The success of genome-wide association studies (GWAS) in identifying common, low-penetrance variant-cancer associations for the past decade is undisputed. However, discovering additional ...high-penetrance cancer mutations in unknown cancer predisposing genes requires detection of variant-cancer association of ultra-rare coding variants. Consequently, large-scale next-generation sequence data with associated phenotype information are needed. Here, we used genotype data on 166,281 Icelanders, of which, 49,708 were whole-genome sequenced and 408,595 individuals from the UK Biobank, of which, 41,147 were whole-exome sequenced, to test for association between loss-of-function burden in autosomal genes and basal cell carcinoma (BCC), the most common cancer in Caucasians. A total of 25,205 BCC cases and 683,058 controls were tested. Rare germline loss-of-function variants in
conferred substantial risks of BCC (OR, 8.0;
= 1.9 × 10
), with a quarter of carriers getting BCC before age 70 and over half in their lifetime. Furthermore, common variants at the
locus were associated with BCC, suggesting
as a new, high-impact BCC predisposition gene. A follow-up investigation of 24 cancers and three benign tumor types showed that
loss-of-function variants are associated with high risk of cervical cancer (OR, 12.7,
= 1.6 × 10
) and low age at diagnosis. Our findings, using power-increasing methods with high-quality rare variant genotypes, highlight future prospects for new discoveries on carcinogenesis. SIGNIFICANCE: This study identifies the tumor-suppressor gene
as a high-impact BCC predisposition gene and indicates that inactivation of
by germline sequence variants may also lead to increased risk of cervical cancer.
ObjectivePituitary 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.DesignThis is a retrospective observational study, including all PAs diagnosed in Iceland from 1955 to 2012.MethodsExtensive 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.ResultsWe 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.ConclusionIn 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.
Ultra thin platinum films were grown by dc magnetron sputtering on thermally oxidized Si (1 0 0) substrates. The electrical resistance of the films was monitored in situ during growth. The ...coalescence thickness was determined for various growth temperatures and found to increase from 1.1 nm for films grown at room temperature to 3.3 nm for films grown at 400 deg C. A continuous film was formed at a thickness of 2.9 nm at room temperature and 7.5 nm at 400 deg C. The room temperature electrical resistivity decreases with increased growth temperature, while the in-plain grain size and the surface roughness, measured with a scanning tunneling microscope (STM), increase. Furthermore, the temperature dependence of the film electrical resistance was explored at various stages during growth.
The FLOHOF field campaign took place in the period July 21 to August 24, 2007 on and in the surroundings of Hofsjökull glacier in Central Iceland. During the campaign, 18 automatic weather stations ...(AWS) recording temperature, humidity, wind speed, wind direction, pressure, and precipitation were deployed on and around the glacier. In addition, atmospheric soundings were performed N and S of Hofsjökull by a tethered balloon, pilot balloons, and two unmanned aerial systems (UAS). An energy balance station, consisting of a net radiometer and an eddy correlation flux measurement station, has also been installed. This paper describes the experimental setup of the campaign and presents first results of the data analysis with respect to transience of mountain-induced gravity waves, the extension of katabatic winds into the surrounding of the glacier, the occurrence of katabatic microfronts, and report on novel approaches to probe the vertical structure of the atmospheric boundary layer by UAS. The observed pressure perturbations related to transient gravity wave activity due to changing inflow conditions were between −2 and 2 hPa in general, with positive values upstream and negative values downstream. Differential heating of the glacier and its surrounding is triggering daytime katabatic flow from the glacier into its surrounding. During the campaign, those katabatic winds typically reached out 4–7 km from the edge of the glacier. During late night in clear sky conditions, frontal-like microstructures have been observed frequently with typical repetition times in the order of 30–60 min indicating the interaction of large-scale synoptic and nighttime katabatic density flows close to the ground. The first research application of the newly developed small unmanned meteorological observer proved the applicability of the system for atmospheric boundary layer research by successfully profiling the atmosphere up to 3.5 km above ground.
People who are experiencing alcohol withdrawal are disadvantaged in terms of their ability to cope with leading questions and interrogative pressure (i.e. interrogative suggestibility). What had not ...been studied previously was the relationship of the severity of alcohol withdrawal symptoms with suggestibility and compliance. Suggestibility and compliance scores, obtained during the first week of hospital admission, were correlated with the severity of alcohol symptoms measured on a daily basis over a 7-day period in a group of 393 patients attending treatment for alcohol abuse problems. Separate analyses were performed for the male and female patients. Significant gender differences emerged. Among males, alcohol withdrawal symptoms correlated positively with suggestibility and compliance across days. In contrast, among the females alcohol withdrawal symptoms were not significantly correlated with suggestibility and compliance, but were related to confabulations in memory recall. The findings suggest that in relation to psychological vulnerabilities during questioning, alcohol withdrawal symptoms are associated with different psychological factors in males and females. The findings have implications for the potential unreliability of information obtained from people interviewed during alcohol withdrawal.
The purpose of this study was to investigate the factors that differentiate best between alcoholic patients who kept their one-year follow-up research appointment and those who did not. Patients ...attending hospital for alcohol detoxification treatment in Reykjavik were assessed psychologically during the first week of their treatment. One year later they were asked to attend a follow-up appointment for a further psychological evaluation. A total of 313 patients were assessed, 70% were male and 30% were female. Eighty-three (27%) of the patients attended the follow-up appointment. Those who failed to keep their follow-up appointment were significantly younger than the other patients, were more disordered in their personality, had higher trait anxiety, and lower social desirability scores. The severity of their alcohol withdrawal symptoms at the time of treatment was not a significant factor. A discriminant function analysis showed that EPQ Psychoticism was the single best factor that discriminated between the two groups after taking into account other variables, including the age of participants and social desirability.
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