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The first families with LRRK2 related Parkinson's disease (PD) were presented around 15 years ago and numerous papers have described the characteristics of the LRRK2 phenotype. The prevalence of autosomal dominant PD varies around the world mainly depending on local founder effects. The highest prevalence of LRRK2 G2019S PD in Norway is located to the central part of the country and most families could be traced back to common ancestors. The typical Norwegian LRRK2 phenotype is not different from classical PD and similar to that seen in most other LRRK2 families. The discovery of LRRK2 PD has allowed us to follow-up multi-incident families and to study their phenotype longitudinally. In the Norwegian LRRK2 families there has been a significantly higher incidence of inflammatory diseases like multiple sclerosis and rheumatoid arthritis that seen in other PD populations. Recent studies in LRRK2 mechanisms have indicated that this protein may be crucial in initiating disease processes. In this short survey of 100 Norwegian mutation carriers followed through more than 15 years are presented. The prevalence of inflammatory diseases among these cases is highlighted. The role of LRRK2 in the conversion process from carrier status to PD phenotype is still unknown and disease generating mechanisms important for initiating LRRK2 PD are still to be identified. [ABSTRACT FROM AUTHOR]

Factitious disorders (FD) like Munchausen syndrome are well known to most physicians, yet the corresponding ICD-10 diagnosis F68.1 remains severely under-assigned and often misdiagnosed. To approach this problem, we conducted a nationwide inquiry for Germany and Norway as well as a comparison between these two countries regarding the incidence of diagnosis of FD. The assignment rates of F68.1 in somatic hospitals from 2008 to 2016 were analyzed based on the Diagnosis Related Groups statistic from the German Federal Statistical Office and the data provided from the Norwegian Patient Registry. The Norwegian data also included information on individual patients whereas the German data only contained the total number of F68.1 assignment due to strict medical confidentiality laws. The incidence of the diagnosis of FD in Germany and Norway showed similar assignment rates with 3.71 and 3.18 per 100,000, respectively. The mean age was 39.4 years for German patients and 35.6 years for Norwegian patients. The gender distribution was almost equal for the individual patients' rate (49% female and 51% male). Furthermore, our results indicate that female patients with FD tend to demand healthcare services more frequently than male patients. Smaller studies focusing on the diagnosis of FD have significantly higher assignment rates compared to nationwide inquiries. Our results illustrate substantial differences between estimations of the incidence of FD and the need for further studies. Besides the many obstacles associated with diagnosis of FD, strict medical confidentiality laws prevent reliable and scientific investigations of this matter. [ABSTRACT FROM AUTHOR]

Background. Systematic studies on factitious disorders and malingering in large populations are rare. To address this issue, we performed a nationwide epidemiological study in Norway on the incidence of these diagnoses in an unselected patient population. In particular, we tried to confirm the diagnoses and to estimate the contribution of Munchausen syndrome to the spectrum of factitious disorders. Methods. We analyzed data obtained from the Norwegian Patient Registry (NPR), which provided a deidentified list of all patients from 2008 to 2016 who had received the ICD-10 diagnosis of F68.1 or the diagnosis code Z76.5. Results. Altogether, 237 patients (99 females; 138 males) received a diagnosis of F68.1. Code Z76.5 was applied to 52 patients (12 females; 40 males), all diagnosed within health institutions. Three of 1700 specialists (somatic specialist, psychologist, or psychiatrist) in private practice had diagnosed a factitious disorder in altogether 87 patients. After contacting these specialists, we could identify no true case of F68.1. For 24 of 146 patients who were equally distributed by gender within health institutions, we managed to identify the diagnosing healthcare providers. Of these 24 patients, only 11 correctly qualified for code F68.1. Only two female patients qualified for a Munchausen syndrome diagnosis. Conclusions. There is a male predominance for the diagnosis of malingering. An earlier suspicion of a female predominance for Munchausen syndrome is upheld. There is significant underdiagnosing and misdiagnosing for both conditions and for factitious disorders in general. To separate the most serious form of factitious disorders from milder forms and to facilitate more systematic research, we recommend a specific ICD diagnosis for Munchausen syndrome. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that variation in the SNCA, MAPT, and GSK3B genes interacts in affecting risk for Parkinson disease (PD). In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD. Three Caucasian PD patient-control series from the United States, Ireland, and Norway (combined n = 1020 patients and 1095 controls) were genotyped for SNCA rs356219, MAPT H1/H2-discriminating SNP rs1052553, and GSK3B rs334558 and rs6438552. Our findings indicate that as previously reported, the SNCA rs356219-G allele and MAPT rs1052553 (H1 haplotype) were both associated with an increased risk of PD, whilst contrary to previous reports, GSK3B variants were not. No pair-wise interaction was observed between SNCA, MAPT, and GSK3B; the risk effects of SNCA rs356219-G and MAPT rs1052553-H1 were seen in a similar manner across genotypes of other variants, with no evidence suggesting synergistic, antagonistic, or deferential effects. In the Caucasian patient-control series examined, risk for PD was influenced by variation in SNCA and MAPT but not GSK3B. Additionally, those three genes did not interact in determining disease risk. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to analyze factors influencing the risk and timing of Alzheimer's disease (AD) in central Norway. The APOE ε4 allele is the only consistently identified risk factor for late onset Alzheimer's disease (LOAD). We have described the allele frequencies of the apolipoprotein E gene (APOE) in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the APOE ε4 allele on the risk and the age at onset of AD in this population. Methods: 376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated. Results: Odds Ratio (OR) for developing AD was significantly increased in carriers of the APOE ε4 allele compared to individuals with the APOE ε3/ε3 genotype. Individuals carrying APOE ε4/ε4 had OR of 12.9 for developing AD, while carriers of APOE ε2/ε4 and APOE ε3/ε4 had OR of 3.2 and 4.2 respectively. The effect of the APOE ε4 allele was weaker with increasing age. Carrying the APOE ε2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the APOE ε4 allele, to 75.3 in carriers of one APOE ε4 allele and 72.9 in carriers of two APOE ε4 alleles. Age at onset in early onset AD (EOAD) was not influenced by APOE ε4 alleles. Conclusion: APOE ε4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly. [ABSTRACT FROM AUTHOR]

Objectives– Mutations in the LRRK2 gene have been associated with both familial and sporadic late-onset Parkinson’s disease. A large number of mutations in this gene have been identified; however, for many of these variants, the pathogenicity and relative frequency are unknown. Herein, we investigate the frequency of a number of recently identified LRRK2 mutations in Norway. Methods– We genotyped eight putatively pathogenic LRRK2 mutations (R793M, R1067Q, I1371V, IVS31+3 A>G, M1869T, R1941H, T2356I and G2385R) in a series of 433 patients with Parkinson’s disease and 587 controls from Norway. An intronic polymorphism previously reported to be associated with disease susceptibility was also examined (rs10506151). Results– The Lrrk2 R793M substitution was found in two healthy individuals. No other LRRK2 mutations were identified in the Norwegian population, and furthermore no association was observed between rs10506151 and Parkinson’s disease ( P = 0.41). Conclusions– LRRK2 mutations other than the Lrrk2 G2019S mutation are rare in Norway. Our results indicate that the Lrrk2 R793M substitution is most likely a rare polymorphism. [ABSTRACT FROM AUTHOR]

• Processing of REE ore from the Fen complex deposit in Norway was studied. • High concentration of TREO can be achieved during rougher flotation. • Process mineralogy methodologies were applied for mineral tracking in flotation of rare earth elements (REE)-bearing minerals. The Fen carbonatite complex, situated in Vestfold and Telemark County, South Norway, is one of the largest known rare earth elements (REE) deposits in Europe with ongoing exploration drilling. Literature regarding the complex processing of the Fen ore is lacking, and thus, the present work investigates for the first time its beneficiation potential and applies process mineralogy studies to understand in a sound manner the performance variations during the processing of REE ore. Flotation kinetics studies revealed that (i) high concentration of total REE-oxide (TREO) can be achieved during rougher flotation; (ii) the high concentration of sulphur (in form of pyrite as main sulphide) can be achieved at the beginning of flotation; (iii) the highest concentration of TREO can be reached after flotation of S. Further processing (i.e., by the addition of cleaning stages and grinding) has a potential to improve the overall recovery of TREO and S. However, the decision of further processing will depend, among other factors, on the definition of following hydrometallurgical routes (e.g., leaching, solvent extraction) and the economic aspects of the overall process. So far, the reported results show that a rather flexible process can be achieved for the material from the Fen deposit. [ABSTRACT FROM AUTHOR]

Abstract: The most common mutation related to Parkinson’s disease (PD) is the p.G2019S mutation in the LRRK2 gene. Global population frequencies and crude estimates of haplotype conservation suggest most carriers are related. A total of 671 Norwegian PD patients and 215 of their family members were screened for the LRRK2 p.G2019S mutation. Twenty-one PD cases and 44 family members were positive for the mutation and all could be traced back to 10 different families. A genealogical study employed data from the Norwegian National Family Record Centre, local parish registers and population censuses. A common ancestor couple (living between 1580 and 1650) was found in six families, and two other families were associated by intermarriage. The remaining two families could not be traced back to either of these ancestors, though chromosome 12q12 haplotype analysis showed p.G2019S carriers shared alleles for 15 markers in the LRRK2 region. The study provides support for a common ancestor in Norwegian families with LRRK2 p.G2019S parkinsonism. The mutation was probably introduced to Norway through tradesmen from Europe. The extended pedigree that now links modern day carriers may help in mapping penetrance modifiers. [ABSTRACT FROM AUTHOR]

The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. More controversial is that the same haplotype has been associated with Parkinson disease (PD). Using H1-specific single-nucleotide polymorphisms, we demonstrate that MAPT H1 is a misnomer and consists of a family of recombining H1 alleles. Population genetics, linkage disequilibrium, and association analyses have shown that specific MAPT H1 subhaplotypes are preferentially associated with Parkinson disease. Using a sliding scale of MAPT H1-specific haplotypes—in age/sex-matched PD cases and controls from central Norway—we have refined the disease association to within an ∼90-kb interval of the 5' end of the MAPT locus. [ABSTRACT FROM AUTHOR]

We investigated the association of Parkinson''s disease (PD) with tau gene H1 haplotypes in the Norwegian population. In a sample of 96 unrelated PD cases and 68 control subjects, we observed an increased risk of PD for persons with the tau H1 haplotype (odds ratio=5.52; 95% confidence interval: 2.64–11.10; P=2.17×10−6). Findings provide evidence that tau participates in the PD pathogenic process and demonstrate the value of isolated populations in mapping complex traits. [Copyright &y& Elsevier]

• Geometallurgical estimations applied to industrial minerals. • Estimation of performance and mineralogical information based neural networks. • Neural network predictions as a cost-effective tool for its use in mining. • Modal mineralogy estimations from bulk chemistry for resource assessment. The present geometallurgical study shows the application of a machine-learning methodology to the prediction of material properties from the Nabbaren nepheline syenite deposit in Norway. The approach used in this study created and tested a shallow neural network along with cluster analysis for the prediction of laboratory concentrate yield and modal mineralogy. The input is bulk chemistry data from the mining company open pit database. The methodology proposed unveils general trends in the deposit to a suitable operational scale for the open pit mine. The accuracy of the prediction models is good, with one of the prediction models achieving a strong correlation coefficient of 0.9. The application of a neural network approach showed a successful attempt in the prediction of concentrate yield and modal mineralogy in the Nabbaren nepheline syenite deposit. However, further investigations in terms of deposit internal variation and mineralogical studies are needed for utilising these prediction models, to further improve the modal mineralogy prediction model by better domaining and for a more representative distribution of samples for modal mineralogy analyses. [ABSTRACT FROM AUTHOR]