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This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer’s disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.
An issue for generic advertising in agricultural markets with unregulated supplies is that the promotion-induced demand shift could lead to a supply response that substantially attenuates the price effects of the promotion. For the generic promotion of fish exports, however, the concern is generally just the opposite—the possibility that extensive government supply controls could render promotion efforts to expand export sales ineffectual due to little or no supply response. This study considers the effects of government whitefish (cod, haddock, and others) supply controls on the effectiveness of the Norwegian Seafood Council (NSC) whitefish export promotion program. We use an econometric simulation model to measure the effectiveness and returns to NSC whitefish export promotion under a range of possible export supply control conditions. Results indicate that effective supply control maximizes the return to promotion and that ineffectual supply control imposes a potentially large opportunity cost on the promoting industry.
In the 2014 reference, the Supreme Court sought to discover the Senate's “essential nature” in order to determine what reforms parliament could legislate unilaterally. Making use of a classification model found in comparative and historical studies, the Court concluded that the Senate was a “complementary legislative body of sober second thought.” This article re-examines the Court's narrow definition of the Senate's perceived role and presents evidence that its essential characteristics are direct continuations of various pre-Confederation design principles. Limiting a description of its architecture to a single model that eclipses all other roles the Senate may play shifts the debate on Senate reform, which in the recent past has laid emphasis on resolving the conflict among the models embedded in the upper chamber's essential characteristics. The article concludes by reviewing previous constitutional initiatives that aimed at bringing those models more in tune with modern Canada and by making suggestions about how reform proposals could better succeed.
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’.
A diverse Permian crinoid fauna is reported from the Taiyuan Formation, Dajian Member (Asselian) at Anyang, northeastern Henan Province of the North China Craton. The specimens are well preserved, including articulated crowns and cups. The fauna contains representatives of each of the major Paleozoic crinoid clades: Cladida (including the Flexibilia), Disparida, and Camerata. Identified genera suggest a greater affinity with North American faunas than with Tethyan faunas. Four new species, Neoprotencrinus anyangensis, Ulocrinus qiaoi, Artichthyocrinus limani, and Synbathocrinus chenae, are proposed herein.
A 1995 surge of Variegated Glacier, Alaska, USA, is discussed in the context of its six 20th-century predecessors, especially the previous surge in 1982/83 which was studied in detail. The average time between surge initiations is 15 years. The 1995 surge was considerably weaker than its predecessors, having a single phase or at most a very weak second phase. The 1995 surge confirms that there is a seasonal cycle, with surge initiation in winter and termination in the first part of the melt season, and a correlation between weather and both surge termination date and surge extent. Two days of record high temperature correlated with the termination of the 1995 surge. The most obvious issue is the absence of a strong second surge phase (as there was in the 1982/83 surge) culminating in a surge extent more in line with that of the predecessors. This is considered in the light of a simple criterion for surge initiation and re-initiation which depends upon the evolving basal shear stress.
The aim of this study was to determine the factors associated with a feeling of well-being using the Edmonton Symptom Assessment Scale (ESAS)–Feeling of Well-Being item (ESAS–FWB; where 0 = best and 10 = worst) among advanced lung or non-colonic gastrointestinal cancer patients who were referred to an outpatient palliative care clinic (OPCC). We also examined the association of performance on the ESAS–FWB with overall survival (OS).
We reviewed the records of consecutive patients with incurable advanced lung cancer and non-colonic gastrointestinal cancer presenting to an OPCC from 1 January 2008 through to 31 December 2013. Descriptive statistics were employed to summarize patient characteristics. Multivariate regression analysis was used to determine the factors associated with ESAS–FWB severity. We also examined the association of ESAS–FWB scores and survival using Kaplan–Meier survival analysis.
A total of 826 evaluable patients were analyzed (median age = 62 years, 57% male). Median ESAS–FWB scores were five times the interquartile range (5 × IQR; 3–7). ESAS–FWB score was found to be significantly associated with ESAS fatigue (OR = 2.31, p < 0.001); anxiety (OR = 1.98, p < 0.001); anorexia (OR = 2.31, p < 0.001); cut down, annoyed, guilty, eye opener (CAGE) score (hazard ratio [HR] = 1.80, p = 0.008); and family caregiver distress (HR = 1.93, p = 0.002). A worse ESAS–FWB score was significantly associated with decreased OS (r = –0.18, p < 0.001). However, ESAS–FWB score was not independently associated with OS in the final multivariate model (p = 0.35), which included known major clinical prognostic factors.
Worse ESAS–FWB scores were significantly associated with high scores on ESAS fatigue, anorexia, anxiety, CAGE, and family caregiver distress. More research is necessary to understand how palliative care interventions are capable of improving the contributory factors related to ESAS–FWB score.
Johns Hopkins has been a leader in paediatric cardiology for over 85 years. In the 1940s, Dr Helen Taussig began training fellows in paediatric cardiology at Johns Hopkins at a time when the diagnosis and treatment of CHD were in the earliest stage. Under her leadership, the fellowship developed a strong foundation that has continued to evolve to meet the current needs of learners and educators. In the current era, the Johns Hopkins programme implements the current theories of adult education and actively engages our fellows in learning as well as teaching. The programme uses techniques such as flipped classroom, structured case-based small-group learning, observed and structured clinical examination, simulations, and innovative educational technology. These strategies combined with our faculty and rich history give our fellows a unique educational experience.
Objectives: To examine the effect of pre-injury alcohol use, acute alcohol intoxication, and post-injury alcohol use on outcome from mild to moderate traumatic brain injury (TBI). Methods: Prospective inception cohort of patients who presented to the Emergency Department with mild to moderate TBI and had a blood alcohol level (BAL) taken for clinical purposes. Those who completed the 1-year outcome assessment were eligible for this study (N=91). Outcomes of interest were the count of post-concussion symptoms (British Columbia Post-Concussion Symptom Inventory), low neuropsychological test scores (Neuropsychological Assessment Battery), and abnormal regions of interest on diffusion tensor imaging (low fractional anisotropy). The main predictors were pre-injury alcohol consumption (Cognitive Lifetime Drinking History interview), BAL, and post-injury alcohol use. Results: The alcohol use variables were moderately to strongly inter-correlated. None of the alcohol use variables (whether continuous or categorical) were related to 1-year TBI outcomes in generalized linear modeling. Participants in this cohort generally had a good clinical outcome, regardless of their pre-, peri-, and post-injury alcohol use. Conclusions: Alcohol may not significantly alter long-term outcome from mild to moderate TBI. (JINS, 2016, 22, 816–827)
Archaeologists working in the Salish Sea (Strait of Georgia and Puget Sound)
region of the Pacific Northwest have unearthed human burials and
non-mortuary features dated to 4000–3500 cal B.P. containing tens and even
hundreds of thousands of stone and shell disc beads. Several sites are
reported here, including burials recently excavated from site DjRw–14
located in the territory of the shíshálh Nation. We argue that the disc
beads constituted an important form of material wealth at this time, based
on the amount of labor that would have been required to produce them and the
capacity for beads to accrue in value after their production. A model of
material wealth-based inequality is developed for a period much older than
many archaeologists working in the region have previously thought.
Evaluations of generic advertising programs by commodity check-off programs involve analyses of counterfactual scenarios in which advertising and promotion expenditures are set to zero over the program's history. In actual practice, the counterfactual is rarely realized. We present a case in which such a natural experiment occurred when generic advertising and promotion expenditures for U.S. orange juice were cut nearly to zero. Using structural econometric and autoregression models, we estimate losses in consumption and sales revenue and examine the time required for the market for orange juice to recover from the check-off's strategy of going nearly dark.
Regular assessments of spiritual distress/spiritual pain among patients in a supportive/palliative care clinic (SCPC) are limited or unavailable. We modified the Edmonton Symptom Assessment Scale (ESAS) by adding spiritual pain (SP) to the scale (0 = best, 10 = worst) to determine the frequency, intensity, and correlates of self-reported SP (≥1/10) (pain deep in your soul/being that is not physical) among these advanced cancer patients.
We reviewed 292 consecutive consults of advanced cancer patients (ACPs) who were evaluated at our SCPC between October of 2012 and January of 2013. Symptoms were assessed using the new instrument (termed the ESAS–FS).
The median age of patients was 61 (range = 22–92). Some 53% were male; 189 (65%) were white, 45 (15%) African American, and 34 (12%) Hispanic. Some 123 of 282 (44%) of ACPs had SP (mean (95% CI) = 4(3.5–4.4). Advanced cancer patients with SP had worse pain [mean (95% CI) = 5.3(4.8, 5.8) vs. 4.5(4.0, 5.0)] (p = 0.02); depression [4.2(3.7, 4.7) vs. 2.1(1.7, 2.6), p < 0.0001]; anxiety [4.2(3.6, 4.7) vs. 2.5(2.0, 3.0), p < 0.0001]; drowsiness [4.2(3.7, 4.7) vs. 2.8(2.3, 3.2), p < 0.0001]; well-being [5.4(4.9, 5.8) vs. 4.5(4.1, 4.9), p = 0.0136]; and financial distress (FD) [4.4(3.9, 5.0) vs. 2.2(1.8, 2.7), p < 0.0001]. Spiritual pain correlated (Spearman) with depression (r = 0.45, p < 0.0001), anxiety (r = 0.34, p < 0.0001), drowsiness (r = 0.26, p < 0.0001), and FD (r = 0.44, p < 0.0001). Multivariate analysis showed an association with FD [OR (95% Wald CI) = 1.204(1.104–1.313), p < 0.0001] and depression [1.218(1.110–1.336), p < 0.0001]. The odds that patients who had SP at baseline would also have SP at follow-up were 182% higher (OR = 2.82) than for patients who were SP-negative at baseline (p = 0.0029). SP at follow-up correlated with depression (r = 0.35, p < 0.0001), anxiety (r = 0.25, p = 0.001), well-being (r = 0.27, p = 0.0006), nausea (r = 0.29, p = 0.0002), and financial distress (r = 0.42, p < 0.0001).
Significance of results:
Spiritual pain, which is correlated with physical and psychological distress, was reported in more than 40% of ACPs. Employment of the ESAS–FS allows ACPs with SP to be identified and evaluated in an SCPC. More research is needed.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Many naturally occurring and man-made plasmas are collisionless and turbulent. It is not yet well understood how the energy in fields and fluid motions is transferred into the thermal degrees of freedom of constituent particles in such systems. The debate at present primarily concerns proton heating. Multiple possible heating mechanisms have been proposed over the past few decades, including cyclotron damping, Landau damping, heating at intermittent structures and stochastic heating. Recently, a community-driven effort was proposed (Parashar & Salem, 2013, arXiv:1303.0204) to bring the community together and understand the relative contributions of these processes under given conditions. In this paper, we propose the first step of this challenge: a set of problems and diagnostics for benchmarking and comparing different types of 2.5D simulations. These comparisons will provide insights into the strengths and limitations of different types of numerical simulations and will help guide subsequent stages of the challenge.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
The potential influence of patient religious and spiritual beliefs on the approach to end-of-life care and resuscitation status preferences is not well understood. The aim of this study was to assess the association between religiosity and resuscitation preferences in advanced-cancer patients.
We performed a secondary analysis of a randomized controlled trial that evaluated the influence of physician communication style on patient resuscitation preferences. All patients completed the Santa Clara Strength of Religious Faith Questionnaire–Short Form (SCSRFQ–SF) and expressed their resuscitation preferences. We determined the frequency of resuscitation preferences and its association with intensity of religiosity.
A total of 78 patients completed the study. The median age was 54 years, with a range of 18–78. Some 46 (59%) were women; 57 patients (73%) were Caucasian, 15 (19%) African American, and 5 (7%) Hispanic. A total of 46 patients (56%) were Protestant and 13 (17%) Catholic. Some 53 of 60 patients who chose Do Not Resuscitate status (DNR) (88%) and 16 of 18 patients who refused DNR (89%) for a video-simulated patient were highly religious (p = 0.64). When asked about a DNR for themselves after watching the videos, 43 of 48 who refused DNR (90%) and 26 of 30 patients who chose DNR (87%) were highly religious (p = 0.08). The Spearman correlation coefficient for patients choosing DNR for themselves and intensity of religiosity was r = –0.16 (p = 0.16). Some 30 patients (38%) who chose DNR for the video patient refused DNR for themselves, and 42 who chose DNR for both the video patient and themselves (54%) were highly religious (p = NS).
Significance of Results:
There was no significant association between intensity of patient religiosity and DNR preference for either the video patient or the patients themselves. Other beliefs and demographic factors likely impact end-of-life discussions and resuscitation status preferences.