IRF4 variants have age-specific effects on nevus count and predispose to melanoma.

High melanocytic nevus count is a strong predictor of melanoma risk. A GWAS of nevus count in Australian adolescent twins identified an association of nevus count with the interferon regulatory factor 4 gene (IRF4 [p = 6 x 10(-9)]). There was a strong genotype-by-age interaction, which was replicated in independent UK samples of adolescents and adults.

An integrated health and social care organisation in Sweden: creation and structure of a unique local public health and social care system.

Research and citizens have noted failures in coordinating health and social services and professionals, and the need to address this issue to realize benefits from increasing specialisation. Different methods have been proposed and one has been structural integration of separate services within one organisation. This paper reports an empirical longitudinal study of the development of an integrated health and social care organisation in Sweden combining service provision, purchasing and political governance for a defined population.

Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign.

Myeloid-derived suppressor cells (MDSC) have emerged as key immune modulators in various tumor models and human malignancies, but their characteristics in humans remain to be unequivocally defined. In this study, we have examined circulating CD14(+)HLA-DR(-/low) MDSC in 34 advanced malignant melanoma (MM) patients. Their frequency is significantly increased and associated with disease activity.

Surgical resection margins do not influence health related quality of life or emotional distress in patients with cutaneous melanoma: results of a prospective randomised trial.

In a prospective randomised Scandinavian trial, patients with localised invasive cutaneous melanoma of the trunk or extremities with tumours more than 2 mm thick were randomly assigned to excision with narrow (2 cm) or wide (4 cm) margins after primary surgery. The aims of the present study were to find out if there were any differences in health-related quality of life (QoL) and emotional distress between patients in the two arms over time. Patients were assessed at four time points: before randomisation, and at 3, 9, and 15 months after inclusion, using the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale and the Impact of Event Scale.

MicroRNA expression profiles associated with mutational status and survival in malignant melanoma.

Malignant cutaneous melanoma is a highly aggressive form of skin cancer. Despite improvements in early melanoma diagnosis, the 5-year survival rate remains low in advanced disease. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment.

Optimisation of tube voltage for conventional urography using a Gd2O2S:Tb flat panel detector.

With the increasing use of computed tomography (CT) for urography examinations, the indications for 'conventional' projection urography have changed and are more focused on high-contrast details. The purpose of the present study was to optimise the beam quality for urography examinations performed with a Gd(2)O(2)S:Tb flat-panel detector for the new conditions. Images of an anthropomorphic phantom were collected at different tube voltages with a CXDI-40G detector (Canon Inc.

The effect of radiation dose reduction on clinical image quality in chest radiography of premature neonates using a dual-side readout technique computed radiography system.

The purpose of the present study was to investigate if the exposure could be reduced from the clinical setting (resulting in an effective dose of 8 microSv for a neonate of weight 0.7 kg and height 25 cm at a tube voltage of 90 kV) without negatively influencing the image quality for a dual-side readout technique computed radiography (CR) system in chest radiography of premature neonates. Chest radiographs of premature neonates were acquired with the double-side readout technique CR system.

Comparison of three methods for determining CT dose profile: presenting the tritium method.

The purpose of the present work was to describe a method of using an imaging plate from a computed radiography system to determine the computed tomography (CT) dose profile (the tritium method) and to compare this method with point-dose measurements using a solid-state detector (CT Dose Profiler; RTI Electronics, Mölndal, Sweden) and the indirect method of comparing the air kerma-length product (P(KL)) at different beam collimations. The three methods were used to determine the full width at half maximum (FWHM) of the dose profile of a multi-slice CT at different nominal beam collimations. For all beam collimations, the obtained deviation between the tritium method and the CT Dose Profiler was smaller than 0.

A practical approach to prioritise among optimisation tasks in X-ray imaging: introducing the 4-bit concept.

According to European and national legislation, as well as international recommendations, X-ray examinations shall be optimised. However, with limited resources and hundreds of different types of X-ray examinations, it may be difficult to prioritise among the optimisation tasks at a radiology department. This work is focused on describing a method that can be used to determine the order of which the examinations should be optimised.

Evaluation of subjective assessment of the low-contrast visibility in constancy control of computed tomography.

The purpose of the present work was to investigate the reliability of subjective assessments of the low-contrast visibility in constancy control of computed tomography (CT). Axial CT images of a low-contrast phantom were acquired on an 8-slice multi-detector CT scanner at nine tube current settings ranging from 75 to 440 mA. Five medical physicists assessed the visibility of the low-contrast details in two sessions.

Genome-wide association study identifies three loci associated with melanoma risk.

We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.

New common variants affecting susceptibility to basal cell carcinoma.

In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.

Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon.

Background: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treatment with recurrence-free interval in two randomized trials that compared intermediate doses of IFN with observation for the treatment of melanoma patients.

Methods: Serum levels of anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined using enzyme-linked immunosorbent assays in 187 and 356 patients in the European Organization for Research and Treatment of Cancer (EORTC) 18952 and Nordic IFN trials, respectively, immediately before and up to 3 years after random assignment.

Use of snus and risk for cardiovascular disease: results from the Swedish Twin Registry.

Objective: To study the association between snus use and the risk for cardiovascular disease, i.e. ischemic heart disease and stroke.

Relations of serum MMP-9 and TIMP-1 levels to left ventricular measures and cardiovascular risk factors: a population-based study.

Background: Extracellular matrix remodeling is a hallmark of pathological left ventricular (LV) hypertrophy and heart failure. This process is tightly controlled by the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We hypothesized that circulating MMP-9 and TIMP-1 levels are altered already in persons with the signs of LV remodeling that forego clinical heart failure.

Species-specific in vivo engraftment of the human BL melanoma cell line results in an invasive dedifferentiated phenotype not present in xenografts.

For clinically relevant studies on melanoma progression and invasiveness, in vivo experimental systems with a human cellular microenvironment would be advantageous. We have compared tumor formation from a human cutaneous malignant melanoma cell line (BL), after injection as conventional xenografts in the mouse, or when injected into a predominantly species-specific environment of human embryonic stem cell-derived teratoma induced in the mouse (the hEST model). The resulting melanoma histology was generally analogous, both systems showing delimited densely packed areas with pleomorphic cells of malignant appearance.

Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site.

A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk signal transduction pathway. Consistent data demonstrate the early appearance, in a mutually exclusive manner, of these mutations. The purpose of this paper is to summarize the literature on NRAS and BRAF activating mutations in melanoma tumors with respect to available data on histogenetic classification as well as body site and presumed UV-exposure.

Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients.

Background: A trial in selected men suggested that antibiotic therapy could be an alternative to appendicectomy in appendicitis. This study aimed to evaluate antibiotic therapy in unselected men and women with acute appendicitis.

Methods: Consecutive patients were allocated to study (antibiotics) or control (surgery) groups according to date of birth.

The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma.

Purpose: We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with stage III-IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the prognosis in stage III-IV malignant melanoma patients.

Family members' perceptions of genetic testing for malignant melanoma--a prospective interview study.

Purpose: The aim was to prospectively explore experiences related to genetic testing for malignant melanoma among unaffected previously untested members of melanoma-prone families in which germline CDKN2A mutations had been identified.

Method: Consecutive members of families with CDKN2A mutation attending a pigmented lesion clinic (n=11) were interviewed and completed questionnaires at four occasions: before genetic testing, at disclosure of genetic test result and six months and one year after disclosure. The following areas were measured: anxiety and depression, risk perception, and sun-related habits.

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.

MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters.

The genetic background of cutaneous malignant melanoma (CMM) includes both germ line aberrations in high-penetrance genes, like CDKN2A, and allelic variation in low-penetrance genes like the melanocortin-1 receptor gene, MC1R. Red-hair colour associated MC1R alleles (RHC) have been associated with red hair, fair skin and risk of CMM. We investigated MC1R and CDKN2A variation in relation to phenotype, clinical factors and CMM risk in the Swedish population.

Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanoma.

Purpose: New prognostic markers are needed for malignant melanoma. Inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) have been described to correlate with progression of melanoma. Moreover, activating mutations in BRAF/NRAS oncogenes are often detected in melanoma.