Methotrexate Encephalopathy: Two Cases in Adult Cancer Patients, Who Recovered with Pathophysiologically Based Therapy

Background/Objectives: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. Results: Case 1 : A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2 : A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high- dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. Conclusions: These two cases suggest that N -methyl d -aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity

Interannual weather variability and the challenges for Great Britain’s electricity market design

Global growth in variable renewable generation has brought significant attention to the challenge of balancing electricity supply and demand. However, inter-annual variability of energy resources has only recently begun to feature in energy system assessments and receives limited recognition in policy discussion, let alone policy design. Meteorological reanalysis datasets that blend modern modelling techniques with historic weather records are seeing increased application in energy system studies. This practice offers insights for market and policy design implications as governments seek to manage the changing energy landscape, as seen with the UK’s introduction of the Electricity Market Reform policy package. Here we apply a concise, Load Duration Curve based approach to consider the market and policy implications of increasing variability in the Great Britain (GB) energy system. Our findings emphasise the growing inter-annual variability in operating opportunity for residual mid-merit and even baseload generation, alongside implications for capacity assurance approaches. The growth in wind generation is seen to bring an accompanying opportunity for increased solar generation, with its lower inter-annual variability and largely uncorrelated annual characteristic. The results underscore the need for an increased recognition of inter-annual variability when addressing market design and incentive mechanisms

Historical database cohort study addressing the clinical patterns prior to idiopathic pulmonary fibrosis (IPF) diagnosis in UK primary care

OBJECTIVE: To explore the clinical pathways, including signs and symptoms, and symptom progression patterns preceding idiopathic pulmonary fibrosis (IPF) diagnosis. DESIGN AND SETTING: A historical cohort study was conducted using primary care patient records from the Optimum Patient Care Research Database. PARTICIPANTS: Patients included were at least 30 years, had IPF diagnosis, identified via clinical-coding and free-text records and had a consultation with a chest specialist prior to IPF diagnosis. OUTCOME MEASURES: The signs and symptoms in the year prior to IPF diagnosis from clinical codes and free-text in primary care electronic records included: cough, dyspnoea, dry cough, weight loss, fatigue/malaise, loss of appetite, crackles and clubbed fingers. The time course of presentations of clinical features and investigations in the years prior to IPF diagnosis were mapped. RESULTS: Within 462 patients identified, the majority (77.9%) had a respiratory consultation within 365 days prior to the chest specialist visit preceding the IPF diagnosis recorded in their primary care records. The most common symptoms recorded in the 1 year prior to IPF diagnosis were dyspnoea (48.7%) and cough (40.9%); other signs and symptoms were rarely recorded (<5%). The majority of patients with cough (58.0%) and dyspnoea (55.0%) in the 1 year before IPF diagnosis had multiple recordings of the respective symptoms. Both cough and dyspnoea were recorded in 23.4% of patients in the year prior to diagnosis. Consultation rates for cough, dyspnoea and both, but not other signs or symptoms, began to increase 4 to 5 years prior diagnosis, with the sharpest increase in the last year. Cough and dyspnoea were often preceded by a reduction in measured weight over 5 years leading to IPF diagnosis. CONCLUSION: Prolonged cough and/or progressive dyspnoea, especially if accompanied with weight loss, should signal for a referral to specialist assessment at the earliest opportunity

Development of Carbon Dioxide Removal Systems for Advanced Exploration Systems 2016-2017

A long-term goal for NASA is to enable crewed missions to Mars: first to the vicinity of Mars, and then to the Mars surface. These missions present new challenges for all aspects of spacecraft design in comparison with the International Space Station, as resupply is unavailable in the transit phase, and early return is not possible. Additionally, mass, power, and volume must be minimized for all phases to reduce propulsion needs. In this paper we describe current and planned developments in the area of carbon dioxide removal to support future crewed Mars missions. Activities are also described that apply to both the resolution of anomalies observed in the ISS CDRA and the design of life support systems for future missions

Spectroscopic survey of the Galaxy with Gaia I. Design and performance of the Radial Velocity Spectrometer

The definition and optimisation studies for the Gaia satellite spectrograph, the Radial Velocity Spectrometer (RVS), converged in late 2002 with the adoption of the instrument baseline. This paper reviews the characteristics of the selected configuration and presents its expected performance. The RVS is a 2.0 by 1.6 degree integral field spectrograph, dispersing the light of all sources entering its field of view with a resolving power R=11 500 over the wavelength range [848, 874] nm. The RVS will continuously and repeatedly scan the sky during the 5 years of the Gaia mission. On average, each source will be observed 102 times over this period. The RVS will collect the spectra of about 100-150 million stars up to magnitude V~17-18. At the end of the mission, the RVS will provide radial velocities with precisions of ~2 km/s at V=15 and \~15-20 km/s at V=17, for a solar metallicity G5 dwarf. The RVS will also provide rotational velocities, with precisions (at the end of the mission) for late type stars of sigma_vsini ~5 km/s at V~15 as well as atmospheric parameters up to V~14-15. The individual abundances of elements such as Silicon and Magnesium, vital for the understanding of Galactic evolution, will be obtained up to V~12-13. Finally, the presence of the 862.0 nm Diffuse Interstellar Band (DIB) in the RVS wavelength range will make it possible to derive the three dimensional structure of the interstellar reddening.Comment: 17 pages, 9 figures, accepted for publication in MNRAS. Fig. 1,2,4,5, 6 in degraded resolution; available in full resolution at http://blackwell-synergy.com/links/doi/10.1111/j.1365-2966.2004.08282.x/pd

Sunny windy Sundays

Rapid expansion of wind and solar capacity in Great Britain presents challenges for managing electricity systems. One concern is the reduction in system inertia during periods where renewables provide a high proportion of demand which has led to some networks imposing system nonsynchronous penetration limits. However, given the lack of operational data, the relationship between renewable generation and demand for the full range of meteorological conditions experienced in Great Britain is poorly understood. This study uses reanalysis datasets to determine the proportion of demand from renewable generation on an hourly resolution for a 36-year period. The days with highest penetration of renewables tend to be sunny, windy weekend days between May and September, when there is a significant contribution of both wind and solar generation and demand is suppressed due to human behaviour. Based on the current distribution of wind and solar capacity, there is very little curtailment for all system non-synchronous penetration limits considered. However, as installed capacity of renewables grows the volume of generation curtailed also increases with a disproportionate volume occurring at weekends. The total volume of curtailment is highly dependent on ratio of wind and solar capacity, with the current blend close to the optimum level

Life-course blood pressure in relation to brain volumes

The impact of blood pressure on brain volumes may be time- or pattern-dependent

Life-course blood pressure in relation to brain volumes

The impact of blood pressure on brain volumes may be time- or pattern-dependent

Global health education: a pilot in trans-disciplinary, digital instruction

Background: The development of new global health academic programs provides unique opportunities to create innovative educational approaches within and across universities. Recent evidence suggests that digital media technologies may provide feasible and cost-effective alternatives to traditional classroom instruction; yet, many emerging global health academic programs lag behind in the utilization of modern technologies. Objective: We created an inter-departmental University of Southern California (USC) collaboration to develop and implement a course focused on digital media and global health. Design: Course curriculum was based on core tenants of modern education: multi-disciplinary, technologically advanced, learner-centered, and professional application of knowledge. Student and university evaluations were reviewed to qualitatively assess course satisfaction and educational outcomes. Results: &#x2018;New Media for Global Health&#x2019; ran for 18 weeks in the Spring 2012 semester with N=41 students (56.1% global health and 43.9% digital studies students). The course resulted in a number of high quality global health-related digital media products available at http://iml420.wordpress.com/. Challenges confronted at USC included administrative challenges related to co-teaching and frustration from students conditioned to a rigid system of teacher-led learning within a specific discipline. Quantitative and qualitative course evaluations reflected positive feedback for the course instructors and mixed reviews for the organization of the course. Conclusion: The development of innovative educational programs in global health requires on-going experimentation and information sharing across departments and universities. Digital media technologies may have implications for future efforts to improve global health education