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To determine associations of alcohol use with cognitive aging among middle-aged men.
Method:
1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003–2007 to 2016–2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1–4 drinks in past 14 days), light (5–14 drinks), moderate (15–28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.
Results:
Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by –0.21 SD (95% CI –0.35, –0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, –0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.
Conclusions:
Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.
Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.
Alzheimer’s disease (AD) is highly heritable, and AD polygenic risk scores (AD-PRSs) have been derived from genome-wide association studies. However, the nature of genetic influences very early in the disease process is still not well known. Here we tested the hypothesis that an AD-PRSs would be associated with changes in episodic memory and executive function across late midlife in men who were cognitively unimpaired at their baseline midlife assessment..
Method:
We examined 1168 men in the Vietnam Era Twin Study of Aging (VETSA) who were cognitively normal (CN) at their first of up to three assessments across 12 years (mean ages 56, 62, and 68). Latent growth models of episodic memory and executive function were based on 6–7 tests/subtests. AD-PRSs were based on Kunkle et al. (Nature Genetics, 51, 414–430, 2019), p < 5×10−8 threshold.
Results:
AD-PRSs were correlated with linear slopes of change for both cognitive abilities. Men with higher AD-PRSs had steeper declines in both memory (r = −.19, 95% CI [−.35, −.03]) and executive functioning (r = −.27, 95% CI [−.49, −.05]). Associations appeared driven by a combination of APOE and non-APOE genetic influences.
Conclusions:
Memory is most characteristically impaired in AD, but executive functions are one of the first cognitive abilities to decline in midlife in normal aging. This study is among the first to demonstrate that this early decline also relates to AD genetic influences, even in men CN at baseline.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
Methods
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Results
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
Conclusions
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
Background: Inappropriate ordering of urine cultures and the resulting unnecessary use of antibiotics can lead to complications of antimicrobial therapy including resistance, adverse effects (eg, disruption of microbiome and C. difficile infection), and increased healthcare costs, as well as the erroneous determination of CAUTI in patients with Foley catheters. A retrospective analysis of patients with CAUTI revealed frequent ordering of urine cultures for conditions and symptoms not supported by current IDSA guidelines. As a result, we created an action plan to reverse the trend of inappropriate urine culture ordering. Methods: Our urine culture reduction campaign was developed with input from the infectious disease service, antibiotic stewardship team (AST), infection prevention, pharmacy, and the microbiology service. The following educational efforts were included: (1) distribution of outpatient pocket cards with communication to providers about appropriate ordering of urine cultures; (2) creation of an evidence-based order set for urinalysis and urine cultures distributed electronically as emails and screensavers on computer stations and in person via didactic sessions with physicians and nursing staff; (3) a practice pointer for staff nurses that included recommended changes to urine culture ordering and encouraged open dialogue with physicians regarding the appropriateness of urine cultures; (4) didactic and personal communications to counter long-standing myths, such as “Urine cultures always for change in mental status”; (5) a peer-review process to evaluate and justify deviations from the testing algorithm.
Results: The first and second months after the introduction of the campaign, the microbiology laboratory reported 23% and 37% reductions in urine cultures ordered, respectively. During the same period, a 48% reduction in CAUTIs was reported for the entire health system. Conclusions: Reducing the number of inappropriate urine cultures is achievable with intense communication utilizing a multifaceted approach. With continued educational activities, we expect to sustain and even improve our successful reduction of inappropriate urine culture orders, ultimately improving patient outcomes.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.
This collection of essays has threaded several lines of argument through and around the topic of autoexoticism. With Minyan Sun we saw how an exoticizing gaze can develop the feedback loop of autoexoticism when the self recognizes its investment in the other and subjects itself to its own desiring attention. Daniele Nunziata and Naomi Charlotte Fukuzawa both traced further complexities of identity that cross the self-other boundary in colonial Cyprus and between Britain and Japan. Peter Hill, Kasia Szymanska, and Valentina Gosetti all explored the tactical potential of autoexotic elements in a politics of representation, in locations as diverse as Syria, Poland, and Flanders. With Adriana Jacobs we found autoexoticism in recent Hebrew poetry to be a “transcreative and relational” imaginative practice. Finally, Xiaofan Amy Li argued that autoexoticism opens “the boundaries of one's subjectivity and culture to change and rupture,” creating “a holistic field of intercultural experience” where “what is considered self and other are transient and plastic,” since they are drawn into an intercultural practice that “consciously selects and re-creates elements and aspects from disparate cultures and identities.” As these accounts reveal, there can be much that is attractive in autoexoticist styles of being, of self-representation, and of encounter. They are formally and linguistically mobile. They have a strong affective charge, provoking reactions of amusement, embarrassment, or outrage. They are courageous, since they run the risk of being dismissed as mere exoticism. And they can loosen established identities, opening them to change.
Whispering gallery modes (WGMs) have been widely studied over the past 20 years for various applications, including biological sensing. While the WGM-based sensing approaches reported in the literature have shown tremendous performance down to single molecule detection, at present such sensing technologies are not yet mature and still have significant practical constraints that limit their use in real-world applications. Our work has focused on developing a practical, yet effective, WGM-based sensing platform capable of being used as a dip sensor for in-vivo biosensing by combining WGM fluorescent microresonators with silica Microstructured Optical Fibers (MOFs).
We recently demonstrated that a suspended core MOF with a dye-doped polymer microresonator supporting WGMs positioned onto the tip of the fiber, can be used as a dip sensor. In this architecture the resonator is anchored to one of the MOF air holes, in contact with the fiber core, enabling a significant portion of the evanescent field from the fiber to overlap with the sphere and hence excite the fluorescent WGMs. This architecture allows for remote excitation and collection of the WGMs. The fiber also permits easy manipulation of the microresonator for dip sensing applications, and hence alleviates the need for a complex microfluidic interface. More importantly, it allows for an increase in both the excitation and collection efficiency compared to free space coupling, and also improves the Q factor.
In this paper we present our recent results on microstructured fiber tip WGM-based sensors and show that this sensing platform can be used in clinical diagnostics, for detecting various clinically relevant biomarkers in complex clinical samples.
Orf virus has a worldwide distribution among sheep and goats. The hypersensitivity reaction erythema multiforme (EM) is a known complication of orf infection in humans; however, its occurrence is poorly understood and has not been extensively reviewed. We present two unrelated cases of orf-associated EM, and a review of the literature, highlighting important clinical, epidemiological and immunological aspects of this condition. Orf and its associated complications can occur in rural areas, as well as urban settings, where it is less well-known, through religious or cultural practices involving animal slaughter. Obtaining a history of animal exposures from patients with lesions suspicious for orf and secondary skin eruptions can guide diagnosis and identification of the inciting immune stimulus. Determining the pathophysiology and relative contribution of host and viral factors contributing to EM and other orf-associated hypersensitivity reactions could facilitate the identification of risk factors and inform treatment decisions.
A main concern of farmers worldwide is how to reduce crop losses to wildlife. Some potentially lethal crop protection methods are non-selective. It is important to understand the impact of such methods on species of conservation concern. Uganda has important populations of Endangered eastern chimpanzees Pan troglodytes schweinfurthii. Farmers sometimes use large metal mantraps to guard their fields against crop-raiding wildlife, particularly baboons Papio anubis and wild pigs Potamochoerus sp.. Chimpanzees that range onto farmland also step in these illegal devices and without rapid veterinary invention face severe injury or eventual death. Unlike inadvertent snaring of great apes in African forests, the problem of mantraps in forest–farm ecotones has received little attention. We report 10 cases of entrapped chimpanzees in the cultivated landscape surrounding Uganda's Budongo Forest during 2007–2011, undoubtedly only a portion of the actual number of cases. Mantraps currently present a substantial threat to ape populations in this important conservation landscape. Our data underscore the need for conservation programmes to consider the techniques used by rural farmers to protect their livelihoods from wild animals.
This book traces the emergence of religious factionalism within an urban community, from Elizabeth's reign until the outbreak of the English Civil War, focusing upon early modern England's second city, Norwich, but placing it in the context of England as a whole. Typically, Tudor and Stuart Norwich has been viewed as a centre of radical puritanism, but through careful study of its rich municipal archive as well as hitherto untapped diocesan and parochial material, the author offers a more rounded account of Norwich's religious life, which considers the appearance of groups at odds with the godly. The first section explores how and why the Reformation flourished in Norwich. Later chapters address the fortunes of the city's puritan movement in relation to successive anti-Calvinist bishops - notably Samuel Harsnett and Matthew Wren - and their local allies [both clerical and lay] during the 1620s and 30s. Reacting to godly complaint, Norwich's anti-puritan tradition evolved into something approaching 'civic Laudianism' in borough affairs under Charles I.
In this chapter, we consider space-time coding strategies for multiple-relay cooperative systems that effectively harness available spatial diversity. More specifically, the goal is to examine ways to forward signals efficiently from multiple relays to the destination while addressing the important practical issue of synchronization among the relays. We assume a general two-phase transmission protocol as illustrated in Figure 6.1. In the first phase of the protocol, the source broadcasts a message which is received by the relays and (possibly) the destination. During the second transmission phase, a subset of the relays, possibly in conjunction with the source, transmits additional information to the destination. This protocol is useful in practical scenarios where signals received at the destination due to transmissions directly from the source (Phase 1) will not carry enough useful information because of noise, fading, and/or interference.
It is expected that Phase 2 will dramatically increase the reliability of the system, but if the symbols cannot be decoded correctly after the second phase, the protocol can restart by returning to Phase 1 or Phase 2.
The primary problem associated with forwarding information from multiple relays to the destination is determining how the information should be spread out among the relays over space and time. This is analogous to the classic spacetime coding problem in point-to-point multiple-transmit-antenna systems, and so it is often called the distributed space-time coding problem.