Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus

Influenza A virus (IAV) is a major global public health burden due to its routine evasion of immunization strategies. Natural killer (NK) cells are innate cytotoxic cells with important antiviral activity in the human body, yet the function of these cells in the control of IAV infection is unclear. The aim of this study was to determine the role of lung NK cell cytotoxic responses to IAV. Human lung explants were infected ex vivo with IAV, and lung NK cell activation was analyzed by flow cytometry. Cytotoxic responses of NK cell subsets against IAV-infected macrophages were measured by flow cytometry and ELISA. Despite reports of hypofunctionality in the pulmonary environment, human lung-associated NK cells responded rapidly to ex vivo IAV infection, with upregulation of surface CD107a 24 h post-infection. The lung NK cell phenotype is similar in maturity and differentiation to NK cells of the peripheral blood but a unique CD56brightCD49a+CD103+CD69+ NK cell population was identified in the lung, indicating NK cell residency within this organ. In response to ex vivo IAV infection a greater proportion of resident CD56brightCD49a+ NK cells expressed surface CD107a compared with CD56brightCD49a− NK cells, suggesting a hyperfunctional NK cell population may be present within human lung tissue and could be the result of innate immunological training. Furthermore, NK cells provided significant antiviral, cytotoxic activity following contact with influenza-infected cells, including the production and release of IFN-γ and granzyme-B resulting in macrophage cell death. These results suggest that a resident, trained NK cell population are present in the human lung and may provide early and important control of viral infection. A greater understanding of this resident mucosal population may provide further insight into the role of these cells in controlling viral infection and generating appropriate adaptive immunity to IAV

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

High prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screening

Background The prevalence of asymptomatic tuberculosis (TB) in recently diagnosed HIV-1-infected persons attending pre-antiretroviral therapy (ART) clinics is not well described. In addition, it is unclear if the detection of Mycobacterium tuberculosis in these patients clearly represents an early asymptomatic phase leading to progressive disease or transient excretion of bacilli. Objective To describe the prevalence and outcome of subclinical TB disease in HIV-1-infected persons not eligible for ART. Methods The study was conducted in 274 asymptomatic ART-naive HIV-1-infected persons in Khayelitsha Day Hospital, Cape Town, South Africa. All participants were screened for TB using a symptom screen and spoligotyping was performed to determine genotypes. Results The prevalence of subclinical TB disease was 8.5% (95% CI 5.1% to 13.0%) (n = 18; median days to culture positivity 17 days), with 22% of patients being smear-positive. Spoligotyping showed a diverse variety of genotypes with all paired isolates being of the same spoligotype, effectively excluding cross-contamination. 56% of patients followed up developed symptoms 3 days to 2 months later. All were well and still in care 6-12 months after TB diagnosis; 60% were started on ART. A positive tuberculin skin test (OR 4.96, p = 0.064), low CD4 count (OR 0.996, p = 0.06) and number of years since HIV diagnosis (OR 1.006, p = 0.056) showed trends towards predicting TB disease. Conclusion This study found a high prevalence but good outcome (retained in care) of subclinical TB disease in HIV-1-infected persons. The results suggest that, in high HIV/TB endemic settings, a positive HIV-1 test should prompt TB screening by sputum culture irrespective of symptoms, particularly in those with a positive tuberculin skin test, longer history of HIV infection and low CD4 count. Operational difficulties in resource-constrained settings with respect to screening with TB culture highlight the need for rapid and affordable point-of-care tests to identify persons with clinical and subclinical TB disease.Immunogenetics and cellular immunology of bacterial infectious disease

Tendinous tissue adaptation to explosive- vs. sustained-contraction strength training

© 2018 Massey, Balshaw, Maden-Wilkinson, Tillin and Folland. The effect of different strength training regimes, and in particular training utilizing brief explosive contractions, on tendinous tissue properties is poorly understood. This study compared the efficacy of 12 weeks of knee extensor explosive-contraction (ECT; n = 14) vs. sustained-contraction (SCT; n = 15) strength training vs. a non-training control (n = 13) to induce changes in patellar tendon and knee extensor tendon-aponeurosis stiffness and size (patellar tendon, vastus-lateralis aponeurosis, quadriceps femoris muscle) in healthy young men. Training involved 40 isometric knee extension contractions (three times/week): gradually increasing to 75% of maximum voluntary torque (MVT) before holding for 3 s (SCT), or briefly contracting as fast as possible to ~80% MVT (ECT). Changes in patellar tendon stiffness and Young's modulus, tendon-aponeurosis complex stiffness, as well as quadriceps femoris muscle volume, vastus-lateralis aponeurosis area and patellar tendon cross-sectional area were quantified with ultrasonography, dynamometry, and magnetic resonance imaging. ECT and SCT similarly increased patellar tendon stiffness (20% vs. 16%, both p < 0.05 vs. control) and Young's modulus (22% vs. 16%, both p < 0.05 vs. control). Tendon-aponeurosis complex high-force stiffness increased only after SCT (21%; p < 0.02), while ECT resulted in greater overall elongation of the tendon-aponeurosis complex. Quadriceps muscle volume only increased after sustained-contraction training (8%; p = 0.001), with unclear effects of strength training on aponeurosis area. The changes in patellar tendon cross-sectional area after strength training were not appreciably different to control. Our results suggest brief high force muscle contractions can induce increased free tendon stiffness, though SCT is needed to increase tendon-aponeurosis complex stiffness and muscle hypertrophy

Seasonality, risk-factors and burden of community-acquired pneumonia in COPD patients: A population database study using linked healthcare records

Community acquired pneumonia (CAP) is more common in patients with chronic obstructive pulmonary disease (COPD) than in the adult general population, with studies of hospitalised CAP consistently reporting COPD as a frequent comorbidity. However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk-factors and burden of CAP in COPD are currently lacking.A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted. Patients with a diagnosis of COPD aged ?40 years were followed for 5 years from the 1st January 2010. CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time. In addition, baseline factors predicting future risk of CAP and hospital admission at CAP, were identified. 14513 COPD patients were identified: 13.4% (n=1938) had ?1 CAP episode, of whom 18.8% suffered from recurrent (?2) CAP. Highest rates of both CAP and exacerbations were seen in winter. A greater proportion of frequent, compared to infrequent exacerbators experienced recurrent CAP (5.1% versus 2.0% respectively, p&lt;0.001) 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations. Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission at CAP. Other independent predictors of future CAP included lower body mass index, inhaled-corticosteroid use, prior frequent exacerbations and comorbidities including ischaemic heart disease and diabetes. CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission at CAP. Highlighting this burden of COPD-associated CAP during the winter period, informs us of the likely triggers and the need for more effective preventive strategies.<br/

A Path Toward the Use of Trail Users’ Tweets to Assess Effectiveness of the Environmental Stewardship Scheme: An Exploratory Analysis of the Pennine Way National Trail

Large and unofficial data sets, for instance those gathered from social media, are increasingly being used in geographical research and explored as decision support tools for policy development. Social media data have the potential to provide new insight into phenomena about which there is little information from conventional sources. Within this context, this paper explores the potential of social media data to evaluate the aesthetic management of landscape. Specifically, this project utilises the perceptions of visitors to the Pennine Way National Trail, which passes through land managed under the Environmental Stewardship Scheme (ESS). The method analyses sentiment in trail users’ public Twitter messages (tweets) with the aim of assessing the extent to which the ESS maintains landscape character within the trail corridor. The method demonstrates the importance of filtering social media data to convert it into useful information. After filtering, the results are based on 161 messages directly related to the trail. Although small, this sample illustrates the potential for social media to be used as a cheap and increasingly abundant source of information. We suggest that social media data in this context should be seen as a resource that can complement, rather than replace, conventional data sources such as questionnaires and interviews. Furthermore, we provide guidance on how social media could be effectively used by conservation bodies, such as Natural England, which are charged with the management of areas of environmental value worldwide

Non-typeable Haemophilus influenzae protein vaccine in adults with COPD:A phase 2 clinical trial

Loss of airway microbial diversity is associated with non-typeable Haemophilus influenzae (NTHi) infection and increased risk of exacerbation in chronic obstructive pulmonary disease (COPD). We assessed the safety and immunogenicity of an investigational vaccine containing NTHi antigens, recombinant protein D (PD) and combined protein E and Pilin A (PE-PilA), and AS01 adjuvant in adults with moderate/-severe COPD and prior exacerbations. In this phase 2, observer-blind, controlled trial (NCT02075541), 145 COPD patients aged 40-80 years randomly (1:1) received two doses of NTHi vaccine or placebo 60 days apart, on top of standard care. Reactogenicity in the 7-day post-vaccination period was higher following NTHi vaccine than placebo. Most solicited adverse events (AEs) were mild/moderate. At least one unsolicited AE was reported during the 30-day post-vaccination period by 54.8% of NTHi vaccine and 51.4% of placebo recipients. One serious AE (placebo group) was assessed by the investigator as vaccine-related. Anti-PD, anti-PE and anti-PiIA geometric mean antibody concentrations increased up to 30 days after each NTHi vaccine dose, waned thereafter, but remained higher than baseline (non-overlapping confidence intervals) up to 13 months post-dose 2. The frequency of specific CD4(+) T cells increased following two doses of NTHi vaccine and remained higher than baseline. Exploratory analysis showed a statistically non-significant lower yearly rate of moderate/severe exacerbations in the NTHi vaccine group than following placebo (1.49 versus 1.73) in the one-year period post-dose 2, with estimated vaccine efficacy of 13.3% (95% confidence interval -24.2 to 39.5; p = 0.44). The NTHi vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in adults with COPD

Raising the participation age in historical perspective : Policy learning from the past?

The raising of the participation age (RPA) to 17 in 2013 and 18 in 2015 marks a historic expansion of compulsory education. Despite the tendency of New Labour governments to eschew historical understanding and explanation, RPA was conceived with the benefit of an analysis of previous attempts to extend compulsion in schooling. This paper assesses the value of a historical understanding of education policy. The period from inception to the projected implementation of RPA is an extended one which has crossed over the change of government, from Labour to Coalition, in 2010. The shifting emphases and meanings of RPA are not simply technical issues but connect to profound historical and social changes. An analysis of the history of the raising of the school leaving age reveals many points of comparison with the contemporary situation. In a number of key areas it is possible to gain insights into the ways in which the study of the past can help to comprehend the present: the role of human capital, the structures of education, in curriculum development and in terms of preparations for change