Global Awakening in Genetic Counseling

The article by Ricki Lewis, Nature, Volume 449,October 18, 2007, correctly points out that the genetic counseling profession is on the "verge of being discovered by the rest of the world". The rapid recognition of genes associated with single-gene disorders and complex conditions has deepened our understanding of the role of genetics in health and illness. The impact of genetic conditions on individuals and families, particularly in ethical, legal and psychosocial arenas, requires specially trained professionals to work in this unique and growing dimension of healthcare. The Transnational Alliance for Genetic Counseling (TAGC) represents fifteen countries currently providing genetic counselor education across five continents

French diplomacy at the Congress of Vienna, 1814-1815

France, a defeated power in the middle of 1814, became a responsible first class power during the Congress of Vienna. French diplomacy, with Talleyrand as the chief negotiator for France, helped to re-create the Europeam system. This paper will attempt to examine the French role at the Congree of Vienna and to illustrate how France was able to occupy again an important role in European diplomacy

Farming Muskoxen for Qiviut in Alaska: A Feasibility Study

Muskoxen (Ovibos moschatus) have been farmed since the 1960s for their fiber, called qiviut, a luxurious and highly valued underwool that is their primary insulation during the Arctic winter. Muskoxen are uniquely adapted to the Arctic. They thrive on local forages, do not require protection from the cold, and adapt well to many traditional husbandry practices. While muskoxen can be farmed for qiviut, the question remains whether it is an economically feasible and potentially sustainable enterprise in subarctic Alaska. This feasibility study was conducted using an enterprise budget for two herd sizes, 36 and 72 muskoxen, to estimate the principal costs and model different sales combinations. Under several revenue-generating scenarios, the feasibility study indicated a potential for economic viability of an established enterprise. The most profitable scenario for either herd size was selling all the qiviut as value-added yarn, coupled with livestock sales. In the absence of selling livestock, the enterprise was profitable at either scale assuming all the qiviut was sold as yarn. Selling qiviut solely as raw fiber was not projected to break even under the model parameters. The modeled enterprise emphasized the importance of value-added goods, economies of scale, low or zero opportunity costs, and the potential of a more active livestock market.Le boeuf musqué (Ovibos moschatus) est élevé depuis les années 1960 pour sa fibre, appelée qiviut, ce duvet somptueux et fort prisé qui sert d’isolant principal à cet animal pendant les hivers de l’Arctique. Le boeuf musqué est remarquablement bien adapté à l’Arctique. Il se nourrit d’aliments qui se trouvent dans la région, n’a pas besoin d’être protégé du froid et se prête bien à de nombreuses pratiques traditionnelles d’élevage. Bien qu’il soit possible d’élever le boeuf musqué pour son qiviut, il n’en reste pas moins qu’il faut se demander s’il s’agit là d’une entreprise rentable et durable dans le subarctique de l’Alaska. Cette étude de faisabilité a été réalisée à l’aide d’un budget d’entreprise pour des troupeaux de deux tailles, soit un troupeau de 36 boeufs musqués et un troupeau de 72 boeufs musqués, afin d’évaluer les principaux coûts et de modéliser diverses combinaisons de ventes. À l’aide de plusieurs scénarios de génération de revenus, l’étude de faisabilité a indiqué des possibilités de rentabilité économique pour une entreprise établie. Le scénario le plus rentable pour l’une ou l’autre taille de troupeau consistait à vendre tout le qiviut en tant que laine à valeur ajoutée, alliée à la vente du bétail. En l’absence de la vente de bétail, l’entreprise était rentable à l’une ou l’autre des échelles, en présumant que tout le qiviut était vendu en tant que laine. La vente du qiviut en tant que fibre brute seulement ne donnait pas lieu à la projection d’un seuil de rentabilité d’après les paramètres du modèle. L’entreprise ayant fait l’objet du modèle mettait l’accent sur l’importance des biens à valeur ajoutée, des économies d’échelle, de coûts faibles ou nuls et de la possibilité d’un marché plus actif pour le bétail

Utilizing Grassland Resources for Sub-Arctic Agriculture: Sustainable Muskox Farming in Alaska

The 2005 Millennium Ecosystem Assessment broadly classifies Alaska as a Polar Ecosystem, characterized as being frozen most of the year and underlain by permafrost. Despite this bleak portrayal, some of the largest herds of grazing ungulates are indigenous to Alaska - and thriving. This is both a testament to the resilience of grazing systems in general as well as a statement to the suitability of grazing systems specifically for Alaska. In a state economy dominated by nonrenewable resource extraction, agricultural production has remained largely undeveloped (Fried 2013). However, today there is increasing interest in local agricultural production with the goal of developing an economically diverse, sustainable agricultural model for Alaska. Muskoxen (Ovibos moschatus) are uniquely adapted to the arctic. They thrive on local forages, do not require protection from the cold and adapt well to many traditional husbandry practices. Muskoxen have been farmed since the 1960’s for their fiber, known as qiviut, a luxurious and highly valued underwool that is their primary insulation during the arctic winter. Adult muskoxen annually shed 1.5-2.5 kg of qiviut throughout their life. While muskoxen can be farmed for qiviut, the question remains whether this endeavor is a sustainable enterprise for northern farms? What impact will grazing practices have on pasture and soil health in sub-arctic environments? In this research, we investigated two aspects of the sustainability triad with respect to farming a non-traditional species, musk oxen, in Alaska: i) economic feasibility ii) potential impact of managed grazing on sub-arctic pasture ecology

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta‐analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta‐analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First‐degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Review of interventions to encourage SMEs to make environmental improvements

Small and medium-sized enterprises (SMEs) are an important part of the world economy but they are thought to be responsible for around 60% of all carbon dioxide emissions and 70% of all pollution. SMEs often have major problems with limited resources, limited knowledge, and limited technical capabilities to deal with their own negative environmental impact. SMEs exhibit widely differing characteristics and commitment where environmental issues are concerned. Yet under these conditions they are all expected to engage in environmental improvement. Interventions that encourage environmental improvement are often polarised between regulation and legislation at one extreme and voluntary environmental agreement at the other. It is clear that a holistic mixture of interventions is necessary to achieve maximum engagement and environmental improvement by all SMEs. In this paper we categorise the different levels of environmental commitment observed in SMEs and develop a selection or &lsquo;toolkit&rsquo; of intervention strategies that might be deployed within each category of SME.<br /

Understanding vaccine hesitancy in Canada: Results of a consultation study by the Canadian Immunization Research Network

"Vaccine hesitancy" is a concept now frequently used in vaccination discourse. The increased popularity of this concept in both academic and public health circles is challenging previously held perspectives that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. A consultation study was designed to assess the opinions of experts and health professionals concerning the definition, scope, and causes of vaccine hesitancy in Canada. We sent online surveys to two panels (1- vaccination experts and 2- front-line vaccine providers). Two questionnaires were completed by each panel, with data from the first questionnaire informing the development of questions for the second. Our participants defined vaccine hesitancy as an attitude (doubts, concerns) as well as a behaviour (refusing some / many vaccines, delaying vaccination). Our findings also indicate that both vaccine experts and front-line vaccine providers have the perception that vaccine rates have been declining and consider vaccine hesitancy an important issue to address in Canada. Diffusion of negative information online and lack of knowledge about vaccines were identified as the key causes of vaccine hesitancy by the participants. A common understanding of vaccine hesitancy among researchers, public health experts, policy-makers and health care providers will better guide interventions that can more effectively address vaccine hesitancy within Canada

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe