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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.
Introduction: Emergency department (ED) staff carry a high risk for the burnout syndrome of increased emotional exhaustion, depersonalization and decreased personal accomplishment. Previous research has shown that task-oriented coping skills were associated with reduced levels of burnout compared to emotion-oriented coping. ED staff at one hospital participated in an intervention to teach task-oriented coping skills. We hypothesized that the intervention would alter staff coping behaviors and ultimately reduce burnout. Methods: ED physicians, nurses and support staff at two regional hospitals were surveyed using the Maslach Burnout Inventory (MBI) and the Coping Inventory for Stressful Situations (CISS). Surveys were performed before and after the implementation of communication and conflict resolution skills training at the intervention facility (I) consisting of a one-day course and a small group refresher 6 to 15 months later. Descriptive statistics and multivariate analysis assessed differences in staff burnout and coping styles compared to the control facility (C) and over time. Results: 85/143 (I) and 42/110 (C) ED staff responded to the initial survey. Post intervention 46 (I) and 23(C) responded. During the two year study period there was no statistically significant difference in CISS or MBI scores between hospitals (CISS: (Pillai's trace = .02, F(3,63) = .47, p = .71, partial η2 = .02); MBI: (Pillai's trace = .01, F(3,63) = .11, p = .95, partial η2 = .01)) or between pre- and post-intervention groups (CISS: (Pillai's trace = .01, F(3,63) = .22, p = .88, partial η2 = .01); MBI: (Pillai's trace = .09, F(3,63) = 2.15, p = .10, partial η2 = .01)). Conclusion: We were not able to measure improvement in staff coping or burnout in ED staff receiving communication skills intervention over a two year period. Burnout is a multifactorial problem and environmental rather than individual factors may be more important to address. Alternatively, to demonstrate a measurable effect on burnout may require more robust or inclusive interventions.
Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04–6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.
In the behavioral sciences, it is common to explain behavior in terms of what was learned in a task, as if any subsequent change in performance had to denote a change in learning. However, learning alone cannot account for variability in performance. Instead, incentive motivation plays a direct role (and is more effective) in controlling moment-to-moment changes in an individual's responses than the learning process. After briefly introducing the history of the study of incentive motivation, we explain that incentive motivation consists of a dopamine-dependent process that does not require consciousness to influence responding to a task. We analyze two Pavlovian situations in which incentive motivation can modulate performance, irrespective of additional learning: the instant transformation of disgust into attraction for salt and the invigoration of responses under reward uncertainty. Finally, we consider drug addiction as an example of motivational dysregulation rather than as a consequence of the habit to consume substances of abuse.
The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1·4), Asian (OR = 2·3), or Black (OR = 1·7), and more likely to live in an urban area (OR = 1·2), report international travel (OR = 1·5), and have infection in autumn or winter (OR = 1·2). Campylobacter upsaliensis patients were more likely female (OR = 1·6), Hispanic (OR = 1·6), have a blood isolate (OR = 2·8), and have an infection in autumn or winter (OR = 1·7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2·9) and have an infection in autumn or winter (OR = 1·7). Campylobacter fetus patients were more likely male (OR = 3·1), hospitalized (OR = 3·5), and have a blood isolate (OR = 44·1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12·5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.
To investigate an outbreak of Pseudomonas aeruginosa infections and colonization in a neonatal intensive care unit.
Infection control assessment, environmental evaluation, and case-control study.
Newly built community-based hospital, 28-bed neonatal intensive care unit.
Neonatal intensive care unit patients receiving care between June 1, 2013, and September 30, 2014.
Case finding was performed through microbiology record review. Infection control observations, interviews, and environmental assessment were performed. A matched case-control study was conducted to identify risk factors for P. aeruginosa infection. Patient and environmental isolates were collected for pulsed-field gel electrophoresis to determine strain relatedness.
In total, 31 cases were identified. Case clusters were temporally associated with absence of point-of-use filters on faucets in patient rooms. After adjusting for gestational age, case patients were more likely to have been in a room without a point-of-use filter (odds ratio [OR], 37.55; 95% confidence interval [CI], 7.16–∞). Case patients had higher odds of exposure to peripherally inserted central catheters (OR, 7.20; 95% CI, 1.75–37.30) and invasive ventilation (OR, 5.79; 95% CI, 1.39–30.62). Of 42 environmental samples, 28 (67%) grew P. aeruginosa. Isolates from the 2 most recent case patients were indistinguishable by pulsed-field gel electrophoresis from water-related samples obtained from these case-patient rooms.
This outbreak was attributed to contaminated water. Interruption of the outbreak with point-of-use filters provided a short-term solution; however, eradication of P. aeruginosa in water and fixtures was necessary to protect patients. This outbreak highlights the importance of understanding the risks of stagnant water in healthcare facilities.
Following the detection of the 9 cm ground-state triplet of CH by Rydbeck et al. (1973), preliminary observations at the CH frequencies were made with the Parkes 64-m telescope (beamwidth ∼6′ arc) in December 1973 and January 1974. We have detected the CH lines in many galactic HII regions and in the direction of the galactic centre.
The infection status of angiostrongylosis in Jamaica was assessed in wild rats and molluscs in the 5 years following the major outbreak of eosinophilic meningitis (EM) in 2000. Parasitological analyses of 297 Rattus rattus and 140 Rattus norvegicus, and 777 terrestrial molluscs from all 14 Parishes on the island revealed Angiostrongylus cantonensis in 32·0% of the rats and in 12·5% of the molluscs. Multivariate analyses confirmed that A. cantonensis occurred significantly more frequently in R. rattus (Odds Ratio [OR] = 1·76), while mean infection intensity in R. rattus was also significantly higher (16·8) than R. norvegicus (11·3) (Mann–Whitney U-test: P = 0·01). Third-stage larvae of A. cantonensis were detected in 29% of 86 Pleurodonte spp.; in 20% of five Poteria spp.; in 18·7% of 369 Thelidomus asper; in 11% of 18 Sagda spp.; and in 6% of 24 veronicellid slugs. Most rodent infections occurred in Northeastern Jamaica (OR = 11·66), a region where infected molluscs were also abundant. Given the prevalence of A. cantonensis infection in rats has significantly increased since the 2000 outbreak, and that a survey of human infections revealed at least ten autochthonous cases in the last 15 years, angiostrongylosis persists as an important zoonosis in Jamaica.
Trypanosomes are blood-borne parasites that can cause severe disease in both humans and animals, yet little is known of the pathogenicity and life-cycles of trypanosomes in native Australian mammals. Trypanosoma copemani is known to be infective to a variety of Australian marsupials and has recently been shown to be potentially zoonotic as it is resistant to normal human serum. In the present study, in vivo and in vitro examination of blood and cultures from Australian marsupials was conducted using light microscopy, immunofluorescence, scanning electron microscopy and fluorescence in situ hybridization. Promastigote, sphaeromastigote and amastigote life-cycle stages were detected in vivo and in vitro. Novel trypanosome-like stages were also detected both in vivo and in vitro representing an oval stage, an extremely thin stage, an adherent stage and a tiny round stage. The tiny round and adherent stages appeared to adhere to erythrocytes causing potential haematological damage with clinical effects similar to haemolytic anaemia. The present study shows for the first time that trypomastigotes are not the only life-cycle stages circulating within the blood stream of trypanosome infected Australian native marsupials and provides insights into possible pathogenic mechanisms of this potentially zoonotic trypanosome species.
We examine the roles of actuaries in UK life offices, along with trends, challenges to and opportunities for actuaries. We carry out an analysis of senior roles in life offices, a questionnaire survey and interviews with relevant senior personnel. We find that actuaries occupy many important roles in life offices and are regarded as having good industry knowledge and technical skills, especially in financial modelling. There are fewer executive directors and more non-executive directors of life offices who are actuaries compared with the position in 1990. A higher proportion of reserved roles is outsourced to consultants than was the case in 1990. Only a small number of Actuarial Function Holders are directors. Actuaries are more siloed than was the case in the past, although actuaries are well represented in the finance and risk functions of many offices. Although actuarial work in connection with the preparation for Solvency II will decline, there will be important ongoing requirements for actuaries following Solvency II implementation. We also see opportunities for actuaries in four areas: in risk management, in financial analysis and management based on Solvency II and international financial reporting standards, in connection with “big data”, and in product development and the customer proposition. There are implications for the examination syllabus, continuing professional development and research.
Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and postnatal influences. Dentition patterns were recorded at ages 1 and 2 years in 2915 children born to women in the Southampton Women’s Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages 1 and 2 years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age 2 years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child’s primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity.
The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:
1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.
2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.
We studied the effect of a cross-conjugated bridging group (χC) on charge-transfer in a push-pull chromophore system. The hyperpolarizability of such molecules was found to be comparable to that of a fully π-conjugated molecule (πC) with the same donor and acceptor. The cross-conjugated moiety was then applied as a pendant to a fully π-conjugated chromophore containing a tricyanopyrroline acceptor (TCP). The addition of a χC moiety did not alter the intrinsic hyperpolarizability and provides an avenue for extending and aiding πC systems. The molecules were examined by X-ray diffraction (XRD), hyper-Raleigh scattering (HRS) and UV-visible (UV-vis) spectroscopy. Experimental results were compared with the predictions of density functional theory (DFT). Cross-conjugated molecules have comparable β values, relative to πC molecules, due to reduced spatial overlap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Thus, the χC architecture could facilitate independent modification of donor and acceptor strengths while minimizing unfavorable effects on electronic transitions and dipole moments.
The use of organic nonlinear optical (ONLO) materials in electro-optic (EO) modulators requires that the active molecular components (chromophores) be acentrically oriented. The fundamental molecular constituents are in a condensed, glassy phase. Molecular orientation in such systems is typically achieved by applying a DC poling field to the glassy material. We are developing efficient coarse-grained classical Monte Carlo (MC) methods to simulate the order of such systems. The most challenging aspects of these simulations are convergence to an experimentally relevant equilibrium ensemble and verification of simulation accuracy. We use a variety of molecular descriptions and a variety of MC methods to achieve proper order in the shortest number of computational cycles possible. Herein, we illustrate a few examples of the types of calculations and compare with experimental results with representative amorphous organic materials, including electro-optic chromophores.