91 research outputs found
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Pumpernickel Valley Geothermal Project Thermal Gradient Wells
The Pumpernickel Valley geothermal project area is located near the eastern edge of the Sonoma Range and is positioned within the structurally complex Winnemucca fold and thrust belt of north-central Nevada. A series of approximately north-northeast-striking faults related to the Basin and Range tectonics are superimposed on the earlier structures within the project area, and are responsible for the final overall geometry and distribution of the pre-existing structural features on the property. Two of these faults, the Pumpernickel Valley fault and Edna Mountain fault, are range-bounding and display numerous characteristics typical of strike-slip fault systems. These characteristics, when combined with geophysical data from Shore (2005), indicate the presence of a pull-apart basin, formed within the releasing bend of the Pumpernickel Valley – Edna Mountain fault system. A substantial body of evidence exists, in the form of available geothermal, geological and geophysical information, to suggest that the property and the pull-apart basin host a structurally controlled, extensive geothermal field. The most evident manifestations of the geothermal activity in the valley are two areas with hot springs, seepages, and wet ground/vegetation anomalies near the Pumpernickel Valley fault, which indicate that the fault focuses the fluid up-flow. There has not been any geothermal production from the Pumpernickel Valley area, but it was the focus of a limited exploration effort by Magma Power Company. In 1974, the company drilled one exploration/temperature gradient borehole east of the Pumpernickel Valley fault and recorded a thermal gradient of 160oC/km. The 1982 temperature data from five unrelated mineral exploration holes to the north of the Magma well indicated geothermal gradients in a range from 66 to 249oC/km for wells west of the fault, and ~283oC/km in a well next to the fault. In 2005, Nevada Geothermal Power Company drilled four geothermal gradient wells, PVTG-1, -2, -3, and -4, and all four encountered geothermal fluids. The holes provided valuable water geochemistry, supporting the geothermometry results obtained from the hot springs and Magma well. The temperature data gathered from all the wells clearly indicates the presence of a major plume of thermal water centered on the Pumpernickel Valley fault, and suggests that the main plume is controlled, at least in part, by flow from this fault system. The temperature data also defines the geothermal resource with gradients >100oC/km, which covers an area a minimum of 8 km2. Structural blocks, down dropped with respect to the Pumpernickel Valley fault, may define an immediate reservoir. The geothermal system almost certainly continues beyond the recently drilled holes and might be open to the east and south, whereas the heat source responsible for the temperatures associated with this plume has not been intersected and must be at a depth greater than 920 meters (depth of the deepest well – Magma well). The geological and structural setting and other characteristics of the Pumpernickel Valley geothermal project area are markedly similar to the portions of the nearby Dixie Valley geothermal field. These similarities include, among others, the numerous, unexposed en echelon faults and large-scale pull-apart structure, which in Dixie Valley may host part of the geothermal field. The Pumpernickel Valley project area, for the majority of which Nevada Geothermal Power Company has geothermal rights, represents a geothermal site with a potential for the discovery of a relatively high temperature reservoir suitable for electric power production. Among locations not previously identified as having high geothermal potential, Pumpernickel Valley has been ranked as one of four sites with the highest potential for electrical power production in Nevada (Shevenell and Garside, 2003). Richards and Blackwell (2002) estimated the total heat loss and the preliminary production capacity for the entire Pumpernickel Valley geothermal system to be at 35MW. A more conservative estimate, for the hot spring area only, was presented by GeothermEx Inc. (2004), which projected that power generation capacities for the Pumpernickel Valley site are 10 MW-30yrs minimum (probablility of >90%), and most likely 13 MW-30yrs
Paleotectonic and structural setting of the western Notre Dame Bay area, Newfoundland Appalachians
The Appalachian Orogen in Newfoundland records the birth and destruction of the Iapetus Ocean. The Dunnage Zone preserves remnants of the oceanic terranes, and is subdivided into the western (Laurentian) Notre Dame Subzone and the eastern (Gondwanan) Exploits Subzone. This focus of this thesis has been to determine the geologic history of the northernmost part of the Notre Dame Subzone, confined between the Green Bay and Lobster Cove Faults. -- The geological history of the western Notre Dame Bay area has been investigated using field, geochemical, geochronological and structural methods. Care was taken to integrate the results obtained from these diverse methods in order to obtain an internally consistent model. As a result of these studies a new stratigraphic order is proposed, a major nappe has been recognized, and the character and tectonic history of one of the oldest intraoceanic sequences in the Notre Dame Subzone of the Newfoundland Appalachians has been determined. -- In simple terms, the geological history of the western Notre Dame Bay area can be described as follows: (1) a pre-500 Ma intraoceanic arc/back-arc stage, which involves deposition of the Lushs Bight Group and the lower part of the Western Arm Group (Sugar Loaves Basalt, Skeleton Pond Formation, and Big Hill Basalt); (2) emplacement of the pre-500 Ma sequence on the Laurentian continental margin and intrusion by high-Mg dykes of sanukitoid/bajaite affinities at 495 Ma; (3) development of a calc-alkalic arc (Cutwell Group and the upper two formations, Welsh Cove and Western Head, of the Western Arm Group) from 485 to 465 Ma, which is dominantly submarine, but whose chemistry is variably influenced by inputs from continental lithospheric sources; (4) development of a major alpine style fold nappe and its southeasterly directed emplacement (Notre Dame Bay Nappe) in the post-lower Silurian; and (5) post-emplacement structural disruption of the nappe, probably in the post-lower Carboniferous
Sustained diabetes risk reduction after real life and primary health care setting implementation of the diabetes in Europe prevention using lifestyle, physical activity and nutritional intervention (DE-PLAN) project
Background: Real life implementation studies performed in different settings and populations proved that lifestyle interventions in prevention of type 2 diabetes can be effective. However, little is known about long term results of these translational studies. Therefore, the purpose of this study was to examine the maintenance of diabetes type 2 risk factor reduction achieved 1 year after intervention and during 3 year follow-up in primary health care setting in Poland. Methods: Study participants (n = 262), middle aged, slightly obese, with increased type 2 diabetes risk ((age 55.5 (SD = 11.3), BMI 32 (SD = 4.8), Finnish Diabetes Risk Score FINDRISC 18.4 (SD = 2.9)) but no diabetes at baseline, were invited for 1 individual and 10 group lifestyle counselling sessions as well as received 6 motivational phone calls and 2 letters followed by organized physical activity sessions combined with counselling to increase physical activity. Measurements were performed at baseline and then repeated 1 and 3 years after the initiation of the intervention. Results: One hundred five participants completed all 3 examinations (baseline age 56.6 (SD = 10.7)), BMI 31.1 (SD = 4.9)), FINDRISC 18.57 (SD = 3.09)). Males comprised 13% of the group, 10% of the patients presented impaired fasting glucose (IFG) and 14% impaired glucose tolerance (IGT). Mean weight of participants decreased by 2.27 kg (SD = 5.25) after 1 year (p = 5% was achieved after 1 and 3 years by 27 and 19% of the participants, respectively. Repeated measures analysis revealed significant changes observed from baseline to year 1 and year 3 in: weight (p = 0.048), BMI (p = 0.001), total cholesterol (p = 0.013), TG (p = 0.061), fasting glucose level (p = 0.037) and FINDRISC (p = 0.001) parameters. The conversion rate to diabetes was 2% after 1 year and 7% after 3 years. Conclusions: Type 2 diabetes prevention in real life primary health care setting through lifestyle intervention delivered by trained nurses leads to modest weight reduction, favorable cardiovascular risk factors changes and decrease of diabetes risk. These beneficial outcomes can be maintained at a 3-year follow-up.Peer reviewe
Predictors of completing a primary health care diabetes prevention intervention programme in people at high risk of type 2 diabetes Experiences of the DE-PLAN project
It has been shown that real-life implementation studies for the prevention of type 2 diabetes (DM2) performed in different settings and populations can be effective. However, not enough information is available on factors influencing the reach of DM2 prevention programmes. This study examines the predictors of completing an intervention programme targeted at people at high risk of DM2 in Krakow, Poland as part of the DE-PLAN project. A total of 262 middle-aged people, everyday patients of 9 general practitioners' (GP) practices, at high risk of DM2 (Finnish Diabetes Risk Score (FINDRISK)>14) agreed to participate in the lifestyle intervention to prevent DM2. Intervention consisted of 11 lifestyle counseling sessions, organized physical activity sessions followed by motivational phone calls and letters. Measurements were performed at baseline and 1 year after the initiation of the intervention. Seventy percent of the study participants enrolled completed the core curriculum (n=184), 22% were men. When compared to noncompleters, completers had a healthier baseline diabetes risk profile (P In multiple logistic regression model, employment reduced the likelihood of completing the intervention 2 times (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25-0.81). Higher glucose 2 hours after glucose load and hypertension were the independent factors decreasing the chance to participate in the intervention (OR 0.79, 95% 0.69-0.92 and OR 0.52, 95% CI 0.27-0.99, respectively). Daily consumption of vegetables and fruits increased the likelihood of completing the intervention (OR 1.86, 95% 1.01-3.41). In conclusion, people with healthier behavior and risk profile are more predisposed to complete diabetes prevention interventions. Male, those who work and those with a worse health profile, are less likely to participate and complete interventions. Targeted strategies are needed in real-life diabetes prevention interventions to improve male participation and to reach those who are working as well as people with a higher risk profile.Peer reviewe
Predictors of long term weight loss maintenance in patients at high risk of type 2 diabetes participating in a lifestyle intervention program in primary health care: The DE-PLAN study
Lifestyle interventions in type 2 diabetes (DM2) prevention implementation studies can be effective and lasting. Long-term weight loss maintenance enhances the intervention effect through a significant decrease in diabetes incidence over time. Our objective was to identify factors predicting long-term successful weight reduction maintenance achieved during a DM2 prevention program in patients with high DM2 risk in primary health care. Study participants (n = 263), middle-aged, slightly obese with baseline increased DM2 risk (Finnish Diabetes Risk Score (FINDRISC)\u3e14), but no diabetes were invited to receive 11 lifestyle counselling sessions, guided physical activity sessions and motivational support during 10- months. The study participants had three clinical examinations during the study (baseline, one and three years). Stepwise regression analysis was used to determine demographic, clinical, and lifestyle predictors of weight reduction maintenance two years after the discontinuation of the intervention. Out of 105 patients who completed all three examinations (baseline age 56.6 (standard deviation (SD) = 10.7), body mass index 31.1 kg/m2 (SD = 4.9), FINDRISC 18.6 (SD = 3.1)), 73 patients (70%) showed weight loss during the intervention (mean weight loss 4.2 kg, SD = 5.1). The total weight loss achieved in the maintainers (27 of 73 study participants) two years after the intervention had finished was 6.54 kg (4.47 kg+2.0 kg). The non-maintainers, on the other hand, returned to their initial weight at the start of the intervention (+0.21 kg). In multivariable analysis baseline history of increased glucose (odds ratio (OR) = 3.7; 95% confidence interval (CI) 1.0–13.6) and reduction of total fat in diet during follow-up (OR = 4.3; 95% CI 1.5–12.2) were independent predictors of successful weight loss. Further studies exploring predictors of weight loss maintenance in diabetes prevention are needed to help health care providers to redesign interventions and improve long-term outcomes of real life interventions
TMJ Disc and Condylar Displacement in the Frontal Plane
It is known from the literature that an anterior disc displacement is as a rule associated with a dorsal and (or) superior condylar displacement, whereas a dorsal disc displacement is connected with an anterior displacement of the condyle in the intercuspal position. No investigations have been done on this subject in the frontal plane. MR investigations of the TMJs were carried out in 38 patients. Disc displacement in the frontal plane was analysed in 72 TMJs. In 47.2% it was associated with condylar displacement in this plane. In 55.5% medial disc displacement was connected with lateral condylar displacement, whereas lateral disc displacement was accompanied by medial displacement of the condyle (p>0.05) in 33.3%. Central position of the condyles was significantly more often (66.6%) noted in TMJs with lateral disc displacement than in TMJs with medial disc displacement (44.4%) (p>0.05). These results were confirmed by tomography in 40 TMJs. CONCLUSION: There is a correlation between disc and condylar displacement in the intercuspal position, not only in the sagittal but also in the frontal plane. To avoid a mistake in the establishment of maxillo-mandibular relationship both the condylar and the disc position should be taken into consideration.
Grant of the State Committee for Scientific Research nr 6 PO5E 043 20
A cross-sectional survey of urinary iodine status in Latvia
Publisher Copyright: © 2014 Lithuanian University of Health Sciences. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.Background and objective: A nationwide survey of schoolchildren was conducted to detect regional differences in urinary iodine excretion in Latvia and to compare the results with data from the newborn thyroid-stimulating hormone (TSH) screening database as well with the results of a similar study performed in Latvia 10 years ago. Materials and methods: We conducted a cross-sectional school-based cluster survey of 915 children aged 9-12 years in 46 randomly selected schools in all regions of Latvia. Urine samples, questionnaires on the consumption of iodized salt and information on socioeconomic status were collected. TSH levels in newborns were also measured. Results: The median creatinine-standardized urinary iodine concentration (UIC) in our study was 107.3 mg/g Cr. UIC measurements indicative of mild iodine deficiency were present in 31.6%, moderate deficiency in 11.9% and severe deficiency in 2.8% of the participants. The prevalence of iodine deficiency was the highest in the southeastern region of Latgale and the northeastern region of Vidzeme. The prevalence of TSH values >5 mIU/L followed a similar pattern. The self-reported prevalence of regular iodized salt consumption was 10.2%. Children from urban schools had a significantly lower UIC than children from rural schools. Conclusions: Our findings suggest that although the overall median UIC in Latvian schoolchildren falls within the lower normal range, almost 50% of the schoolchildren are iodine deficient, especially in urban schools and in the eastern part of Latvia. The absence of amandatory salt iodization program puts a significant number of children and pregnantwomen at risk.publishersversionPeer reviewe
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Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts cohesin binding at these elements and Etv6 interacts with cohesin at chromatin. Depletion of cohesin severely impairs erythroid differentiation, particularly at Etv6-prebound loci, but augments self-renewal programs. Together with corroborative findings in acute myeloid leukemia and myelodysplastic syndrome patient samples, these data suggest cohesin-mediated alleviation of Etv6 repression is required for dynamic expression at critical erythroid genes during differentiation and how this may be perturbed in myeloid malignancies
Development of resistance to type II JAK2 inhibitors in MPN depends on AXL kinase and is targetable.
PURPOSE
Myeloproliferative neoplasms (MPN) dysregulate JAK2 signaling. Since clinical JAK2 inhibitors have limited disease-modifying effects, type II JAK2 inhibitors such as CHZ868 stabilizing inactive JAK2 and reducing MPN clones, gain interest. We studied whether MPN cells escape from type ll inhibition.
METHODS
MPN cells were continuously exposed to CHZ868. We used phosphoproteomic analyses and ATAC-/RNA-sequencing to characterize acquired resistance to type II JAK2 inhibition, and targeted candidate mediators in MPN cells and mice.
RESULTS
MPN cells showed increased IC50 and reduced apoptosis upon CHZ868 reflecting acquired resistance to JAK2 inhibition. Among >2500 differential phospho-sites, MAPK pathway activation was most prominent, while JAK2-STAT3/5 remained suppressed. Altered histone occupancy promoting AP-1/GATA binding motif exposure associated with upregulated AXL kinase and enriched RAS target gene profiles. AXL knockdown resensitized MPN cells and combined JAK2/AXL inhibition using bemcentinib or gilteritinib reduced IC50 to levels of sensitive cells. While resistant cells induced tumor growth in NSG mice despite JAK2 inhibition, JAK2/AXL inhibition largely prevented tumor progression. Since inhibitors of MAPK pathway kinases such as MEK are clinically used in other malignancies, we evaluated JAK2/MAPK inhibition with trametinib to interfere with AXL-MAPK-induced resistance. Tumor growth was halted similarly to JAK2/AXL inhibition and in a systemic cell line-derived mouse model, marrow infiltration was decreased supporting dependency on AXL-MAPK.
CONCLUSIONS
We report on a novel mechanism of AXL-MAPK-driven escape from type II JAK2 inhibition, which is targetable at different nodes. This highlights AXL as mediator of acquired resistance warranting inhibition to enhance sustainability of JAK2 inhibition in MPN
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