Learning to Recommend from Positive Evidence

In recent years, many systems and approaches for recommending information, goods, or other kinds of objects have been developed. In these systems, often machine learning methods are used that need training input to acquire a user interest profile. Such methods typically need positive and negative evidence of the user’s interests. To obtain both kinds of evidence, many systems make users rate relevant objects explicitly. Others merely observe the user’s behavior, which fairly obviously yields positive evidence; in order to be able to apply the standard learning methods, these systems mostly use heuristics that attempt to find also negative evidence in observed behavior. In this paper, we present several approaches to learning interest profiles from positive evidence only, as it is contained in observed user behavior. Thus, both the problem of interrupting the user for ratings and the problem of somewhat artificially determining negative evidence are avoided. The learning approaches were developed and tested in the context of the Web-based ELFI information system that is in real use by more than 1000 people. We give a brief sketch of ELFI and describe the experiments we made based on ELFI usage logs to evaluate the different proposed method

Luteal Presence and Ovarian Response at the Beginning of a Timed Artificial Insemination Protocol for Lactating Dairy Cows Affect Fertility: A Meta-Analysis

Progesterone (P4) concentration during follicular growth has a major impact on fertility response in timed artificial insemination (TAI) protocols. Luteal presence at the beginning of a TAI protocol and ovarian response after the first gonadotropin-releasing hormone (GnRH) injection (G1) affect P4 concentration and subsequently pregnancy per artificial insemination (P/AI). A systematic review of the literature and meta-analytical assessment was performed with the objective of evaluating the magnitude of the effect of luteal presence and ovarian response at the beginning of a TAI protocol on P/AI in lactating dairy cows. We considered only studies using synchronisation protocols consisting of GnRH and prostaglandin F (2 alpha). The time interval between G1 and prostaglandin F (2 alpha) (PGF (2 alpha)) had to range from 5 to 7 d. The time interval between the PGF (2 alpha) injection and G2 had to range from 48 to 72 h. We used 28 controlled experiments from 27 published manuscripts including 16,489 cows with the objective of evaluating the effect size of having a functional corpus luteum (CL) at G1 on P/AI. Information regarding ovulatory response after G1 was available for 5676 cows. In a subset of cows (n = 4291), information was available for luteal presence and ovulatory response at the initiation of the TAI protocol. A functional CL at G1 increased (p < 0.001) the relative risk of conceiving (RR (relative risk) = 1.32; 95% CI = 1.21-1.45) in lactating dairy cows. Ovulation after G1 increased (p < 0.001) the relative risk of conceiving (RR = 1.29; 95% CI = 1.20-1.38) in lactating dairy cows. The effect of ovulatory response on P/AI after G1 was affected by luteal presence at G1. In summary, there was a clear benefit on P/AI for cows starting a TAI protocol with a functional CL (+10.5 percentage units) and cows ovulating at the beginning of a TAI protocol (+11.0 percentage units)

Observation of Long-Lived Muonic Hydrogen in the 2S State

The kinetic energy distribution of ground state muonic hydrogen atoms mu-p(1S) is determined from time-of-flight spectra measured at 4, 16, and 64 hPa H2 room-temperature gas. A 0.9 keV-component is discovered and attributed to radiationless deexcitation of long-lived mu-p(2S) atoms in collisions with H2 molecules. The analysis reveals a relative population of about 1%, and a pressure-dependent lifetime (e.g. (30.4 +21.4 -9.7) ns at 64 hPa) of the long-lived mu-p(2S) population, equivalent to a 2S-quench rate in mu-p(2S) + H2 collisions of (4.4 +2.1 -1.8) 10^11 s^-1 at liquid hydrogen density.Comment: 4 pages, 2 figures, accepted for publication in Physical Review Letter

Safety, pharmacokinetics and pharmacodynamics of a novel anti-asthmatic drug, XC8, in healthy probands

Introduction: XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies. Objective: The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties. Methods: 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively. The subjects received a single dose of the drug at Day 1 and then once-daily for 14 days (Days 8-21). Results: No severe adverse events occurred. The number of adverse events was similar in the treatment arms compared to placebo and all subjects completed the study as planned. No clinically significant changes occurred in hematologic and biochemical blood tests in subjects receiving XC8. The pharmacokinetic data showed similar dose and time dependent mean plasma XC8 concentrations after single (Day 1) and multiple (Day 21) dosing. The mean maximum concentrations were 114-1993 ng/mL after single and 115-2089 ng/mL after multiple dosing. The mean times to maximum concentration were 0.68-1.01 and 0.67-0.98 h, respectively. There was no evidence for accumulation of XC8 after multiple dosing. Conclusion: XC8 was safe and well tolerated. A phase 2 study is being performed to further evaluate the potential role of XC8 in asthma treatment.Peer reviewe

Hydrogen-Deuterium Isotope Shift: From the 1S-2s-Transition Frequency to the Proton-Deuteron Charge-Radius Difference

We analyze and review the theory of the hydrogen-deuterium isotope shift for the 1S-2S transition, which is one of the most accurately measured isotope shifts in any atomic system, in view of a recently improved experiment. A tabulation of all physical effects that contribute to the isotope shift is given. These include the Dirac binding energy, quantum electrodynamic effects, including recoil corrections, and the nuclear-size effect, including the pertaining relativistic and radiative corrections. From a comparison of the theoretical result Δfth=670999566.90(66)(60)kHz (exclusive of the nonrelativistic nuclear-finite-size correction) and the experimental result Δfexpt=670994334605(15) Hz, we infer the deuteron-proton charge-radius difference (r2)d- (r2)p=3.82007(65) fm2 and the deuteron structure radius rstr=1.97507(78) fm

Barrier functions and paracellular integrity in human cell culture models of the proximal respiratory unit.

International audienceAirway epithelial cells provide a barrier to the translocation of inhaled materials. Tight (TJ) and adherens junctions (AJ) play a key role in maintaining barrier functions, and are responsible for the selective transport of various substances through the paracellular pathway. In this study we compared a bronchial cell line (16HBE14o-) and primary bronchial cells (HBEC), both cocultivated with the fibroblast cell line Wi-38, with respect to their structural differentiation and their reaction to cytokine stimulation. HBEC formed a pseudostratified epithelial layer and expressed TJ and AJ proteins after 2 weeks in coculture. Mucus-producing and ciliated cells were found within 24 days. Additionally, a beating activity of the ciliated HBEC (14-19 Hz) could be detected. 16HBE14o-in coculture showed a multilayered growth without differentiation to a pseudostratified airway epithelium. Simultaneous exposure to TNF-a-and IFN-c-induced significant changes in barrier function and paracellular permeability in the cocultures of HBEC/Wi-38 but not in the 16HBE14o-/Wi-38. In summary, HBEC in coculture mimic the structure of native polarized bronchial epithelium showing basal, mucus-producing and ciliated cells. Our system provides an opportunity to examine the factors that influence barrier and mucociliary function of bronchial epithelium within a time frame of 3 weeks up to 3 months in an in vivo-like differentiated model

Allergic Rhinitis and Asthma Symptoms in a Real-Life Study of MP-AzeFlu to Treat Multimorbid Allergic Rhinitis and Asthma

Acknowledgements We would like to thank the subjects who participated in the trial. Funding This study was supported by MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany. Technical, editorial, and medical writing assistance was provided under the direction of the authors by Strategix, an affiliate of The Lynx Group, LLC. Funding for this support was provided by Mylan Inc.Peer reviewedPublisher PD

MP-AzeFlu Improves the Quality-of-Life of Patients with Allergic Rhinitis

Acknowledgments: We would like to thank the subjects who participated in the trial. The abstract of this paper was presented at the EAACI Congress 2020 as an oral presentation. The presentation’s abstract was published in Allergy: Van Weissenbruch R, Klimek L, Galffy G, et al. MP-Azeflu improves quality of life of patients with allergic rhinitis: a real-world study Funding: Technical, editorial, and medical writing assistance were provided under the direction of the authors by Erin Burns, PhD, and Strategix, an affiliate of The Lynx Group, LLC. Funding for this support was provided by Mylan Inc.Peer reviewedPublisher PD

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology