Early- Mid Pleistocene environments in the Valsequillo Basin, Central Mexico: a reassessment

The Valsequillo Basin in Central Mexico has been of interest due to the presence of megafauna and evidence for early human occupation, but research has been controversial. It has been suggested that extensive and deep lakes characterised the Early Pleistocene environment but sediment exposure is highly fragmentary and reliable dating has been difficult. Here we report, for the first time, Early Pleistocene palaeoenvironmental reconstructions using stable isotopes,diatoms, tephra and pollen. We studied several stratigraphic sections of mainly non-volcanic rocks, containing the 1.3 Ma Xalnene Ash as a stratigraphic marker. The isotope and other proxy data show that topographically low points in the basin were occupied by spring-fed, shallow water lakes during the Early – Mid Pleistocene, with a trend to drier conditions. The basin was a dynamic volcaniclastic environment during this period, with the production of the Toluquilla Volcano sequence and other rhyolitic-dacitic volcanic ashes interbedded with the lake sediments at the sections studied. There is no evidence from the sections for extensive and deep lakes before or after the Xalnene ash deposition. The presence of lakes in the basin during the Early Pleistocene would have made it attractive for megafauna

Randomized phase II study investigating pazopanib versus weekly paclitaxel in relapsed or progressive urothelial cancer

Purpose: Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy. Patients and Methods: This randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m2 days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS). Results: Between August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned. The study was terminated early on the recommendation of the independent data monitoring committee because of futility. Final analysis after the preplanned number of deaths (n = 110) occurred after a median follow-up of 18 months. One hundred fifteen deaths had occurred at the final data extract presented here. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P = .89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0 to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09; 80% CI, 0.85 to 1.40; one-sided P = .67). Discontinuations for toxicity occurred in 7.8% and 23.1% for paclitaxel and pazopanib, respectively. Conclusion: Pazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior OS for paclitaxel

Five Younger Dryas black mats in Mexico and their stratigraphic and paleoenvironmental context

The Younger Dryas interval (YD) was a period of widespread, abrupt climate change that occurred between 12,900 and 11,700 cal yr BP (10,900–10,000 14 C BP). Many sites in the Northern Hemisphere preserve a sedimentary record across the onset of the YD interval, including sites investigated in sedimentary basins located in central Mexico (Chapala, Cuitzeo, Acambay), the Basin of Mexico (Tocuila), and northern Mexico (El Cedral). Deposits consist of lacustrine or marginal lake sediments that were deposited during the Pleistocene and the Holocene. At the Tocuila and Acambay sites, Pleistocene fossil vertebrate assemblages, mainly mammoths (Mammuthus columbi), are found in association with a distinctive organic layer, sometimes called the black mat that formed during the YD. At the Chapala, Cuitzeo, Acambay, and Tocuila sites the black mats contain a suite of distinctive microscopic and mineralogical signatures and are accompanied by a sharp change in the depositional environments as supported by diatom and pollen studies reported here. The signatures include magnetic, Fe-rich microspherules, silica melted droplets with aerodynamic shapes (tektites), large amounts of charcoal, and sometimes nanodiamonds (Cuitzeo), all of which were deposited at the onset of the YD. The geochemistry of the microspherules indicates that they are not anthropogenic, authigenic or of cosmic or volcanic origin, and instead, were produced by melting and quenching of terrestrial sediments. Here, we present the stratigraphy at five field sites, the analyses of magnetic microspherules, including major element composition and scanning electron microscopy images. All of these materials are associated with charcoal and soot, which are distinctive stratigraphic markers for the YD layer at several sites in Mexico. © 2017 Springer Science+Business Media B.V

Sensors and Actuators for the Advanced LIGO+ Upgrade

Advanced Laser Interferometer Gravitational-wave Observatory (LIGO A+) is a major upgrade to LIGO—the Laser Interferometer Gravitational-wave Observatory. For the A+ project, we have developed, produced, and characterized sensors and electronics to interrogate new optical suspensions designed to isolate optics from vibrations. The central element is a displacement sensor with an integrated electromagnetic actuator known as a BOSEM (Birmingham Optical Sensor and ElectroMagnetic actuator) and its readout and drive electronics required to integrate them into LIGO’s control and data system. In this paper, we report on the improvements to the sensors and the testing procedures undertaken to meet the enhanced performance requirements set out by the A+ upgrade to the detectors. The best devices reach a noise level of 4.5 ×10−11m/√Hz at a measurement frequency of 1 Hz, an improvement of 6.7 times over standard devices

Long-term outcomes with intensive induction chemotherapy (carboplatin, bleomycin, vincristine and cisplatin/bleomycin, etoposide and cisplatin) and standard bleomycin, etoposide and cisplatin in poor prognosis germ cell tumours: A randomised phase II trial (ISRCTN53643604).

Background Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, vincristine and cisplatin/BEP), met response targets in a randomised, phase II trial (74% complete response or partial response marker negative, 90% confidence interval (CI) 61%-85%).Aim To assess long-term outcomes and late toxicity associated with CBOP/BEP.Methods Patients with poor prognosis extracranial GCT were randomised to 4xBEP or CBOP/BEP (2xCBOP, 2xBO, 3xBEP with 15,000iu of bleomycin). Low-dose, stabilising chemotherapy before entry was permitted. Response rates (primary outcome) were reported previously. Here, we report secondary outcomes: progression-free survival (PFS), overall survival (OS) and late toxicity. Prognostic factors and the impact of marker decline are assessed in exploratory analysis.Results Eighty-nine patients (43 CBOP/BEP) were randomised. After median 63 months follow-up, 3-year PFS is 55.7% (95% CI: 39.7%, 69.0%) for CBOP/BEP and 38.7% (95% CI: 24.7%, 52.4%) for BEP (hazard ratio [HR]: 0.59 (0.33, 1.06), p = 0.079). Three-year OS is 65.0% (48.8%, 77.2%) and 58.5% (43.0%, 71.2%), respectively (HR: 0.79 (0.41, 1.52), p = 0.49). Twelve-month toxicity was affected by subsequent treatments, with no clear differences between arms. Stabilising chemotherapy was associated with poorer PFS (HR: 2.09 (1.14, 3.81), p = 0.017), whereas unfavourable marker decline, in 60 (70%) patients, was not.Conclusion Although not powered for PFS, results for CBOP/BEP are promising. Impact on OS was less clear (and will be affected by subsequent therapy). Further study in an international phase III trial is warranted.Trial registration ISRCTN 53643604