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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.
As practitioners of a historical science, paleontologists and geoscientists are well versed in the idea that the ability to understand and to anticipate the future relies upon our collective knowledge of the past. Despite this understanding, the fundamental role that the history of paleontology and the geosciences plays in shaping the structure and culture of our disciplines is seldom recognized and therefore not acted upon sufficiently. Here, we present a brief review of the history of paleontology and geology in Western countries, with a particular focus on North America since the 1800s. Western paleontology and geology are intertwined with systematic practices of exclusion, oppression, and erasure that arose from their direct participation in the extraction of geological and biological resources at the expense of Black, Indigenous, and People of Color (BIPOC). Our collective failure to acknowledge this history hinders our ability to address these issues meaningfully and systemically in present-day educational, academic, and professional settings. By discussing these issues and suggesting some ways forward, we intend to promote a deeper reflection upon our collective history and a broader conversation surrounding racism, colonialism, and exclusion within our scientific communities. Ultimately, it is necessary to listen to members of the communities most impacted by these issues to create actionable steps forward while holding ourselves accountable for the past.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
Fishes, here defined as ‘non-digitate aquatic vertebrates’, first appear in the Cambrian Period at least 520 million years ago (Ma). They are first represented by fusiform taxa lacking well-developed fins and dermal bone covering. The first fishes to bear external dermal bones forming a protective and supporting framework appear in the mid-Ordovician, about 460 Ma, represented by fusiform heterostracans and other associated taxa, found in Australia and South America. By the late Ordovician, fishes were widespread across the globe and the first jawed vertebrates, gnathostomes, had possibly appeared. The oldest gnathostome remains are enigmatic small placoid-like scales with chondrichthyan affinity, but cannot be resolved without more complete material. The oldest jawed vertebrates, both placoderms and stem chondrichthyans (‘acanthodians’), come from what is today China, with articulated diverse remains of placoderms and the first osteichthyans in the upper Silurian (Ludlow) of Yunnan. These forms include maxillate placoderms like Entelognathus and Qilinyu as well as heavily spined sarcopterygian (osteichthyan) fishes like Guiyu. At the start of the Early Devonian we see a new placoderm fish fauna emerging globally which has little resemblance to the late Silurian taxa of China, with some five main clades of placoderms and a few smaller groups of uncertain affinity. Osteichthyans diversified into two major clades, one of which, the Actinopterygii, or ray-fins, were represented by early forms with rhombic scales and fixed cheek-mouth complexes, loosely termed ‘paleoniscoids’. The Sarcopterygii, which include Actinistia (coelacanths), Dipnomorpha (dipnoans and porolepiforms), Onychodontiformes, and stem tetrapods (Tetrapodomorpha), had all appeared by the end of the early Devonian. Since the end of the Palaeozoic the non-tetrapod sarcopterygians are represented only by lungfishes and coelacanths. Chondrichthyans are known from isolated teeth, scales, and spines in the early Devonian with one articulated fish from the Emsian. By the late Devonian chondrichthyans had radiated into many families, including the first stem holocephalans, like Cladoselache. The Carboniferous saw a huge radiation of chondrichthyans and actinopterygians. Neopterygians appeared by the late Carboniferous with the first teleosteans by the late Triassic. Since the Mesozoic percomorphans especially have diversified to comprise the great majority of all fish families extant today, represented by some 29,000 spp. of teleosteans. Chondrichthyans also underwent a secondary radiation when batoids and modern sharks appeared in the Jurassic. Today there are some 1,200 species of living chondrichthyans.
The earliest tetrapodomorph fishes appear in Chinese deposits of Early Devonian age, and by the Middle Devonian they were widespread globally. Evidence for the earliest digitated tetrapods comes from largely uncontested Middle Devonian trackways and Late Devonian body fossils. The East Gondwana Provence (Australasia, Antarctica) fills vital gaps in the phylogenetic and biogeographic history of the tetrapods, with the Gondwanan clade Canowindididae exhibiting a high degree of endemism within the early part of the stem tetrapod radiation. New anatomical details of Koharalepis, from the Middle Devonian Aztec Siltstone of Antarctica, are elucidated from synchrotron scan data. These include the position of the orbit, the condition of the hyomandibular, the shape of the palate and arrangement of the vomerine fangs. Biogeographical and phylogenetic models of stem tetrapod origins and radiations are discussed.
The San Francisco Fire Department’s (SFFD; San Francisco, California USA) Homeless Outreach and Medical Emergency (HOME) Team is the United States’ first Emergency Medical Services (EMS)-based outreach effort using a specially trained paramedic to redirect frequent users of EMS to other types of services. The effectiveness of this program at reducing repeat use of emergency services during the first seven months of the team’s existence was examined.
A retrospective analysis of EMS use frequency and demographic characteristics of frequent users was conducted. Clients that used emergency services at least four times per month from March 2004 through May 2005 were contacted for intervention. Patterns for each frequent user before and after intervention were analyzed. Changes in EMS use during the 15-month study interval was the primary outcome measurement.
A total of 59 clients were included. The target population had a median age of 55.1 years and was 68% male. Additionally, 38.0% of the target population was homeless, 43.4% had no primary care, 88.9% had a substance abuse disorder at time of contact, and 83.0% had a history of psychiatric disorder. The HOME Team undertook 320 distinct contacts with 65 frequent users during the study period. The average EMS use prior to HOME Team contact was 18.72 responses per month (SD=19.40), and after the first contact with the HOME Team, use dropped to 8.61 (SD=10.84), P<.001.
Frequent users of EMS suffer from disproportionate comorbidities, particularly substance abuse and psychiatric disorders. This population responds well to the intervention of a specially trained paramedic as measured by EMS usage.
TangherliniN, VillarJ, BrownJ, RodriguezRM, YehC, FriedmanBT, WadaP. The HOME Team: Evaluating the Effect of an EMS-based Outreach Team to Decrease the Frequency of 911 Use Among High Utilizers of EMS. Prehosp Disaster Med. 2016;31(6):603–607.
To determine the contribution of forest foods to dietary intake and estimate their association with household food insecurity.
Cross-sectional survey conducted among 279 households. Using a 7 d recall questionnaire, information on household food consumption was collected from women and used to determine the household dietary diversity score, food variety score and forest food consumption score (FFCS). Household Food Insecurity Access Scale (HFIAS) score was determined and Spearman rank correlation was used to establish the relationship between consumption of forest foods and HFIAS score. Women’s dietary intake was estimated from two 24 h recalls. The contribution of forest foods to women’s nutrient intakes was calculated and women’s nutrient intakes were compared with estimated average nutrient requirements.
Rural forest-dependent households in twelve villages in eastern and southern Cameroon.
Household heads and their non-pregnant, non-lactating spouses.
Forty-seven unique forest foods were identified; of these, seventeen were consumed by 98 % of respondents over the course of one week and by 17 % of women during the two 24 h recall periods. Although forest foods contributed approximately half of women’s total daily energy intake, considerably greater contributions were made to vitamin A (93 %), Na (100 %), Fe (85 %), Zn (88 %) and Ca (89 %) intakes. Despite a highly biodiverse pool of foods, most households (83 %) suffered from high food insecurity based on the HFIAS. A significant inverse correlation was observed between the HFIAS score and the FFCS (r2=−0·169, P=0·0006), demonstrating that forest foods play an important role in ensuring food security in these forest-dependent communities.
Forest foods are widely consumed by forest-dependent communities. Given their rich nutrient content, they have potential to contribute to food and nutrition security.
A patient with no risk factors for malaria was hospitalized in New York City with Plasmodium falciparum infection. After investigating all potential sources of infection, we concluded the patient had been exposed to malaria while hospitalized less than 3 weeks earlier. Molecular genotyping implicated patient-to-patient transmission in a hospital setting.
Infect. Control Hosp. Epidemiol. 2015;37(1):113–115
TO investigate and describe the relationship between indigenous Australian populations, residential aged care services, and community-onset Staphylococcus aureus bacteremia (SAB) among patients admitted to public hospitals in Queensland, Australia.
We used administrative healthcare data linked to microbiology results from patients with SAB admitted to Queensland public hospitals from 2005 through 2010 to identify community-onset infections. Data about indigenous Australian population and residential aged care services at the local government area level were obtained from the Queensland Office of Economic and Statistical Research. Associations between community-onset SAB and indigenous Australian population and residential aged care services were calculated using Poisson regression models in a Bayesian framework. Choropleth maps were used to describe the spatial patterns of SAB risk.
We observed a 21% increase in relative risk (RR) of bacteremia with methicillin-susceptible S. aureus (MSSA; RR, 1.21 [95% credible interval, 1.15–1.26]) and a 24% increase in RR with nonmultiresistant methicillin-resistant S. aureus (nmMRSA; RR, 1.24 [95% credible interval, 1.13–1.34]) with a 10% increase in the indigenous Australian population proportion. There was no significant association between RR of SAB and the number of residential aged care services. Areas with the highest RR for nmMRSA and MSSA bacteremia were identified in the northern and western regions of Queensland.
The RR of community-onset SAB varied spatially across Queensland. There was increased RR of community-onset SAB with nmMRSA and MSSA in areas of Queensland with increased indigenous population proportions. Additional research should be undertaken to understand other factors that increase the risk of infection due to this organism.
Planet migration plays a crucial role in shaping planetary systems, and has therefore received a lot of attention in recent years in an effort to compare the statistical properties of observed exoplanets with the predictions of planet formation and migration theories. By modifying the propagation properties of the waves induced by the planet in the disk, the presence of a strong magnetic field can dramatically influence planet migration, in some cases reversing its direction. The more realistic case of a weaker magnetic field is less clear, although turbulent MHD simulations by Baruteau et al. (2011) suggest an effect on the corotation torque. Here, we present a study of the corotation torque in 2D laminar disks containing a toroidal magnetic field. We performed MHD simulations of the interaction between the magnetic field and the horseshoe motion of the gas, and found that this results in an additional corotation torque. This additional torque can be strong enough to reverse migration even for a field which pressure is only one percent of the thermal pressure. We speculate that this could lead to long range outward migration in the outer part of protoplanetary disks and may explain the observations by direct imaging of planets at several tens of AU from their star like the 4 planets system HR 8799.
Craniofacial reconstruction (CFR) can be a useful tool in the identification of a corpse that is unrecognisable due to its state of decomposition, soft-tissue mutilation or incineration, and if no other identification evidence is available. Traditional CFR methods are based on manual reconstruction by physically modelling a face on a skull replica with clay or plasticine. The progress in computer science and the improvement of medical imaging technologies during recent years have fostered the development of fast and flexible computer-based reconstruction programs. This chapter presents a comprehensive review of computerised three-dimensional (3D) CFR algorithms with particular emphasis on the more recent statistical based reconstruction methods, including a discussion of the various alternatives and problems that arise during the process of designing a CFR program.
Forensic identification of an unknown body is based on comparisons of ante- and post-mortem data, such as medical files, dental records, X-rays or DNA. Sometimes ante-mortem records are not available or incomplete; sometimes the preservation of DNA may be so poor as to make comparisons impossible. Similarly, when identifying features are completely missing or have decomposed beyond recognition but partial or complete skull fragments are available, CFR may assist the investigation. The goal of CFR is to recreate a likeness of the face of an individual immediately prior to their death. Different 2D and 3D manual or computer-aided CFR techniques have been developed for this purpose and all are based on the assumed relationship between the soft-tissue envelope and the underlying skull substrate.
Low-grade inflammation is a characteristic of the obese state, and adipose tissue releases many inflammatory mediators. The source of these mediators within adipose tissue is not clear, but infiltrating macrophages seem to be especially important, although adipocytes themselves play a role. Obese people have higher circulating concentrations of many inflammatory markers than lean people do, and these are believed to play a role in causing insulin resistance and other metabolic disturbances. Blood concentrations of inflammatory markers are lowered following weight loss. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation, and this is exaggerated by a high meal content of advanced glycation end products (AGE) and partly ablated by inclusion of certain antioxidants or antioxidant-containing foods within the meal. Healthy eating patterns are associated with lower circulating concentrations of inflammatory markers. Among the components of a healthy diet, whole grains, vegetables and fruits, and fish are all associated with lower inflammation. AGE are associated with enhanced oxidative stress and inflammation. SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3 PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the circulating concentrations of inflammatory markers. Potential mechanisms are described and research gaps, which limit our understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identified.
In an article published in the Guardian in 2004, the West Indian-born, British-raised novelist Caryl Phillips remarked on the curious absence in 1950s British literature of a phenomenon that was visibly transforming the nation throughout that decade. Immigration from the far-flung possessions of an empire that had begun decolonising in earnest after the war burgeoned in the 1950s, with the West Indies and Africa especially supplying hundreds of thousands of new residents to Britain (and to London in particular). Yet despite what Phillips calls 'the daily presence of these new people on the streets, on the buses, and working in hospitals and factories all over the country' at the time, leading British-born writers such as Kingsley Amis and John Osborne displayed a general - and perhaps, Phillips suggests, even a wilful - blindness to the nation's emerging multiracial and multicultural reality. The key exception, he notes, was Colin MacInnes, who was born in London in 1914, grew up in Australia, eventually moved back to London, and, in the late 1950s, wrote three important novels that feature multiracial groups of protagonists and vividly depict a city in flux. Of the three, Phillips gives pride of place to MacInnes's first, City of Spades, published in 1957.
Many computer science departments are debating the role of programming languages in the curriculum. These discussions often question the relevance and appeal of programming-languages content for today's students. In our experience, domain-specific, “little languages” projects provide a compelling illustration of the importance of programming-language concepts. This paper describes projects that prototype mainstream applications such as PowerPoint, TurboTax, and animation scripting. We have used these exercises as modules in non-programming languages courses, including courses for first year students. Such modules both encourage students to study linguistic topics in more depth and provide linguistic perspective to students who might not otherwise be exposed to the area.
Based on structural, geochemical, sedimentological and geochronological studies, we have formulated a model for the evolution of the late Archaean Abitibi greenstone belt of the Superior Province of Canada. The southern volcanic zone (SVZ) of the belt is dominated by komatiitic to tholeiitic volcanic plateaux and large, bimodal, mafic-felsic volcanic centres. These volcanic rocks were erupted between approximately 2710 Ma and 2700 Ma in a series of rift basins formed as a result of wrench-fault tectonics.
The SVZ superimposes an older volcanic terrane which is characterized in the northern volcanic zone (NVZ) of the Abitibi belt and is approximately 2720 Ma or older. The NVZ comprises basaltic to andesitic and dacitic subaqueous massive volcanics which are cored by comagmatic sill complexes and layered mafic-anorthositic plutonic complexes. These volcanics are overlain by felsic pyroclastic rocks that were comagmatic with the emplacement of tonalitic plutons at 2717 ±2 Ma.
The tectonic model envisages the SVZ to have formed in a series of rift basins which dissected an earlier formed volcanic arc (the NVZ). Analogous rift environments have been postulated for the Hokuroko basin of Japan, the Taupo volcanic zone of New Zealand and the Sumatra and Nicaragua arcs. The difference between rift related ‘submergent’ volcanism in the SVZ and ‘emergent’ volcanism in the NVZ resulted in the contrasting metallogenic styles, the former being characterized by syngenetic massive sulphide deposits, whilst the latter was dominated by epigenetic ‘porphyry-type’ Cu(Au) deposits.
We evaluated sea urchin Strongylocentrotus droebachiensis predation on egg masses of the whelk Buccinum undatum. The urchin actively grazes on the egg masses, even as they are being deposited on the bottom. Whelks preferentially lay their egg masses on vertical areas where urchin densities are 4-fold less than on flat areas. This strategy is advantageous, as experimental trials showed that the loss in the mass of capsules was 4 fewer on walls than on flat areas. Nevertheless, a high proportion of egg masses on walls show damage from predation. Urchins provided with egg masses in the laboratory, ingested the capsules at a steady rate over a 9-d period (5 urchins ingested 2.8 g.d-1). Urchins provided agar discs that included a preferred alga and whelk capsule walls ingested the discs at a rate that was half that observed for discs that only included the alga. Discs that included the preferred alga and capsule contents were eaten at the same rate as discs that only included the alga. Thus, capsule walls, but not the capsule contents, provide a defence against urchin predation. Laying aggregate egg masses likely provides only a limited advantage, as the attachment surface does not increase with the number of egg masses deposited together, so the risk of detachment increases. Consideration of the interactions between urchins and whelks is important in managing the fisheries of the two species.
Background and objectives: Until recently, attention and treatment strategies have focused mainly on patients in the early phases of Alzheimer's disease (AD). The objectives of this study were to collect information on moderately severe and severe AD patients (Mini-mental State Examination score < 15) in terms of epidemiological, clinical and economic characteristics and disease change in the later stages of AD, and to compare this specific AD population over 6 months with those in the earlier stages.
Methods: This descriptive analysis recruited institutionalized patients and patients living within the community from the city of London and the South-East region of the U.K. Subgroup analyses at baseline and 6 months were performed using the study population from the London and South-East Region Alzheimer's Disease (LASER-AD) Study. Data from a range of clinical scales, a quality of life (QOL) scale and a resource-utilization questionnaire were analyzed.
Results: People with moderately severe or severe AD are a heterogeneous group with varying QOL, cognitive and functional disabilities, neuropsychological symptoms and relatively low health care resource consumption. This patient group continued to decline but progression of the disease was observed only in some domains.
Conclusion: Even at the later stages of AD, patients show varying rates of decline. Improved knowledge about the characteristics and progression of the disease reveals that moderately severe and severe patients cannot be regarded as beyond help and have the potential to experience varying and even high levels of QoL.