No abstract

Recent national focus on the value of increasing US supplies of indigenous renewable energy underscores the need for re-evaluating all alternatives, particularly those that are large and well distributed nationally. A panel was assembled in September 2005 to evaluate the technical and economic feasibility of geothermal becoming a major supplier of primary energy for US base-load generation capacity by 2050. Primary energy produced from both conventional hydrothermal and enhanced (or engineered) geothermal systems (EGS) was considered on a national scale. This paper summarizes the work of the panel which appears in complete form in a 2006 MIT report, 'The future of geothermal energy' parts 1 and 2.In the analysis, a comprehensive national assessment of US geothermal resources, evaluation of drilling and reservoir technologies and economic modelling was carried out. The methodologies employed to estimate geologic heat flow for a range of geothermal resources were utilized to provide detailed quantitative projections of the EGS resource base for the USA. Thirty years of field testing worldwide was evaluated to identify the remaining technology needs with respect to drilling and completing wells, stimulating EGS reservoirs and converting geothermal heat to electricity in surface power and energy recovery systems. Economic modelling was used to develop long-term projections of EGS in the USA for supplying electricity and thermal energy. Sensitivities to capital costs for drilling, stimulation and power plant construction, and financial factors, learning curve estimates, and uncertainties and risks were considered.

Purpose Poorly-differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors including papillary thyroid cancer (PTC) and ATC are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1-targeting agents for the treatment of aggressive cancer. We developed a third-generation CAR targeting ICAM-1 to leverage adoptive T cell therapy as a new treatment modality. Experimental Design ICAM-1 CAR T cells were applied on multiple malignant and non-malignant target cells to investigate specific target cell death and ‘off-tumor’ toxicity in vitro. In vivo therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases. Results ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines in vitro. Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable. In mice with systemic ATC, a single administration of ICAM-1 CAR-T cells mediated profound tumor killing that resulted in long term remission and significantly improved survival. Patient-derived ATC cells overexpressed ICAM-1 and were largely eliminated by autologous ICAM-1 CAR T cells in vitro and in animal models. Conclusions Our findings are the first demonstration of CAR T therapy for metastatic, thyroid cancer cell line and advanced ATC patient-derived tumors that exhibit dramatic therapeutic efficacy and survival benefit in animal studies.

Gastroesophageal reflux disease (GERD) is a very common disorder with increasing prevalence. It is estimated that up to 20%-25% of Americans experience symptoms of GERD weekly. Excessive reflux of acidic often with alkaline bile salt gastric and duodenal contents results in a multitude of symptoms for the patient including heartburn, regurgitation, cough, and dysphagia. There are also associated complications of GERD including erosive esophagitis, Barrett's esophagus, stricture and adenocarcinoma of the esophagus. While first line treatments for GERD involve mainly lifestyle and non-surgical therapies, surgical interventions have proven to be effective in appropriate circumstances. Anti-reflux operations are aimed at creating an effective barrier to reflux at the gastroesophageal junction and thus attempt to improve physiologic and mechanical issues that may be involved in the pathogenesis of GERD. The decision for surgical intervention in the treatment of GERD, moreover, requires an objective confirmation of the diagnosis. Confirmation is achieved using various preoperative evaluations including: ambulatory pH monitoring, esophageal manometry, upper endoscopy (esophagogastroduodenoscopy) and barium swallow. Upon confirmation of the diagnosis and with appropriate patient criteria met, an anti-reflux operation is a good alternative to prolonged medical therapy. Currently, minimally invasive gastro-esophageal fundoplication is the gold standard for surgical intervention of GERD. Our review outlines the many factors that are involved in surgical decision-making. We will review the prominent features that reflect appropriate anti-reflux surgery and present suggestions that are pertinent to surgical practices, based on evidence-based studies.

Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.

n March 1, 2020, the first case of coronavirus disease 2019 (COVID-19) was confirmed in New York City (NYC) and rapidly emerged as the nation's epicenter with more than 366 000 (22% of the US) confirmed cases and 29 000 (30% of the US) deaths as of May 27, 2020 (Figure 1). 1,2 At the peak in mid-April, NewYork-Presbyterian Hospital/Weill Cornell Medicine (NYP-WC) was treating 474 patients who had tested positive for COVID-19, with 237 (50.0%) admitted to the intensive care unit (ICU) and 212 (44.7%) requiring mechanical ventilation. Owing to the exponential rise in critical care needs, 3-5 NYC hospitals sought to quickly restructure existing systems to expand critical care capacities while limiting clinical care in nones-sential areas. Plans to restructure surgery programs have been previously described, 6-8 but the experience of a region as profoundly affected as NYC has yet to be reported. This restructuring had a particularly pronounced effect on surgery departments and training as elective cases were suspended. 9,10 On March 16, 2020, in response to the US Centers for Disease Control and Prevention recommendations in consensus with multiple surgical societies such as the American College of Surgeons and an order from the New York State governor, NYP-WC announced that elective surgeries would be postponed. 11 General surgery training in NYC was uniquely affected by decreased operative training opportunities lost during the 2019-On March 1, 2020, the first case of coronavirus disease 2019 (COVID-19) was confirmed in New York, New York. Since then, the city has emerged as an epicenter for the ongoing pandemic in the US. To meet the anticipated demand caused by the predicted surge of patients with COVID-19, the Department of Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medicine developed and executed an emergent restructuring of general surgery resident teams and educational infrastructure. The restructuring of surgical services described in this Special Communication details the methodology used to safely deploy the necessary amount of the resident workforce to support pandemic efforts while maintaining staffing for emergency surgical care, limiting unnecessary exposure of residents to infection risk, effectively placing residents in critical care units, and maintaining surgical education and board eligibility for the training program as a whole.

GEOPHIRES (GEOthermal energy for the Production of Heat and Electricity (“IR”) Economically Simulated) is a software tool that combines reservoir, wellbore, and power plant models with capital and operating cost correlations and financial levelized cost models to assess the technical and economic performance of Enhanced Geothermal Systems (EGS). It is an upgrade and expansion of the “MIT-EGS” program used in the 2006 “Future of Geothermal Energy” study. GEOPHIRES includes updated cost correlations for well drilling and completion, resource exploration, and Organic Rankine Cycle (ORC) and flash power plants. It also has new power plant efficiency correlations based on AspenPlus and MATLAB simulations. The structure of GEOPHIRES enables feasibility studies of using geothermal resources not only for electricity generation but also for direct-use heating, and combined heat and power (CHP) applications. Full documentation on GEOPHIRES is provided in the supplementary material. Using GEOPHIRES, the levelized cost of electricity (LCOE) and the levelized cost of heat (LCOH) have been estimated for 3 cases of resource grade (low-, medium-, and high-grade resource corresponding to a geothermal gradient of 30, 50, and 70 °C/km) in combination with 3 levels of technological maturity (today's, mid-term, and commercially mature technology corresponding to a productivity of 30, 50, and 70 kg/s per production well and thermal drawdown rate of 2%, 1.5%, and 1%). The results for the LCOE range from 4.6 to 57 ¢/kWhe and for the LCOH from 3.5 to 14 $/MMBTU (1.2 to 4.8 ¢/kWhth). The results for the base-case scenario (medium-grade resource and mid-term technology) are 11 ¢/kWhe and 5 $/MMBTU (1.7 ¢/kWhth), respectively. To account for parameter uncertainty, a sensitivity analysis has been included. The results for the LCOE and LCOH have been compared with values found in literature for EGS as well as other energy technologies. The key findings suggest that given today's technology maturity, electricity and direct-use heat from EGS are not economically competitive under current market conditions with other energy technologies. However, with moderate technological improvements, electricity from EGS is predicted to become cost-effective with respect to other renewable and non-renewable energy sources for medium- and high-grade geothermal resources. Direct-use heat from EGS is calculated to become cost-effective even for low-grade resources. This emphasizes that EGS for direct-use heat may not be neglected in future EGS development.

RRBS is associated with a shorter length of stay than LRBS in complex procedures and has at least an equivalent safety profile. Long-term follow-up data is needed.