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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
This paper traces France’s role in the Antarctic from 1840, when explorer Jules Dumont d’Urville discovered the slice of the white continent he named Terre Adélie, to the present day. Since World War II, Terre Adélie has been the site of a host of performances of sovereignty: the French have built bases, drawn maps, conducted scientific investigations and erected plaques. But France’s commitment to Terre Adélie has been tested and has fallen into crisis several times. The history of France in Antarctica is a tale of ambition, ambivalence, trade-offs and political strategy. This paper aims to elucidate this story, focusing on the concept of sovereignty and the nexus of scientific and political interests. I argue that France’s relationship with the Antarctic has been characterised by continual tension, by peaks and troughs and by brinkmanship on the part of actors with their own stakes. While there is broad agreement that Terre Adélie serves a fundamental national interest, I show that France’s ambitions on the white continent are far from decided. With its focus on France, which has largely been left out of the growing body of literature on the Antarctic, this paper contributes to building a robust historical understanding of Antarctic claims.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Ga proverbial wisdom holds that “hate has no medicine,” but there is a sacred court in Accra where people can calm the animosity that emerges from social conflicts. A unique form of vernacular jurisprudence has emerged at the Nae We Shrine Tribunal, which manages the consequences of civil, criminal, and supernatural crimes without raising the ire of human rights activists. Using records from this shrine court, the authors of this article demonstrate how the Tribunal offers social and spiritual wellbeing in a manner that cannot be provided by the chiefly and state judicial systems.
OBJECTIVES/SPECIFIC AIMS: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences.The objective was to test the effectiveness of a prediabetes SDM intervention. METHODS/STUDY POPULATION: This was a cluster-randomized controlled trial in 20 primary care clinics within a large regional health system. Participants were overweight/obese adults with prediabetes (BMI>24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics.Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention; DPP, DPP +/− metformin, metformin only, or usual care. RESULTS/ANTICIPATED RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n=351) than controls receiving usual care (n = 1,028; 38% vs. 2%, p<.001). At 12-months follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (−5.3 vs. −0.2, p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4-months and weight loss at 12-months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk.
The subantarctic island of South Georgia provides terrestrial and coastal marine records of climate variability, which are crucial for the understanding of the drivers of Holocene climate changes in the subantarctic region. Here we investigate a sediment core (Co1305) from a coastal inlet on South Georgia using elemental, lipid biomarker, diatom, and stable isotope data to infer changes in environmental conditions and to constrain the timing of late-glacial and Holocene glacier fluctuations. Because of the scarcity of terrestrial macrofossils and the presence of redeposited and relict organic matter in the sediments, age control for the record was obtained by compound-specific radiocarbon dating of mostly marine-derived n-C16 fatty acids. A basal till layer recovered in Little Jason Lagoon was likely deposited during an advance of local glaciers during the Antarctic cold reversal. After glacier retreat, an oligotrophic lake occupied the site, which transitioned to a marine inlet around 8.0±0.9 ka because of relative sea-level rise. From 7.0±0.6 to 4.0±0.4 ka, reduced vegetation coverage in the catchment, as well as high siliciclastic input and deposition of ice-rafted debris, indicates glacier advances in the terrestrial catchment and likely in the adjacent fjord. A second, less extensive period of glacier advances occurred in the late Holocene, after 1.8±0.3 ka.
Genetic variants associated with dietary intake may be important as factors underlying the development of obesity. We investigated the associations between the obesity candidate genes (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor) and total energy intake and percentage of energy from macronutrients and ultra-processed foods before and during pregnancy. A sample of 149 pregnant women was followed up in a prospective cohort in Rio de Janeiro, Brazil. A FFQ was administered at 5–13 and 30–36 weeks of gestation. Genotyping was performed using real-time PCR. Associations between polymorphisms and the outcomes were investigated through multiple linear regression and ANCOVA having pre-pregnancy dietary intake as a covariate. The A-allele of FTO-rs9939609 was associated with a −6·5 % (95 % CI −12·3, −0·4) decrease in the percentage of energy from protein and positively associated with the percentage of energy from carbohydrates before pregnancy (β=2·6; 95 % CI 0·5, 4·8) and with a 13·3 % (95 % CI 0·7, 27·5) increase in the total energy intake during pregnancy. The C-allele of MC4R-rs17782313 was associated with a −7·6 % (95 % CI −13·8, −1·0) decrease in the percentage of energy from protein, and positively associated with the percentage of energy from ultra-processed foods (β=5·4; 95 % CI 1·1, 9·8) during pregnancy. ANCOVA results revealed changes in dietary intake from pre-pregnancy to pregnancy for FTO-rs9939609 (percentage of energy from ultra-processed foods, P=0·03), MC4R-rs17782313 (total energy intake, P=0·02) and LEP-rs7799039 (total energy intake, P=0·04; percentage of energy from protein, P=0·04). These findings suggest significant associations between FTO-rs9939609, MC4R-rs17782313 and LEP-rs7799039 genes and the components of dietary intake in pregnant women.
The timing of the late Middle Paleolithic and late disappearance of Neanderthals in the Iberian Peninsula are hotly debated subjects in Paleolithic archeology. Several studies suggested a late survival in South and Central Iberia until about 32 ka, but were probably subject to significant age underestimation due to contamination of dating samples, undiagnostic lithic assemblages, and/or lack of stratigraphic integrity. We conducted a radiocarbon and luminescence-dating study backed by detailed sedimentological and micromorphological investigations at the newly discovered rock shelter sequence of Abrigo del Molino (Central Spain). Accumulation of the sediment sequence was rapid. It started with deposition of paleoflood slack-water deposits at around 48 ka and continued until about 41 ka with deposition of colluvial and detrital sediments. These contain two Mousterian levels, which place the latest Neanderthal occupation at around 45 to 41 ka, i.e., between Heinrich Stadials 5 and 4, and probably during a time of climate amelioration. Abrigo del Molino thus provides a detailed and chronologically well-constrained record of Late Neanderthal presence and morphodynamic change in Central Iberia during times of millennial-scale climate changes. The site gives further evidence for an early disappearance of Neanderthals in Central Iberia.
The solar magnesium II core-to-wing ratio has been a well-studied proxy for chromospheric activity since 1978. Daily measurements at high spectral (0.1 nm) resolution began with the launch of the Solar Radiation and Climate Experiment (SORCE) in 2003. The next generation of measurements from the Extreme Ultraviolet Sensor (EUVS) on the Geostationary Operational Environmental Satellite 16 (GOES-16) will add high time cadence (every 30 seconds) to the observational Mg II irradiance record. We present a comparison of the two measurements during the period of overlap.
Patients are the people who, with their informed consent, receive medical interventions. It is important, therefore, that patients have an understanding of interventions and their potential as a treatment for their condition. Patients are becoming more informed about their health care and the treatments that are available to them. At a population level, the potential benefits and harms of treatments need to be regularly assessed. This is part of healthcare decision making at a policy level about what treatments are publically available. As technology develops and old methods are replaced by new and evidence-based interventions and procedures, healthcare payers look to streamline their payment schedules and disinvest in old technologies and procedures. Some users of health care are reluctant to let go of outmoded methods, so disinvestment is best achieved through transparent processes. Successful engagement with key stakeholders of health care, engaging with payers, health service administrators, clinicians and patients, can facilitate implementation of disinvestment processes.
To assist in this process, Health Technology Assessment International (HTAi) Interest Groups and EuroScan have come together to develop the following key points to consider in the involvement and engagement of clinicians, patients, and the public in the disinvestment of services and technologies.
The best time to involve clinicians and patient representatives is right at the beginning of the process. Clinicians and patients can make valuable contributions as advisory committee members. The disinvestment processes may be led by clinicians, payers, or independent organizations. This will likely influence commitment of clinicians to the process.
Broader consultation with clinicians, patients and the public in the development and consideration of draft reports and recommendations can increase the transparency of the disinvestment process. Consultation is an important means of obtaining buy in. Feedback needs to be seen as taken seriously, and explanations given for any changes made or not made to the report and its recommendations.
The Spanish National Network (REDETS) is a group of eight agencies, units and services, depending on National and Regional Governments that coordinate their work within a common methodological framework, guided by the principles of mutual recognition and cooperation. The necessity of considering a Quality Management System has been detected and, consequently, a common tool for all the members needs to be developed. We describe in this study the process to achieve that goal.
Based on both a review of previous literature and the proposal for a self-evaluating tool, a group of experts from each agency through consensus have developed a tool for self-evaluation in Health Technology Assessment (HTA) agencies. Through the structure described in the handbook of the Andalusian Agency for Healthcare Quality (ACSA), each standard should have a statement or proposal that needs to also include evidence or good practices, and the corresponding evaluation questions. In separate workgroups, the definition of these proposals, evidence and evaluation questions were developed. One face-to-face meeting and two meetings via teleconference were necessary to achieve a final document with all the quality standards.
From a proposed structure of sixty-six standards, the titles, definitions, statements and evidence as well as good practices and evaluation questions were established in workgroups with consensus among all of the members (1 - 3). The final version of the self-assessment tool was composed of sixty-eight standards, grouped in twelve quality criteria structured in four dimensions: I Responsibility, II Clients and Stakeholders, III Production Process, and IV Resources.
Quality management requires an evaluation tool and this version, based on a systematic review and consensus, is a useful and practical instrument for developing a handbook by each member of REDETS. An online version of the tool is in process of development.
In southern Africa, Middle Stone Age sites with long sequences have been the
focus of intense international and interdisciplinary research over the past
decade (cf. Wadley 2015). Two techno-complexes of the Middle Stone Age—the
Still Bay and Howiesons Poort—have been associated with many technological
and behavioural innovations of Homo sapiens. The classic
model argues that these two techno-complexes are temporally separated
‘horizons’ with homogenous material culture (Jacobs et al.
2008), reflecting demographic pulses and supporting large subcontinental
networks. This model was developed on the basis of evidence from southern
African sites regarded as centres of subcontinental developments.
As part of the Z-PAndAS Keck II DEIMOS survey of resolved stars in our neighboring galaxy, Andromeda (M31), we have built up a unique data set of measured velocities and chemistries for thousands of stars in the Andromeda stellar halo, particularly probing its rich and complex substructure. In this contribution, we will discuss the structural, dynamical and chemical properties of Andromeda's dwarf spheroidal galaxies, and how there is no observational evidence for a difference in the evolutionary histories of those found on and off M31's vast plane of satellites. We will also discuss a possible extension to the most significant merger event in M31 - the Giant Southern Stream - and how we can use this feature to refine our understanding of M31's mass profile, and its complex evolution.
Objectives: Canada has witnessed expansion of the health technology assessment (HTA) infrastructure in the last 25 years. Local HTA entities at the hospital or regional level are emerging to assist decision makers in the acquisition, implementation, maintenance, and disinvestment of healthcare technologies. There is a need to facilitate collaboration and exchange of expertise and knowledge between these entities regarding the role of local HTA in Canada.
Methods: In November 2013, the pan-Canadian Collaborative hosted a symposium, Hospital/Regional HTA: Local Evidence-based Decisions for Health Care Sustainability, bringing together over 60 HTA producers, researchers, stakeholders, and manufacturers involved in local HTA across Canada. The objective was to showcase the diversity of local HTA in Canada, while highlighting common gaps to be addressed.
Results: The Symposium focused on current practices in local HTA in Canada to support informed decision making, and opportunities for information sharing and provide equal access to timely evidence-based information to decision makers. The main themes included assessment of evidence for local HTA, contextualization, stakeholder engagement in local HTA, knowledge translation and impact of recommendations, and challenges and opportunities for local HTA.
Conclusions: Local HTA in Canada complements HTAs conducted at the provincial and federal levels to improve the efficient and effective health service delivery in institutions or regions faced with limited resources. Some challenges faced by local HTA producers to influence hospital policies and clinical practice involve the engagement of healthcare professionals and potential lack of training and support necessary for the introduction of a new technology.
We aimed to examine telemedicine as a form of home and additional support for traditional outpatient care as a way to remotely monitor and manage the symptoms of patients with advanced cancer.
In total, 12 patients were monitored through monthly consultations with a multidisciplinary healthcare team and weekly web conferences. To evaluate and treat pain and other symptoms, the Edmonton Symptom Assessment System (ESAS) was applied during all remote or in-person interviews.
During monitoring, the team contacted the patients on 305 occasions: there were 89 consultations at the hospital, 19 in-person assistances to the family (without the patient), 77 web conferences, 38 telephone calls, 80 emails, and 2 home visits. The mean monitoring time until death was 195 ± 175.1 days. Eight patients who completed the ESAS in all interviews had lower mean distress symptom scores according to web conferences than in person.
Significance of results:
Telemedicine allowed greater access to the healthcare system, reduced the need to employ emergency services, improved assessment/control of symptoms, and provided greater orientation and confidence in the care given by family members through early and proactive interventions. Web conferencing proved to be a good adjuvant to home monitoring of symptoms, complementing in-person assistance.