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

Molecular dynamics simulation of the order-disorder phase transition in solid NaNO2_2

We present molecular dynamics simulations of solid NaNO$_2$ using pair potentials with the rigid-ion model. The crystal potential surface is calculated by using an \emph{a priori} method which integrates the \emph{ab initio} calculations with the Gordon-Kim electron gas theory. This approach is carefully examined by using different population analysis methods and comparing the intermolecular interactions resulting from this approach with those from the \emph{ab initio} Hartree-Fock calculations. Our numerics shows that the ferroelectric-paraelectric phase transition in solid NaNO$_2$ is triggered by rotation of the nitrite ions around the crystallographical c axis, in agreement with recent X-ray experiments [Gohda \textit{et al.}, Phys. Rev. B \textbf{63}, 14101 (2000)]. The crystal-field effects on the nitrite ion are also addressed. Remarkable internal charge-transfer effect is found.Comment: RevTeX 4.0, 11 figure

Risk Theory with Affine Dividend Payment Strategies

We consider a classical compound Poisson risk model with affine dividend payments. We illustrate how both by analytical and probabilistic techniques closed-form expressions for the expected discounted dividends until ruin and the Laplace transform of the time to ruin can be derived for exponentially distributed claim amounts. Moreover, numerical examples are given which compare the performance of the proposed strategy to classical barrier strategies and illustrate that such affine strategies can be a noteworthy compromise between profitability and safety in collective risk theory

The Stern-Gerlach Experiment Revisited

The Stern-Gerlach-Experiment (SGE) of 1922 is a seminal benchmark experiment of quantum physics providing evidence for several fundamental properties of quantum systems. Based on today's knowledge we illustrate the different benchmark results of the SGE for the development of modern quantum physics and chemistry. The SGE provided the first direct experimental evidence for angular momentum quantization in the quantum world and thus also for the existence of directional quantization of all angular momenta in the process of measurement. It measured for the first time a ground state property of an atom, it produced for the first time a `spin-polarized' atomic beam, it almost revealed the electron spin. The SGE was the first fully successful molecular beam experiment with high momentum-resolution by beam measurements in vacuum. This technique provided a new kinematic microscope with which inner atomic or nuclear properties could be investigated. The original SGE is described together with early attempts by Einstein, Ehrenfest, Heisenberg, and others to understand directional quantization in the SGE. Heisenberg's and Einstein's proposals of an improved multi-stage SGE are presented. The first realization of these proposals by Stern, Phipps, Frisch and Segr\`e is described. The set-up suggested by Einstein can be considered an anticipation of a Rabi-apparatus. Recent theoretical work is mentioned in which the directional quantization process and possible interference effects of the two different spin states are investigated. In full agreement with the results of the new quantum theory directional quantization appears as a general and universal feature of quantum measurements. One experimental example for such directional quantization in scattering processes is shown. Last not least, the early history of the `almost' discovery of the electron spin in the SGE is revisited.Comment: 50pp, 17 fig

Optical guided dispersions and subwavelength transmissions in dispersive plasmonic circular holes

The light transmission through a dispersive plasmonic circular hole is numerically investigated with an emphasis on its subwavelength guidance. For a better understanding of the effect of the hole diameter on the guided dispersion characteristics, the guided modes, including both the surface plasmon polariton mode and the circular waveguide mode, are studied for several hole diameters, especially when the metal cladding has a plasmonic frequency dependency. A brief comparison is also made with the guided dispersion characteristics of a dispersive plasmonic gap [K. Y. Kim, et al., Opt. Express 14, 320-330 (2006)], which is a planar version of the present structure, and a circular waveguide with perfect electric conductor cladding. Finally, the modal behavior of the first three TM-like principal modes with varied hole diameters is examined for the same operating mode.Comment: 20 pages, 5 figures, 1 tabl

Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases)

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

High pTp_{T} non-photonic electron production in pp+pp collisions at s\sqrt{s} = 200 GeV

We present the measurement of non-photonic electron production at high transverse momentum ($p_T >$ 2.5 GeV/$c$) in $p$ + $p$ collisions at $\sqrt{s}$ = 200 GeV using data recorded during 2005 and 2008 by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The measured cross-sections from the two runs are consistent with each other despite a large difference in photonic background levels due to different detector configurations. We compare the measured non-photonic electron cross-sections with previously published RHIC data and pQCD calculations. Using the relative contributions of B and D mesons to non-photonic electrons, we determine the integrated cross sections of electrons ($\frac{e^++e^-}{2}$) at 3 GeV/$c < p_T <~$10 GeV/$c$ from bottom and charm meson decays to be ${d\sigma_{(B\to e)+(B\to D \to e)} \over dy_e}|_{y_e=0}$ = 4.0$\pm0.5$({\rm stat.})$\pm1.1$({\rm syst.}) nb and ${d\sigma_{D\to e} \over dy_e}|_{y_e=0}$ = 6.2$\pm0.7$({\rm stat.})$\pm1.5$({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.