Protocol for a longitudinal qualitative interview study: maintaining psychological well-being in advanced cancer - what can we learn from patients' and carers' own coping strategies?

IntroductionPeople with advanced cancer and their carers experience stress and uncertainty which affects the quality of life and physical and mental health. This study aims to understand how patients and carers recover or maintain psychological well-being by exploring the strategies employed to self-manage stress and uncertainty.Methods and analysisA longitudinal qualitative interview approach with 30 patients with advanced cancer and 30 associated family or informal carers allows the exploration of contexts, mechanisms and outcomes at an individual level. Two interviews, 4–12?weeks apart, will not only enable the exploration of individuals’ evolving coping strategies in response to changing contexts but also how patients’ and carers’ strategies inter-relate. Patient and Carer focus groups will then consider how the findings may be used in developing an intervention. Recruiting through two major tertiary cancer centres in the North West and using deliberately broad and inclusive criteria will enable the sample to capture demographic and experiential breadth.Ethics and disseminationThe research team will draw on their considerable experience to ensure that the study is sensitive to a patient and carer group, which may be considered vulnerable but still values being able to contribute its views. Public and patient involvement (PPI) is integral to the design and is evidenced by: a research advisory group incorporating patient and carers, prestudy consultations with the PPI group at one of the study sites and a user as the named applicant. The study team will use multiple methods to disseminate the findings to clinical, policy and academic audiences. A key element will be engaging health professionals in patient and carer ideas for promoting self-management of psychological well-being. The study has ethical approval from the North West Research Ethics Committee and the appropriate NHS governance clearance.RegistrationNational Institute for Health Research (NIHR) Clinical Studies Portfolio, UK Clinical Research Network (UKCRN) Study number 11725

Early Interferon-γ Production in Human Lymphocyte Subsets in Response to Nontyphoidal Salmonella Demonstrates Inherent Capacity in Innate Cells

Background Nontyphoidal Salmonellae frequently cause life-threatening bacteremia in sub-Saharan Africa. Young children and HIV-infected adults are particularly susceptible. High case-fatality rates and increasing antibiotic resistance require new approaches to the management of this disease. Impaired cellular immunity caused by defects in the T helper 1 pathway lead to intracellular disease with Salmonella that can be countered by IFNγ administration. This report identifies the lymphocyte subsets that produce IFNγ early in Salmonella infection. Methodology Intracellular cytokine staining was used to identify IFNγ production in blood lymphocyte subsets of ten healthy adults with antibodies to Salmonella (as evidence of immunity to Salmonella), in response to stimulation with live and heat-killed preparations of the D23580 invasive African isolate of Salmonella Typhimurium. The absolute number of IFNγ-producing cells in innate, innate-like and adaptive lymphocyte subpopulations was determined. Principal Findings Early IFNγ production was found in the innate/innate-like lymphocyte subsets: γδ-T cells, NK cells and NK-like T cells. Significantly higher percentages of such cells produced IFNγ compared to adaptive αβ-T cells (Student's t test, P<0.001 and ≤0.02 for each innate subset compared, respectively, with CD4+- and CD8+-T cells). The absolute numbers of IFNγ-producing cells showed similar differences. The proportion of IFNγ-producing γδ-T cells, but not other lymphocytes, was significantly higher when stimulated with live compared with heat-killed bacteria (P<0.0001). Conclusion/Significance Our findings indicate an inherent capacity of innate/innate-like lymphocyte subsets to produce IFNγ early in the response to Salmonella infection. This may serve to control intracellular infection and reduce the threat of extracellular spread of disease with bacteremia which becomes life-threatening in the absence of protective antibody. These innate cells may also help mitigate against the effect on IFNγ production of depletion of Salmonella-specific CD4+-T lymphocytes in HIV infection

Optically Controlled Excitonic Transistor

Optical control of exciton fluxes is realized for indirect excitons in a crossed-ramp excitonic device. The device demonstrates experimental proof of principle for all-optical excitonic transistors with a high ratio between the excitonic signal at the optical drain and the excitonic signal due to the optical gate. The device also demonstrates experimental proof of principle for all-optical excitonic routers

Predicting lung cancer recurrence from circulating tumour DNA. Commentary on 'Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution'

No abstract available

The Frequency and Content of Discussions About Alcohol Use in Primary Care and Application of the Chief Medical Officer’s Low-Risk Drinking Guidelines: A Cross-Sectional Survey of General Practitioners and Practice Nurses in the UK

ABSTRACT Aims: To examine how often General Practitioners (GPs) and Practice Nurses (PNs) working in primary care discuss alcohol with patients, what factors prompt discussions, how they approach patient discussions, and whether the Chief Medical Officer’s (CMO’s) revised low-risk drinking guidelines are appropriately advised. Methods: Cross-sectional survey with GPs and PNs working in primary care in the UK, conducted January-March 2017 (n=2,020). A vignette exercise examined what factors would prompt a discussion about alcohol, whether they would discuss before or after a patient reported exceeded the revised CMO guidelines (14 units per week), and whether the CMO’s drinking guidelines were appropriately advised. For all patients, participants were asked how often they discussed alcohol and how they approached the discussion (e.g. used screening tool). Results: The most common prompts to discuss alcohol in the vignette exercise were physical cues (44.7% of participants) or alcohol-related symptoms (23.8%). Most practitioners (70.1%) said they would wait until a patient was exceeding CMO guidelines before instigating discussion. Two-fifths (38.1%) appropriately advised the CMO guidelines in the vignette exercise, with PNs less likely to do so than GPs (OR=0.77, p=0.03). Less than half (44.7%) reportedly asked about alcohol always/often with all patients, with PNs more likely to ask always/often than GPs (OR=2.22, p<0.001). Almost three-quarters said they would enquire by asking about units (70.3%), compared to using screening tools. Conclusion: Further research is required to identify mechanisms to increase the frequency of discussions about alcohol and appropriate recommendation of the CMO drinking guidelines to patients.This research was supported by funding from Cancer Research UK. JMB is supported by the Medical Research Council (MRC) (Grant MC_UU_12015/4)

Lymphocyte subsets in healthy Malawians: Implications for immunologic assessment of HIV infection in Africa

BackgroundCD4+T lymphocyte measurements are the most important indicator of mortality in HIV-infected individuals in resource-limited settings. There is currently a lack of comprehensive immunophenotyping data from African populations to guide the immunologic assessment of HIV infection.ObjectiveTo quantify variation in absolute and relative lymphocyte subsets with age in healthy Malawians.MethodsLymphocyte subsets in peripheral blood of 539 healthy HIV-uninfected Malawians stratified by age were enumerated by flow cytometry.ResultsB and T–lymphocyte and T-lymphocyte subset absolute concentrations peaked in early childhood then decreased to adult levels, whereas lymphocyte subset proportions demonstrated much less variation with age. Adult lymphocyte subsets were similar to those in developed countries. In contrast, high B-lymphocyte and CD8+T-lymphocyte levels among children under 2 years, relative to those in developed countries, resulted in low CD4+T-lymphocyte percentages that varied little between 0 and 5 years (35% to 39%). The CD4+T-lymphocyte percentages in 35% of healthy children under 1 year and 18% of children age 1 to 3 years were below the World Health Organization threshold defining immunodeficiency in HIV-infected children in resource-limited settings. Thirteen percent of healthy children under 18 months old had a CD4:CD8T-lymphocyte ratio <1.0, which is commonly associated with HIV infection. All immunologic parameters except absolute natural killer lymphocyte concentration varied significantly with age, and percentage and overall absolute CD4+T-lymphocyte counts were higher in females than males.ConclusionAlthough lymphocyte subsets in Malawian adults are similar to those from developed countries, CD4+T-lymphocyte percentages in young children are comparatively low. These findings need to be considered when assessing the severity of HIV-related immunodeficiency in African children under 3 years

Transport of indirect excitons in high magnetic fields

We present spatially and spectrally resolved photoluminescence measurements of indirect excitons in high magnetic fields. Long indirect exciton lifetimes give the opportunity to measure magnetoexciton transport by optical imaging. Indirect excitons formed from electrons and holes at zeroth Landau levels (0e−0h indirect magnetoexcitons) travel over large distances and form a ring emission pattern around the excitation spot. In contrast, the spatial profiles of 1e−1h and 2e−2h indirect magnetoexciton emission closely follow the laser excitation profile. The 0e−0h indirect magnetoexciton transport distance reduces with increasing magnetic field. These effects are explained in terms of magnetoexciton energy relaxation and effective mass enhancement