RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis.

Background: In EGFR mutation-positive NSCLC, dual EGFR/VEGFR inhibition compared to EGFR alone increases anti-tumor efficacy. The Phase III RELAY trial demonstrated superior PFS for ramucirumab plus erlotinib (RAM + ERL) over placebo plus erlotinib (PBO + ERL) (HR 0.591 [95% CI 0.461–0.760], p<0.0001). EGFR mutated NSCLC is less prevalent in Western versus Asian patients. This prespecified analysis evaluates efficacy and safety of RAM + ERL in EU and US patients enrolled in RELAY. Patients and Methods: Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease. Patients were stratified by geographic region (East Asia vs "other" [EU/US and Canada (EU/US)]). Objectives included PFS, ORR, DoR, OS, PFS2, safety and biomarker analysis. Results: EU/US subset included 113/449 (25.9%) patients (58 RAM + ERL, 55 PBO + ERL). RAM + ERL improved PFS (20.6 vs 10.9 months, HR 0.605 [95% CI: 0.362–1.010]). ORR and DCR were similar, but median DoR was longer with RAM + ERL (18.0 vs 10.1 months, HR 0.527 [95% CI: 0.296–0.939]). OS and PFS2 were immature at data cut-off (censoring rates 81.0–81.8% and 67.3–79.3%, respectively). Most commonly reported Grade ≥3 TEAE for RAM + ERL was hypertension (17 [29.8%]) and for PBO + ERL, dermatitis acneiform (5 [9.1%]). Conclusion: EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC

Understanding the influences on successful quality improvement in emergency general surgery: learning from the RCS Chole-QuIC project

Abstract: Background: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy. Methods: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams’ ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project. Results: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others’ experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway. Conclusion: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

SuperCam Calibration Targets: Design and Development

SuperCam is a highly integrated remote-sensing instrumental suite for NASA’s Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Evidence that the mediobasal hypothalamus is the primary site of action of estradiol in inducing the preovulatory gonadotropin releasing hormone surge in the ewe

International audienc

Evidence that the mediobasal hypothalamus is the primary site of action of estradiol in inducing the preovulatory gonadotropin releasing hormone surge in the ewe

International audienc

Pra Desain Pabrik Lube Base Oil dari Oli Bekas dengan Proses Ekstraksi Solvent

Minyak pelumas dasar  merupakan bahan baku dari pembuatan minyak pelumas atau oli yang digunakan untuk berbagai jenis permesinan baik berat maupun ringan. Sebagian besar pelumas terdiri dari lube base oil 80% dan 20% merupakan aditive. Minyak pelumas, baik yang berasal dari ekstraksi  crude oil atau yang berasal dari minyak sintetis telah digunakan secara luas dalam dunia industri, dari proses pelumasan, transfer panas, metal cutting dan sebagainya. Dari proses pengaplikasian tersebut, minyak pelumas yang digunakan  akan terkontaminasi dan atau terdegradasi. Minyak inilah yang selanjutnya disebut minyak pelumas bekas (used oil). Hal ini secara otomatis memunculkan permasalahan baru dengan hadirnya limbah minyak peIumas atau oli bekas yang sangat melimpah tersebut. sehingga akan berdampak bagi kesehatan dan lingkungan. Minyak pelumas bekas mengandung sejumlah zat yang bisa mengotori udara, tanah, dan air. Di Indonesia terdapat beberapa perusahaaan yang telah memproduksi minyak pelumas dari baik dari crude oil maupun dari oli bekas. Menurut Kemenperin (2008 - 2012), impor lube base oil ataupun minyak pelumas terus mengalami peningkatan. Melihat banyaknya penggunaan minyak pelumas bekas yang tersedia di Indonesia dan kebutuhan akan minyak pelumas yang semakin meningkat, maka direncanakan akan didirikan pabrik pengolohan lube base oil (minyak pelumas dasar) dari oli bekas. Selain untuk memenuhi kebutuhan, proses ini juga untuk mengurangi jumlah limbah oli bekas yang merupakan limbah B3. Terdapat beberapa  proses pembuatan minyak pelumas dasar dari oli bekas ini, diantaranya proses hidrotreathing dan ekstraksi solvent. Pada proses hidrotreathing, minyak pelumas dasar dipisahkan dari fraksi unsaturated melalui reaksi hidrogenasi. Pada proses ini digunakan gas hidrogen. Sedangkan pada proses ekstraksi solvent, minyak pelumas bekas diekstraksi menggunakan pelarut organik untuk memisahkan fraksi minyak pelumas dasar dan unsaturated/sludge nya. Dari masing- masing proses tersebut, dapat dihasilkan produk samping yang juga bernilai ekonomi tinggi. Diantaranya adalah asphalt, fuel oil, dsb. Pabrik Minyak pelumas dasar direncanakan berdiri pada tahun 2019 yang berlokasi di Cilegon dengan kapasitas produksi adalah sebesar 30700 kL/tahun dengan menggunakan bahan baku Minyak pelumas bekas     sebesar 54.101.520 kg /tahun, N-Metil-2-Pyrrolidone 69.068.471 kg/tahun, Larutan NaOH 48% 1.127 kg/tahun. Pabrik lube base oil ini direncanakan beroperasi secara kontinyu selama 24 jam dengan waktu produksi 330 hari/tahun. Operasi pabrik lube base oil ini memiliki perencanaan sebagai berikut: modal tetap (FCI) sebesar Rp.               72.968.078.246, modal kerja                sebesar Rp. 12.876.719.692, investasi total (TCI) sebesar Rp. 85.844.797.937, Internal Rate of Return sebesar 46,7 %, Pay Out Time sebesar 2,74  tahun, dan  BEP sebesar 22,86