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

Toward Common Data Elements for International Research in Long-term Care Homes: Advancing Person-Centered Care

To support person-centered, residential long-term care internationally, a consortium of researchers in medicine, nursing, behavioral, and social sciences from 21 geographically and economically diverse countries have launched the WE-THRIVE consortium to develop a common data infrastructure. WE-THRIVE aims to identify measurement domains that are internationally relevant, including in low-, middle-, and high-income countries, prioritize concepts to operationalize domains, and specify a set of data elements to measure concepts that can be used across studies for data sharing and comparisons. This article reports findings from consortium meetings at the 2016 meeting of the Gerontological Society of America and the 2017 meeting of the International Association of Gerontology and Geriatrics, to identify domains and prioritize concepts, following best practices to identify common data elements (CDEs) that were developed through the US National Institutes of Health/National Institute of Nursing Research's CDEs initiative. Four domains were identified, including organizational context, workforce and staffing, person-centered care, and care outcomes. Using a nominal group process, WE-THRIVE prioritized 21 concepts across the 4 domains. Several concepts showed similarity to existing measurement structures, whereas others differed. Conceptual similarity (convergence; eg, concepts in the care outcomes domain of functional level and harm-free care) provides further support of the critical foundational work in LTC measurement endorsed and implemented by regulatory bodies. Different concepts (divergence; eg, concepts in the person-centered care domain of knowing the person and what matters most to the person) highlights current gaps in measurement efforts and is consistent with WE-THRIVE's focus on supporting resilience and thriving for residents, family, and staff. In alignment with the World Health Organization's call for comparative measurement work for health systems change, WE-THRIVE's work to date highlights the benefits of engaging with diverse LTC researchers, including those in low-, middle-, and high-income countries, to develop a measurement infrastructure that integrates the aspirations of person-centered LTC

Passivation of a Metal Contact with a Tunneling Layer

AbstractThe potential of contact passivation for increasing cell performance is indicated by several results reported in the literature. However, scant characterization of the tunneling layers used for that purpose has been reported. In this paper, contact passivation is investigated by insertion of an ultra-thin AlOx layer between an n-type emitter and a Ti/Pd/Ag contact. By using a 1.5nm thick layer, an increase of the minority carrier lifetime by a factor of 2.7 is achieved. Since current-voltage measurements indicate that an ohmic behavior is conserved for AlOx layers as thick as 1.5nm, a 1.5nm AlOx layer is found to be a candidate of choice for contact passivation

Longitudinal evaluation of peritoneal macrophage function and activation during CAPD: Maturity, cytokine synthesis and arachidonic acid metabolism

Longitudinal evaluation of peritoneal macrophage function and activation during CAPD: Maturity, cytokine synthesis and arachidonic acid metabolism. The release of cytokines and prostaglandins (PG) by peritoneal macrophages (PMØ) may influence the cytokine network controlling peritoneal inflammation and in the long-term the function of the peritoneum as a dialysis membrane. In the present study, an evaluation of the long-term effects of peritoneal dialysis on the release of cytokines and prostaglandins, and the expression of surface markers of cellular maturation on blood and mononuclear cells has been performed in patients during their first year on CAPD. Spontaneous release of tumour necrosis factor α (TNFα) and interleukin 6 (IL-6) by PMØ, after 4 or 24 hours in culture, increased significantly with time on CAPD, while there was a small but significant decrease in release of prostaglandin E2 (PGE2). Production of TNFα and IL-6 was enhanced following incubation of the cells with lipopolysaccharide (LPS), but the effect of LPS was proportionally greater on blood monocytes than on PMØ. There was a significant increase in the concentrations of PGE2 and 6-keto-prostaglandin F1α in overnight dwell peritoneal dialysis effluent with time on CAPD. The levels of TNFα and IL-6 in uninfected PDE were below the detection limit of the immunoassay over the whole time period studied. Expression of CD15, which correlates with immaturity, by PMØ and blood monocytes increased with time on CAPD, while expression of CD11c, a marker of maturation, decreased on blood monocytes, but did not change significantly on PMØ. There was also a slight increase in expression of transferrin receptor in both PMØ and monocytes, but this did not reach statistical significance. These findings suggest that peritoneal macrophages and blood monocytes isolated from CAPD patients over a one year period become increasingly immature with time, and this is accompanied by a significant modulation of their ability to secrete inflammatory cytokines. Dysregulation of macrophage function may have important consequences with respect to inflammatory processes and the long-term function of the peritoneal membrane in CAPD patients

Deformation-enhanced recrystallization of titanite drives decoupling between U-Pb and trace elements

Titanite is a common accessory mineral that is useful in determining both age (U-Pb isotopes) and pressure-temperature (P–T) conditions (trace-element composition: Zr, rare earth elements (REE)). However, titanite has a propensity to recrystallize during metamorphism, fluid flow, and deformation, which can result in modifications to its isotopic and trace-element compositions. This modification has implications for the interpretation of titanite dates and the evaluation of pressure–temperature–time paths. The impact of deformation and recrystallization on trace-element mobility in titanite is investigated through microstructural and compositional mapping of titanite crystals from a sheared orthogneiss within an ultrahigh-pressure domain of the Western Gneiss Region (WGR), Norway. Results show that optically coherent titanite single crystals deformed in the dislocation creep regime and recrystallized by the process of grain-boundary migration, forming aggregates of titanite grains. Some of the aggregate grains record Caledonian-exhumation dates, whereas others have an inherited isotopic composition. Individual grains within the aggregate, regardless of their U-Pb isotopic composition, contain patchy zoning that formed during syn- to post-recrystallization fluid alteration and that is characterized by generally decreasing Ca and Ti and increasing Al and Fe from cores to rims. However, Zr and Sr concentrations are broadly zoned with respect to the long axis of the host crystal, without regard for the aggregate grain boundaries. REE do not show any obvious correlation with microstructure or age. These results indicate that many trace elements in titanite are unaffected by multi-stage, deformation-driven recrystallization; in contrast, Pb is variably mobile in these deformed titanite crystals. The combination of microstructural and high-spatial resolution geochemical and isotopic data reveals the potential extent of decoupling between the U-Pb isotopic system and the behavior of trace elements as pressure–temperature conditions change through time

The effect of near-surface plastic deformation on the hot corrosion and high temperature corrosion-fatigue response of a nickel-based superalloy

Surface treatments such as shot peening to inhibit fatigue crack initiation are essential processes when designing gas turbine components for aerospace applications. It is therefore crucial to understand the effects of shot peening in representative service environments. Here, the influence of surface treatment on the high temperature corrosion fatigue response of a polycrystalline nickel-based superalloy is considered, an area that has not previously been explored. Two shot peening conditions; 110H 7A 200% and 330H 7A 200%, along with a polished surface were chosen. Specimens were salted and exposed to SO2 gas during fatigue testing at 700 °C. A range of novel techniques including SEM, EBSD and axial chromatism profilometry were used to analyse the near surface cold work and surface condition before and after testing. EBSD local misorientation maps, paired with an increase in corrosion-fatigue life, suggest that a greater depth of cold work produced by the smaller shot size (110H), is providing a significant benefit in terms of hot corrosion and corrosion-fatigue performance. This paper concludes that the presence of a substantial layer of cold work is required to account for any metal loss due to the effects of hot corrosion. It is also evident that cold work hinders fatigue crack initiation and delays the onset of pit to crack transition

Kondo effect in systems with dynamical symmetries

This paper is devoted to a systematic exposure of the Kondo physics in quantum dots for which the low energy spin excitations consist of a few different spin multiplets $|S_{i}M_{i}>$. Under certain conditions (to be explained below) some of the lowest energy levels $E_{S_{i}}$ are nearly degenerate. The dot in its ground state cannot then be regarded as a simple quantum top in the sense that beside its spin operator other dot (vector) operators ${\bf R}_{n}$ are needed (in order to fully determine its quantum states), which have non-zero matrix elements between states of different spin multiplets $\ne 0$. These "Runge-Lenz" operators do not appear in the isolated dot-Hamiltonian (so in some sense they are "hidden"). Yet, they are exposed when tunneling between dot and leads is switched on. The effective spin Hamiltonian which couples the metallic electron spin ${\bf s}$ with the operators of the dot then contains new exchange terms, $J_{n} {\bf s} \cdot {\bf R}_{n}$ beside the ubiquitous ones $J_{i} {\bf s}\cdot {\bf S}_{i}$. The operators ${\bf S}_{i}$ and ${\bf R}_{n}$ generate a dynamical group (usually SO(n)). Remarkably, the value of $n$ can be controlled by gate voltages, indicating that abstract concepts such as dynamical symmetry groups are experimentally realizable. Moreover, when an external magnetic field is applied then, under favorable circumstances, the exchange interaction involves solely the Runge-Lenz operators ${\bf R}_{n}$ and the corresponding dynamical symmetry group is SU(n). For example, the celebrated group SU(3) is realized in triple quantum dot with four electrons.Comment: 24 two-column page

Role of electromagnetically induced transparency in resonant four-wave-mixing schemes.

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Quantum Interference in Superconducting Wire Networks and Josephson Junction Arrays: Analytical Approach based on Multiple-Loop Aharonov-Bohm Feynman Path-Integrals

We investigate analytically and numerically the mean-field superconducting-normal phase boundaries of two-dimensional superconducting wire networks and Josephson junction arrays immersed in a transverse magnetic field. The geometries we consider include square, honeycomb, triangular, and kagome' lattices. Our approach is based on an analytical study of multiple-loop Aharonov-Bohm effects: the quantum interference between different electron closed paths where each one of them encloses a net magnetic flux. Specifically, we compute exactly the sums of magnetic phase factors, i.e., the lattice path integrals, on all closed lattice paths of different lengths. A very large number, e.g., up to $10^{81}$ for the square lattice, exact lattice path integrals are obtained. Analytic results of these lattice path integrals then enable us to obtain the resistive transition temperature as a continuous function of the field. In particular, we can analyze measurable effects on the superconducting transition temperature, $T_c(B)$, as a function of the magnetic filed $B$, originating from electron trajectories over loops of various lengths. In addition to systematically deriving previously observed features, and understanding the physical origin of the dips in $T_c(B)$ as a result of multiple-loop quantum interference effects, we also find novel results. In particular, we explicitly derive the self-similarity in the phase diagram of square networks. Our approach allows us to analyze the complex structure present in the phase boundaries from the viewpoint of quantum interference effects due to the electron motion on the underlying lattices.Comment: 18 PRB-type pages, plus 8 large figure