV-RoM increases after a course of spinal manipulation, to explore relationships between any IV-RoM increases and clinical outcomes and to compare palpation with objective measurement in the detection of hypo-mobile segments. Method: Thirty patients with nonspecific neck pain and 30 healthy controls matched for age and gender received quantitative fluoroscopy (QF) screenings to measure flexion and extension IV-RoM (C1-C6) at baseline and 4-week follow-up between September 2012-13. Patients received up to 12 neck manipulations and completed NRS, NDI and Euroqol 5D-5L at baseline, plus PGIC and satisfaction questionnaires at follow-up. IV-RoM accuracy, repeatability and hypo-mobility cut-offs were determined. Minimal detectable changes (MDC) over 4 weeks were calculated from controls. Patients and control IV-RoMs were compared at baseline as well as changes in patients over 4 weeks. Correlations between outcomes and the number of manipulations received and the agreement (Kappa) between palpated and QF-detected of hypo-mobile segments were calculated. Results: QF had high accuracy (worst RMS error 0.5o) and repeatability (highest SEM 1.1o, lowest ICC 0.90) for IV-RoM measurement. Hypo-mobility cut offs ranged from 0.8o to 3.5o. No outcome was significantly correlated with increased IV-RoM above MDC and there was no significant difference between the number of hypo-mobile segments in patients and controls at baseline or significant increases in IV-RoMs in patients. However, there was a modest and significant correlation between the number of manipulations received and the number of levels and directions whose IV-RoM increased beyond MDC (Rho=0.39, p=0.043). There was also no agreement between palpation and QF in identifying hypo-mobile segments (Kappa 0.04-0.06). Conclusions: This study found no differences in cervical sagittal IV-RoM between patients with non-specific neck pain and matched controls. There was a modest dose-response relationship between the number of manipulations given and number of levels increasing IV-RoM - providing evidence that neck manipulation has a mechanical effect at segmental levels. However, patient-reported outcomes were not related to this

The significance of measuring monocyte tissue factor activity in patients with breast and colorectal cancer

Monocytes express tissue factor (mTF) in several conditions including cancer where levels may be valuable in assessing tumour presence and progression. Using a two-stage kinetic chromogenic assay (KCA), mTF levels were measured in controls [normal subjects (n = 60) and patients undergoing hernia repair or cholecystectomy (n = 60)], in patients with benign and malignant disease of the breast (n = 83) and of the large bowel (n = 62). This was performed under fresh (resting) conditions and after incubation for 6 h without (unstimulated) and with (stimulated) Escherichia coli endotoxin. The malignant groups showed higher mTF levels than each of the three controls for resting (P &lt; 0.05 breast, P &lt; 0.05 colorectal) unstimulated (P &lt; 0.05 breast, P &lt; 0.05 colorectal) and stimulated cells (P &lt; 0.001 breast, P &lt; 0.01 colorectal). Similarly, the benign inflammatory groups had higher mTF levels than controls for resting (P &lt; 0.05 colorectal), unstimulated (P &lt; 0.05 colorectal) and stimulated cells (P &lt; 0.01 breast, P &lt; 0.01 colorectal). There was no significant difference between malignant and benign inflammatory groups in each organ. mTF levels showed an increase corresponding to that of histological tumour progression and were higher in non-surviving patients. In conclusion, mTF levels are raised in malignant and inflammatory disease compared to controls and patients with non-inflammatory conditions. Stimulated cells give better discrimination between the groups and may be of value in identifying high risk individuals. mTF levels showed an association with tumour grade or stage and the patients' survival time

When to Start Antiretroviral Therapy

The question of when to start combination antiretroviral therapy for treatment-naïve patients has always been controversial. This is particularly true in the current era, with major guidelines recommending very different treatment strategies. Despite a lack of clarity regarding the optimal time to begin therapy, there has been a recent shift toward earlier initiation. This more aggressive approach is driven by several observations. First, effective viral suppression with therapy can prevent non-AIDS-related morbidity and mortality. Second, therapy can prevent irreversible harm to the human immune system. Third, therapy may prevent transmission of HIV to others, and thus have a potential public health benefit. For patients who are motivated and willing to initiate early treatment, the collective benefits of early therapy may outweigh the well-documented risks of antiretroviral medications

Different regulation of cigarette smoke induced inflammation in upper versus lower airways

Background: Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure. Methods: C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3 alpha, RORc, IL-17, FoxP3, and TGF-beta 1 in nasal turbinates and lungs by RT-PCR. Results: In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3a and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs. Conclusions: Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Application and Validation of Case-Finding Algorithms for Identifying Individuals with Human Immunodeficiency Virus from Administrative Data in British Columbia, Canada

Objective To define a population-level cohort of individuals infected with the human immunodeficiency virus (HIV) in the province of British Columbia from available registries and administrative datasets using a validated case-finding algorithm. Methods Individuals were identified for possible cohort inclusion from the BC Centre for Excellence in HIV/AIDS (CfE) drug treatment program (antiretroviral therapy) and laboratory testing datasets (plasma viral load (pVL) and CD4 diagnostic test results), the BC Centre for Disease Control (CDC) provincial HIV surveillance database (positive HIV tests), as well as databases held by the BC Ministry of Health (MoH); the Discharge Abstract Database (hospitalizations), the Medical Services Plan (physician billing) and PharmaNet databases (additional HIV-related medications). A validated case-finding algorithm was applied to distinguish true HIV cases from those likely to have been misclassified. The sensitivity of the algorithms was assessed as the proportion of confirmed cases (those with records in the CfE, CDC and MoH databases) positively identified by each algorithm. A priori hypotheses were generated and tested to verify excluded cases. Results A total of 25,673 individuals were identified as having at least one HIV-related health record. Among 9,454 unconfirmed cases, the selected case-finding algorithm identified 849 individuals believed to be HIV-positive. The sensitivity of this algorithm among confirmed cases was 88%. Those excluded from the cohort were more likely to be female (44.4% vs. 22.5%; p&lt;0.01), had a lower mortality rate (2.18 per 100 person years (100PY) vs. 3.14/100PY; p&lt;0.01), and had lower median rates of health service utilization (days of medications dispensed: 9745/100PY vs. 10266/100PY; p&lt;0.01; days of inpatient care: 29/100PY vs. 98/100PY; p&lt;0.01; physician billings: 602/100PY vs. 2,056/100PY; p&lt;0.01). Conclusions The application of validated case-finding algorithms and subsequent hypothesis testing provided a strong framework for defining a population-level cohort of HIV infected people in BC using administrative databases