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Identify risk factors for central line-associated bloodstream infections (CLABSI) in pediatric intensive care settings in an era with high focus on prevention measures.
Design:
Matched, case–control study.
Setting:
Quaternary children’s hospital.
Patients:
Cases had a CLABSI during an intensive care unit (ICU) stay between January 1, 2015 and December 31, 2020. Controls were matched 4:1 by ICU and admission date and did not develop a CLABSI.
Methods:
Multivariable, mixed-effects logistic regression.
Results:
129 cases were matched to 516 controls. Central venous catheter (CVC) maintenance bundle compliance was >70%. Independent CLABSI risk factors included administration of continuous non-opioid sedative (adjusted odds ratio (aOR) 2.96, 95% CI [1.16, 7.52], P = 0.023), number of days with one or more CVC in place (aOR 1.42 per 10 days [1.16, 1.74], P = 0.001), and the combination of a chronic CVC with administration of parenteral nutrition (aOR 4.82 [1.38, 16.9], P = 0.014). Variables independently associated with lower odds of CLABSI included CVC location in an upper extremity (aOR 0.16 [0.05, 0.55], P = 0.004); non-tunneled CVC (aOR 0.17 [0.04, 0.63], P = 0.008); presence of an endotracheal tube (aOR 0.21 [0.08, 0.6], P = 0.004), Foley catheter (aOR 0.3 [0.13, 0.68], P = 0.004); transport to radiology (aOR 0.31 [0.1, 0.94], P = 0.039); continuous neuromuscular blockade (aOR 0.29 [0.1, 0.86], P = 0.025); and administration of histamine H2 blocking medications (aOR 0.17 [0.06, 0.48], P = 0.001).
Conclusions:
Pediatric intensive care patients with chronic CVCs receiving parenteral nutrition, those on non-opioid sedative infusions, and those with more central line days are at increased risk for CLABSI despite current prevention measures.
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
Methods
Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
Results
Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
Conclusions
Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
This paper explores the feasibility of a break-even-class mirror referred to as BEAM (break-even axisymmetric mirror): a neutral-beam-heated simple mirror capable of thermonuclear-grade parameters and $Q\sim 1$ conditions. Compared with earlier mirror experiments in the 1980s, BEAM would have: higher-energy neutral beams, a larger and denser plasma at higher magnetic field, both an edge and a core and capabilities to address both magnetohydrodynamic and kinetic stability of the simple mirror in higher-temperature plasmas. Axisymmetry and high-field magnets make this possible at a modest scale enabling a short development time and lower capital cost. Such a $Q\sim 1$ configuration will be useful as a fusion technology development platform, in which tritium handling, materials and blankets can be tested in a real fusion environment, and as a base for development of higher-$Q$ mirrors.
Dietary patterns (DP) rich in plant foods are associated with improved health and reduced non-communicable disease risk. In October 2021, the Nutrition Society hosted a member-led conference, held online over 2 half days, exploring the latest research findings examining plant-rich DP and health. The aim of the present paper is to summarise the content of the conference and synopses of the individual speaker presentations are included. Topics included epidemiological analysis of plant-rich DP and health outcomes, the effects of dietary interventions which have increased fruit and vegetable (FV) intake on a range of health outcomes, how adherence to plant-rich DP is assessed, the use of biomarkers to assess FV intake and a consideration of how modifying behaviour towards increased FV intake could impact environmental outcomes, planetary health and food systems. In conclusion, although there are still considerable uncertainties which require further research, which were considered as part of the conference and are summarised in this review, adopting a plant-rich DP at a population level could have a considerable impact on diet and health outcomes, as well as planetary health.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
Shade coffee is a well-studied cultivation strategy that creates habitat for tropical birds while also maintaining agricultural yield. Although there is a general consensus that shade coffee is more “bird-friendly” than a sun coffee monoculture, little work has investigated the effects of specific shade tree species on insectivorous bird diversity. This study involved avian foraging observations, mist-netting data, temperature loggers, and arthropod sampling to investigate bottom-up effects of two shade tree taxa - native Cordia sp. and introduced Grevillea robusta - on insectivorous bird communities in central Kenya. Results indicate that foliage-dwelling arthropod abundance, and the richness and overall abundance of foraging birds were all higher on Cordia than on Grevillea. Furthermore, multivariate analyses of the bird community indicate a significant difference in community composition between the canopies of the two tree species, though the communities of birds using the coffee understorey under these shade trees were similar. In addition, both shade trees buffered temperatures in coffee, and temperatures under Cordia were marginally cooler than under Grevillea. These results suggest that native Cordia trees on East African shade coffee farms may be better at mitigating habitat loss and attracting insectivorous birds that could promote ecosystem services. Identifying differences in prey abundance and preferences in bird foraging behaviour not only fills basic gaps in our understanding of the ecology of East African coffee farms, it also aids in developing region-specific information to optimize functional diversity, ecosystem services, and the conservation of birds in agricultural landscapes.
To examine the association between adherence to plant-based diets and mortality.
Design:
Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods.
Setting:
The VA Million Veteran Program.
Participants:
315 919 men and women aged 19–104 years who completed a FFQ at the baseline.
Results:
We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, Ptrend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, Ptrend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, Ptrend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.
Conclusions:
A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.
Through laboratory experiments and numerical simulations, we examine the evolution of buoyant plumes as they are influenced by background rotation in a uniform density ambient fluid. The source Rossby number is sufficiently large that rotation does not directly affect the plume at early times. However, on a time scale of the order of half a rotation period, the plume becomes deflected from the vertical axis. For some experiments and simulations, the deflection persists and the flow precesses about the vertical axis. In other cases, shortly after being deflected, the plume laminarizes near the source to form a near-vertical columnar vortex, which we refer to as a ‘tornado’. Tornado formation occurs in some experiments and not in others even if the source and background rotation parameters are identical. However, their formation is more likely if the plumes are ‘lazy’. Simulations reveal that this is a consequence of the competing dynamics that occurs on comparable time scales. As a consequence of entrainment, vertical vorticity builds up within the plume reducing the Rossby number and suppressing vertical motion at distances progressively closer to the source. Meanwhile, the swirl (the ratio of the azimuthal to vertical flow) around the vicinity of the source increases, which tends to suppress three-dimensional turbulence in the near-source flow. Although the former process ultimately acts to deflect the plume off axis, in some instances, the swirl around the source succeeds in laminarizing the flow, resulting in tornado formation.
Clinical trials are a fundamental tool in evaluating the safety and efficacy of new drugs, medical devices, and health system interventions. Clinical trial visits generally involve eligibility assessment, enrollment, intervention administration, data collection, and follow-up, with many of these steps performed during face-to-face visits between participants and the investigative team. Social distancing, which emerged as one of the mainstay strategies for reducing the spread of SARS-CoV-2, has presented a challenge to the traditional model of clinical trial conduct, causing many research teams to halt all in-person contacts except for life-saving research. Nonetheless, clinical research has continued during the pandemic because study teams adapted quickly, turning to virtual visits and other similar methods to complete critical research activities. The purpose of this special communication is to document this rapid transition to virtual methodologies at Clinical and Translational Science Awards hubs and highlight important considerations for future development. Looking beyond the pandemic, we envision that a hybrid approach, which implements remote activities when feasible but also maintains in-person activities as necessary, will be adopted more widely for clinical trials. There will always be a need for in-person aspects of clinical research, but future study designs will need to incorporate remote capabilities.
This chapter comprises the following sections: names, taxonomy, subspecies and distribution, descriptive notes, habitat, movements and home range, activity patterns, feeding ecology, reproduction and growth, behavior, parasites and diseases, status in the wild, and status in captivity.
Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.
Methods
Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.
Results
No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.
Conclusions
The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.
To measure fatty acid composition, particularly whole-blood PUFA content, in acutely malnourished children and identify associations with markers of nutritional and health status.
Design:
PUFA were assessed in dried blood spots obtained from a cross-sectional study. Nutritional and health status were assessed by anthropometry, haemoglobinopathies, inflammation and blood counts.
Setting:
Cambodia.
Participants:
The study was conducted with 174 children aged 0·5–18 years with acute malnutrition.
Results:
Among total fatty acids (FA), the relative percentage of total PUFA was 20 % FA, with 14 % of the children having very low PUFA (mead acid (MA):arachidonic acid (AA) >0·02, n-6 docosapentaenoic acid:DHA >0·2 and total n-6:n-3 PUFA >10·5). Wasting was not associated with any PUFA. Stunting and low height were consistently positively associated with total PUFA and positively with n-6 PUFA. Height was positively associated with n-3 long-chain PUFA (LCPUFA). The presence of haemoglobinopathies or inflammation was positively associated with MA:AA, but not total PUFA. Elevated blood platelet counts were positively correlated with linoleic acid and appeared to be influenced by anaemia (P = 0·010) and inflammation (P = 0·002). Monocyte counts were high during inflammation (P = 0·052) and correlated positively with n-6 LCPUFA and n-3 LCPUFA.
Conclusions:
Children with acute malnutrition or stunting had low PUFA, while elevated platelets and monocytes were associated with high PUFA. In acutely malnourished children, inflammation could lead to elevated blood cell counts resulting in increased whole-blood PUFA which does not reflect dietary intake or nutritional status.
A clean hot-water drill was used to gain access to Subglacial Lake Whillans (SLW) in late January 2013 as part of the Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project. Over 3 days, we deployed an array of scientific tools through the SLW borehole: a downhole camera, a conductivity–temperature–depth (CTD) probe, a Niskin water sampler, an in situ filtration unit, three different sediment corers, a geothermal probe and a geophysical sensor string. Our observations confirm the existence of a subglacial water reservoir whose presence was previously inferred from satellite altimetry and surface geophysics. Subglacial water is about two orders of magnitude less saline than sea water (0.37–0.41 psu vs 35 psu) and two orders of magnitude more saline than pure drill meltwater (<0.002 psu). It reaches a minimum temperature of –0.55~C, consistent with depression of the freezing point by 7.019 MPa of water pressure. Subglacial water was turbid and remained turbid following filtration through 0.45 µm filters. The recovered sediment cores, which sampled down to 0.8 m below the lake bottom, contained a macroscopically structureless diamicton with shear strength between 2 and 6 kPa. Our main operational recommendation for future subglacial access through water-filled boreholes is to supply enough heat to the top of the borehole to keep it from freezing.
The ways in which productivity, stability, population interactions, and community structure are regulated in ecosystems have been a central focus of ecology for over a century. At large spatial scales, major insights into these dynamics have been principally derived from analyses of changes induced from hunting, harvesting, and agricultural practices – so-called “natural experiments.” In terrestrial ecosystems estimates of the fraction of land transformed or degraded by human activity fall within the range of 39 to 75% (Vitousek et al., 1997; Ellis et al., 2010). Equally profound is the reality that up to 75% of the global oceans and in particular the continental shelf, transitional slope water areas, and reef habitats have been strongly impacted by human activity (Halpern et al., 2008).
One of the most widely studied human impacts has been the over-exploitation of large-bodied species. Berger et al. (2001) estimated that the spatial distribution of large mammalian carnivores that once played a dominant role in terrestrial ecosystems has declined by 95–99%. In the global oceans large predatory fish biomass may be as low as 10% of pre-industrial levels (Myers and Worm, 2003). These changes have created a vertical compaction and blunting of the trophic pyramid (Duffy, 2003; Chapter 14, this volume). On a global scale, these losses are attributable to a positive association between body size and sensitivity to population declines experienced by larger species which exhibit a greater susceptibility to decline or collapse as a consequence of their lower population densities, greater times to maturity, lower clutch sizes, and larger home ranges (Schipper et al., 2008). This reduction in the abundance of apex predators has led to abnormally high densities of their former prey in a wide range of ecosystems, which has, in turn, resulted in sometimes catastrophic changes in the ecosystems occupied. This has led some to conclude that large-bodied species are essential to the maintenance of ecosystem structure and stability (Hildrew et al., 2007; Estes et al., 2011).