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The aim of this paper was to understand the relevance of accounting for geothermal resource dynamics for sustainable energy system planning in Iceland. This included assessing the implications of transition to electric vehicles as a decarbonisation strategy in Iceland. Therefore, the energy and transport system model (UniSyD_IS) was linked to a geothermal resource dynamics model. This allowed to capture the effects of geothermal resource utilization for electricity production on a national energy systems level. A total of 16 different scenarios that vary in the rate of economic growth, conditions for electric vehicles and consideration of geothermal resource dynamics were analysed in relation to production patterns, cost, resource availability and emissions. Incorporating geothermal resource dynamics allows to provide more holistic insights for sustainable energy system planning in Iceland, especially regarding the availability of geothermal resources and production cost.

An audience response system (ARS) is an excellent tool for improving interactive learning in radiology residents. Traditional ARSs have long allowed text-based interactions between teacher and students. However, little attention has been given to techniques which allow students in large groups to interact directly with an image. Fortunately, a growing number of ARSs are beginning to add this ability. However, it is not the technology but the pedagogy that matters the most. The purpose of this article is to review those ARSs, and to present an array of pedagogical techniques that can take advantage of this technology.

Objectives There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor. Materials and methods This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1–3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients. Results A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%–32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient. Conclusion Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

Introduction L’association ipilimumab (IPI) + nivolumab (NIVO) offre un taux de réponse et de guérison supérieur aux anti-PD1 en monothérapie mais expose à des événements indésirables immunitaires (EII) plus fréquents. La COVID-19 a tué plus de 3 M de personnes. Comme les patients atteints de cancers sont particulièrement exposés aux formes sévères/mortelles, la vaccination est recommandée. Il n’existe pas de données testant la relation entre vaccination et développement/exacerbation des EII au cours du traitement par ICI. Nous rapportons un cas de myopathie nécrosante survenue 10 jours après la vaccination contre la COVID-19 chez un patient atteint d’un mélanome avancé traité par IPI + NIVO. Matériel et méthodes Un homme de 43 ans était inclus en 2015 dans l’essai adjuvant EORTC MK-3475 (pembrolizumab vs. placebo) pour un mélanome stade IIIb. E n 02/2021 une récidive ganglionnaire lombo-aortique, non opérable survenait. Malgré un statut BRAF (+) et une levée d’aveugle révélant qu’il avait reçu le pembrolizumab (sans EII à l’époque), un traitement par IPI + NIVO était alors débuté. Il recevait sa 1ère et 2e injection les 25/02 et 19/03/21. Le 12/03, il recevait sa 1ère dose de vaccin COVID-19 (Pfizer/BioNTech), sans réaction immédiate. Le 22/03 il développait un tableau associant: myalgies, faiblesse musculaire des membres, dysphagie, dyspnée, dysphonie et diplopie bilatérale avec rhabdomyolyse (CK 12647 U/L). Le bilan immunologique revenait négatif. L’ENMG décrivait un syndrome myogène. L’IRM musculaire révélait un aspect de myosite (muscles rotateurs du cou/de la cuisse) et l’histologie retrouvait un aspect de myopathie inflammatoire avec nécrose multifocale de myocytes et infiltrat inflammatoire à prédominance macrophagique. Le diagnostic de myopathie nécrosante grade IV était retenu. L’immunothérapie était arrêtée et une corticothérapie (bolus puis per os) permettait une amélioration progressive. Le patient est toujours sous corticothérapie orale, la surveillance oncologique montre à ce jour une réponse partielle. La 2e injection du vaccin n’a pas été faite d’autant plus que les IgG étaient fortement positives. Discussion Des myosites secondaires aux ICI, au COVID-19 et de façon plus anecdotique à la vaccination ont été rapportées. Ici, l’association temporelle étroite de la bi-ICI et du diagnostic de myopathie suggère que la myopathie est un EII et que la vaccination a contribué au développement de la myopathie par un effet de boost immunitaire. Le scénario inverse ne peut être exclu. Parce que de plus en plus de patients traités par ICI seront vaccinés dans les prochains mois, les cliniciens doivent être conscients de cette association potentielle du vaccin COVID-19 et de l’exacerbation des EII. Des données prospectives de pharmacovigilance sont nécessaires.

Background Effective analgesia following total knee arthroplasty (TKA) is important for maximizing patient satisfaction, early participation in physical therapy and reducing the hospital stay. This trial compared continuous catheter femoral nerve block (cFNB) to single injection femoral nerve block (sFNB) in terms of analgesia, opioid consumption, and participation in physical therapy and associated side effects. Methods This randomized, double blinded trial was conducted in a non-university hospital setting, without major changes to anesthesia or surgical clinical pathways. A total of 85 patients scheduled for primary TKA were randomized to receive either cFNB (n = 44) or sFNB (n = 41). All patients had FNB with 0.5% ropivacaine bolus followed by subarachnoid block for surgery. Postoperatively, 0.2% ropivacaine infusion was commenced in cFNB group and a sham catheter was taped to the skin in sFNB group. All patients received a structured multimodal analgesia regimen throughout hospital stay. The primary outcomes were peak resting visual analogue scale (VAS) scores and morphine consumption at 48 h postoperatively. Results VAS scores (Mean difference 0.25, 95% Confidence Interval (CI) − 0.56 to 1.06; [P = 0.196]) and morphine consumption (Mean difference 0.95 mg, 95% CI − 9.99 to 11.89; [P = 0.863]) were not significantly different among patients who received cFNB versus sFNB at 48 h. There was no difference in hospital stay (P = 0.517) or long-term functional recovery between the two groups (P = 0.385). Conclusions sFNB block provides equal pain relief compared with cFNB, after TKA with no significant difference in opioid consumption, hospital stay, physical therapy outcomes or associated side effects.

Kenya's current electricity production is mainly relying on hydro and geothermal resources. Both of these resources are subject to complex dynamics that affect their sustainable utilization. Neither the current power expansion plan for Kenya, nor the existing electricity supply models address such effects. The research question in this paper is: What are the implications of hydro and geothermal resource dynamics for short- and long-term (sustainable) electricity system planning in Kenya? To answer this question a bottom-up system dynamics model representing the most prevalent technologies of Kenya's future electricity system, including the dynamics of geothermal and hydro resource utilization, is developed. The stock-flow system dynamics modelling allows to capture the resources characteristics and the link to electricity production. Due to the stock-like nature of geothermal resource, excessive utilization can lead to production capacity losses. In the case of hydro resources, climate change can reduce their availability significantly. A total of eight scenarios varying in demand size and consideration of resource dynamics are simulated and compared. The results indicate that when geothermal and hydro resource dynamics are considered, higher installed capacity will be required in the long-term to compensate production losses, which in turn leads to a higher electricity generation cost.

Extracellular vesicles are central players in intercellular communication and are released from the plasma membrane under tightly regulated conditions, depending on the physiological and pathophysiological state of the producing cell. Their heterogeneity requires a spectrum of methods for isolation and characterization, where pre-analytical parameters have profound impact on vesicle analysis, particularly in blood, since sampling, addition of anticoagulants, as well as post-sampling vesicle generation may influence the outcome. Here, we characterized microvesicles directly in whole blood using a combination of flow cytometry and imaging flow cytometry. We assessed the influence of sample agitation, anticoagulation, and temperature on post-sampling vesicle generation, and show that vesicle counts remained stable over time in samples stored without agitation. Storage with gentle rolling mimicking agitation, in contrast, resulted in strong release of platelet-derived vesicles in blood anticoagulated with citrate or heparin, whereas vesicle counts remained stable upon anticoagulation with EDTA. Using imaging flow cytometry, we could visualize microvesicles adhering to blood cells and revealed an anticoagulant-dependent increase in vesicle-cell aggregates over time. We demonstrate that vesicles adhere preferentially to monocytes and granulocytes in whole blood, while no microvesicles could be visualized on lymphocytes. Our data underscore the relevance of pre-analytical parameters in vesicle analysis and demonstrate that imaging flow cytometry is a suitable tool to study the interaction of extracellular vesicles with their target cells.

Purpose Extracorporeal photopheresis (ECP) is an accepted treatment option for acute and chronic rejection after solid organ transplantation but the mode of action is not fully elucidated. In a randomized controlled trial that investigates the addition of prophylactic use of ECP to a tacrolimus-based immunosuppressive regimen after lung transplantation, a comprehensive phenotypic immune monitoring is performed to assess the immunomodulatory effects of ECP. Methods To date, 40 (from a calculated sample size of 62) end-stage chronic obstructive pulmonary disease (COPD) patients underwent bilateral lung transplantation and were randomized into 2 treatment arms - the control group received standard triple immunosuppression consisting of tacrolimus, mycophenolate mofetil and steroids while the second group additionally received 16 ECP treatments in the first three months after surgery. For monitoring a comprehensive set of leukocyte subsets such as regulatory T cells (CD4+CD25+FoxP3+ Tregs) polychromatic flow cytometry analysis was performed on fresh whole blood samples using validated, standardized, lyophilized monoclonal antibody panels (DuraClone). Samples were acquired before and 3 months after transplantation, when the last ECP treatment was performed, as well as 6 months after transplantation. Statistical analysis was conducted by using a two-tailed paired and unpaired t-test. Results From 40 double lung transplanted patients, 32 patients have reached their three-month-visit and 28 patients their 6-months-visit. No significant difference in the frequency of Tregs was found between both groups at baseline (p=0.425). At 3 months, Tregs have significantly decreased in the control group (p=0.009) while in the ECP-treated group no significant decline was seen (p=0.141). Six months after transplantation the frequency of Tregs was significantly decreased in both groups when compared to baseline (p=0.043 in control; p=0.030 in ECP-treated). Conclusion Preliminary data from this interim analysis of double lung transplanted patients receiving ECP as prophylactic treatment provide evidence that during ECP treatments the post-transplant decline in Treg frequency seen with standard immunosuppression is prevented.

If geothermal resources are utilized excessively for electricity production, the reservoir can be temporarily (almost) depleted. Regeneration of an overutilized resource can take a long time. This paper presents a System Dynamics model for geothermal power plant expansion considering the dynamics of geothermal resources on a system’s level. The model consists of three main modules: resource dynamics, plant construction, and geothermal economics. Thereby, it captures the following dynamics: The geothermal field stock decreases due to utilization for electricity production and increases through natural recharging. Changes in geothermal stock, and thus in well production capacity, lead to additional well requirements to maintain electricity production levels. This influences the unit cost of electricity. To show the effect of geothermal resource dynamics on a national system’s level the model is applied to Iceland’s geothermal resources. Four main scenarios are simulated and compared based on the level of resource utilization, assuming high and low demand growth (i.e. 2% and 4.4%), and whether geothermal resource dynamics are incorporated or not. Sensitivity analysis is performed with respect to well capital cost and natural recharging rates for geothermal fields. The findings indicate that geothermal resource dynamics significantly increase costs because of the well drilling activities that are required to maintain production.

A microfluidic system for rapid and quantitative detection of plasma biomarkers from patients at intensive care units is presented. The system integrates a magnetic bead based immunoassay onto a microfluidic disposable chip. Biomarker concentrations down to 10 pg/mL were detected within 40 minutes with the presented system. Chemiluminescence is used as detection method, which enables signal readout with a lens-less photodiode as optical detection unit. Due to the combination of an efficient detection system and simple chip fabrication, our system fulfills the requirements for a potential point-of-care device: cost efficiency, speed, and high sensitivity.

A hallmark of tumor cell survival is the maintenance of elongated telomeres. It is known that antiviral reverse transcriptase inhibitors (RTIs) such as azidothymidine (AZT) and didanosine (ddI) lead to telomere shortening at high, potentially toxic concentrations. We hypothesized that those drugs might have synergistic effects enabling successful therapy with low, nontoxic concentrations. Biologic effects of AZT and ddI were analyzed at concentrations that correspond to minimal plasma levels achieved during human immunodeficiency virus therapy. Long-term coapplication of low-dose AZT and ddI induced a significant shortening of telomeres in the tumor cell lines HCT-116, SkMel-28, MelJuso, and Jurkat. Treatment of cells with both RTI, but not with single RTI, led to a significant accumulation of γH2AX, to p53 phosphorylation, and to cell apoptosis in all cell lines. Oral low-dose dual RTI application but not low-dose single RTI application was associated with a significantly reduced tumor growth of HCT-116 cells in mice. This antiproliferative activity of the combined use of AZT and ddI at low, clinically applicable concentrations warrants clinical testing in human solid cancer.

The idiopathic Parkinson syndrome (IPS) affects multiple structures of the central nervous system and exhibits a broad variety of clinical symptoms that are only partially treatable by pharmacological treatment. Therefore, non-pharmacological approaches are highly warranted. The aim of this study was to identify, categorize and rate studies on rehabilitative therapeutic approaches for IPS regarding not only study design and statistics, but also clinical relevance. For reasons of homogeneity, only studies applying a rehabilitative program targeting three or more symptoms were included and studies treating isolated symptoms were excluded. Study design and statistics were rated by using an established rating system. To evaluate clinical relevance a rating system was developed considering effectiveness, everyday life relevance, long-term effect, therapy frequency and setting, duration of the therapy units, effects on quality of life, and assessment. Applying this rating system to 17 studies, we found four studies with a Level I of statistical quality and four studies with high clinically relevant information. This novel method of analysing may help to gain valuable data from studies that may lack strong methodology, and may help to promote further research.

The objective of this work was to evaluate the effect of selected biologicals on direct seeded and transplanted squash plant growth and mineral contentunder salinitystress.The studywasconducted inpotexperiments usingamixture ofsandy loamsoil:vermiculite(1:1,v:v)undercontrolled greenhouse conditions. Biologicals tested included AgBlend, SoilBuilder, Yield Shield, PlantShield, Inoculaid and Equity. Salinity treatments were established by adding 0, 50 and 100 mM of NaCl to a base complete nutrient solution (Hydro-Sol + Ca(NO3)2). Pots were irrigated with NaCl solutions and biological treatments were included in thewater. Yield Shield was applied as a seed treatment. Salinity negatively affected growth of squash; however, biological treatments significantly increased fresh weight compared to non-treated plants that were challenged with salt stress. Furthermore, biological treatments tested increased the uptake of potassium compared to the non-treated control in both direct seeded and transplanted squash. Sodium concentration was not affected by biologicals in directed seeded squash except for SoilBuilder, Yield Shield and Equity at 100 mM, while AgBlend, SoilBuilder, Inoculaid and Equity decreased sodium uptake in transplants under salt stress. The most effective biologicals increased the K + /Na + ratio, which was positively correlated with plant growth. Alteration of mineral uptake may be one mechanism for the alleviation of salt stress. Based on the results of the experiment reported herein, the use of biological treatments may provide a means of facilitating plant growth under salt stress. # 2006 Elsevier B.V. All rights reserved.

Monoterpenes are ubiquitous in forested environments and are subject to reactions with OH radicals, NO3 radicals and O3 both within and above forest canopies. While reactions of monoterpenes with OH and O3 have received considerable attention with regard to their reaction kinetics, reaction products and secondary organic aerosol (SOA) formation those with NO3 have received relatively little consideration. To redress this imbalance and to try and assess the possible importance of NO3+monterpene reactions within forest canopies investigations have been performed on selected monterpenes. The products and aerosol formation from the NO3 radical initiated oxidation of limonene and α-pinene have been investigated in the EUPHORE photoreactor facility, and the secondary chemistry of the observed major products was then investigated in a large volume laboratory photoreactor. In addition to large yields of yet unidentified organic nitrates, pinonaldehyde and endolim have been identified as the major reaction products of the NO3 radical initiated oxidation of α-pinene and limonene, respectively. The aerosol formation has been investigated in the presence of different seed aerosols and also water vapour. The reactions lead to the formation of SOA and the results indicate the importance of the chemical character of the seed aerosol in determining the SOA yield in NO3+monoterpene reactions. The possible pathways leading to SOA formation and also their potential importance are discussed based on the laboratory results on the reaction of NO3 with the two major products.