Properties and behavior of quartz for the silicon process

PhD i geologi og bergteknikkPhD in Geology and Mineral Resources Engineerin

Long-Term Outcomes of Genetic Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1-2% of people by the age of 70 years. Age is the most important risk factor, and most cases are sporadic without any known environmental or genetic causes. Since the late 1990s, mutations in the genes SNCA, PRKN, LRRK2, PINK1, DJ-1, VPS35, and GBA have been shown to be important risk factors for PD. In addition, common variants with small effect sizes are now recognized to modulate the risk for PD. Most studies in genetic PD have focused on finding new genes, but few have studied the long-term outcome of patients with the specific genetic PD forms. Patients with known genetic PD have now been followed for more than 20 years, and we see that they may have distinct and different prognoses. New therapeutic possibilities are emerging based on the genetic cause underlying the disease. Future medication may be based on the pathophysiology individualized to the patient's genetic background. The challenge is to find the biological consequences of different genetic variants. In this review, the clinical patterns and long-term prognoses of the most common genetic PD variants are presented.publishedVersionCopyright © 2020 The Korean Movement Disorder Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

Bilateral Optic Neuritis Associated with the Use of Infliximab

A 40 year old man was admitted with a 2 weeks history of headache, blurred vision and bilateral optic neuritis. During the 6 months period prior to admission he had treated with infliximab infusions for prsoriasis arthritis. He had 0.2 vision in right eye and 0.5 in left Fundoscopy showed moderate disc swelling more on the right than on the left side and right-sided splinter heamorrhages at the disc margin. The intracranial pressure was normal. He was treated with oral methylprednisolone, 100 mg daily for 1 week. His vision improved gradually and when seen 10 weeks later his visual acuity was 1.0 in both eyes and he had normal visual fields. Optic neuritis is a rare but well recognized serious adverse effect of treatments with tumor necrosis factor (TNF) antagonists. This case report illustrates a rare but typical side effect of a TNF alpha inhibitors used for treating a number of inflammatory diseases. These reactions usually appear during first year of treatments and never after the first one or two infusions. Both genders and all ages are affected. In some patients the visual defects are irreversible

The effect of graphite filler in sample preparation for automated mineralogy – a preliminary study

Mineral particulate sample material is often prepared as polished sections for SEM based automated quantitative mineralogical analysis. A common practice is to mix ultra-pure graphite with sample material to avoid segregation and touching particles, and aid random orientation, as suggested by Jackson et al. (1984). However, the actual effect of adding graphite on these parameters is not well documented. This paper presents a preliminary study on the effect of adding graphite on segregation and touching particles. A mineral particle concentrate, with equal volumes of quartz and pyrite, was made in two size fractions (53 74 µm and 104-147 µm). Each fraction was mixed with graphite in sample:graphite weight ratios 1:1 and 1:2. In addition, 1:3 was made for the finer fraction. Two types of graphite were used: fine grained (<20 µm) ultra-pure graphite, and coarse grained ultra-pure graphite in the same size range as the sample material. Reference samples without graphite were made for both fractions.The results suggest that using graphite as filler does not necessarily prevent segregation. However, it introduces a positive effect on preventing touching particles; fine graphite is the most efficient. The epoxy resin:sample ratio needs to be better controlled to confirm the results.publishedVersionCopyright © 2018 by the authors

Clinical and Imaging Markers of Prodromal Parkinson's Disease

The diagnosis of Parkinson's disease (PD) relies on the clinical effects of dopamine deficiency, including bradykinesia, rigidity and tremor, usually manifesting asymmetrically. Misdiagnosis is common, due to overlap of symptoms with other neurodegenerative disorders such as multiple system atrophy and progressive supranuclear palsy, and only autopsy can definitively confirm the disease. Motor deficits generally appear when 50–60% of dopaminergic neurons in the substantia nigra are already lost, limiting the effectiveness of potential neuroprotective therapies. Today, we consider PD to be not just a movement disorder, but rather a complex syndrome non-motor symptoms (NMS) including disorders of sleep-wake cycle regulation, cognitive impairment, disorders of mood and affect, autonomic dysfunction, sensory symptoms and pain. Symptomatic LRRK2 mutation carriers share non-motor features with individuals with sporadic PD, including hyposmia, constipation, impaired color discrimination, depression, and sleep disturbance. Following the assumption that the pre-symptomatic gene mutation carriers will eventually exhibit clinical symptoms, their neuroimaging results can be extended to the pre-symptomatic stage of PD. The long latent phase of PD, termed prodromal-PD, represents an opportunity for early recognition of incipient PD. Early recognition could allow initiation of possible neuroprotective therapies at a stage when therapies might be most effective. The number of markers with the sufficient level of evidence to be included in the MDS research criteria for prodromal PD have increased during the last 10 years. Here, we review the approach to prodromal PD, with an emphasis on clinical and imaging markers and report results from our neuroimaging study, a retrospective evaluation of a cohort of 39 participants who underwent DAT-SPECT scan as part of their follow up. The study was carried out to see if it was possible to detect subclinical signs in the preclinical (neurodegenerative processes have commenced, but there are no evident symptoms or signs) and prodromal (symptoms and signs are present, but are yet insufficient to define disease) stages of PD.publishedVersionCopyright © 2020 Hustad and Aasly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Increased Mortality in Young-Onset Parkinson's Disease

Objective Few studies have followed Parkinson’s disease (PD) patients from the time of diagnosis to the date of death. This study compared mortality in the Trondheim PD cohort to the general population, investigated causes of death and analyzed the associations between mortality and age at disease onset (AAO) and cognitive decline defined as Montreal Cognitive Assessment (MoCA) score below 26. Methods The cohort was followed longitudinally from 1997. By the end of January 2020, 587 patients had died. Comparisons to the Norwegian population were performed by calculating standardized mortality ratios (SMRs). Survival curves were estimated using the standard Kaplan-Meier estimator, and multivariable Cox proportional hazard models were estimated to investigate associations. Results SMR was 2.28 [95% confidence interval (CI): 2.13–2.44] for the whole cohort. For participants with AAO 20–39 years, the SMR was 5.55 (95% CI: 3.38–8.61). Median survival was 15 years (95% CI: 14.2–15.5) for the whole cohort. Early-onset PD (EOPD) patients (AAO < 50 years) had the longest median survival time. For all groups, there was a significant shortening in median survival time and an almost 3-fold higher age- and sex-adjusted hazard ratio for death when the MoCA score decreased below 26. Conclusion PD patients with an AAO before 40 years had a more than fivefold higher mortality rate compared to a similar general population. EOPD patients had the longest median survival; however, their life expectancy was reduced to a greater degree than that of late-onset PD patients. Cognitive impairment was strongly associated with mortality in PD.publishedVersio

Mineralogy and texture of the Storforshei iron formation, and their effect on grindability

Investigating how ore mineralogy and texture affect the recovery from the processing plant is important for any mining operation. The results will assist in production planning and optimising the utilisation of a deposit. Easily available validated tests are desirable and useful. The Storforshei iron formation (IF) consists of several iron oxide deposits with mineralogical and textural differences. Although the Fe grades of the ores are similar, mineralogical and textural characteristics of the deposits affect the individual recoveries from the magnetic separation. For this paper three of the ore deposits were sampled, and important mineralogical and textural properties were investigated and tested. The investigations included geological mapping and optical microscopy, and the test work involved surface hardness measurements by Schmidt hammer and Equotip, and autogenous milling tests (i.e., grindability). The aim of the study was to investigate whether ore mineralogy and textures can be correlated to surface hardness measurements, and whether these three parameters can be used to evaluate grindability. The ores were classified into six ore types based on mineralogy and textures. The results show that the ore mineralogy and texture influence the surface hardness. Fine-grained ore types with irregular-to-no visible grain boundaries have higher surface hardness than coarser-grained ore types with straight grain boundaries. Furthermore, surface hardness measurements and grindability evaluations (using throughput (kg/h) and specific energy consumption (kWh/tonne)) of samples from three of the iron oxide deposits indicate that grindability decreases with increasing surface hardness. The relationship found between the parameters ore mineralogy, texture, surface hardness, and grindability suggests that geological mapping and surface hardness measurements can be used to evaluate grindability, and thus assess ore processing performance.acceptedVersion© 2018. This is the authors’ accepted and refereed manuscript to the article. Locked until 14.6.2020 due to copyright restrictions. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

BACKGROUND: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. METHODS: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. RESULTS: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients. CONCLUSIONS: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers. © 2019 International Parkinson and Movement Disorder Society

What have we learned from cerebrospinal fluid studies about biomarkers for detecting LRRK2 Parkinson's disease patients and healthy subjects with Parkinson's-associated LRRK2 mutations?

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known cause of autosomal dominant Parkinson’s disease (PD) and sporadic PD (sPD). The clinical presentation of LRRK2 PD is similar to sPD, and except for genetic testing, no biochemical or imaging markers can differentiate LRRK2 PD from sPD. Discovery of such biomarkers could indicate neuropathological mechanisms that are unique to or increased in LRRK2 PD. This review discusses findings in 17 LRRK2 - related CSF studies found on PubMed. Most of these studies compared analyte concentrations between four diagnostic groups: LRRK2 PD patients, sPD patients, asymptomatic control subjects carrying PD-associated LRRK2 mutations (LRRK2 CTL), and healthy control subjects lacking LRRK2 mutations (CTL). Analytes examined in these studies included Aβ1-42, tau, α-synuclein, oxidative stress markers, autophagy-related proteins, pteridines, neurotransmitter metabolites, exosomal LRRK2 protein, RNA species, inflammatory cytokines, mitochondrial DNA (mtDNA), and intermediary metabolites. FINDINGS: Pteridines, α-synuclein, mtDNA, 5-hydroxyindolacetic acid, β-D-glucose, lamp2, interleukin-8, and vascular endothelial growth factor were suggested to differentiate LRRK2 PD from sPD patients; 8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-isoprostane (8-ISO), 2-hydroxybutyrate, mtDNA, lamp2, and neopterin may differentiate between LRRK2 CTL and LRRK2 PD subjects; and soluble oligomeric α-synuclein, 8-OHdG, and 8-ISO might differentiate LRRK2 CTL from CTL subjects. CONCLUSIONS: The low numbers of investigations of each analyte, small sample sizes, and methodological differences limit conclusions that can be drawn from these studies. Further investigations are indicated to determine the validity of the analytes identified in these studies as possible biomarkers for LRRK2 PD patients and/or LRRK2 CTL subjects.publishedVersio

LRRTM3 Interacts with APP and BACE1 and Has Variants Associating with Late-Onset Alzheimer's Disease (LOAD)

Leucine rich repeat transmembrane protein 3 (LRRTM3) is member of a synaptic protein family. LRRTM3 is a nested gene within α-T catenin (CTNNA3) and resides at the linkage peak for late-onset Alzheimer’s disease (LOAD) risk and plasma amyloid β (Aβ) levels. In-vitro knock-down of LRRTM3 was previously shown to decrease secreted Aβ, although the mechanism of this is unclear. In SH-SY5Y cells overexpressing APP and transiently transfected with LRRTM3 alone or with BACE1, we showed that LRRTM3 co-localizes with both APP and BACE1 in early endosomes, where BACE1 processing of APP occurs. Additionally, LRRTM3 co-localizes with APP in primary neuronal cultures from Tg2576 mice transduced with LRRTM3-expressing adeno-associated virus. Moreover, LRRTM3 co-immunoprecipitates with both endogenous APP and overexpressed BACE1, in HEK293T cells transfected with LRRTM3. SH-SY5Y cells with knock-down of LRRTM3 had lower BACE1 and higher CTNNA3 mRNA levels, but no change in APP. Brain mRNA levels of LRRTM3 showed significant correlations with BACE1, CTNNA3 and APP in ∼400 humans, but not in LRRTM3 knock-out mice. Finally, we assessed 69 single nucleotide polymorphisms (SNPs) within and flanking LRRTM3 in 1,567 LOADs and 2,082 controls and identified 8 SNPs within a linkage disequilibrium block encompassing 5′UTR-Intron 1 of LRRTM3 that formed multilocus genotypes (MLG) with suggestive global association with LOAD risk (p = 0.06), and significant individual MLGs. These 8 SNPs were genotyped in an independent series (1,258 LOADs and 718 controls) and had significant global and individual MLG associations in the combined dataset (p = 0.02–0.05). Collectively, these results suggest that protein interactions between LRRTM3, APP and BACE1, as well as complex associations between mRNA levels of LRRTM3, CTNNA3, APP and BACE1 in humans might influence APP metabolism and ultimately risk of AD.© 2013 Lincoln et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited