Klovlidelsers betydning, forebyggelse og behandling i malkekvaegsbesaetninger

The dairy cow needs an optimal environment and a good status of health to deliver what we expect from it in today's intensive farming. An arising problem is hoof disorders which over the last few decades has become a more and more increasing problem that every year costs dairy farmers millions of kroner. This subject is interesting as there today is no room for mistakes to slow the production down and hoof diseases are exactly an unattended fact that has not been given the needed thoughts and attention. This mainly because of lack of awareness and knowledge from the farmer. Apart from lameness and a general negative effect on the well-being of the cow, hoof diseases cause great economical losses in production due to decreases in milk and meat production, poor fertility and higher risk of mastitis caused by the difficulties in lying down and getting up. This costs the dairy farmer from 200-700 kr. pr cow/year. A lot of the disorders are sub clinical and are therefore not given the right treatment in time which is fatal. Only 3-8% of the cows in Swedish and Danish herds are treated for hoof diseases every year by the veterinary while it has shown to be a problem in up till 70% of the cows in the herds. The disorders we see are often laminitis which in a more server form causes sole lesions. It has been connected to wrong feeding with too little an amount of structure. Especially young cows are sensitive to the great pressure on their not fully developed bodies and sudden changes in the environment. Interdigital phlegmone or foul in the foot and heel horn erosion are primarily caused by the wet and aggressive environment surrounding the hoofs which often is seen in the free stall barns. Digital dermatitis is contagious and has spread from southern Europe and can now be found in 50% of the herds here in Scandinavia. Digital dermatitis spreads as bacteria. Lots of these disorders can be prevented by good and simple management and a lot can be avoided by keeping the environment dry and clean. Treatment often includes a solution containing 5-10% copper sulphate which leads to environmental problems. The Carematic treatment boxes with Hooffit liquid and The Kovex Foam Activator system are two interesting examples of weekly hoof treatment systems to control hoof diseases in the future.Malkekoen er et effektivt produktionsapparat, som der i dagens produktionssystemer kræves optimal ydelse fra hver dag. For at den skal kunne klare dette kræves, et godt miljø og en god sundheds status. Et stigende problem i danske og svenske malkekvægsbesætninger er klovlidelser, som hvert år koster landbruget store summer. Emnet er interessant, fordi der i dagens effektive system ikke er plads til stopklodser, og klovlidelser kan netop betegnes som en overset stopklods, der pga. manglende fokus fra landmandens og hans konsulenters side, ikke har fået den nødvendige opmærksomhed. Klovlidelser betyder dårligere økonomi i besætningen pga., at der opnås en lavere mælkeydelse end forventet, en ringere tilvækst samt en dårligere fungerende reproduktion. Alle besætninger har klovlidelser, nogle så mange, at de taber op imod 700 kr. pr ko pr år. Mange af klovlidelserne er subkliniske og opdages aldrig og behandles derfor ikke retmæssigt i tide med en forværring som følge. Kun 3-8% af køerne i svenske og danske besætninger behandles årligt for klovlidelser, mens det har vist sig at være et problem hos op til 70% af køerne i besætningerne. Laminitis, som i et senere stadie kan udvikle såleknusninger, er sat i forbindelse med forkert fodring med for lille andel struktur, specielt hos unge 1. og 2. gangs kælvere optræder dette problem. Klovbrandbylder og balleforrådnelser er primært miljøbetingede, og den våde og ammoniakholdige gødning på spalterne i løsdriftsstaldene har et stort ansvar i sammenhængen. Digital dermatitis har bredt sig fra syd Europa i løbet af få år tier, og har nu inficeret ca. halvdelen af besætningerne her hjemme. Denne lidelse er smitsom og spredes som bakterier i miljøet. Mange klovlidelser kan forebygges ved simpel god management fra driftslederens side, og mange kan undgås ved at give klovene et tørt og rent miljø. Praksis viser dog, at behandlinger er nødvendige i mange tilfælde. Behandlingen af klovlidelser sker i øjeblikket i stor udstrækning med ugentlige klov bade, som indeholder kobbersulfat. Landbruget leder på denne konto hvert år op til 117 kg kobber ud i miljøet efter behandling af 75 køer, og fremtidens accept af dette er tvivlsom. Nye metoder må derfor i brug. Carematic behandlingsboks med Hoof- fit liquid og Kovex Foam Activator er to gode eksempler på afløsere til fodbadene. Carematic er dyr i indkøb og kræver en ekstra boks installeret i stalden, mens Kovex er en billig og simpel løsning, der passer ind i mange nuværende systemer. Brugen af Carematic leder betydelig mindre mængder kobber ud i naturen sammenlignet med forbadene, mens Kovex kun bruger naturligt nedbrydelige syrer. Behandlinger med vand alene bliver udøvet i enkelte besætninger og viser resultater mod bedre klovhelse

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe