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Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.
Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.
More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.
Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Identifying options for the sustainable intensification of cropping systems in southern Africa under prevailing high climate risk is needed. With this in mind, we tested an intercropping system that combined the staple crop maize with lablab, a local but underutilised legume. Grain and biomass productivity was determined for four variants (i) sole maize (sole-maize), (ii) sole lablab (sole-lablab), (iii) maize/lablab with both crops sown simultaneously (intercropped-SP) and (iv) maize/lablab with lablab sown 28 days after the maize crop (intercropped-DP). Soil water and weather data were monitored and evaluated. The trial was conducted for two seasons (2015/2016 and 2016/2017) at two sites in the Limpopo Province, South Africa: Univen (847 mm rainfall, 29.2 °C maximum and 18.9 °C minimum temperature average for the cropping season over the years 2008–2017) and Syferkuil (491 mm rainfall, with 27.0 °C maximum and 14.8 °C minimum temperature). Analysis revealed three key results: The treatment with intercropped-SP had significantly lower maize yields (2320 kg ha−1) compared with maize in intercropped-DP (2865 kg ha−1) or sole-maize (2623 kg ha−1). As expected, maize yields in the El Niño affected in season 2015/2016 were on average 1688 kg ha−1 lower than in 2016/2017. Maize yields were significantly lower (957 kg ha−1) at Univen, the warmer site with higher rainfall, than at Syferkuil. In 2015/2016, maximum temperature at Univen exceeded 40 °C around anthesis. Furthermore, soil water was close to the estimated permanent wilting point (PWP) for most of the cropping season, which indicates possible water limitations. In Syferkuil, the soil water was maintained well above PWP. Lablab yields were low, around 500 ha−1, but stable as they were not affected by treatment across season and site. Overall, the study demonstrated that intercropped-DP appears to use available soil water more efficiently than sole maize. Intercropped-DP could therefore be considered as an option for sustainable intensification under high climate risk and resource-limited conditions for smallholders in southern Africa.
Introduction: Little is known about the variety of roles volunteers play in the emergency department (ED), and the potential impact they have on patient experience. The objective of this scoping review was to identify published and unpublished reports that described volunteer programs in EDs, and determine how these programs impacted patient experiences or outcomes. Methods: Electronic searches of Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and CINAHL were conducted and reference lists were hand-searched. A grey literature search was also conducted (Web of Science, ProQuest, Canadian Business and Current Affairs Database ProQuest Dissertations and Theses Global). Two reviewers independently screened titles and abstracts, reviewed full text articles, and extracted data. Results: The search strategy yielded 4,589 potentially relevant citations. After eliminating duplicate citations and articles that did not meet eligibility criteria, 87 reports were included in the review. Of the included reports, 18 were peer-reviewed articles, 6 were conference proceedings, 59 were magazine or newspaper articles, and 4 were graduate dissertations or theses. Volunteer activities were categorized as non-clinical tasks (e.g., provision of meals/snacks, comfort items and mobility assistance), navigation, emotional support/communication, and administrative duties. 52 (59.8%) programs had general volunteers in the ED and 35 (40.2%) had volunteers targeting a specific patient population, including pediatrics, geriatrics, patients with mental health and addiction issues and other vulnerable populations. 20 (23.0%) programs included an evaluative component describing how ED volunteers affected patient experiences and outcomes. Patient satisfaction, follow-up and referral rates, ED and hospital costs and length of stay, subsequent ED visits, medical complications, and malnutrition in the hospital were all reported to be positively affected by volunteers in the ED. Conclusion: This scoping review demonstrates the important role volunteers play in enhancing patient and caregiver experience in the ED. Future volunteer engagement programs implemented in the ED should be formally described and evaluated to share their success and experience with others interested in implementing similar programs in the ED.
A common property regime was established at the founding of the Maya site of Actuncan, Belize, in the Terminal Preclassic period (175 BC–AD 300), which governed access to land until the Terminal Classic period (AD 780–1000). This interpretation is based on urban settlement patterns documented through household excavation and remote-sensing programs. Excavations of all visible patio-focused groups in the urban core provided data to reconstruct residential histories, and a 60,621 m2 gradiometer survey resulted in a magnetic gradient map that was used to document buried constructions. Twenty ground-truth testpits correlated types of magnetic signatures to buried patio-focused groups and smaller constructions, including walled plots in agricultural field systems that were later exposed more fully through large-scale excavations. Combined, these methods provided data to reconstruct four correlates of land tenure systems: (1) the spatial proximity of residential units to land and resources, (2) diachronic changes in community settlement patterns, (3) land subdivision and improvements, and (4) public goods. Spatial analyses documented that houselots did not cluster through time, but instead became gradually improved, lending evidence to suggest the transgenerational inheritance of property rights in the Late and Terminal Classic periods.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
Farmers’ market interventions are a popular strategy for addressing chronic disease disparities in low-income neighbourhoods. With limited resources, strategic targeting of interventions is critical. The present study used spatial analysis to identify where market interventions have the greatest impact on healthy food access within a geographic region.
All farmers’ markets in a mixed urban/rural county were mapped and those that accepted Supplemental Nutrition Assistance Program (SNAP) electronic benefit transfer (EBT) cards identified. Households were grouped into small neighbourhoods and mapped. The area of ‘reasonable access’ around each market (walking distance (0·8 km; 0·5mile) in urban areas, driving distance (15 min) in rural areas) was calculated using spatial analysis. The percentage of county low-income households within a market’s access area, and the percentage of county SNAP-participating households within an EBT-accepting market’s access area, were calculated. The ten neighbourhoods with the most low-income households and with the most SNAP-participating households were then identified, their access areas calculated and mapped, and those lacking access identified. County-level gains resulting from improving market accessibility in these areas were calculated.
Honolulu County, Hawaii, USA.
Only 44 % of SNAP-participating households had EBT-market access. Six of the ten highest SNAP-participant neighbourhoods lacked access. Improving access for these neighbourhoods increased county-level access by 23 %. Market access for low-income households was 74 %. Adding markets to these low-income neighbourhoods without market access increased county-level access by 4 %.
Geographic identification of market access demographics, and strategic targeting of EBT interventions, could improve regional access to healthy foods.
Serial spherical linkages have been used in the design of a number of robots for minimally invasive surgery, in order to mechanically constrain the surgical instrument with respect to the incision. However, the typical serial spherical mechanism suffers from conflicting design objectives, resulting in an unsuitable compromise between avoiding collision with the patient and producing good kinematic and workspace characteristics. In this paper, we propose a multi-robot system composed of two redundant serial spherical linkages to achieve this purpose. A multi-objective optimization for achieving the aforementioned design goals is presented first for a single redundant robot and then for a multi-robot system. The problem of mounting multiple robots on the operating table as well as the way cooperative actions can be performed is addressed. The sensitivity of each optimal solution (single-robot and multi-robot) to uncertainties in the design parameters is investigated.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences.
Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project.
The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [rG = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females.
Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.
Australian tea tree oil (TTO) and its extract terpinen-4-ol (T4O) are found to be effective in moderating demodex-related diseases. Their possible effects are lowering the mite counts, relieving the demodex-related symptoms and modulating the immune system especially the inflammatory response. This review summarizes the topical treatments of TTO and T4O in human demodicosis, their possible mechanism of actions, side-effects and potential resistance in treating this condition. Although current treatments other than TTO and T4O are relatively effective in controlling the demodex mite population and the related symptoms, more research on the efficacy and drug delivery technology is needed in order to assess its potential as an alternative treatment with minimal side-effect profile, low toxicity and low risk of demodex resistance.
The purpose of this study was to investigate the 10-year impact of Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along with contributing risk factors and any alteration in chronobiology of AMI.
A single-center, retrospective, comparison study of AMI incidence was performed at Tulane University Health Sciences Center from 2 years before Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and 10-year, post-Katrina cohort were also compared according to pre-specified demographic, clinical, and chronobiological data.
AMI incidence increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001). The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs. 47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2% vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non-adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%, P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8% vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001).
Even 10 years after the storm, Hurricane Katrina continues to be associated with increased incidence of AMI, higher prevalence of traditional cardiovascular and psychosocial risk factors, and an altered chronobiology of AMI toward nights and weekends. (Disaster Med Public Health Preparedness. 2019;13:217–222)
The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use.
A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype.
Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency.
There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.