Lab-Scale Permeability Enhancement by Chemical Treatment in Fractured Granite (Cornubian Batholith) for the United Downs Deep Geothermal Power Project, Cornwall (UK)

A hydrothermal doublet system was drilled in a fault-related granitic reservoir in Cornwall. It targets the Porthtowan Fault Zone (PTF), which transects the Carnmenellis granite, one of the onshore plutons of the Cornubian Batholith in SW England. At 5058 m depth (TVD, 5275 m MD) up to 190 °C were reached in the dedicated production well. The injection well is aligned vertically above the production well and reaches a depth of 2393 m MD. As part of the design process for potential chemical stimulation of the open-hole sections of the hydrothermal doublet, lab-scale acidification experiments were performed on outcrop analogue samples from the Cornubian Batholith, which include mineralised veins. The experimental setup comprised autoclave experiments on sample powder and plugs, and core flooding tests on sample plugs to investigate to what degree the permeability of natural and artificial (saw-cut) fractures can be enhanced. All samples were petrologically and petrophysically analysed before and after the acidification experiments to track all changes resulting from the acidification. Based on the comparison of the mineralogical composition of the OAS samples with the drill cuttings from the production well, the results can be transferred to the hydrothermally altered zones around the faults and fractures of the PTF. Core Flooding Tests and Autoclave Experiments result in permeability enhancement factors of 4 to >20 and 0.1 to 40, respectively. Mineral reprecipitation can be avoided in the stimulated samples by sufficient post-flushing

Cardiac pathology in neuronal ceroid lipofuscinoses (NCL): More than a mere co-morbidity

The neuronal ceroid lipofuscinoses (NCLs) are mostly seen as diseases affecting the central nervous system, but there is accumulating evidence that they have co-morbidities outside the brain. One of these co-morbidities is a decline in cardiac function. This is becoming increasingly recognised in teenagers and adolescents with juvenile CLN3, but it may also occur in individuals with other NCLs. The purpose of this review is to summarise the current knowledge of the structural and functional changes found in the hearts of animal models and people diagnosed with NCL. In addition, we present evidence of structural changes that were observed in a systematic comparison of the cardiomyocytes from CLN3Δex7/8 mice

Study on Occupational Allergy Risks (SOLAR II) in Germany: Design and methods

<p>Abstract</p> <p>Background</p> <p>SOLAR II is the 2^ndfollow-up of a population-based cohort study that follows the participants of ISAAC Phase Two recruited in Munich and Dresden in 1995/6. A first follow-up study was conducted 2002 and 2003 (SOLAR I). The aims of SOLAR II were to investigate the course of atopic diseases over puberty taking environmental and occupational risk factors into account. This paper describes the methods of the 2^ndfollow-up carried out from 2007 to 2009 and the challenges we faced while studying a population-based cohort of young adults.</p> <p>Methods</p> <p>Wherever possible, the same questionnaire instruments were used throughout the studies. They included questions on respiratory and allergic diseases, domestic and occupational exposure and work related stress. Furthermore, clinical examinations including skin prick tests, spirometry and bronchial challenge with methacholine, exhaled nitric oxide (FeNO) and blood samples were employed at baseline and 2^ndfollow-up. As information from three studies was available, multiple imputation could be used to handle missing data.</p> <p>Results</p> <p>Of the 3053 SOLAR I study participants who had agreed to be contacted again, about 50% had moved in the meantime and had to be traced using phone directories and the German population registries. Overall, 2904 of these participants could be contacted on average five years after the first follow-up. From this group, 2051 subjects (71%) completed the questionnaire they received via mail. Of these, 57% participated at least in some parts of the clinical examinations. Challenges faced included the high mobility of this age group. Time constraints and limited interest in the study were substantial. Analysing the results, selection bias had to be considered as questionnaire responders (54%) and those participating in the clinical part of the study (63%) were more likely to have a high parental level of education compared to non-participants (42%). Similarly, a higher prevalence of parental atopy (e.g. allergic rhinitis) at baseline was found for participants in the questionnaire part (22%) and those participating in the clinical part of the study (27%) compared to non-participants (11%).</p> <p>Conclusions</p> <p>In conclusion, a 12-year follow-up from childhood to adulthood is feasible resulting in a response of 32% of the baseline population. However, our experience shows that researchers need to allocate more time to the field work when studying young adults compared to other populations.</p

Inherited Glutathione Reductase Deficiency and Plasmodium falciparum Malaria—A Case Study

In Plasmodium falciparum-infected red blood cells (RBCs), the flavoenzyme glutathione reductase (GR) regenerates reduced glutathione, which is essential for antioxidant defense. GR utilizes NADPH produced in the pentose phosphate shunt by glucose-6-phosphate dehydrogenase (G6PD). Thus, conditions affecting host G6PD or GR induce increased sensitivity to oxidants. Hereditary G6PD deficiency is frequent in malaria endemic areas and provides protection against severe malaria. Furthermore, GR deficiency resulting from insufficient saturation of the enzyme with its prosthetic group FAD is common. Based on these naturally occurring phenomena, GR of malaria parasites and their host cells represent attractive antimalarial drug targets. Recently we were given the opportunity to examine invasion, growth, and drug sensitivity of three P. falciparum strains (3D7, K1, and Palo Alto) in the RBCs from three homozygous individuals with total GR deficiency resulting from mutations in the apoprotein. Invasion or growth in the GR-deficient RBCs was not impaired for any of the parasite strains tested. Drug sensitivity to chloroquine, artemisinin, and methylene blue was comparable to parasites grown in GR-sufficient RBCs and sensitivity towards paraquat and sodium nitroprusside was only slightly enhanced. In contrast, membrane deposition of hemichromes as well as the opsonizing complement C3b fragments and phagocytosis were strongly increased in ring-infected RBCs of the GR-deficient individuals compared to ring-infected normal RBCs. Also, in one of the individuals, membrane-bound autologous IgGs were significantly enhanced. Thus, based on our in vitro data, GR deficiency and drug-induced GR inhibition may protect from malaria by inducing enhanced ring stage phagocytosis rather than by impairing parasite growth directly

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment