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Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.
Alteplase is an effective treatment for ischaemic stroke patients, and it is widely available at all primary stroke centres. The effectiveness of alteplase is highly time-dependent. Large tertiary centres have reported significant improvements in their door-to-needle (DTN) times. However, these same improvements have not been reported at community hospitals.
Red Deer Regional Hospital Centre (RDRHC) is a community hospital of 370 beds that serves approximately 150,000 people in their acute stroke catchment area. The RDRHC participated in a provincial DTN improvement initiative, and implemented a streamlined algorithm for the treatment of stroke patients. During this intervention period, they implemented the following changes: early alert of an incoming acute stroke patient to the neurologist and care team, meeting the patient immediately upon arrival, parallel work processes, keeping the patient on the Emergency Medical Service stretcher to the CT scanner, and administering alteplase in the imaging area. Door-to-needle data were collected from July 2007 to December 2017.
A total of 289 patients were treated from July 2007 to December 2017. In the pre-intervention period, 165 patients received alteplase and the median DTN time was 77 minutes [interquartile range (IQR): 60–103 minutes]; in the post-intervention period, 104 patients received alteplase and the median DTN time was 30 minutes (IQR: 22–42 minutes) (p < 0.001). The annual number of patients that received alteplase increased from 9 to 29 in the pre-intervention period to annual numbers of 41 to 63 patients in the post-intervention period.
Community hospitals staffed with community neurologists can achieve median DTN times of 30 minutes or less.
Nearly 800,000 primary hip and knee arthroplasty procedures are performed annually in North America. Approximately 1% of these are complicated by a complex surgical site infection (SSI), leading to very high healthcare costs. However, population-based studies to properly estimate the economic burden are lacking. We aimed to address this knowledge gap.
Economic burden study.
Using administrative health and clinical databases, we created a cohort of all patients in Alberta, Canada, who received a primary hip or knee arthroplasty between April 1, 2012, and March 31, 2015. All patients who developed a complex SSI postoperatively were identified through a provincial infection prevention and control database. A combination of corporate microcosting data and gross costing methods were used to determine total mean 12- and 24-month costs, enabling comparison of costs between the infected and noninfected patients.
Mean 12-month total costs were significantly greater in patients who developed a complex SSI compared to those who did not (CAD$95,321 [US$68,150] vs CAD$19,893 [US$14,223]; P < .001). The magnitude of the cost difference persisted even after controlling for underlying patient factors. The most commonly identified causative pathogen (38%) was Staphylococcus aureus (95% MSSA).
Complex SSIs following hip and knee arthroplasty lead to high healthcare costs, which are expected to rise as the yearly number of surgeries increases. Using our costing estimates, the cost-effectiveness of different strategies to prevent SSIs should be investigated.
The Latino population in the United States is rapidly growing and faces profound health disparities; however, engagement of Latinos in biomedical research remains low. Our community-based participatory research partnership has recruited 2083 Spanish-speaking Latinos into 21 studies over 15 years. We sought to identify and describe the strategies we have used to successfully recruit and retain Spanish-speaking Latinos in research.
We abstracted and analyzed data from archived study notes, progress reports, team meeting minutes, and in-depth interviews conducted annually from community-based participatory research partnership members. We used a nominal group process to refine and prioritize strategies.
Overall, 13 recruitment strategies and 12 retention strategies emerged. These strategies relied on the creativity and perseverance of the study team and partners.
It is essential that we develop and disseminate effective recruitment and retention strategies that engage Latinos in biomedical research to reduce health disparities and promote health equity.
The objective of this study was to examine the association between dietary inflammatory potential and memory and cognitive functioning among a representative sample of the US older adult population. Cross-sectional data from the 2011–2012 and 2013–2014 National Health and Nutrition Examination Survey were utilised to identify an aggregate sample of adults 60–85 years of age (n 1723). Dietary inflammatory index (DII®) scores were calculated using 24-h dietary recall interviews. Three memory-related assessments were employed, including the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) Word Learning subset, the Animal Fluency test and the Digit Symbol Substitution Test (DSST). Inverse associations were observed between DII scores and the different memory parameters. Episodic memory (CERAD) (badjusted=−0·39; 95 % CI −0·79, 0·00), semantic-based memory (Animal Fluency Test) (badjusted=−1·18; 95 % CI −2·17, −0·20) and executive function and working-memory (DSST) (badjusted=−2·80; 95 % CI −5·58, −0·02) performances were lowest among those with the highest mean DII score. Though inverse relationships were observed between DII scores and memory and cognitive functioning, future work is needed to further explore the neurobiological mechanisms underlying the complex relationship between inflammation-related dietary behaviour and memory and cognition.
Molecular studies have shown the type collection of Omphalina oreades to be conspecific with a small brown basidiolichen from the Appalachian range in Newfoundland, both with 4-spored basidia. Two sequences deposited in GenBank, originally identified as O. grisella, fell in the same clade. Sequences of the type collection of Omphalia grisella, with 2-spored basidia, formed a sister clade together with two GenBank deposits, one identified as O. grisella and the other as Omphalina velutina. Omphalina oreades is recombined here as Lichenomphalia oreades comb. nov., and the species redescribed and illustrated. Sequences of the internal transcribed spacer regions of nuclear ribosomal DNA (ITS rDNA) from the algae associated with two collections of L. oreades fell within a highly supported clade with members of an undetermined species of Coccomyxa. The most abundant algal ribosomal large subunit sequence from granules at the base of a different collection matched GenBank sequences identified as Chloroidium ellipsoideum, which is probably either a free-living algal species or a partner to a species of Trapeliopsis. The second most abundant sequence matched Coccomyxa subellipsoidea and is the most likely photobiont of L. oreades. Further studies are required to elucidate the relationship of L. velutina to these taxa.
Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.
The current project seeks to integrate literatures on personality risk for antisocial behavior (ASB) by examining how callous–unemotional traits relate to (a) the development of disinhibited traits and (b) the association between disinhibited traits and ASB. In Study 1, using a nationally representative sample of youth (N > 7,000), we examined whether conduct problems and lack of guilt assessed during ages 4–10 years predicted levels of and changes in disinhibited traits over the course of adolescence, and moderated associations between these traits and ASB. High levels of childhood conduct problems were associated with higher levels of impulsivity, sensation seeking, and ASB in early adolescence, whereas lack of guilt was associated with lower levels of sensation seeking. Neither conduct problems nor lack of guilt significantly predicted changes in impulsivity or sensation seeking, and associations among changes in sensation seeking, impulsivity, and ASB were also consistent across levels of conduct problems and lack of guilt. In Study 2, using a cross-sectional sample of adolescents (N = 970), we tested whether callous–unemotional traits moderated associations between disinhibited traits and ASB. Consistent with the results of Study 1, associations between disinhibited personality and ASB were consistent across a continuous range of callous–unemotional traits.
Cortisol is the primary output of the hypothalamic–pituitary–adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function.
In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80–19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type.
Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone.
Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.
Background: Stroke patients of lower socioeconomic status have worse outcomes. It remains poorly understood whether this is due to illness severity or personal or health system barriers. We explored the experiences of stroke patients with financial barriers in a qualitative descriptive pilot study, seeking to capture perceived challenges that interfere with their poststroke health and recovery. Methods: We interviewed six adults with a history of stroke and financial barriers in Alberta, Canada, inquiring about their: (1) experiences after stroke; (2) experience of financial barriers; (3) perceived reasons for financial barriers; (4) health consequences of financial barriers; and (5) mechanisms for coping with financial barriers. Two reviewers analyzed data using inductive thematic analysis. Results: The participants developed new or worsened financial circumstances as a consequence of stroke-related disability. Poststroke impairments and financial barriers took a toll on their mental health. They struggled to access several aspects of long-term poststroke care, including allied health professional services, medications, and proper nutrition. They described opportunity costs and tradeoffs when accessing health services. In several cases, they were unaware of health resources available to them and were hesitant to disclose their struggles to their physicians and even their families. Conclusion: Some patients with financial barriers perceive challenges to accessing various aspects of poststroke care. They may have inadequate knowledge of resources available to them and may not disclose their concerns to their health care team. This suggests that providers themselves might consider asking stroke patients about financial barriers to optimize their long-term poststroke care.
Observational evidence suggests that increased whole grain (WG) intake reduces the risks of many non-communicable diseases, such as CVD, type 2 diabetes, obesity and certain cancers. More recently, studies have shown that WG intake lowers all-cause and cause-specific mortality. Much of the reported evidence on risk reduction is from US and Scandinavian populations, where there are tangible WG dietary recommendations. At present there is no quantity-specific WG dietary recommendation in the UK, instead we are advised to choose WG or higher fibre versions. Despite recognition of WG as an important component of a healthy diet, monitoring of WG intake in the UK has been poor, with the latest intake assessment from data collected in 2000–2001 for adults and in 1997 for children. To update this information we examined WG intake in the National Diet and Nutrition Survey rolling programme 2008–2011 after developing our database of WG food composition, a key resource in determining WG intake accurately. The results showed median WG intakes remain low in both adults and children and below that of countries with quantity-specific guidance. We also found a reduction in C-reactive protein concentrations and leucocyte counts with increased WG intake, although no association with other markers of cardio-metabolic health. The recent recommendations by the UK Scientific Advisory Committee on Nutrition to increase dietary fibre intake will require a greater emphasis on consuming more WG. Specific recommendations on WG intake in the UK are warranted as is the development of public health policy to promote consumption of these important foods.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.
We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.
Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.
During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.
Firestone & Scholl (F&S) rely on three problematic assumptions about the mind (modularity, reflexiveness, and context-insensitivity) to argue cognition does not fundamentally influence perception. We highlight evidence indicating that perception, cognition, and emotion are constructed through overlapping, distributed brain networks characterized by top-down activity and context-sensitivity. This evidence undermines F&S's ability to generalize from case studies to the nature of perception.
After a little more than forty years of work related to the interplanetary plasma and the heliosphere the IAU's Commission 49 was formally discontinued in 2015. The commission started its work when the first spacecraft were launched to measure the solar wind in–situ away from Earth orbit, both inward and outward from 1 AU. It now hands over its activities to a new commission during an era of space research when Voyager 1 measures in–situ the parameters of the local interstellar medium at the edge of the heliosphere. The commission will be succeeded by C.E3 with a similar area of responsibility but with more focused specific tasks that the community intends to address during the coming several years. This report includes a short description of the motivation for this commission and of the historical context. It then describes work from 2012 to 2015 during the present solar cycle 24 that has been the weakest in the space era so far. It gave rise to a large number of studies on solar energetic particles and cosmic rays. Other studies addressed e.g. the variation of the solar wind structure and energetic particle fluxes on long time scales, the detection of dust in the solar wind and the Voyager measurements at the edge of the heliosphere. The research is based on measurements from spacecraft that are at present operational and motivated by the upcoming Solar Probe + and Solar Orbiter missions to explore the vicinity of the Sun. We also report here the progress on new and planned radio instruments and their importance for heliospheric studies. Contributors to this report are Carine Briand, Yoichiro Hanaoka, Eduard Kontar, David Lario, Ingrid Mann, John D. Richardson.