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Badgers are an important reservoir of bovine TB in the UK. We discuss how the combination of individual epidemiological data, tracking studies and modelling frameworks enabled exploration of host–pathogen theories in relation to badger life history and disease ecology, focusing on heterogeneity in host susceptibility and infectiousness, two components of the superspreader phenotype. Studies pairing empirical data with modelling approaches suggest sex differences are underpinned by immunological mechanisms. We discuss how studies have moved away from the simplistic assumption of randomly mixing homogeneous populations towards recognition of heterogeneity in host association patterns at group, class and individual levels. Interactions between individuals are non-random with high within-group contacts and lower between-group contact rates. Contact heterogeneity is fundamental to understanding what drives/restricts the spatial spread of disease through a population. We explore a demographic perspective on disease ecology, showing how demographic intricacies provide further understanding of the mechanisms underpinning persistence of infected badger populations. The understanding gained from longitudinal studies of host–pathogen field systems is important ecological and epidemiological theory development and informs evidence-based disease control strategies’ development.
Recent European studies suggest that fathers’ leave-taking may contribute to parental relationship stability. Paternity leave-taking may signal a commitment by fathers toward a greater investment in family life, which may reduce the burden on mothers and strengthen parental relationships. This study uses longitudinal data from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) to analyze the association between paternity leave-taking and relationship stability in the United States. Results indicate that paternity leave-taking, and taking relatively short leaves (i.e. two weeks or less) in particular, is associated with greater relationship stability. These findings increase our understanding of the potential benefits of paternity leave, and can inform policy decisions that aim to increase family stability.
Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.
Design, setting, participants, and measurements:
We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.
Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.
These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
Sexually reproducing pathogens such as Cyclospora cayetanensis often produce genetically heterogeneous infections where the number of unique sequence types detected at any given locus varies depending on which locus is sequenced. The genotypes assigned to these infections quickly become complex when additional loci are analysed. This genetic heterogeneity confounds the utility of traditional sequence-typing and phylogenetic approaches for aiding epidemiological trace-back, and requires new methods to address this complexity. Here, we describe an ensemble of two similarity-based classification algorithms, including a Bayesian and heuristic component that infer the relatedness of C. cayetanensis infections. The ensemble requires a set of haplotypes as input and assigns arbitrary distances to specimen pairs reflecting their most likely relationships. The approach was applied to data generated from a test cohort of 88 human fecal specimens containing C. cayetanensis, including 30 from patients whose infections were associated with epidemiologically defined outbreak clusters of cyclosporiasis. The ensemble assigned specimens to plausible clusters of genetically related infections despite their complex haplotype composition. These relationships were corroborated by a significant number of epidemiological linkages (P < 0.0001) suggesting the ensemble's utility for aiding epidemiological trace-back investigations of cyclosporiasis.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Functional gastrointestinal disorders including constipation affect up to 14 % of the world's population. Treatment is difficult and challenging resulting in a need for alternative safe and effective therapies. The present study investigated whether daily consumption of three gold-fleshed kiwifruit could alleviate constipation and improve gastrointestinal discomfort in mildly constipated individuals with and without pain. A total of thirty-two participants were enrolled in a 16-week randomised, single-blind, crossover study. Participants received either three ‘Zesy002’ kiwifruit or 14·75 g Metamucil® (5 g dietary fibre/d (a positive control)) for 4 weeks each with a 4-week washout between treatments. A 2-week washout period was included at the beginning and end of the study. Daily bowel habit diaries were kept throughout the study. The primary outcome measure was differences in the number of complete spontaneous bowel movements (CSBM). Secondary outcome measures were bowel movement frequency and stool form as well as digestive symptoms and comfort. The number of CSBM per week was significantly greater during daily consumption of three kiwifruit compared with the baseline (6·3 v. 3·3; P < 0·05) and the Metamucil® treatment (6·3 v. 4·5; P < 0·05). Stool consistency was also improved, with kiwifruit producing softer stools and less straining (P < 0·05). Gastrointestinal discomfort was also improved compared with baseline for abdominal pain, constipation and indigestion (P < 0·05) during the kiwifruit intervention and constipation during the Metamucil® intervention (P < 0·05). This randomised controlled trial demonstrates that daily consumption of three gold-fleshed kiwifruit is associated with a significant increase of two CSBM per week and reduction in gastrointestinal discomfort in mildly constipated adults.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.
Cougar Mountain Cave is located in Oregon's Fort Rock Basin. In 1958, avocationalist John Cowles excavated most of the cave's deposits and recovered abundant fiber, lithic, wood, and osseous artifacts. A crew from the University of California, Davis returned to the site in 1966 to evaluate the potential for further research, collecting additional lithic and fiber artifacts from disturbed deposits and in situ charcoal from apparently undisturbed deposits. Because Cowles took few notes or photographs, the Cougar Mountain Cave collection—most of which is housed at the Favell Museum in Klamath Falls, Oregon—has largely gone unstudied even though it contains diagnostic artifacts spanning the Holocene and, potentially, the terminal Pleistocene. We recently submitted charcoal and basketry from the site for radiocarbon dating, providing the first reliable sense of when Cougar Mountain Cave was first occupied. Our results indicate at least a Younger Dryas age for initial occupation. The directly dated basketry has provided new information about the age ranges and spatial distributions of diagnostic textile types in the northwestern Great Basin.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
The x-ray energy emitted from laser-produced plasmas has been measured under various experimental conditions. Two Nd-glass lasers were used in separate experiments to focus pulsed laser light on planar targets. X-ray fluences were measured with newly developed silicon detector calorimeters. Results for various experimental conditions are reported in terms of the efficiency with which the laser light was converted to x-ray energy by plasma production.
Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.
A point-prevalence study of antimicrobial use among inpatients at 5 public hospitals in Sri Lanka revealed that 54.6% were receiving antimicrobials: 43.1% in medical wards, 68.0% in surgical wards, and 97.6% in intensive care wards. Amoxicillin-clavulanate was most commonly used for major indications. Among patients receiving antimicrobials, 31.0% received potentially inappropriate therapy.
Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)