F(T) gravity and k-essence

Modified teleparallel gravity theory with the torsion scalar have recently gained a lot of attention as a possible explanation of dark energy. We perform a thorough reconstruction analysis on the so-called $F(T)$ models, where $F(T)$ is some general function of the torsion term, and derive conditions for the equivalence between of $F(T)$ models with purely kinetic k-essence. We present a new class models of $F(T)$-gravity and k-essence. We also proposed some new models of generalized gases and knot universes as well as some generalizations of $F(T)$ gravity.Comment: 25 page

Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50.

Purpose We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS).Methods Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point.Results Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti-PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3-40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48-0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure.Conclusion Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%

Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

<p>Abstract</p> <p>Background</p> <p>Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.</p> <p>Methods</p> <p>Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.</p> <p>Results</p> <p>1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).</p> <p>Conclusions</p> <p>Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.</p> <p>Trial Registration</p> <p>clinicaltrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00451412">NCT00451412</a></p

Structure of the Head of the Bartonella Adhesin BadA

Trimeric autotransporter adhesins (TAAs) are a major class of proteins by which pathogenic proteobacteria adhere to their hosts. Prominent examples include Yersinia YadA, Haemophilus Hia and Hsf, Moraxella UspA1 and A2, and Neisseria NadA. TAAs also occur in symbiotic and environmental species and presumably represent a general solution to the problem of adhesion in proteobacteria. The general structure of TAAs follows a head-stalk-anchor architecture, where the heads are the primary mediators of attachment and autoagglutination. In the major adhesin of Bartonella henselae, BadA, the head consists of three domains, the N-terminal of which shows strong sequence similarity to the head of Yersinia YadA. The two other domains were not recognizably similar to any protein of known structure. We therefore determined their crystal structure to a resolution of 1.1 Å. Both domains are β-prisms, the N-terminal one formed by interleaved, five-stranded β-meanders parallel to the trimer axis and the C-terminal one by five-stranded β-meanders orthogonal to the axis. Despite the absence of statistically significant sequence similarity, the two domains are structurally similar to domains from Haemophilus Hia, albeit in permuted order. Thus, the BadA head appears to be a chimera of domains seen in two other TAAs, YadA and Hia, highlighting the combinatorial evolutionary strategy taken by pathogens

The establishment of the Standard Cosmological Model through observations

Over the last decades, observations with increasing quality have revolutionized our understanding of the general properties of the Universe. Questions posed for millenia by mankind about the origin, evolution and structure of the cosmos have found an answer. This has been possible mainly thanks to observations of the Cosmic Microwave Background, of the large-scale distribution of matter structure in the local Universe, and of type Ia supernovae that have revealed the accelerated expansion of the Universe. All these observations have successfully converged into the so-called "concordance model". In spite of all these observational successes, there are still some important open problems, the most obvious of which are what generated the initial matter inhomogeneities that led to the structure observable in today's Universe, and what is the nature of dark matter, and of the dark energy that drives the accelerated expansion. In this chapter I will expand on the previous aspects. I will present a general description of the Standard Cosmological Model of the Universe, with special emphasis on the most recent observations that have us allowed to consolidate this model. I will also discuss the shortfalls of this model, its most pressing open questions, and will briefly describe the observational programmes that are being planned to tackle these issues.Comment: Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry.

Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data-clinical, pathologic, and molecular features-were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Conclusion Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients

Efficacy of acupuncture for chronic low back pain: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Chronic back pain is a major public health problem and the primary reason patients seek acupuncture treatment. Therefore, an objective assessment of acupuncture efficacy is critical for making informed decisions about its appropriate role for patients with this common condition. This study addresses methodological shortcomings that have plagued previous studies evaluating acupuncture for chronic low back pain.</p> <p>Methods and Design</p> <p>A total of 640 participants (160 in each of four arms) between the ages of 18 and 70 years of age who have low back pain lasting at least 3 months will be recruited from integrated health care delivery systems in Seattle and Oakland. They will be randomized to one of two forms of Traditional Chinese Medical (TCM) acupuncture needling (individualized or standardized), a "control" group (simulated acupuncture), or to continued usual medical care. Ten treatments will be provided over 7 weeks. Study participants and the "Diagnostician" acupuncturists who evaluate participants and propose individualized treatments will be masked to the acupuncture treatment actually assigned each participant. The "Therapist" acupuncturists providing the treatments will not be masked but will have limited verbal interaction with participants. The primary outcomes, standard measures of dysfunction and bothersomeness of low back pain, will be assessed at baseline, and after 8, 26, and 52 weeks by telephone interviewers masked to treatment assignment. General health status, satisfaction with back care, days of back-related disability, and use and costs of healthcare services for back pain will also be measured. The primary analysis comparing outcomes by randomized treatment assignment will be analysis of covariance adjusted for baseline value. For both primary outcome measures, this trial will have 99% power to detect the presence of a minimal clinically significant difference among all four treatment groups and over 80% power for most pairwise comparisons. Secondary analyses will compare the proportions of participants in each group that improve by a clinically meaningful amount.</p> <p>Conclusion</p> <p>Results of this trial will help clarify the value of acupuncture needling as a treatment for chronic low back pain.</p> <p>Trial registration</p> <p>Clinical Trials.gov NCT00065585.</p

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit