Isotopic Signature of Massive, Buried Ice in Eastern Taylor Valley, Antarctica: Implications for Its Origin

The coastal regions of the McMurdo Dry Valleys, Antarctica, contain deposits of the Ross Sea Drift, sedimentary material left from the Ross Sea ice sheet from the advance of the West Antarctic ice sheet during the Last Glacial Maximum. Much of this deposit is ice-cored, but data on the stable isotopic composition of water from this ice, which may contain a valuable climate archive, are sparse or incomplete. Widespread thermokarstic ground subsidence in this “coastal thaw zone” of the McMurdo Dry Valleys suggests that these potential records are rapidly being lost due to the melting of ground ice and permafrost. We collected samples of massive buried ice from the Ross Sea Drift in eastern Taylor Valley for δ18O-H2O and δ2H-H2O and measured a broad range of values (δ18O = −27.7 to −37.3 ‰; δ2H = −210 to −295 ‰). These buried ice deposits do not show evidence of alteration through sublimation or evaporation, plot along the local meteoric water line, and have values that indicate ice deposition under a colder climate than present conditions. We propose that this ice was sourced from the Ross Sea ice sheet during the Last Glacial Maximum and contains a valuable and accessible climate record

Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma.

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. RESULTS: 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). CONCLUSIONS: SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses. TRIAL REGISTRATION NUMBER: NCT01416831

The New Horizons Spacecraft

The New Horizons spacecraft was launched on 19 January 2006. The spacecraft was designed to provide a platform for seven instruments that will collect and return data from Pluto in 2015. The design drew on heritage from previous missions developed at The Johns Hopkins University Applied Physics Laboratory (APL) and other missions such as Ulysses. The trajectory design imposed constraints on mass and structural strength to meet the high launch acceleration needed to reach the Pluto system prior to the year 2020. The spacecraft subsystems were designed to meet tight mass and power allocations, yet provide the necessary control and data handling finesse to support data collection and return when the one-way light time during the Pluto flyby is 4.5 hours. Missions to the outer solar system require a radioisotope thermoelectric generator (RTG) to supply electrical power, and a single RTG is used by New Horizons. To accommodate this constraint, the spacecraft electronics were designed to operate on less than 200 W. The spacecraft system architecture provides sufficient redundancy to provide a probability of mission success of greater than 0.85, even with a mission duration of over 10 years. The spacecraft is now on its way to Pluto, with an arrival date of 14 July 2015. Initial inflight tests have verified that the spacecraft will meet the design requirements.Comment: 33 pages, 13 figures, 4 tables; To appear in a special volume of Space Science Reviews on the New Horizons missio

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Direct and indirect costs associated with stereotactic radiosurgery or open surgery for medial temporal lobe epilepsy: Results from the ROSE trial

Objective To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery. Methods We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing. Results Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95$79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up. Significance Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies

A phase Ib study of interleukin-2 plus pembrolizumab for patients with advanced melanoma.

INTRODUCTION: High-dose interleukin-2 (HD IL-2) and pembrolizumab are each approved as single agents by the U.S. F.D.A. for the treatment of metastatic melanoma. There is limited data using the agents concurrently. The objectives of this study were to characterize the safety profile of IL-2 in combination with pembrolizumab in patients with unresectable or metastatic melanoma. METHODS: In this Phase Ib study, patients received pembrolizumab (200 mg IV every 3 weeks) and escalating doses of IL-2 (6,000 or 60,000 or 600,000 IU/kg IV bolus every 8 hours up to 14 doses per cycle) in cohorts of 3 patients. Prior treatment with a PD-1 blocking antibody was allowed. The primary endpoint was the maximum tolerated dose (MTD) of IL-2 when co-administered with pembrolizumab. RESULTS: Ten participants were enrolled, and 9 participants were evaluable for safety and efficacy. The majority of the evaluable participants (8/9) had been treated with PD-1 blocking antibody prior to enrollment. Patients received a median of 42, 22, and 9 doses of IL-2 in the low, intermediate, and high dose cohorts, respectively. Adverse events were more frequent with increasing doses of IL-2. No dose limiting toxicities were observed. The MTD of IL-2 was not reached. One partial response occurred in 9 patients (11%). The responding patient, who had received treatment with an anti-PD-1 prior to study entry, was treated in the HD IL-2 cohort. DISCUSSION: Although the sample size was small, HD IL-2 therapy in combination with pembrolizumab appears feasible and tolerable. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02748564

Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors

Objective: The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice. Methods: We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables. Results: The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p \u3c.001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose–positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06–3.29; p =.033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60–5.28; p = \u3c.001), high density (HD) EEG (OR 2.80; 95% CI 1.27–6.24; p =.011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19–4.10; p =.014), and Wada (OR 2.16; 95% CI 1.28–3.66; p =.004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24–7.89; p =.016). Significance: In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE