Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ.

Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre-Tfh) but no associated increase in germinal centre (GC)-Tfh cells in aged mice, suggesting age-driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch-associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age-associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age-induced changes in T-cell activation that affects the differentiation and ultimately the function of effector T cells

Distance determination to 12 Type II-P Supernovae using the Expanding Photosphere Method

We use early-time photometry and spectroscopy of 12 Type II plateau supernovae (SNe IIP) to derive their distances using the expanding photosphere method (EPM). We perform this study using two sets of Type II supernova (SN II) atmosphere models, three filter subsets ($\{BV\}$, $\{BVI\}$, $\{VI\}$), and two methods for the host-galaxy extinction, which leads to 12 Hubble diagrams. We find that systematic differences in the atmosphere models lead to $\sim$50% differences in the EPM distances and to a value of ${\rm H_0}$ between 52 and 101 ${\rm km s^{-1} Mpc^{-1}}$. Using the $\{VI\}$ filter subset we obtain the lowest dispersion in the Hubble diagram, {${\rm \sigma_{\mu} = 0.32}$ mag}. We also apply the EPM analysis to the well-observed SN IIP 1999em. With the $\{VI\}$ filter subset we derive a distance ranging from 9.3 $\pm$ 0.5 Mpc to 13.9 $\pm$ 1.4 Mpc depending on the atmosphere model employed.Comment: Accepted for publication in the Astrophysical Journa

Using the behaviour change technique taxonomy v1 (BCTTv1) to identify the active ingredients of pharmacist interventions to improve non-hospitalised patient health outcomes

© Author(s) (or their employer(s)) 2020. Objectives The aim of this study was to identify which behaviour change techniques (BCTs) were present in intervention and control groups of randomised controlled trials (RCTs) included in a Cochrane systematic review. Setting The RCTs included were conducted in community, primary and/or ambulatory-care settings. Participants The data set was derived from 86 RCTs from an interim update of the Cochrane review of the effectiveness of pharmacist services on non-hospitalised patient outcomes. Primary and secondary outcome measures The primary outcome was the identification of BCTs scheduled for delivery in intervention and control groups of the RCTs. The secondary outcome measure was to identify which BCTs are not being utilised in intervention and control groups of the RCTs. Results The intervention and control groups included 31 and 12 BCTs, respectively. The number of identifiable BCTs/study ranged from 0 to 12 in the intervention groups (mean 3.01 (SD 2.4)) and 0 to 6 in the control groups (mean 0.38 (SD 0.84)). The most commonly identified BCTs in the intervention groups were: instruction on how to perform the behaviour (55%, n=47) (also the most common BCT in control groups); problem solving (29%, n=25); information about health consequences (24%, n=21); social support (practical) (24%, n=21); and social support (unspecified) (23%, n=20) (the second most common BCT in control groups). Thirteen trials had no identifiable BCTs in either group. Conclusion The pharmacist interventions presented in this study did not use the full range of available BCTs. Furthermore, the reporting of BCTs was incomplete for both intervention and control groups, thereby limiting the utility and reproducibility of the interventions. Future interventions should be designed and reported using relevant taxonomies and checklists for example, BCT taxonomy and TIDieR (the template for intervention description and replication).Chief Scientist Office, grant number CZH/4/1041; MdB: Professor Roy Weir Career Development Fellowship; MCW: Health Foundation Improvement Science Fellowship

Description et évaluation d'un réseau d'épidémiosurveillance des pathologies porcines mis en place dans un district du Nord Vietnam

Background and objective: Early menarche is increasing in prevalence worldwide, prompting clinical andpublic health interest on its links with pulmonary function. We aimed to investigate the relationship betweenearly menarche and lung function in middle age.Methods: The population-based Tasmanian LongitudinalHealth Study (born 1961; n = 8583), was initiated in 1968.The 5th Decade follow-up data (mean age: 45 years)included age at menarche and complex lung function testing. The 6th Decade follow-up (age: 53 years) repeated spirometry and gas transfer factor. Multiple linear regressionand mediation analyses were performed to determine theassociation between age at menarche and adult lung function and investigate biological pathways, including the proportion mediated by adult-attained height.Results: Girls reporting an early menarche (Conclusion:Early menarche was associated withreduced adult lung function. This is the first study toinvestigate post-BD outcomes and quantify the partialrole of adult height in this association

Pharmacist services for non-hospitalised patients (Review)

This is the peer reviewed version of the following article: de Barra M, Scott CL, Scott NW, Johnston M, de Bruin M, Nkansah N, Bond CM, Matheson CI, Rackow P, Williams AJ, Watson MC. Pharmacist services for non‐hospitalised patients. Cochrane Database of Systematic Reviews. 2018(9)., which has been published in final form at https://doi.org/10.1002/14651858.CD013102. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

The Novel Object and Unusual Name (NOUN) database: a collection of novel images for use in experimental research

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects’ novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects’ colors. Results from a similarity sorting task (and subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprise both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in language, categorization, perception, visual memory and related domains

Adult asthma and traffic exposure at residential address, workplace address, and self-reported daily time outdoor in traffic: A two-stage case-control study

<p>Abstract</p> <p>Background</p> <p>Most epidemiologic studies use traffic at residential address as a surrogate for total traffic exposure when investigating effects of traffic on respiratory health. This study used GIS (Geographical Information Systems) to estimate traffic exposure, not only on residential, but also on workplace address, in addition to survey questions on time spent in traffic during commuting or other daily activities.</p> <p>The aim was to investigate 1) if there is an association between traffic exposure and prevalence of adult asthma and asthma symptoms, and 2) if so, does this association become stronger using more complete traffic exposure information.</p> <p>Methods</p> <p>This study was conducted in two stages: A first cross-sectional survey in Southern Sweden 2004 (n = 24819, 18-80 years, response rate 59%) was followed by a case-control study in 2005 to obtain more detailed exposure and confounder information (n = 2856, asthmatics and controls (1:3), 86% response rate). In the first survey, only residential address was known. In the second survey, questions about workplace addresses and daily time spent in traffic were also included. Residential and workplace addresses were geocoded and linked with GIS to road data and dispersion modelled outdoor concentrations of NO_x(annual mean, 250 × 250 m resolution).</p> <p>Results</p> <p>Living within 50 m of a road (measured by GIS) with traffic intensity of >10 cars/minute (compared with no road within this distance) was associated with an increased prevalence of asthma, (OR = 1.8, 95% CI = (1.1-2.8), and with asthma symptoms last 12 months. No statistically significant effects were seen for traffic exposure at workplace address, daily time spent in traffic, or commuting time to work, after adjustment for confounders. A combined total exposure estimate did not give a stronger association with asthma prevalence or asthma symptoms.</p> <p>Conclusions</p> <p>Traffic exposure at close proximity to residential address showed association with asthma prevalence and asthma symptoms last 12 months, among adults in southern Sweden. The associations were not stronger when accounting for total traffic exposure. This could reflect exposure misclassfication at workplace address and for other daily time in traffic, but also that residential address remains the main determinant for traffic exposure among adults.</p

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal

Background: Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Methods. Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Results: Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI - mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI - mid shaft (ICC 0.99; CV% 3.2). Conclusions: The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2 nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures

Mortality in Western Australian seniors with chronic respiratory diseases: a cohort study

<p>Abstract</p> <p>Background</p> <p>Relatively few studies have examined survival by pharmacotherapy level and the effects of patient characteristics on mortality by pharmacotherapy level in older chronic respiratory disease (CRD) patients. This study aimed to investigate these issues in older (≥ 65) CRD patients in Western Australia.</p> <p>Methods</p> <p>We identified 108,312 patients ≥ 65 years with CRD during 1992-2006 using linked medical, pharmaceutical, hospital and mortality databases held by the Commonwealth and State governments. Pharmacotherapy classification levels were designed by a clinical consensus panel. Cox regression was used to investigate the study aim.</p> <p>Results</p> <p>Patients using only short acting bronchodilators experienced similar, but slightly worse survival than patients in the highest pharmacotherapy level group using high dose inhaled corticosteroids (ICS) ± long acting bronchodilators (LABs) ± oral steroids. Patients using low to medium dose ICS ± LABs experienced relatively better survival. Also, male gender was associated with all-cause mortality in all patients (HR = 1.72, 95% CI 1.65-1.80) and especially in those in the highest pharmacotherapy level group (HR = 1.97, 95%CI = 1.84-2.10). The P-value of interaction between gender and pharmacotherapy level for the effect on all-cause death was significant (0.0003).</p> <p>Conclusions</p> <p>Older patients with CRD not using ICS experienced the worst survival in this study and may benefit from an escalation in therapeutic regime. Males had a higher risk of death than females, which was more pronounced in the highest pharmacotherapy level group. Hence, primary health care should more actively direct disease management to mild-to-moderate disease patients.</p