A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo

In vivo imaging has revolutionized understanding of the spatiotemporal complexity that subserves the generation of successful effector and regulatory immune responses. Until now, invasive surgery has been required for microscopic access to lymph nodes (LNs), making repeated imaging of the same animal impractical and potentially affecting lymphocyte behavior. To allow longitudinal in vivo imaging, we conceived the novel approach of transplanting LNs into the mouse ear pinna. Transplanted LNs maintain the structural and cellular organization of conventional secondary lymphoid organs. They participate in lymphocyte recirculation and exhibit the capacity to receive and respond to local antigenic challenge. The same LN could be repeatedly imaged through time without the requirement for surgical exposure, and the dynamic behavior of the cells within the transplanted LN could be characterized. Crucially, the use of blood vessels as fiducial markers also allowed precise re-registration of the same regions for longitudinal imaging. Thus, we provide the first demonstration of a method for repeated, noninvasive, in vivo imaging of lymphocyte behavior

An Australian longitudinal pilot study examining health determinants of cardiac outcomes 12 months post percutaneous coronary intervention

Background Percutaneous coronary intervention (PCI) is a very common revascularisation procedure for coronary artery disease (CAD). The purpose of this study was to evaluate cardiac outcomes, health related quality of life (HRQoL), resilience and adherence behaviours in patients who have undergone a PCI at two time points (6 and 12 months) following their procedure. Methods A longitudinal pilot study was conducted to observe the cardiac outcomes across a cohort of patients who had undergone a percutaneous coronary intervention (PCI). Participants who had undergone PCI 6 months prior were invited. Those participants who met the inclusion criteria and provided consent then completed a telephone survey (time point 1). These participants were then contacted 6 months later (i.e. 12 months post-intervention, time point 2) and the measures were repeated. Results All patients (n = 51) were recorded as being alive at time point 1. The multiple model indicated that controlling for other factors, gender was significantly associated with a linear combination of outcome measures (p = 0.004). The effect was moderate in magnitude (partial-η2 = 0.303), where males performed significantly better than females 6 months after the PCI procedure physically and with mood. Follow-up univariate ANOVAs indicated that gender differences were grounded in the scale measuring depression (PHQ9) (p = 0.005) and the physical component score of the short form measuring HRQoL (SF12-PCS) (p = 0.003). Thirteen patients were lost to follow-up between time points 1 and 2. One patient was confirmed to have passed away. The pattern of correlations between outcome measures at time point 2 revealed statistically significant negative correlation between the PHQ instrument and the resilience scale (CD-RISC) (r = -0.611; p < 0.001); and the physical component score of the SF-12 instrument (r = -0.437; p = 0.054). Conclusions Men were performing better than women in the 6 months post-PCI, particularly in the areas of mood (depression) and physical health. This pilot results indicate gender-sensitive practices are recommended particularly up to 6 months post-PCI. Any gender differences observed at 6 month appear to disappear at 12 months post-PCI. Further research into the management of mood particularly for women post-PCI is warranted. A more detailed inquiry related to access/attendance to secondary prevention is also warranted

Skunk River Review January 1992, vol 3

https://openspace.dmacc.edu/skunkriver/1006/thumbnail.jp

Breast screening atypia and subsequent development of cancer: protocol for an observational analysis of the Sloane database in England (Sloane atypia cohort study).

INTRODUCTION: The National Health Service (NHS) Breast Screening Programme aims to detect cancer earlier when treatment is more effective but can harm women by over diagnosing and overtreating cancers which would never have become symptomatic. As well as breast cancer, a spectrum of atypical epithelial proliferations (atypia) can also be detected as part of screening. This spectrum of changes, while not cancer, may mean that a woman is more likely to develop breast cancer in the future. Follow-up of atypia is not evidence based. We currently do not know which atypia should be detected to avoid future cancer. This study will explore how atypia develops into breast cancer in terms of number of women, time of cancer development, cancer type and severity, and whether this varies for different types of atypia. METHODS AND ANALYSIS: The Sloane cohort study began in April 2003 with ongoing data collection including atypia diagnosed through screening at screening units in the UK. The database for England has 3645 cases (24 September 2020) of epithelial atypia, with follow-up from 1 to 15 years. The outcomes include subsequent invasive breast cancer and the nature of subsequent cancer. Descriptive statistics will be produced. The observed rates of breast cancer at 1, 3 and 6 years for types of atypia will be reported with CIs, to enable comparison to women in the general population. Time to event methods will be used to describe the time to breast cancer diagnosis for the types of atypia, including flexible parametric modelling if appropriate. Patient representatives from Independent Cancer Patients' Voice are included at every stage of the research. ETHICS AND DISSEMINATION: The study has received research ethics approval from the University of Warwick Biomedical and Scientific Research Ethics Committee (BSREC 10/20-21, 8 October 2020), Public Health England office for data release approvals (ODR1718_313) and approval from the English Breast Research Advisory Committee (BSPRAC_031). The findings will be disseminated to breast screening clinicians (via journal publication and conference presentation), to the NHS Breast Screening Programme to update their guidelines on how women with atypia should be followed up, and to the general public

Disentangling host, pathogen, and environmental determinants of a recently emerged wildlife disease: lessons from the first 15 years of amphibian chytridiomycosis research

The amphibian fungal disease chytridiomycosis, which affects species across all continents, recently emerged as one of the greatest threats to biodiversity. Yet, many aspects of the basic biology and epidemiology of the pathogen, Batrachochytrium dendrobatidis (Bd), are still unknown, such as when and from where did Bd emerge and what is its true ecological niche? Here, we review the ecology and evolution of Bd in the Americas and highlight controversies that make this disease so enigmatic. We explore factors associated with variance in severity of epizootics focusing on the disease triangle of host susceptibility, pathogen virulence, and environment. Reevaluating the causes of the panzootic is timely given the wealth of data on Bd prevalence across hosts and communities and the recent discoveries suggesting co‐evolutionary potential of hosts and Bd. We generate a new species distribution model for Bd in the Americas based on over 30,000 records and suggest a novel future research agenda. Instead of focusing on pathogen “hot spots,” we need to identify pathogen “cold spots” so that we can better understand what limits the pathogen's distribution. Finally, we introduce the concept of “the Ghost of Epizootics Past” to discuss expected patterns in postepizootic host communities.We review the ecology and evolution of amphibian fungal disease chytridiomycosis in the Americas, where it has recently emerged as one of the greatest threats to biodiversity and highlight controversies that make this disease so enigmatic. We explore factors associated with variance in severity of epizootics focusing on the disease triangle of host susceptibility, pathogen virulence, and environment. We generate a new species distribution model for Bd in the Americas based on over 30,000 records, which suggests emphasis needs to be placed on studying pathogen “cold spots” so that we can better understand what biotic and abiotic factors limit the pathogen's distribution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113682/1/ece31672_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113682/2/ece31672.pd

Long-Term Conditions Questionnaire (LTCQ): initial validation survey among primary care patients and social care recipients in England

Objective: The aim of this study was to validate a new generic patient-reported outcome measure, the Long-Term Conditions Questionnaire (LTCQ), among a diverse sample of health and social care users in England. Design: Cross-sectional validation survey. Data were collected through postal surveys (February 2016 - January 2017). The sample included a health care cohort of patients recruited through primary care practices, and a social care cohort recruited through local government bodies that provide social care services. Participants: 1,211 participants (24% confirmed social care recipients) took part in the study. Health care participants were recruited on the basis of having one of eleven specified LTCs, and social care participants were recruited on the basis of receiving social care support for at least one LTC. The sample exhibited high multi-morbidity, with 93% reporting two or more LTCs and 43% reporting a mental health condition. Outcome measures: The LTCQ’s construct validity was tested with reference to the EQ-5D (5-level version), the Self-efficacy for Managing Chronic Disease scale, an Activities of Daily Living scale, and the Bayliss burden of morbidity scale. Results: Low levels of missing data for each item indicate acceptability of the LTCQ across the sample. The LTCQ exhibits high internal consistency (Cronbach’s α = 0.95) across the scale’s 20 items and excellent test-retest reliability (ICC = 0.94, 95% CI 0.93 to 0.95). Associations between the LTCQ and all reference measures were moderate to strong and in the expected directions, indicating convergent construct validity. Conclusions: This study provides evidence for the reliability and validity of the Long-Term Conditions Questionnaire, which has potential for use in both health and social care settings. The LTCQ could meet a need for holistic outcome measurement that goes beyond symptoms and physical function, complementing existing measures to fully capture what it means to live well with LTCs

Dealing with Alcohol-related problems in the Night-Time Economy: A Study Protocol for Mapping trends in harm and stakeholder views surrounding local community level interventions

<p>Abstract</p> <p>Background</p> <p>This project will provide a comprehensive investigation into the prevalence of alcohol-related harms and community attitudes in the context of community-based interventions being implemented to reduce harm in two regional centres of Australia. While considerable experimentation and innovation to address these harms has occurred in both Geelong and Newcastle, only limited ad-hoc documentation and analysis has been conducted on changes in the prevalence of harm as a consequence, leaving a considerable gap in terms of a systematic, evidence-based analysis of changes in harm over time and the need for further intervention. Similarly, little evidence has been reported regarding the views of key stakeholder groups, industry, government agencies, patrons or community regarding the need for, and the acceptability of, interventions to reduce harms. This project will aim to provide evidence regarding the impact and acceptability of local initiatives aimed at reducing alcohol-related harms.</p> <p>Methods/Design</p> <p>This study will gather existing police data (assault, property damage and drink driving offences), Emergency Department presentations and Ambulance attendance data. Further, the research team will conduct interviews with licensed venue patrons and collect observational data of licensed venues. Key informant interviews will assess expert knowledge from key industry and government stakeholders, and a community survey will assess community experiences and attitudes towards alcohol-related harm and harm-reduction strategies. Overall, the project will assess: the extent of alcohol-related harm in the context of harm-reduction interventions, and the need for and acceptability of further intervention.</p> <p>Discussion</p> <p>These findings will be used to improve evidence-based practice both nationally and internationally.</p> <p>Ethical Approval</p> <p>This project has been approved by Deakin University HREC.</p

Beliefs About Medication and Uptake of Preventive Therapy in Women at Increased Risk of Breast Cancer: Results From a Multicenter Prospective Study

Introduction Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy. Patients and Methods Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis. Results Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036). Conclusion Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making

DACC Resting State Functional Connectivity as a Predictor of Pain Symptoms Following Motor Vehicle Crash: A Preliminary Investigation

There is significant heterogeneity in pain outcomes following motor vehicle crashes (MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain months after injury while others recover. Despite variable outcomes, the pathogenesis of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting state functional magnetic resonance imaging studies find increased functional connectivity (FC) between the dACC and regions involved in pain processing in those with chronic pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore relate to pain severity. The present study completed rsfMRI scans on N=22 survivors of MVCs collected within two weeks of the incident to test whole-brain dACC-FC as a predictor of pain severity six months later. At two weeks, pain symptoms were predicted by positive connectivity between the dACC and the premotor cortex. Controlling for pain symptoms at two weeks, pain symptoms at six months were predicted by negative connectivity between the dACC and the precuneus. Previous research implicates the precuneus in the individual subjective awareness of pain. Given a relatively small sample size, approximately half of which did not experience chronic pain at six months, findings warrant replication. Nevertheless, this study provides preliminary evidence of enhanced dACC connectivity with motor regions and decreased connectivity with pain processing regions as immediate and prospective predictors of pain following MVC. Perspective: This article presents evidence of distinct neural vulnerabilities that predict chronic pain in motor vehicle crash survivors based on whole-brain connectivity with the dorsal anterior cingulate cortex