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

New Detections of Optical Emission from Kiloparsec-scale Quasar Jets

We report initial results from the detection of optical emission in the arcsecond-scale radio jets of two quasars utilizing images from the {\it Hubble Space Telescope} archive. The optical emission has a very knotty appearance and is consistent with synchrotron emission from highly relativistic electrons in the jet. Combining these observations with those of previously reported features in other quasars, an emerging trend appears to be that their radio-to-optical spectral indices are steeper than those of similar features in jets of lower power radio sources.Comment: 4 pgs, 2 figs, Proc of The Physics of Relativistic Jets in the Chandra and XMM Era workshop, eds. G. Brunetti, D.E. Harris, R.M. Sambruna, and G. Setti, submitted to New Astronomy Review. Quality of figure 1 degraded to fit into preprint server. Includes elsart.cls fil

Raman Scattering versus Infrared Conductivity: Evidence for one-dimensional Conduction in La_{2-x}Sr_{x}CuO_{4}

Raman and Infrared (IR) spectra of an underdoped La_{1.90}Sr_{0.10}CuO_{4} single crystal have been measured as a function of temperature. Both techniques provide unconventional low-energy spectra. The IR conductivity exhibits features peaked at finite frequencies which do not have a counterpart in the Raman response. Below approximately 100 K a transfer of both Raman and IR spectral weight towards lower energies is found and a new component in the Raman response builds up being characterized by a very long lifetime of electrons propagating along the Cu-O bonds.Comment: 4 pages, 3 eps figure

Assessing the growth and climate sensitivity of secondary forests in highly deforested Amazonian landscapes

Tropical forests hold 30% of Earth’s terrestrial carbon and at least 60% of its terrestrial biodiversity, but forest loss and degradation are jeopardizing these ecosystems. Although the regrowth of secondary forests has the potential to offset some of the losses of carbon and biodiversity, it remains unclear if secondary regeneration will be affected by climate changes such as higher temperatures and more frequent extreme droughts. We used a data set of 10 repeated forest inventories spanning two decades (1999–2017) to investigate carbon and tree species recovery and how climate and landscape context influence carbon dynamics in an older secondary forest located in one of the oldest post‐Columbian agricultural frontiers in the Brazilian Amazon. Carbon accumulation averaged 1.08 Mg·ha−1·yr−1, and species richness was effectively constant over the studied period. Moreover, we provide evidence that secondary forests are vulnerable to drought stress: Carbon balance and growth rates were lower in drier periods. This contrasts with drought responses in primary forests, where changes in carbon dynamics are driven by increased stem mortality. These results highlight an important climate change–vegetation feedback, whereby the increasing dry‐season lengths being observed across parts of Amazonia may reduce the effectiveness of secondary forests in sequestering carbon and mitigating climate change. In addition, the current rate of forest regrowth in this region was low compared with previous pan‐tropical and Amazonian assessments—our secondary forests reached just 41.1% of the average carbon and 56% of the tree diversity in the nearest primary forests—suggesting that these areas are unlikely to return to their original levels on politically meaningful time scales

A Multi-band Study of the Remarkable Jet in Quasar 4C+19.44

We present arcsecond-resolution data in the radio, IR, optical, and X-ray for 4C+19.44 (=PKS 1354+195), the longest and straightest quasar jet with deep X-ray observations. We report results from radio images with half to one arcsecond angular resolution at three frequencies, plus Hubble Space Telescope and Spitzer data. The Chandra data allow us to measure the X-ray spectral index in 10 distinct regions along the 18'' jet and compare with the radio index. The radio and X-ray spectral indices of the jet regions are consistent with a value of $\alpha =0.80$ throughout the jet, to within $2\sigma$ uncertainties. The X-ray jet structure to the south extends beyond the prominent radio jet and connects to the southern radio lobe, and there is extended X-ray emission, both in the direction of the unseen counter-jet, and also coincident with the northern radio lobe. This jet is remarkable because its straight appearance over a large distance allows the geometry factors to be taken as fixed along the jet. Using the model of inverse Compton scattering of the cosmic microwave background (iC/CMB) by relativistic electrons, we find that the magnetic field strengths and Doppler factors are relatively constant along the jet. If instead the X-rays are synchrotron emission, they must arise from a population of electrons distinct from the particles producing the radio synchrotron spectrum

Search for B -> h(*) nu nubar Decays at Belle

We present a search for the rare decays B -> h(*) nu nubar, where h(*) stands for a light meson. A data sample of 535 million BBbar pairs collected with the Belle detector at the KEKB e+e- collider is used. Signal candidates are required to have an accompanying B meson fully reconstructed in a hadronic mode and signal-side particles consistent with a single h(*) meson. No significant signal is observed and we set upper limits on the branching fractions at 90% confidence level. The limits on B0 -> K*0 nu nubar and B+ -> K+ nu nubar decays are more stringent than the previous constraints, while the first searches for B0 -> K0 nu nubar, pi0 nu nubar, rho0 nu nubar, phi nu nubar and B+ -> K*+ nu nubar, rho+ nu nubar are reported.Comment: 6 pages, 2 figures, submit to PR

Targeting Potential Drivers of COVID-19: Neutrophil Extracellular Traps

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19

Improved measurement of CP-violating parameters in rho+rho- decays

We present a measurement of the CP-violating asymmetry in rho+rho- decays using 535 million BBbar pairs collected with the Belle detector at the KEKB e+e- collider. We measure CP-violating coefficients A = 0.16 +- 0.21(stat) +- 0.07 (syst) and S = 0.19 +- 0.30(stat) +- 0.07 (syst}. These values are used to determine the unitarity triangle angle phi_2 using an isospin analysis; the solution consistent with Standard Model lies in the range 53 < phi_2 < 114 deg. at 90 C.L.Comment: 6 pages, 4 figures, presented at JPS/DPF 2006 (Added KEK, BELLE preprint numbers, submitted to PRD(RC)

Observation of B+ -> K+ eta gamma

We report measurements of radiative B decays with K eta gamma final states, using a data sample of 253 /fb recorded at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- storage ring. We observe B+ -> K+ eta gamma for the first time with a branching fraction of (8.4 +- 1.5(stat) +1.2 -0.9(syst)) X 10^{-6} for M(Keta) K0 eta gamma. We also search for B -> K3*(1780) gamma.Comment: 12 pages, 5 figures, accepted by Phys. Lett.

Measurement of the ratio B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) and the time-integrated CP asymmetry in D0->pi+pi-pi0

We report a high-statistics measurement of the relative branching fraction B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) using a 532 fb^{-1} data sample collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The measured value of the relative branching fraction is B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) = (10.12 +/- 0.04(stat) +/- 0.18(syst))x10^{-2} which has an accuracy comparable to the world average. We also present a measurement of the time-integrated CP asymmetry in D0->pi+pi-pi0 decay. The result, A_{CP} = (0.43 +/- 1.30)%, shows no significant CP violation.Comment: 15 pages, 11 figures, submitted to Physics Letters