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Various forms of oral involvement have been reported in patients with neurofibromatosis 1 (NF1). Here, we analyze register‐based associations between NF1 and hospital visits related to oral infections. The Finnish NF1 cohort encompasses all individuals with verified NF1 who have visited the Finnish central and university hospitals in 1987–2011. The Finnish Care Register for Health Care allowed the follow‐up of 1349 individuals with NF1, their 1894 siblings without NF1, and 13,870 matched controls for diagnoses related to oral infections in 1998–2014. We observed clearly increased hazards for hospital visits associated with dental caries (ICD‐10 K02; NF1 vs. controls, hazard ratio [HR] 4.42, 95% CI 3.23–6.04), diseases of pulp and periapical tissues (K04; HR 3.85, 95% CI 2.68–5.54), and gingivitis and periodontal diseases (K05; HR 3.63, 95% CI 2.37–5.56). In contrast, hospital visits related to diseases of salivary glands (K11), and stomatitis and related lesions (K12) did not show significantly increased hazard in NF1 compared with the controls or the non‐NF1 siblings. In conclusion, the findings suggest that hospital visits related to oral infections are relatively common among individuals with NF1. The results highlight the need for early detection, proactive prevention, and timely treatment of oral infections in individuals with NF1. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze hypertension in neurofibromatosis type 1 (NF1) in a Finnish population‐based cohort in 1996–2014. Methods: A cohort of 1365 individuals with confirmed NF1 was compared with a control cohort of 13,923 individuals matched for age, sex, and area of residence. Diagnoses of hypertension were retrieved from the Finnish Care Register for Health Care. These registered data were separately analyzed for secondary and essential hypertension. Purchases of antihypertensive drugs were queried from the Finnish Register of Reimbursed Drug Purchases. Results: We identified 115 NF1 patients with hospital diagnosis of hypertension. Our findings revealed a hazard ratio (HR) of 1.64 (95% CI 1.34–2.00, p < 0.001) in NF1 versus controls. NF1 patients presented with a significantly increased hazard for both secondary hypertension (n = 9, HR 3.76, 95% CI 1.77–7.95, p < 0.001) and essential hypertension (n = 98, HR 1.73, 95% CI 1.39–2.14, p < 0.001). No difference in the HR of hypertension was observed between men and women, while NF1 patients with essential hypertension were, on average, younger than the controls. The proportions of individuals with antihypertensive medication did not differ between NF1 patients and controls (OR 0.85). Conclusion: NF1 is a risk factor for hypertension. Despite the recognized risk for secondary hypertension, essential hypertension is the predominant type in NF1. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary exercise testing with lactate and ammonia samples is used in the diagnostics of metabolic myopathies. As the effect of age and sex on the exercise lactate and ammonia levels are incompletely characterized for clinical associations, our aim was to assess the effects of these factors on healthy subjects to improve the test's interpretation. Methods: Seventy‐three subjects (34 men and 39 women; age < 35 years, n = 26, 35–50 years, n = 23 and >50 years, n = 24) performed cardiopulmonary exercise tests with venous blood gases, plasma lactate and ammonia analyses at rest, during exercise, and 2, 4, 6, 10, 20 and 30 min into recovery. Results: The lactate (p = 0.021–0.044) and ammonia values (p = 0.002–0.038) differed between men and women measured during recovery and between three age groups point‐by‐point in maximal exercise and the recovery phase and also longitudinally, most notably between <35‐ and >50‐year‐groups (lactate p = <0.001–0.040, ammonia p = 0.002–0.03). In the linear model, the yearly reduction of lactate was maximally −0.119 mmol/L and that of ammonia −1.514 µmol/L. The yearly reduction of lactate was greater in women than in men (−0.131 vs.−0.099 2 min into recovery), but for ammonia, the results were not as clear. Conclusions: Plasma lactate and ammonia concentrations measured during cardiopulmonary exercise were lower in older age groups, and their yearly reduction was also influenced by sex. These data give new information on lactate and ammonia levels and the effect of aging on them during exercise and recovery and may help assess cardiopulmonary exercise testing results. [ABSTRACT FROM AUTHOR]

Introduction: The long‐term risk of cancer among first‐degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers. Material and methods: Using registry data, we conducted a retrospective cohort study with a total of 6501 first‐degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach). Results: The overall number of cancers was not increased among the first‐degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27–2.79), mostly explained by a 2.30‐fold (95% CI 1.46–3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient. Conclusions: In our study cohort, we did not observe an increase in the overall cancer risk among the first‐degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives. [ABSTRACT FROM AUTHOR]

While the serotypes of Streptococcus pneumoniae are known to compete during colonization in human hosts, our knowledge of how competition occurs is still incomplete. New insights of pneumococcal between‐type competition could be generated from carriage data obtained by molecular‐based detection methods, which record more complete sets of serotypes involved in co‐carriage than when detection is done by culture. Here, we develop a Bayesian estimation method for inferring between‐type interactions from longitudinal data recording the presence/absence of the types at discrete observation times. It allows inference from data containing co‐carriage of two or more serotypes, which is often the case when pneumococcal presence is determined by molecular‐based methods. The computational burden posed by the increased number of types detected in co‐carriage is addressed by approximating the likelihood under a multi‐state model with the likelihood of only those trajectories with minimum number of acquisition and clearance events between observation times. The proposed method's performance was validated on simulated data. The estimates of the interaction parameters of acquisition and clearance were unbiased in settings with short sampling intervals between observation times. With less frequent sampling, the estimates of the interaction parameters became more biased, but their ratio, which summarizes the total interaction, remained unbiased. Confounding due to unobserved heterogeneity in exposure could be corrected by including individual‐level random effects. In an application to empirical data about pneumococcal carriage in infants, we found new evidence for between‐serotype competition in clearance, although the effect size was small. [ABSTRACT FROM AUTHOR]

Objectives: Clinical diagnostics in adults with hereditary neurological diseases is complicated by clinical and genetic heterogeneity, as well as lifestyle effects. Here, we evaluate the effectiveness of exome sequencing and clinical costs in our difficult‐to‐diagnose adult patient cohort. Additionally, we expand the phenotypic and genetic spectrum of hereditary neurological disorders in Finland. Methods: We performed clinical exome sequencing (CES) to 100 adult patients from Finland with neurological symptoms of suspected genetic cause. The patients were classified as myopathy (n = 57), peripheral neuropathy (n = 16), ataxia (n = 15), spastic paraplegia (n = 4), Parkinsonism (n = 3), and mixed (n = 5). In addition, we gathered the costs of prior diagnostic work‐up to retrospectively assess the cost‐effectiveness of CES as a first‐line diagnostic tool. Results: The overall diagnostic yield of CES was 27%. Pathogenic variants were found for 14 patients (in genes ANO5, CHCHD10, CLCN1, DES, DOK7, FKBP14, POLG, PYROXD1, SCN4A, TUBB3, and TTN) and likely pathogenic previously undescribed variants for 13 patients (in genes ABCD1, AFG3L2, ATL1, CACNA1A, COL6A1, DYSF, IRF2BPL, KCNA1, MT‐ATP6, SAMD9L, SGCB, and TPM2). Age of onset below 40 years increased the probability of finding a genetic cause. Our cost evaluation of prior diagnostic work‐up suggested that early CES would be cost‐effective in this patient group, in which diagnostic costs increase linearly with prolonged investigations. Conclusions: Based on our results, CES is a cost‐effective, powerful first‐line diagnostic tool in establishing the molecular diagnosis in adult neurological patients with variable symptoms. Importantly, CES can markedly shorten the diagnostic odysseys of about one third of patients. [ABSTRACT FROM AUTHOR]

Introduction: Hysterectomy has been one of the most common surgical procedures in women in Finland. We studied the population‐based trends of hysterectomy and its indications from 1986 to 2017. Material and methods: A retrospective population‐based cohort was created from the Care Register for Health Care by identifying women who had a hysterectomy from 1986 to 2017 and calculating the number of women from the Digital and Population Data Services Agency. We estimated the number and incidence of hysterectomy by period and age as well as by indication. We considered the primary diagnosis at the time of surgery as the indication of hysterectomy. Results: The number of hysterectomies increased from 7492 procedures in 1986 to 12 404 procedures in 1998, and reduced substantially after that to 5971 procedures in 2017, the turning point being in 1999. The incidence rate of hysterectomy has decreased on average by 2.5% annually from 432.6 per 100 000 women in 1998–2001 to 224.5 per 100 000 women in 2014–2017. The median age at the time of hysterectomy has increased from 51 years in 1998–2001 to 55 years in 2014–2017. The cumulative burden of hysterectomy by age of 60 years has nearly halved from the first 4‐year period (23%) to the last (12%). After 2010, the most common indication has been genital prolapse and incontinence, whereas earlier it was uterine fibroids. Conclusions: The number and incidence of hysterectomies have fluctuated during the observation period 1986–2017 and decreased considerably during the past 17 years in Finland. This is probably a result of the availability of hormonal and other conservative treatment options for bleeding disorders and uterine fibroids. As hysterectomy practically removes the risk for endometrial cancer, the change in hysterectomy incidence over time emphasizes the importance of correcting endometrial cancer incidence according to hysterectomy incidence. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme‐labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy taken <12 months apart, a mitochondrial disorder would have been identified in 70% with analysis of FGF21 and GDF15 compared to 50% of patients whom could have been identified with muscle biopsy alone. Muscle findings were nondiagnostic in 72% (children) and 45% (adults). Induction of FGF21 and GDF15 suggest a mitochondrial etiology as an underlying cause of a muscle manifesting disease. Normal biomarker values do not, however, rule out a mitochondrial disorder, especially if the disease does not manifest in muscle. We suggest that FGF21 and GDF15 together should be first‐line diagnostic investigations in mitochondrial disease complementing muscle biopsy. [ABSTRACT FROM AUTHOR]

Objective: ITPR3, encoding inositol 1,4,5‐trisphosphate receptor type 3, was previously reported as a potential candidate disease gene for Charcot‐Marie‐Tooth neuropathy. Here, we present genetic and functional evidence that ITPR3 is a Charcot‐Marie‐Tooth disease gene. Methods: Whole‐exome sequencing of four affected individuals in an autosomal dominant family and one individual who was the only affected individual in his family was used to identify disease‐causing variants. Skin fibroblasts from two individuals of the autosomal dominant family were analyzed functionally by western blotting, quantitative reverse transcription PCR, and Ca2+ imaging. Results: Affected individuals in the autosomal dominant family had onset of symmetrical neuropathy with demyelinating and secondary axonal features at around age 30, showing signs of gradual progression with severe distal leg weakness and hand involvement in the proband at age 64. Exome sequencing identified a heterozygous ITPR3 p.Val615Met variant segregating with the disease. The individual who was the only affected in his family had disease onset at age 4 with demyelinating neuropathy. His condition was progressive, leading to severe muscle atrophy below knees and atrophy of proximal leg and hand muscles by age 16. Trio exome sequencing identified a de novo ITPR3 variant p.Arg2524Cys. Altered Ca2+‐transients in p.Val615Met patient fibroblasts suggested that the variant has a dominant‐negative effect on inositol 1,4,5‐trisphosphate receptor type 3 function. Interpretation: Together with two previously identified variants, our report adds further evidence that ITPR3 is a disease‐causing gene for CMT and indicates altered Ca2+ homeostasis in disease pathogenesis. [ABSTRACT FROM AUTHOR]

Poor chemotherapy response remains a major treatment challenge for high‐grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient‐derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment‐naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment‐naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment‐naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K‐mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K‐mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment‐naive tumours. EGFR, mTOR‐PI3K and aurora kinase inhibitors are candidates for targeting this cell population. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: In this study we assessed the value of genetic screening for Fabry disease (FD) and hereditary ATTR amyloidosis in patients with idiopathic small-fiber neuropathy (SFN) or mixed neuropathy in a clinical setting.Methods: This was a Nordic multicenter study with 9 participating centers. Patients with idiopathic SFN or mixed neuropathy were included. Genetic sequencing of the TTR and GLA genes was performed.Results: There were 172 patients enrolled in the study. Genetic screening was performed in 155 patients. No pathogenic mutations in the TTR gene were found. A single patient had a possible pathogenic variant, R118C, in the GLA gene, but clinical investigation showed no firm signs of FD.Discussion: Screening for hereditary ATTR amyloidosis and FD in patients with idiopathic SFN or mixed neuropathy without any additional disease-specific symptoms or clinical characteristics in a Nordic population appears to be of little value in a clinical setting. Muscle Nerve 59:354-357, 2019. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Patients with unknown clinical or radiological asymmetry in the face structures combined with atrophy and weakness of the masticatory muscles should be comprehensively examined clinically and with MRI, neurophysiological measurements, and serologically. Malignant lesions or benign idiopathic unilateral trigeminal motor neuropathy should be considered as an etiological explanation for the asymmetry. [ABSTRACT FROM AUTHOR]

Cognition, sleep and estrogen - menopause is really not just about hot flashes Although these studies often have not been absolutely perfectly designed, we can be quite confident, that HRT prevents osteoporosis, can protect from cardiovascular disease if started early in menopause, and can increase breast cancer risk, if estrogen-progesterone therapy is given. The finding that good sleep perhaps protects from Alzheimer's disease has relevance to estrogens and menopause. [Extracted from the article]

Objectives Mutations in the CHCHD10 gene, which encodes a mitochondrially targeted protein, have emerged as an important cause of motor neuron disease and frontotemporal lobar degeneration. The aim of this study was to assess the clinical variability in a large family carrying the p.Gly66Val mutation of the CHCHD10 gene. This mutation has recently been reported to cause late-onset spinal muscular atrophy ( SMAJ) or sensorimotor axonal Charcot-Marie-Tooth neuropathy ( CMT2) in the Finnish population. Materials and methods Nine affected members of an extended Finnish pedigree were included in the study. Detailed clinical and neurophysiological examinations were performed. The CHCHD10 p.Gly66Val mutation was examined by Sanger sequencing. Results The heterozygous p.Gly66Val mutation was present in all affected individuals from whom a DNA sample was available. The clinical phenotype varied from proximal sensorimotor neuropathy to spinal muscular atrophy and in one case resembled motor neuron disease ALS at its early stages. The age of onset varied from 30 to 73 years. Conclusions Our data demonstrate that even within the same family, the p.Gly66Val variant can cause variable phenotypes ranging from CMT2-type axonal neuropathy to spinal muscular atrophy, which may also present as an ALS-like disease. The spectrum of CHCHD10-related neuromuscular disease has widened rapidly, and we recommend keeping the threshold for genetic testing low particularly when dominant inheritance or mitochondrial pathology is present. [ABSTRACT FROM AUTHOR]

We evaluated the overall coverage, frequency and costs of Pap testing by screening modality and health care provider in Finland. Information about Pap testing in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. Among women aged 25-69 years, 87% had had a Pap test taken within or outside the organised programme at least once during the last 5 years and half of those screened in the organised programme had also had at least one Pap test taken outside the programme. Of the annual average of 530,000 Pap tests taken, 84% were taken for screening purposes and 16% as follow-up. Forty percent of the 446,000 annual screening tests were taken in the organised programme, 55% as opportunistic tests in public primary or student health care or by private providers and 5% in public secondary health care. One-fifth of all opportunistic screening Pap tests were taken from women aged <25. The voluminous opportunistic Pap testing in public primary health care was concentrated in young women aged 25-29 whereas the bulk of opportunistic testing in private health occurred in age groups eligible for organised screening. The total cost of all screening Pap tests was €22.4 million, of which 71% incurred in opportunistic screening. Of the 84,000 annual follow-up Pap tests and their €8.3 million total costs, ∼60% incurred in organised screening or in secondary health care. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the total burden and health care provider costs of prevention, management and treatment of HP-related genital disease outcomes including all organized and opportunistic screening tests. Information about HPV-related disease outcomes in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. We estimated the incidence, health care resource use, health provider costs and life years lost due to cervical, vaginal and vulvar cancer and intraepithelial neoplasia (CIN, VaIN, VIN), cervical adenocarcinoma in situ, and external genital warts. The average annual disease burden of HPV-related genital disease in the female population of Finland comprises altogether 241 cases of cervical, vaginal and vulvar cancer, 2,898 new cases of CIN, 34,432 cases of minor cytological abnormalities, and almost 4,000 cases of external genital warts. The total annual costs of screening, further diagnostics and treatment of HPV-related genital disease were €44.7 million of which the annual costs due to cervical cancer screening were €22.4 million and due to diagnostics, management and treatment of HPV-related genital disease outcomes were €22.3 million. The latter included €8.4 million due to minor cervical abnormalities detected by the current cervical screening practice. The extensive opportunistic Pap testing fails to keep the incidence of cervical cancer from increasing among women aged 30-34. In addition opportunistic screening among this and younger age group detects a significant number of cytological abnormalities, most of which are probably treated unnecessarily. [ABSTRACT FROM AUTHOR]

We describe a novel Bayesian approach to estimate acquisition and clearance rates for many competing subtypes of a pathogen in a susceptible-infected-susceptible model. The inference relies on repeated measurements of the current status of being a non-carrier (susceptible) or a carrier (infected) of one of the n q > 1 subtypes. We typically collect the measurements with sampling intervals that may not catch the true speed of the underlying dynamics. We tackle the problem of incompletely observed data with Bayesian data augmentation, which integrates over possible carriage histories, allowing the data to contain intermittently missing values, complete dropouts of study subjects, or inclusion of new study subjects during the follow-up. We investigate the performance of the described method through simulations by using two different mixing groups (family and daycare) and different sampling intervals. For comparison, we describe crude maximum likelihood-based estimates derived directly from the observations. We apply the estimation algorithm to data about transmission of Streptococcus pneumonia in Bangladeshi families. The computationally intensive Bayesian approach is a valid method to account for incomplete observations, and we found that it performs generally better than the simple crude method, in particular with large amount of missing data. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To survey the centers that can provide subspecialty surgical training and education in gynecological oncology in the Nordic countries, we developed an online questionnaire in co-operation with the Nordic Society of Gynecological Oncology. The link to the survey was mailed to 22 Scandinavian gynecological centers in charge of surgical treatment of cancer patients. Twenty (91%) centers participated. Four centers reported to be accredited European subspecialty training centers, a further six were interested in being accredited, and 11 centers were accredited by the respective National Board. Fourteen (74%) centers were interested in being listed for exchange of fellows. Our data show a large Nordic potential and interest in improving the gynecologic oncology standards and can be used to enhance the awareness of gynecologic oncology training in Scandinavia and to facilitate the exchange of fellows between Nordic countries. [ABSTRACT FROM AUTHOR]

Objective/Design. We performed a systematic review of studies that evaluate the role of gynecological cancer surveillance in women who carry a hereditary nonpolyposis colorectal cancer (HNPCC) mutation or belong to a family that fulfills the criteria for HNPCC. Methods. The PubMed database and a clinical trials database were used to identify relevant studies. We included studies that reported results of gynecological cancer surveillance in women who carry a HNPCC mutation, belong to a family in which a HNPCC mutation was detected or belong to a family fulfilling the Amsterdam II criteria. Main Outcome Measures. Number and stage of cancers, interval cancers and cancer precursor states detected at screening. Results. Five studies fulfilled our review criteria. Surveillance modalities for endometrial cancer included transvaginal ultrasound combined with endometrial sampling when indicated, or transvaginal ultrasound with a routine endometrial biopsy, and, in certain studies, the tumor marker CA-125. The highest yield of pathological findings in surveillance visits, from 5 to 6.5%, occurred in studies that included routine endometrial biopsies. Without a routine sampling, 7/14 cancers and 11/18 hyperplasias would have been missed. One case of advanced ovarian cancer was detected at surveillance. Conclusions. Currently available published studies on gynecological cancer surveillance in women with HNPCC do not adequately allow for evidence-based clinical decisions. Detection of endometrial cancer or hyperplasia in nonsymptomatic women belonging to an HNPCC family is improved by adding routine endometrial sampling along with transvaginal ultrasound for surveillance visits. No benefit was shown for ovarian cancer surveillance. [ABSTRACT FROM AUTHOR]

Previously, we introduced the use of individual cortical location and orientation constraints in the spatiotemporal Bayesian dipole analysis setting proposed by Jun et al. ([2005]; Neuroimage 28:84-98). However, the model's performance was limited by slow convergence and multimodality of the numerically estimated posterior distribution. In this paper, we present an intuitive way to exploit functional magnetic resonance imaging (fMRI) data in the Markov chain Monte Carlo sampling -based inverse estimation of magnetoencephalographic (MEG) data. We used simulated MEG and fMRI data to show that the convergence and localization accuracy of the method is significantly improved with the help of fMRI-guided proposal distributions. We further demonstrate, using an identical visual stimulation paradigm in both fMRI and MEG, the usefulness of this type of automated approach when investigating activation patterns with several spatially close and temporally overlapping sources. Theoretically, the MEG inverse estimates are not biased and should yield the same results even without fMRI information, however, in practice the multimodality of the posterior distribution causes problems due to the limited mixing properties of the sampler. On this account, the algorithm acts perhaps more as a stochastic optimizer than enables a full Bayesian posterior analysis. Hum Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A recently introduced Bayesian model for magnetoencephalographic (MEG) data consistently localized multiple simulated dipoles with the help of marginalization of spatiotemporal background noise covariance structure in the analysis [Jun et al., (): Neuroimage 28:84-98]. Here, we elaborated this model to include subject's individual brain surface reconstructions with cortical location and orientation constraints. To enable efficient Markov chain Monte Carlo sampling of the dipole locations, we adopted a parametrization of the source space surfaces with two continuous variables (i.e., spherical angle coordinates). Prior to analysis, we simplified the likelihood by exploiting only a small set of independent measurement combinations obtained by singular value decomposition of the gain matrix, which also makes the sampler significantly faster. We analyzed both realistically simulated and empirical MEG data recorded during simple auditory and visual stimulation. The results show that our model produces reasonable solutions and adequate data fits without much manual interaction. However, the rigid cortical constraints seemed to make the utilized scheme challenging as the sampler did not switch modes of the dipoles efficiently. This is problematic in the presence of evidently highly multimodal posterior distribution, and especially in the relative quantitative comparison of the different modes. To overcome the difficulties with the present model, we propose the use of loose orientation constraints and combined model of prelocalization utilizing the hierarchical minimum-norm estimate and multiple dipole sampling scheme. Hum Brain Mapp 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The number of newly diagnosed cancer cases is increasing across Europe, much due to the increasing age of the population and exposure to risk factors such as obesity and smoking.[1] At the same time, treatment options for cancer are expanding, but many of these new drugs are costly. Cervical cancer screening was the first full-scale cancer screening program to be implemented in the Nordic countries. The EU report[5] shows that of the estimated 153 million women and men in the age group 50-74 years of age, 72% are already targeted by colorectal cancer screening in EU Member States which have adopted at least some policies to implement, pilot or plan for population-based screening programs. [Extracted from the article]

Disappointments in replicating initial findings in gene mapping for complex traits are often attributed to small sample sizes and inadequate techniques to determine the threshold value. This is clearly not the whole truth. More fundamental reasons lie in the inherent heterogeneity related to disease, including genetic heterogeneity, differences in allele frequencies, and context-dependency in genetic architecture. There are also other reasons related to the data collection and analysis. Replication may remain a source of frustration unless more emphasis is put on controlling these sources of heterogeneity between studies. [ABSTRACT FROM AUTHOR]