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Intracranial aneurysm (IA) is an expansion of the weakened arterial wall that is often asymptomatic until rupture, resulting in subarachnoid hemorrhage. Here we describe the high prevalence of familial IA in a cohort of Newfoundland ancestry. We began to investigate the genetic etiology of IA in affected family members, as the inheritance of this disease is poorly understood.
Whole exome sequencing was completed for a cohort of 12 affected individuals from two multiplex families with a strong family history of IA. A filtering strategy was implemented to identify rare, shared variants. Filtered variants were prioritized based on validation by Sanger sequencing and segregation within the families.
In family R1352, six variants passed filtering; while in family R1256, 68 variants remained, so further filtering was pursued. Following validation by Sanger sequencing, top candidates were investigated in a set of population controls, namely, C4orf6 c.A1G (p.M1V) and SPDYE4c.C103T (p.P35S). Neither was detected in 100 Newfoundland control samples.
Rare and potentially deleterious variants were identified in both families, though incomplete segregation was identified for all filtered variants. Alternate methods of variant prioritization and broader considerations regarding the interplay of genetic and environmental factors are necessary in future studies of this disease.
Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49–81 years (mean 63·6 (sd 7·4) years) from the Women’s Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture’s Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.
The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12–23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.
To characterize the current state of Canadian emergency medicine (EM) resident research and develop recommendations to promote excellence in this area.
We performed a systematic review of MEDLINE, Embase, and ERIC using search terms relevant to EM resident research. We conducted an online survey of EM residency program directors from the Royal College of Physicians and Surgeons of Canada (RCPSC) and College of Family Physicians of Canada (CFPC). An expert panel reviewed these data, presented recommendations at the Canadian Association of Emergency Physicians 2014 Academic Symposium, and refined them based on feedback received.
Of 654 potentially relevant citations, 35 articles were included. These were categorized into four themes: 1) expectations and requirements, 2) training and assessment, 3) infrastructure and support, and 4) dissemination. We received 31 responses from all 31 RCPSC-EM and CFPC-EM programs. The majority of EM programs reported requiring a resident scholarly project; however, we found wide-ranging expectations for the type of resident research performed and how results were disseminated, as well as the degree of completion expected. Although 93% of RCPSC-EM programs reported providing formal training on how to conduct research, only 53% of CFPC-EM programs reported doing so. Almost all programs (94%) reported having infrastructure in place to support resident research, but the nature of support was highly variable. Finally, there was marked variability regarding the number of resident-published abstracts and manuscripts.
Based on the literature, our national survey, and discussions with stakeholders, we offer 14 recommendations encompassing goals, expectations, training, assessment, infrastructure, and dissemination in order to improve Canadian EM resident research.
In recent decades there has been an increase in opportunities for people to view wildlife in tourism settings such as wildlife tours, national parks and captive environments such as zoos. This in turn has provided increasing opportunities to educate people of all ages about the value of wildlife and their habitats. One concept useful for enhancing learning is that of mindfulness. This concept suggests characteristics of interpretation that attract and sustain the focused attention of visitors. Using open-ended descriptions of best wildlife experiences from 790 respondents, this study found that 84% of descriptions contained at least one element consistent with the mindfulness concept. This paper argues that a mindfulness model can be used to understand visitor responses to wildlife tourism and direct the design of experiences that enhance learning and enjoyment.
Background: Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis. Aims: To investigate schemas over time in a large sample of CHR individuals and healthy controls. Method: Sample included 765 CHR participants and 280 healthy controls. Schemas were assessed at baseline, 6 and 12 months using the Brief Core Schema Scale (BCSS). Baseline schemas were compared to 2-year clinical outcome. Results: CHR participants evidenced stable and more maladaptive schemas over time compared to controls. Schemas at initial contact did not vary amongst the different clinical outcome groups at 2 years although all CHR outcome groups evidenced significantly worse schemas than healthy controls. Although there were no differences on baseline schemas between those who later transitioned to psychosis compared to those who did not, those who transitioned to psychosis had more maladaptive negative self-schemas at the time of transition. Associations between negative schemas were positively correlated with earlier abuse and bullying. Conclusions: These findings demonstrate a need for interventions that aim to improve maladaptive schemas among the CHR population. Therapies targeting self-esteem, as well as schema therapy may be important work for future studies.
Aspects of eudaimonic well-being, such as personal growth (PG) and purpose in life (PL), have been highlighted as important to older adults’ health. We investigated the relationship of PG and PL with patterns of survival to the age of 85 years and older.
The sample included 8,880 women from the Women's Health Initiative cohort who reached 85 years of age by December 1, 2013, and for whom data on the PG and PL constructs were available. Women were classified into mutually exclusive outcomes: Healthy, Prevalent, Incident, Disabled, and Deceased. PG and PL were each assessed using a modified seven-item measure derived from the Psychological Well-Being scale.
Women were most commonly classified as Healthy (38.2%, n = 3,395), followed by Incident (24.4%, n = 2,163), Disabled (19.0%, n = 1,685), Prevalent (14.3%, 1,273), and Deceased (4.1%, n = 364). Women with low PL and PG levels were more likely to have prevalent mobility disability and disease or incident death before the age of 85 years. Specifically, those who reported low levels of PG and PL had a 2.1- and 3.6-fold higher risk, respectively, of death.
These findings indicate that even among the oldest old, experience of purposeful life engagement and continuing PG may contribute to better health outcomes.
The purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics.
Women age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories.
A five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories.
Aging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.
Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study—I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon–Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention.
Background: The extent to which care home residents with severe dementia show awareness is influenced by the extent to which the environment provides opportunities for engagement and by the way in which care staff interact with them. We aimed to establish whether training care staff to observe and identify signs of awareness in residents with severe dementia resulted in improved quality of life for residents.
Methods: In this pilot cluster randomized trial, care staff in four homes (n = 32) received training and supervision and carried out structured observations of residents using the AwareCare measure (n = 32) over an eight-week period, while staff in four control homes (n = 33) had no training with regard to their residents (n = 33) and no contact with the research team. The primary outcome was resident quality of life. Secondary outcomes were resident well-being, behavior and cognition, staff attitudes and well-being, and care practices in the home.
Results: Following intervention, residents in the intervention group had significantly better quality of life as rated by family members than those in the control group, but care staff ratings of quality of life did not differ. There were no other significant between-group differences. Staff participating in the intervention identified benefits in terms of their understanding of residents’ needs.
Conclusions: Staff were able to use the observational measure effectively and relatives of residents in the intervention homes perceived an improvement in their quality of life.
This study set out to determine the efficacy of a school-based early intervention program (the Kiwi ACE program) with Māori and Pacific adolescents experiencing depressive symptoms. A large group (N = 419) of Māori and Pacific students (average age 14 years) was screened for depressive symptoms and, from a pool of students scoring greater than 63 on the Children's Depression Inventory (CDI), 56 students were randomly assigned to either an intervention or control group. After attrition, the final sample constituted 24 young people after one year. The intervention comprised eight 90-minute sessions conducted in school time. Students were taught to more fully understand the relationships between thinking, feeling and behaviour, to challenge beliefs and to solve interpersonal problems. At immediate posttest (p = .045) and at one-year follow-up (p < .001) a significant effect for condition was obtained: the intervention group reported lower depressive symptoms. Efficacy of the intervention was supported by qualitative data obtained from focus groups. Further controlled trials on a larger scale are recommended to establish the durability and generalisability of the effects of program participation.
Heterogeneous nucleation and crystal growth on protein substrates are critical steps in biological hard tissue formation. Self assembled monolayers can be derivatized with various organic functional groups to mimic the “nucleation proteins” for induction of mineral growth. Studies of nucleation and growth on SAMs can provide a better understanding of biomineralization and can also form the basis of a superior thin film deposition process. We demonstrate that micron-scale, electron and ion beam, lithographic techniques can be used to pattern SAMs with functional organic groups that either inhibit or promote mineral deposition. Patterned films of iron oxyhydroxide were deposited on the areas patterned with nucleation sites. Studies of the deposition kinetic of these films show that the surface indeed induces heterogeneous nucleation and that film formation does not occur via absorption of polymers or colloidal material formed homogeneously in solution. The nucleus interfacial free energy was calculated to be 88 mJ/m2 on a SAM surface composed entirely of sulfonate groups.
Research studies for the treatment of the putative prodromal phase of
psychotic disorders have begun to appear
To obtain preliminary evidence of the short-term efficacy and safety of
aripiprazole treatment in people with the psychosis prodrome
Fifteen participants meeting prodrome criteria (mean age 17.1 years,
s.d.=5.5) enrolled in an open-label, single-site trial with
fixed-flexible dosing of aripiprazole (5–30 mg/day) for 8 weeks
In the mixed-effects repeated-measures analysis, improvement from
baseline on the Scale of Prodromal Symptoms total score was statistically
significant by the first week. No participant converted to psychosis and
13 completed treatment. Neuropsychological measures showed no consistent
improvement; mean weight gain was 1.2 kg. Akathisia emerged in 8
participants, but the mean Barnes Akathisia Scale score fell to baseline
levels by the final visit. Adverse events were otherwise minimal
Aripiprazole shows a promising efficacy and safety profile for the
psychosis prodrome. Placebo-controlled studies are indicated