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The Kilmaluag Formation on the Isle of Skye, Scotland, provides one of the richest Mesozoic vertebrate fossil assemblages in the UK, and is among the richest globally for Middle Jurassic tetrapods. Since its discovery in 1971, this assemblage has predominantly yielded small-bodied tetrapods, including salamanders, choristoderes, lepidosaurs, turtles, crocodylomorphs, pterosaurs, dinosaurs, non-mammalian cynodonts and mammals, alongside abundant fish and invertebrates. It is protected as a Site of Special Scientific Interest and by Nature Conservancy Order. Unlike contemporaneous localities from England, this assemblage yields associated partial skeletons, providing unprecedented new data. We present a comprehensive updated overview of the Kilmaluag Formation, including its geology and the fossil collections made to date, with evidence of several species occurrences presented here for the first time. We place the vertebrate faunal assemblage in an international context through comparisons with relevant contemporaneous localities from the UK, Europe, Africa, Asia and the US. This wealth of material reveals the Kilmaluag Formation as a vertebrate fossil assemblage of global significance, both in terms of understanding Middle Jurassic faunal composition and the completeness of specimens, with implications for the early evolutionary histories of mammals, squamates and amphibians.
Electroconvulsive therapy (ECT) is recommended in treatment guidelines as an efficacious therapy for treatment-resistant depression. However, it has been associated with loss of autobiographical memory and short-term reduction in new learning.
To provide clinically useful guidelines to aid clinicians in informing patients regarding the cognitive side-effects of ECT and in monitoring these during a course of ECT, using complex data.
A Committee of clinical and academic experts from Australia and New Zealand met to the discuss the key issues pertaining to ECT and cognitive side-effects. Evidence regarding cognitive side-effects was reviewed, as was the limited evidence regarding how to monitor them. Both issues were supplemented by the clinical experience of the authors.
Meta-analyses suggest that new learning is impaired immediately following ECT but that group mean scores return at least to baseline by 14 days after ECT. Other cognitive functions are generally unaffected. However, the finding of a mean score that is not reduced from baseline cannot be taken to indicate that impairment, particularly of new learning, cannot occur in individuals, particularly those who are at greater risk. Therefore, monitoring is still important. Evidence suggests that ECT does cause deficits in autobiographical memory. The evidence for schedules of testing to monitor cognitive side-effects is currently limited. We therefore make practical recommendations based on clinical experience.
Despite modern ECT techniques, cognitive side-effects remain an important issue, although their nature and degree remains to be clarified fully. In these circumstances it is useful for clinicians to have guidance regarding what to tell patients and how to monitor these side-effects clinically.
Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer’s disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient’s lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer’s Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.
To examine the association between long-term intake of total and the six classes of dietary flavonoids and decline in cognitive function over a follow-up period of up to 15 years.
In this longitudinal study, we evaluated change in eight cognitive domain scores (verbal and visual memory, verbal learning, attention and concentration, abstract reasoning, language, visuoperceptual organisation and the global function) based on three neuropsychological exams and characterised the annualised change between consecutive exams. Long-term intakes of total and six flavonoid classes were assessed up to four times by a validated FFQ. Repeated-measures regression models were used to examine the longitudinal association between total and six flavonoid classes and annualised change in the eight cognitive domains.
The Framingham Heart Study (FHS), a prospective cohort study.
One thousand seven hundred and seventy-nine subjects who were free of dementia, aged ≥45 years and had attended at least two of the last three FHS Offspring cohort study exams.
Over a median follow-up of 11·8 years with 1779 participants, nominally significant trends towards a slower decline in cognitive function were observed among those with higher flavanol and flavan-3-ol intakes for global function, verbal and visual memory; higher total flavonoids and flavonoid polymers for visual memory; and higher flavanols for verbal learning.
In spite of modest nominal trends, overall, our findings do not support a clear association between higher long-term flavonoid intake and slowing age-related cognitive decline.
Controlling norovirus transmission in units with immunocompromised patients is challenging. We present a cluster of norovirus cases that occurred on a stem-cell transplant unit and the prevention efforts that were implemented to limit the outbreak. Protocols developed to control this cluster may provide a model for other facilities.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
This study used repeated measures data to identify developmental profiles of elevated risk for ADHD (i.e., six or more inattentive and/or hyperactive-impulsive symptoms), with an interest in the age at which ADHD risk first emerged. Risk factors that were measured across the first 3 years of life were used to predict profile membership. Participants included 1,173 children who were drawn from the Family Life Project, an ongoing longitudinal study of children's development in low-income, nonmetropolitan communities. Four heuristic profiles of ADHD risk were identified. Approximately two thirds of children never exhibited elevated risk for ADHD. The remaining children were characterized by early childhood onset and persistent risk (5%), early childhood limited risk (10%), and middle childhood onset risk (19%). Pregnancy and delivery complications and harsh-intrusive caregiving behaviors operated as general risk for all ADHD profiles. Parental history of ADHD was uniquely predictive of early onset and persistent ADHD risk, and low primary caregiver education was uniquely predictive of early childhood limited ADHD risk. Results are discussed with respect to how changes to the age of onset criterion for ADHD in DSM5 may affect etiological research and the need for developmental models of ADHD that inform ADHD symptom persistence and desistance.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
CVD and associated metabolic diseases are linked to chronic inflammation, which can be modified by diet. The objective of the present study was to determine whether there is a difference in inflammatory markers, blood metabolic and lipid panels and lymphocyte gene expression in response to a high-fat dairy food challenge with or without milk fat globule membrane (MFGM). Participants consumed a dairy product-based meal containing whipping cream (WC) high in saturated fat with or without the addition of MFGM, following a 12 h fasting blood draw. Inflammatory markers including IL-6 and C-reactive protein, lipid and metabolic panels and lymphocyte gene expression fold changes were measured using multiplex assays, clinical laboratory services and TaqMan real-time RT-PCR, respectively. Fold changes in gene expression were determined using the Pfaffl method. Response variables were converted into incremental AUC, tested for differences, and corrected for multiple comparisons. The postprandial insulin response was significantly lower following the meal containing MFGM (P < 0·01). The gene encoding soluble epoxide hydrolase (EPHX2) was shown to be more up-regulated in the absence of MFGM (P = 0·009). Secondary analyses showed that participants with higher baseline cholesterol:HDL-cholesterol ratio (Chol:HDL) had a greater reduction in gene expression of cluster of differentiation 14 (CD14) and lymphotoxin β receptor (LTBR) with the WC+MFGM meal. The protein and lipid composition of MFGM is thought to be anti-inflammatory. These exploratory analyses suggest that addition of MFGM to a high-saturated fat meal modifies postprandial insulin response and offers a protective role for those individuals with higher baseline Chol:HDL.
In the current opioid epidemic, identifying high-risk patients among those with substance and opioid use may prevent deaths. The objective of this study was to determine whether frequent emergency department (ED) use and degree of frequent use are associated with mortality among ED patients with substance and opioid use.
This cohort study used linked population-based ED (National Ambulatory Care Reporting System) and mortality data from Alberta. All adults ≥ 18 years with substance or opioid use-related visits based on diagnostic codes from April 1, 2012, to March 31, 2013, were included (n = 16,389). Frequent use was defined by ≥ 5 visits in the previous year. Outcomes were unadjusted and adjusted (for age, sex, income) mortality within 90 days (primary), and 30 days, 365 days, and 2 years (secondary). To examine degree, frequent use was subcategorized into 5–10, 11–15, 16–20, and > 20 visits.
Frequent users were older, lower income, and made lower acuity visits than non-frequent users. Frequent users with substance use had higher mortality at 365 days (hazard ratio [HR] 1.36 [1.04, 1.77]) and 2 years (HR 1.32 [1.04, 1.67]), but not at 90 or 30 days. Mortality did not differ for frequent users with opioid use overall. By degree, patients with substance use and > 20 visits/year and with opioid use and 16–20 visits/year demonstrated a higher 365-day and 2-year mortality.
Among patients with substance use, frequent ED use and extremely frequent use (> 20 visits/year) were associated with long-term but not short-term mortality. These findings suggest a role for targeted screening and preventive intervention.
We aim to evaluate the effect of caloric restriction (CR) in cognition by comparing performance in neuropsychological tests for working memory between a group of non-obese healthy subjects doing CR for 2 years with another consuming ad libitum diet (AL).
This study was part of a larger multicenter trial called CALERIE that consisted of a randomized clinical trial with parallel-group comparing 2 years of 25% CR and AL in 220 volunteers with a BMI between 22 and 28 kg/m2, across 3 sites. The cognitive tests used were the Cambridge Neuropsychological Tests Automated Battery (CANTAB) for Spatial Working Memory (SWM) including the total number of errors (SWMTE) and strategy (SWMS). Included as possible moderators were sleep quality, mood states, perceived stress, and energy expenditure. Analyses were performed at baseline and months 12 and 24.
After adjustments, there was a significantly greater improvement in working memory assessed by the SWM for CR individuals, compared to AL. At month 24, it was related mostly to lower protein intake, compared to other macronutrients. Changes in SWM were moderated by changes in sleep quality, physical activity, and energy expenditure.
On the long term, CR in healthy individuals seems to have a slightly positive effect on working memory. The study of brain CR targets opens new possibilities to prevent and treat cognitive deficits.
To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition.
In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15–28 weeks) and third trimester (28–39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes.
Women were recruited from twelve US sites (2009–2013).
Non-obese women with singleton pregnancies (n 2334).
A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (−0·57 to −0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (−0·05 to 0·06 mm per week).
The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
Field research was conducted in 2012 and 2013 in Georgia, New York, and North Carolina to evaluate the effect of trifluralin PPI on turnip root production. Treatments included trifluralin PPI at 0, 0.42, 0.56, 0.84, 1.12, 1.68, 2.24, and 3.36 kg ai ha−1. Aboveground injury to turnip varied by location and increased from 0% to 85% as trifluralin rate increased from 0.42 to 3.36 kg ha−1. Trifluralin at 0.42 to 0.84 kg ha−1 caused ≤7% injury, except at Clayton, NC, and Freeville, NY, where injury ≤32%. Trifluralin at 0.42 to 0.84 kg ha−1 reduced turnip root yield ≤11% at all locations, except Clinton, NC, where yield was reduced 29% and 43% by 0.56 and 0.84 kg ha−1, respectively. Turnip roots were not injured internally by trifluralin. Our research results suggest that up to 0.84 kg ha−1 trifluralin PPI is safe to use in turnip roots.
Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.