High-Temperature Nuclear Power Cycle Using Either Helium or s-CO2

The goal of this process was to model the helium-based modular, nuclear reactor power cycle after the existing MIT Pebble-Bed Nuclear Reactor Power Cycle (Kadak, 2005), and to improve on the design by changing the working fluid to supercritical carbon dioxide (s-CO2). The power output of the process as specified in the problem statement, provided by Adam Brostow, was 120 MW. S-CO2 is a much denser fluid, and should theoretically require smaller equipment sizes, making it the more economically viable option for this process. However, it was found that with a return on investment (ROI) of -2.13% and a net present value (NPV) of -$489 million, this process was not economically feasible, due to the high temperatures, pressures, and flow rates required. This process had an electrical output of 118 MW, while the helium met the design condition of 120 MW. The helium process had a ROI of 11$241 million. For this reason, helium is recommended as the working fluid for a nuclear reactor power cycle of this magnitude

An analysis of GAVI, the Global Fund and World Bank support for human resources for health in developing countries

Shortages, geographic imbalances and poor performance of health workers pose major challenges for improving health service delivery in developing countries. In response, multilateral agencies have increasingly recognized the need to invest in human resources for health (HRH) to assist countries in achieving their health system goals. In this paper we analyse the HRH-related activities of three agencies: the Global Alliance for Vaccines and Immunisation (GAVI); the Global Fund for Aids, Tuberculosis, and Malaria (the Global Fund); and the World Bank. First, we reviewed the type of HRH-related activities that are eligible for financing within each agency. Second, we reviewed the HRH-related activities that each agency is actually financing. Third, we reviewed the literature to understand the impact that GAVI, Global Fund and World Bank investments in HRH have had on the health workforce in developing countries. Our analysis found that by far the most common activity supported across all agencies is short-term, in-service training. There is relatively little investment in expanding pre-service training capacity, despite large health worker shortages in developing countries. We also found that the majority of GAVI and the Global Fund grants finance health worker remuneration, largely through supplemental allowances, with little information available on how payment rates are determined, how the potential negative consequences are mitigated, and how payments are to be sustained at the end of the grant period. Based on the analysis, we argue there is an opportunity for improved co-ordination between the three agencies at the country level in supporting HRH-related activities. Existing initiatives, such as the International Health Partnership and the Health Systems Funding Platform, could present viable and timely vehicles for the three agencies to implement this improved co-ordinatio

Developing Performance Indicators to Evaluate the Management Effectiveness of the Massachusetts Ocean Management Plan

In June 2009, the Massachusetts Executive Office of Energy and Environmental Affairs (EEA) released its draft Massachusetts Ocean Management Plan (draft plan) for public comment. The plan is required by the Oceans Act of 2008 to, among other things, be adaptive to evolving knowledge and understanding of the ocean environment. The plan’s Science Framework establishes a blueprint for future research and data acquisition and ensuring that the plan evolves and its management measures adapt to this new and enhanced information. As stated in Chapter 5 of the draft plan, an important part of the science framework is the development and implementation of a performance evaluation system with a series of indicators to help EEA and stakeholders evaluate the implementation of the Massachusetts Ocean Management Plan, identify the environmental and socio-economic impacts of plan management decisions, and identify new or emerging issues. Volume 2 of the draft plan contains a section entitled Development of Evaluation Measures for the Massachusetts Ocean Management Plan. This section outlines a proposed process “to identify measures of success or indicators that can be used to measure performance of management strategies in achieving desired outcomes.” As the development of indicators is a high priority of the draft plan, the Massachusetts Ocean Partnership (MOP) in consultation with EEA contracted with the Urban Harbors Institute (UHI) of the University of Massachusetts Boston (UMass Boston). The project team1 and other professionals from organizations and agencies experienced with the selection and use of indicators conducted the process outlined in Volume 2 of the draft plan to identify and select a set of environmental, socio-economic, and governmental indicators to evaluate the effectiveness of the Massachusetts Ocean Management Plan. The work described in this report also contributes to a broader interest and goal of the Massachusetts Ocean Partnership which is to coordinate indicator initiatives to inform ocean management and to advance the development and use of indicators of the ocean’s ability to provide ecosystem services. Currently, there are a number of initiatives, focusing on the coastal and ocean areas of the Northwest Atlantic/Gulf of Maine region, to develop indicators for various purposes and audiences. The process and products of this work in support of the Massachusetts Ocean Management Plan (e.g., the list of indicators and associated data) will be useful in collaborative efforts to integrate and coordinate these regional efforts

Clinical outcome after particle therapy for meningiomas of the skull base: toxicity and local control in patients treated with active rasterscanning

Background: Meningiomas of the skull base account for 25–30% of all meningiomas. Due to the complex structure of the cranial base and its close proximity to critical structures, surgery is often associated with substantial morbidity. Treatment options include observation, aggressive surgical intervention, stereotactic or conventional radiotherapy. In this analysis we evaluate the outcome of 110 patients with meningiomas of the skull base treated with particle therapy. It was performed within the framework of the “clinical research group heavy ion therapy” and supported by the German Research Council (DFG, KFO 214). Methods: Between May 2010 and November 2014, 110 Patients with skull base meningioma were treated with particle radiotherapy at the Heidelberg Ion Therapy Center (HIT). Primary localizations included the sphenoid wing (n = 42), petroclival region (n = 23), cavernous sinus (n = 4), sella (n = 10) and olfactory nerve (n = 4). Sixty meningiomas were benign (WHO °I); whereas 8 were high-risk (WHO °II (n = 7) and °III (n = 1)). In 42 cases histology was not examined, since no surgery was performed. Proton (n = 104) or carbon ion (n = 6) radiotherapy was applied at Heidelberg Ion Therapy Center (HIT) using raster-scanning technique for active beam delivery. Fifty one patients (46.4%) received radiotherapy due to tumor progression, 17 (15.5%) after surgical resection and 42 (38.2%) as primary treatment. Results: Median follow-up in this analysis was 46,8 months (95% CI 39,9–53,7; Q1-Q3 34,3–61,7). Particle radiotherapy could be performed safely without toxicity-related interruptions. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered excellent overall local control rates with 100% progression-free survival (PFS) after 36 months and 96.6% after 60 months. Median PFS was not reached due to the small number of events. Histology significantly impacted PFS with superior PFS after 5 years for low-risk tumors (96.6% vs. 75.0%, p = 0,02). Overall survival was 96.2% after 60 months and 92.0% after 72 months from therapy. Of six documented deaths, five were definitely not and the sixth probably not meningioma-related. Conclusion Particle radiotherapy is an excellent treatment option for patients with meningiomas of the skull base and can lead to long-term tumor control with minimal side effects. Other prospective studies with longer follow-up will be necessary to further confirm the role of particle radiotherapy in skull base meningioma

Evaluation of particle radiotherapy for the re-irradiation of recurrent intracranial meningioma

Background: With the advance of modern irradiation techniques, the role of radiotherapy (RT) for intracranial meningioma has increased significantly throughout the past years. Despite that tumor’s generally favorable outcome with local control rates of up to 90% after ten years, progression after RT does occur. In those cases, re-irradiation is often difficult due to the limited radiation tolerance of the surrounding tissue. The aim of this analysis is to determine the value of particle therapy with its better dose conformity and higher biological efficacy for re-irradiating recurrent intracranial meningioma. It was performed within the framework of the “clinical research group heavy ion therapy” and funded by the German Research Council (DFG, KFO 214). Methods: Forty-two patients treated with particle RT (protons (n = 8) or carbon ions (n = 34)) for recurrent intracranial meningioma were included in this analysis. Location of the primary lesion varied, including skull base (n = 31), convexity (n = 5) and falx (n = 6). 74% of the patients were categorized high-risk according to histology with a WHO grading of II (n = 25) or III (n = 6), in the remaining cases histology was either WHO grade I (n = 10) or unknown (n = 1). Median follow-up was 49,7 months. Results: In all patients, re-irradiation could be performed safely without interruptions due to side effects. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered good overall local control rates with 71% progression-free survival (PFS) after 12 months, 56,5% after 24 months and a median PFS of 34,3 months (95% CI 11,7–56,9). Histology had a significant impact on PFS yielding a median PFS of 25,7 months (95% CI 5,8–45,5) for high-risk histology (WHO grades II and III) while median PFS was not reached for low-risk tumors (WHO grade I) (p = 0,03). Median time to local progression was 15,3 months (Q1-Q3 8,08–34,6). Overall survival (OS) after re-irradiation was 89,6% after 12 months and 71,4% after 24 months with a median OS of 61,0 months (95% CI 34,2–87,7). Again, WHO grading had an effect, as median OS for low-risk patients was not reached whereas for high-risk patients it was 45,5 months (95% CI 35,6–55,3). Conclusion: Re-irradiation using particle therapy is an effective method for the treatment of recurrent meningiomas. Interdisciplinary decision making is necessary to guarantee best treatment for every patient

β-cell metabolic alterations under chronic nutrient overload in rat and human islets

The aim of this study was to assess multifactorial β-cell responses to metabolic perturbations in primary rat and human islets. Treatment of dispersed rat islet cells with elevated glucose and free fatty acids (FFAs, oleate:palmitate = 1:1 v/v) resulted in increases in the size and the number of lipid droplets in β-cells in a time- and concentration-dependent manner. Glucose and FFAs synergistically stimulated the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1). A potent mTORC1 inhibitor, rapamycin (25 nM), significantly reduced triglyceride accumulation in rat islets. Importantly, lipid droplets accumulated only in β-cells but not in α-cells in an mTORC1-dependent manner. Nutrient activation of mTORC1 upregulated the expression of adipose differentiation related protein (ADRP), known to stabilize lipid droplets. Rat islet size and new DNA synthesis also increased under nutrient overload. Insulin secretion into the culture medium increased steadily over a 4-day period without any significant difference between glucose (10 mM) alone and the combination of glucose (10 mM) and FFAs (240 μM). Insulin content and insulin biosynthesis, however, were significantly reduced under the combination of nutrients compared with glucose alone. Elevated nutrients also stimulated lipid droplet formation in human islets in an mTORC1-dependent manner. Unlike rat islets, however, human islets did not increase in size under nutrient overload despite a normal response to nutrients in releasing insulin. The different responses of islet cell growth under nutrient overload appear to impact insulin biosynthesis and storage differently in rat and human islets

Cohort profile: the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) cohort study.

BACKGROUND Cerebral Palsy (CP) is a group of permanent disorders of movement and posture that follow injuries to the developing brain. It results in motor dysfunction and a wide variety of comorbidities like epilepsy; pain; speech, hearing and vision disorders; cognitive dysfunction; and eating and digestive difficulties. Central data collection is essential to the study of the epidemiology, clinical presentations, care, and quality of life of patients affected by CP. CP specialists founded the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) in 2017. This paper describes the design, structure, aims and achievements of Swiss-CP-Reg and presents its first results. METHODS Swiss-CP-Reg records patients of any age diagnosed with CP who are born, are treated, or live in Switzerland. It collects data from medical records and reports, from questionnaires answered by patients and their families, and from data linkage with routine statistics and other registries. The registry contains information on diagnosis, clinical presentation, comorbidities, therapies, personal information, family history, and quality of life. RESULTS From August 2017 to August 2021, 546 participants (55% male, mean age at registration 8 years [interquartile range IQR: 5-12]), were enrolled in Swiss-CP-Reg. Most had been born at term (56%), were less than two years old at diagnosis (73%, median 18 months, IQR: 9-25), and were diagnosed with spastic CP (76%). Most (59%) live with a mild motor impairment (Gross Motor Function Classification System [GMFCS] level I or II), 12% with a moderate motor impairment (GMFCS level III), and 29% with a severe motor impairment (GMFCS level IV or V). In a subset of 170 participants, we measured intelligence quotient (IQ) and saw lower IQs with increasing GMFCS level. Swiss-CP-Reg has a strong interest in research, with four nested projects running currently, and many more planned. CONCLUSIONS Swiss-CP-Reg collects and exchanges national data on people living with CP to answer clinically relevant questions. Its structure enables retrospective and prospective data collection and knowledge exchange between experts to optimise and standardise treatment and to improve the health and quality of life of those diagnosed with CP in Switzerland

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability

Biomechanical factors in atherosclerosis: mechanisms and clinical implications†

Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors—mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current ‘state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future researc