Microbiology of the rumen in relation to the nutrition and physiology of the animal

No Abstrac

Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials

STUDY QUESTION What is an objective approach that employs measurable and reproducible physiologic changes as the basis for the classification of ovarian hyperstimulation syndrome (OHSS) in order to facilitate more accurate reporting of incidence rates within and across clinical trials? SUMMARY ANSWER The OHSS flow diagram is an objective approach that will facilitate consistent capture, classification and reporting of OHSS within and across clinical trials. WHAT IS KNOWN ALREADY OHSS is a potentially life-threatening iatrogenic complication of the early luteal phase and/or early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). The clinical picture of OHSS (the constellation of symptoms associated with each stage of the disease) is highly variable, hampering its appropriate classification in clinical trials. Although some degree of ovarian hyperstimulation is normal after stimulation, the point at which symptoms transition from those anticipated to those of a disease state is nebulous. STUDY DESIGN, SIZE, DURATION An OHSS working group, comprised of subject matter experts and clinical researchers who have significantly contributed to the field of fertility, was convened in April and November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS The OHSS working group was tasked with reaching a consensus on the definition and the classification of OHSS for reporting in clinical trials. The group engaged in targeted discussion regarding the scientific background of OHSS, the criteria proposed for the definition and the rationale for universal adoption. An agreement was reached after discussion with all members. MAIN RESULTS AND THE ROLE OF CHANCE One of the following conditions must be met prior to making the diagnosis of OHSS in the context of a clinical trial: (i) the subject has undergone OS (either controlled OS or OI) AND has received a trigger shot for final oocyte maturation (e.g. hCG, GnRH agonist [GnRHa] or kisspeptin) followed by either fresh transfer or segmentation (cryopreservation of embryos) or (ii) the subject has undergone OS or OI AND has a positive pregnancy test. All study patients who develop symptoms of OHSS should undergo a thorough examination. An OHSS flow diagram was designed to be implemented for all subjects with pelvic or abdominal complaints, such as lower abdominal discomfort or distention, nausea, vomiting and diarrhea, and/or for subjects suspected of having OHSS. The diagnosis of OHSS should be based on the flow diagram. LIMITATIONS, REASONS FOR CAUTION This classification system is primarily intended to address the needs of the clinical investigator undertaking clinical trials in the field of OS and may not be applicable for the use in clinical practice or with OHSS occurring under natural circumstances. WIDER IMPLICATIONS OF THE FINDINGS The proposed OHSS classification system will enable an accurate estimate of the incidence and severity of OHSS within and across clinical trials performed in women with infertility. STUDY FUNDING/COMPETING INTERESTS Financial support for the advisory group meetings was provided by Merck & Co., Inc., Kenilworth, NJ, USA. P.H. reports unrestricted research grants from MSD, Merck and Ferring, and honoraria for lectures from MSD, Merck and IBSA. S.M.N. reports that he has received fees and grant support from the following companies (in alphabetic order): Beckman Coulter, Besins, EMD Serono, Ferring Pharmaceuticals, Finox, MSD and Roche Diagnostics over the previous 5 years. P.D., C.C.C., J.L.F., H.M.F., and P.L. report no relationships that present a potential conflict of interest. B.C.T. reports: grants and honorarium from Merck Serono; unrestricted research grants, travel grants and honorarium, and participation in a company-sponsored speaker's bureau from Merck Sharp & Dohme; grants, travel grants, honoraria and advisory board membership from IBSA; travel grants from Ferring; and advisory board membership from Ovascience. L.B.S. reports current employment with Merck & Co, Inc., Kenilworth, NJ, USA, and owns stock in the company. K.G. and B.J.S. report prior employment with Merck & Co., Inc., Kenilworth, NJ, USA, and own stock in the company. All reported that competing interests are outside the submitted work. No other relationships or activities exist that could appear to have influenced the submitted work

Women, men and coronary heart disease: a review of the qualitative literature

Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

Dynamical aspects of quantum entanglement for weakly coupled kicked tops

We investigate how the dynamical production of quantum entanglement for weakly coupled, composite quantum systems is influenced by the chaotic dynamics of the corresponding classical system, using coupled kicked tops. The linear entropy for the subsystem (a kicked top) is employed as a measure of entanglement. A perturbative formula for the entanglement production rate is derived. The formula contains a correlation function that can be evaluated only from the information of uncoupled tops. Using this expression and the assumption that the correlation function decays exponentially which is plausible for chaotic tops, it is shown that {\it the increment of the strength of chaos does not enhance the production rate of entanglement} when the coupling is weak enough and the subsystems (kicked tops) are strongly chaotic. The result is confirmed by numerical experiments. The perturbative approach is also applied to a weakly chaotic region, where tori and chaotic sea coexist in the corresponding classical phase space, to reexamine a recent numerical study that suggests an intimate relationship between the linear stability of the corresponding classical trajectory and the entanglement production rate.Comment: 16 pages, 11 figures, submitted to Phys. Rev.

Collisionless hydrodynamics for 1D motion of inhomogeneous degenerate electron gases: equivalence of two recent descriptions

Recently I. Tokatly and O. Pankratov (''TP'', Phys. Rev. B 60, 15550 (1999)) used velocity moments of a semiclassical kinetic equation to derive a hydrodynamic description of electron motion in a degenerate electron gas. Independently, the present authors (Theochem 501-502, 327 (2000)) used considerations arising from the Harmonic Potential Theorem (Phys. Rev. Lett. 73, 2244 (1994)) to generate a new form of high-frequency hydrodynamics for inhomogeneous degenerate electron gases (HPT-N3 hydrodynamics). We show here that TP hydrodynamics yields HPT-N3 hydrodynamics when linearized about a Thomas-Fermi groundstate with one-dimensional spatial inhomnogeneity.Comment: 17p

Patency of endoscopic ultrasound-guided gastroenterostomy in the treatment of malignant gastric outlet obstruction

Background and study aims Endoscopic ultrasoundguided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent (LAMS) is a novel, minimally invasive technique in the palliative treatment of malignant gastric outlet obstruction (GOO). Several studies have demonstrated feasibility and safety of EUS-GE, but evidence on long-term durability is limited. The aim of this study was to evaluate patency of EUS-GE in treatment of malignant GOO. Patients and Methods An international multicenter study was performed in seven centers in four European countries. Patients who underwent EUS-GE with a LAMS between March 2015 and March 2019 for palliative treatment of symptomatic malignant GOO were included retrospectively. Our main outcome was recurrent obstruction due to LAMS dysfunction; other outcomes of interest were technical success, clinical success, adverse events (AEs), and survival. Results A total of 45 patients (mean age 69.9 ± 12.3 years and 48.9% male) were included. Median duration of followup was 59 days (interquartile range [IQR] 41–128). Recurrent obstruction occurred in two patients (6.1 %), after 33 and 283 days of follow-up. Technical success was achieved in 39 patients (86.7 %). Clinical success was achieved in 33 patients (73.3 %). AEs occurred in 12 patients (26.7 %), of which five were fatal. Median overall survival was 57 days (IQR 32–114). Conclusions EUS-GE showed a low rate of recurrent obstruction. The relatively high number of fatal AEs underscores the importance of careful implementation of EUSGE in clinical practice

An efficient adaptive multigrid algorithm for predicting thin film flow on surfaces containing localised topographic features

Gravity-driven continuous thin film flow over a plane, containing well-defined single and grouped topographic features, is modelled as a Stokes flow using lubrication theory. The associated time dependent, nonlinear, coupled set of governing equations are solved using a Full Approximation Storage (FAS) Multigrid algorithm by employing automatic mesh adaptivity, the power efficiency and accuracy of which is demonstrated by comparing the results with corresponding global fine-mesh solutions.. These show that automatic grid refinement effectively restricts the use of find grids to regions of rapid flow development which, for flow over the topographies considered, includes the topography itself, the upstream Capillary ridge, downstream sure region, and the characteristic bow wave. It is shown that for the accurate solution of such flow problems, adaptive Multigridding offers increased flexibility together with a significant reduction in memory requirement. This is further demonstrated by solving the problem of transient flow over a trench topography, generated by a sinusoidally varying inlet condition

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk:Rationale and design of the ODYSSEY DM-INSULIN trial

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening. ≥. 70. mg/dL (1.81. mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24. weeks of alirocumab 75. mg every 2. weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C. ≥. 70. mg/dL at week 8 underwent a blinded dose increase to 150. mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. Results: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. Conclusion: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy

Innovative solutions to novel drug development in mental health

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders