Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.Swedish Research Council Knut and Alice Wallenberg Foundation AFA Foundation Swedish Brain Foundatio

Efficacy and safety of hormonal treatment of cryptorchidism: current state of the art

To access publisher full text version of this article. Please click on the hyperlink in Additional LinkMeta-analyses of randomised trials using hCG or GnRH for treatment on testicular descent show in most studies overall efficacy of about 20%, less if retractile testes were excluded. In recent years a number of potentially serious side effects have been reported. Conclusion: Considering the efficacy and the possible side effects of the hormonal treatment, the general use of hCG and GnRH in the treatment of cryptorchidism cannot be further recommended

Screening for diabetic retinopathy

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldA screening program for diabetic eye disease was established in Iceland in 1980. Diabetics involved in the screening program have a low prevalence of blindness, 1% in type 1 and 1.6% in type 2. We examined ways to make the screening program more efficient by identifying subgroups at low risk of developing eye disease that require treatment and therefore need less frequent screening. We studied whether diabetic eye disease screening programs may be trimmed by excluding children and examining diabetics without retinopathy biannually. Our results indicate that diabetic children under the age of 12 years do not need regular screening for eye disease. Biannual examinations seem to suffice in type 1 and 2 diabetic patients without retinopathy. However, in a setting where the eye clinic is located apart from the diabetes clinics, biannual examinations present practical problems which could result in a less effective screening for diabetic eye disease

Larger head circumference in Icelandic children 0-4 years of age compared to the World Health Organization and Swedish growth charts

AIM: The World Health Organization (WHO) published universal growth standards for children below five year of age in 2006. Traditionally, Swedish growth references have been used to monitor growth of children in Iceland, but it is not yet known how they compare with these reference charts. METHODS: A total of 2128 longitudinal measurements of length or height, 2132 of weight and 2126 of head circumference between birth and four years of age were collected in 1996-2000 from 199 healthy children (53% boys) recruited at Landspitali University Hospital. Measurements were converted to z-scores using the WHO growth standards and Swedish growth references for further analysis with mixed-effects models. RESULTS: Length or height, weight and in particular head circumference largely exceeded the WHO standards, with average z-scores that fluctuated between 0.5 and 1.5. Likewise, the proportion of children with a z-score larger than 2 SD increased about 10-fold. Icelandic children were longer and heavier than their Swedish peers during the first six months of life, but differences were less pronounced thereafter. CONCLUSION: The growth of Icelandic children deviated significantly from the WHO growth standards. Although more comparable to the Swedish references, significant differences were found, suggesting that a national growth reference would be more appropriate.status: publishe

Larger head circumference in Icelandic children 0-4 years of age compared to the World Health Organization and Swedish growth charts.

To access publisher's full text version of this article click on the hyperlink belowAim: The World Health Organization (WHO) published universal growth standards for children below five year of age in 2006. Traditionally, Swedish growth references have been used to monitor growth of children in Iceland, but it is not yet known how they compare with these reference charts. Methods: A total of 2128 longitudinal measurements of length or height, 2132 of weight and 2126 of head circumference between birth and four years of age were collected in 1996-2000 from 199 healthy children (53% boys) recruited at Landspitali University Hospital. Measurements were converted to z-scores using the WHO growth standards and Swedish growth references for further analysis with mixed-effects models. Results: Length or height, weight and in particular head circumference largely exceeded the WHO standards, with average z-scores that fluctuated between 0.5 and 1.5. Likewise, the proportion of children with a z-score larger than 2 SD increased about 10-fold. Icelandic children were longer and heavier than their Swedish peers during the first six months of life, but differences were less pronounced thereafter. Conclusion: The growth of Icelandic children deviated significantly from the WHO growth standards. Although more comparable to the Swedish references, significant differences were found, suggesting that a national growth reference would be more appropriate. Keywords: Growth anthropometry; Iceland; growth reference; growth standards; head circumference

Cabbage Tree Bay, Manly, New South Wales, ca. 1880 [picture] /

Part of collection: Collection of photographs of New South Wales, ca. 1876-1897.; Title devised by cataloguer based on inscription on verso.; "C. Bayliss Photo Sydney" -- photographer's blind stamp lower left.; Inscription: "Cabbage Tree Bay, Manly" --In pencil on verso.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4193262

The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pagePituitary adenomas (PA) are among the most common human neoplasms. To describe the epidemiology and assess the disease burden of clinically significant PAs, population-based studies are needed. Iceland has a small well-defined population. The aim of this study is to describe the epidemiology of PAs in Iceland over an expanded period of time.This is a retrospective observational study, including all PAs diagnosed in Iceland from 1955 to 2012.Extensive clinical information was gathered in a database. Prevalence rates for all PA subtypes were calculated along with standardized incidence rates (SIR). Sex ratios and relationships with adenoma size, age, and symptoms were assessed.We identified 471 individuals: 190 men and 281 women. Total prevalence in 2012 was 115.57/100, 000, prolactinomas were most prevalent (54.37/100, 000) followed by non-functioning adenomas (NFPAs) (42.32/100 ,000). Throughout the period, NFPAs were most common (43.0%) followed by prolactinomas (39.9%) and 11.3% had acromegaly and 5.7% Cushing's disease. Women are diagnosed younger with smaller adenomas. Total SIR has increased significantly and is now 5.8/100 000 per year.In this nationwide study spanning six decades, we have confirmed PAs rising prevalence and incidence rates noted in recent studies. We demonstrated higher overall prevalence and incidence rates than ever previously recorded with an increasing predominance of NFPAs, which is not explained by incidental findings alone. There is a relationship with the introduction of imaging modalities, but the vast majority of patients are symptomatic at diagnosis. This underlines the importance of increased awareness, education, and appropriate allocation of resources for this growing group of patients

Cryptorchidism: classification, prevalence and long-term consequences

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldUndescended testis is a common finding in boys, and the majority of cases have no discernible aetiology. There are unexplained geographical differences and temporal trends in its prevalence. Cryptorchidism, especially bilateral, is associated with impaired spermatogenesis and endocrine function and increases the risk of testicular cancer. There is an urgent need to identify factors that adversely affect testicular development and optimize treatment. Conclusion: Cryptorchidism may reflect a primary testicular maldevelopment with long-term consequences

Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability.

To access publisher's full text version of this article click on the hyperlink belowSequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10(-10)), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7.5% per allele, P = 4.9 × 10(-11) and 7.3% per allele, P = 7.5 × 10(-18), respectively). Variants that increase mean and between-subject variance in fasting glucose levels tend to increase T2D risk, whereas those that increase the mean but reduce variance do not (r(2) = 0.61). The variants that increase between-subject variance increase fasting glucose heritability estimates. Intuitively, our results show that increasing the mean and variance of glucose levels is more likely to cause pathologically high glucose levels than increase in the mean offset by a decrease in variance.NRCI Research Project National Research Council of the Islamic Republic of Ira