Deformation of a renormalization-group equation applied to infinite-order phase transitions

By adding a linear term to a renormalization-group equation in a system exhibiting infinite-order phase transitions, asymptotic behavior of running coupling constants is derived in an algebraic manner. A benefit of this method is presented explicitly using several examples.Comment: 6 pages, 5 figures, revtex4, typo corrected, references adde

Cerebrospinale rhinorrhoe

Cerebrospinaler hinorrhoe is het verschijnsel waarbij liquor cerebrospinalis door de neus naar buiten komt. Een rhinorrhoe kan pas optreden als er een dura- en botdefect is. Vooral bij schedelbasisfracturen en aangezichtsfracturen kunnen we een rhinorrhoe verwachten. De duur van de rhinorrhoe kan varieren van enige uren tot jaren na het ongeval. ... Zie: Samenvattin

Assessment of practical applicability and clinical relevance of a commonly used LDL-C polygenic score in patients with severe hypercholesterolemia

Background and aims: Low-density lipoprotein cholesterol (LDL-C) levels vary in patients with familial hypercholesterolemia (FH) and can be explained by a single deleterious genetic variant or by the aggregate effect of multiple, common small-effect variants that can be captured in a polygenic score (PS). We set out to investigate the contribution of a previously published PS to the inter-individual LDL-C variation and coronary artery disease (CAD) risk in patients with a clinical FH phenotype. Methods: First, in a cohort of 628 patients referred for genetic FH testing, we evaluated the distribution of a PS for LDL-C comprising 12 genetic variants. Next, we determined its association with coronary artery disease (CAD) risk using UK Biobank data. Results: The mean PS was higher in 533 FH-variant-negative patients (FH/M-) compared with 95 FH-variant carriers (1.02 vs 0.94, p < 0.001). 39% of all patients had a PS equal to the top 20% from a population-based reference cohort and these patients were less likely to carry an FH variant (OR 0.22, 95% CI 0.10–0.48) compared with patients in the lowest 20%. In UK Biobank data, the PS explained 7.4% of variance in LDL-C levels and was associated with incident CAD. Addition of PS to a prediction model using age and sex and LDL-C did not increase the c-statistic for predicting CAD risk. Conclusions: This 12-variant PS was higher in FH/M- patients and associated with incident CAD in UK Biobank data. However, the PS did not improve predictive accuracy when added to the readily available characteristics age, sex and LDL-C, suggesting limited discriminative value for CAD

Founder mutations in the Netherlands: geographical distribution of the most prevalent mutations in the low-density lipoprotein receptor and apolipoprotein B genes

Background In the Netherlands, a screening programme was set up in 1994 in order to identify all patients with familial hypercholesterolaemia (FH). After 15 years of screening, we evaluated the geographical distribution, possible founder effects and clinical phenotype of the 12 most prevalent FH gene mutations. Methods Patients who carried one of the 12 most prevalent mutations, index cases and those identified between 1994 and 2009 through the screening programme and whose postal code was known were included in the study. Low-density lipoprotein cholesterol (LDL-C) levels at the time of screening were retrieved. The prevalence of identified patients in each postal code area was calculated and visualised in different maps. Results A total of 10,889 patients were included in the study. Mean untreated LDL-C levels ranged from 4.4 to 6.4 mmol/l. For almost all mutations, a region of high prevalence could be observed. In total, 51 homozygous patients were identified in the Netherlands, of which 13 true homozygous for one of the 12 most prevalent mutations. The majority of them were living in high-prevalence areas for that specific mutation. Conclusions Phenotypes with regard to LDL-C levels varied between the 12 most prevalent FH mutations. For most of these mutations, a founder effect was observed. Our observations can have implications with regard to the efficiency of molecular screening and physician's perception of FH and to the understanding of the prevalence and distribution of homozygous patients in the Netherland

Arm hand skilled performance in cerebral palsy: activity preferences and their movement components

Background: Assessment of arm-hand use is very important in children with cerebral palsy (CP) who encounter arm-hand problems. To determine validity and reliability of new instruments to assess actual performance, a set of standardized test situations including activities of daily living (ADL) is required. This study gives information with which such a set for upper extremity skill research may be fine-tuned, relative to a specific research question. Aim of this study is to a) identify upper extremity related ADL children with CP want to improve on, b) determine the 10 most preferred goals of children with CP, and c) identify movement components of all goals identified. Method: The Canadian Occupational Performance Measure was used to identify upper extremity-related ADL preferences (goals) of 53 children with CP encountering arm-hand problems (mean age 9 +/- 4.5 year). Goals were ranked based on importance attributed to each goal and the number of times a goal was mentioned, resulting in a gross list with goals. Additionally, two studies were performed, i.e. study A to determine the 10 most preferred goals for 3 age groups (2.5-5 years; 6-11 years, 12-19 years), based on the total preference score, and study B to identify movement components, like reaching and grasping, of all goals identified for both the leading and the assisting arm-hand. Results: Seventy-two goals were identified. The 10 most preferred goals differed with age, changing from dressing and leisure-related goals in the youngest children to goals regarding personal care and eating for children aged 6-11 years. The oldest children preferred goals regarding eating, personal care and computer use. The movement components 'positioning', 'reach', 'grasp', and 'hold' were present in most tasks. 'Manipulating' was more important for the leading arm-hand, whereas 'fixating' was more important for the assisting arm-hand. Conclusion: This study gave insight into the preferences regarding ADL children with CP would like to improve on, and the movement components characterizing these activities. This information can be used to create a set of standardized test situations, which can be used to assess the validity and reliability of new measurement instruments to gauge actual arm-hand skilled performance

Opsporing van patiënten met familiaire hypercholesterolemie in Nederland

To inventory the possibilities of tracing relatives of patients with familial hypercholesterolaemia (FH) by means of family tree research and DNA diagnostics. Descriptive. Blood from patients with the clinical diagnosis of 'FH' was sent, through one of the lipid outpatient clinics in the country, to the Foundation for Tracing Hereditary Hypercholesterolaemia (StOEH) for DNA examination, to characterize the genetic defect. If a mutation was diagnosed in this index patient, he was invited by telephone by a StOEH staff member to have DNA testing done in relatives (especially those of the first degree). The data were stored in a data base. The analysis concerns the patients approached in 1994-1997, as well as those in whom the serum concentration of LDL cholesterol was also determined in 1993-1995. A total of 3013 persons were approached and examined: 146 index patients and 2867 relatives. The DNA diagnosis of 'FH' was made in 1067 relatives (37.2%), 585 (54.8%) women and 482 (45.2%) men. Of these, 21.2% were younger than 20 years, 37.0% 20-39 years, 26.6% 40-59 years and 15.2% > or = 60 years; 44.1% reported being known with a raised cholesterol level, 29.4% were treated with cholesterol-reducing drugs and 6.1% were suffering from a cardiovascular disease. Of the 990 persons in whom the serum LDL cholesterol level was determined, 325 (32.8%) were carriers of a mutation in the LDL receptor gene. 21.2% Of them had a LDL cholesterol level P95. Tracing FH patients is feasible in practice and leads to detection of as yet untreated patient

EFFICACY OF ALIROCUMAB IN 1,191 PATIENTS WITH A WIDE SPECTRUM OF MUTATIONS IN GENES CAUSATIVE FOR FAMILIAL HYPERCHOLESTEROLEMIA

Background Mutation(s) in genes involved in the low-density lipoprotein receptor (LDLR) pathway are typically the underlying cause of familial hypercholesterolemia. Objective The objective of the study was to examine the influence of genotype on treatment responses with alirocumab. Methods Patients from 6 trials (n = 1191, including 758 alirocumab-treated; Clinicaltrials.gov identifiers: NCT01266876; NCT01507831; NCT01623115; NCT01709500; NCT01617655; NCT01709513) were sequenced for mutations in LDLR , apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), LDLR adaptor protein 1, and signal-transducing adaptor protein 1 genes. New mutations were confirmed by Sanger sequencing. Results One or more specific gene mutations were found in 898 patients (75%): 387 and 437 patients had heterozygous LDLR defective and negative mutations, respectively; 46 had a heterozygous APOB -defective mutation; 8 patients had a heterozygous PCSK9 gain-of-function mutation; 293 (25%) had no identifiable mutation in the genes investigated. LDL cholesterol reductions at Week 24 were generally similar across genotypes: 48.3% (n = 131) and 54.3% (n = 89) in LDLR -defective heterozygotes with alirocumab 75 mg Q2W (with possible increase to 150 mg at Week 12) and 150 mg Q2W, respectively; 49.7% (n = 168) and 60.7% (n = 88) in LDLR -negative heterozygotes; 54.1% (n = 20) and 50.1% (n = 6) in APOB -defective heterozygotes; 60.5% (n = 5) and 94.0% (n = 1) in PCSK9 heterozygotes; and 44.9% (n = 85) and 55.4% (n = 69) in patients with no identified mutations. Overall rates of treatment-emergent adverse events were similar for alirocumab vs controls (placebo in 5 trials, ezetimibe control or atorvastatin calibrator arm in 1 trial), with only a higher rate of injection-site reactions with alirocumab. Conclusions In this large patient cohort, individuals with a wide spectrum of mutations in genes underlying familial hypercholesterolemia responded substantially and similarly to alirocumab treatment

A functional polymorphism in the glucocorticoid receptor gene and its relation to cardiovascular disease risk in familial hypercholesterolemia

Context: Individuals with the functional ER22/23EK variant in the glucocorticoid receptor gene are relatively resistant to the downstream consequences of glucocorticoids. Evidence suggests that carriers have a more favorable cardiovascular risk profile, but the relationship between this ER22/23EK variant and cardiovascular disease has not been hitherto assessed. Objective: We, therefore, determined whether carriership of the ER22/23EK improves cardiovascular disease risk in patients with severe hypercholesterolemia. Design, Setting, and Participants: In a multicenter cohort study, 2024 patients with heterozygous familial hypercholesterolemia, aged 18 yr and older, were genotyped for the ER22/23EK polymorphism. Patients were identified at lipid clinics throughout The Netherlands between 1989 and 2002. Main Outcome Measures: The primary outcome measure was cardiovascular disease. Results: Seventy-six (7.8%) of 977 men and 72 (6.9%) of 1047 women were carriers of the ER22/23EK variant. A total of 395 men and 247 women had a cardiovascular event. In contrast to expected results, we observed no significant association of the ER22/23EK variant with cardiovascular disease risk (men: relative risk, 0.75; 95% confidence interval, 0.50-1.14; P = 0.2; women: relative risk, 1.37;95%confidence interval, 0.82-2.28;P = 0.2). However, we found a significant interaction between gender and the polymorphism on cardiovascular disease (P = 0.02). Conclusions: In this large cohort of individuals with very high risk of cardiovascular disease, the association between the functional ER22/23EK polymorphism and cardiovascular risk was not significant overall, although it varied significantly by gender. Copyrigh