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

Emergence of Bulk CsCl Structure in (CsCl)nCs+ Cluster Ions

The emergence of CsCl bulk structure in (CsCl)nCs+ cluster ions is investigated using a mixed quantum-mechanical/semiempirical theoretical approach. We find that rhombic dodecahedral fragments (with bulk CsCl symmetry) are more stable than rock-salt fragments after the completion of the fifth rhombic dodecahedral atomic shell. From this size (n=184) on, a new set of magic numbers should appear in the experimental mass spectra. We also propose another experimental test for this transition, which explicitely involves the electronic structure of the cluster. Finally, we perform more detailed calculations in the size range n=31--33, where recent experimental investigations have found indications of the presence of rhombic dodecahedral (CsCl)32Cs+ isomers in the cluster beams.Comment: LaTeX file. 6 pages and 4 pictures. Accepted for publication in Phys. Rev.

Magnetically-controlled velocity selection in a cold atom sample using stimulated Raman transitions

We observe velocity-selective two-photon resonances in a cold atom cloud in the presence of a magnetic field. We use these resonances to demonstrate a simple magnetometer with sub-mG resolution. The technique is particularly useful for zeroing the magnetic field and does not require any additional laser frequencies than are already used for standard magneto-optical traps. We verify the effects using Faraday rotation spectroscopy.Comment: 5 pages, 6 figure

Superconductor-Nanowire Devices from Tunneling to the Multichannel Regime: Zero-Bias Oscillations and Magnetoconductance Crossover

We present transport measurements in superconductor-nanowire devices with a gated constriction forming a quantum point contact. Zero-bias features in tunneling spectroscopy appear at finite magnetic fields, and oscillate in amplitude and split away from zero bias as a function of magnetic field and gate voltage. A crossover in magnetoconductance is observed: Magnetic fields above ~ 0.5 T enhance conductance in the low-conductance (tunneling) regime but suppress conductance in the high-conductance (multichannel) regime. We consider these results in the context of Majorana zero modes as well as alternatives, including Kondo effect and analogs of 0.7 structure in a disordered nanowire.Comment: Supplemental Material here: https://dl.dropbox.com/u/1742676/Churchill_Supplemental.pd

Breaking FOV-Aperture Trade-Off with Multi-Mode Nano-Photonic Antennas

Nano-photonic antennas are one of the key components in integrated photonic transmitter and receiver systems. Conventionally, grating couplers, designed to couple into an optical fiber, suffering from limitations such as large footprint and small field-of-view (FOV) have been used as on-chip antennas. The challenge of the antenna design is more pronounced for the receiver systems, where both the collected power by the antenna and its FOV often need to be maximized. While some novel solutions have been demonstrated recently, identifying fundamental limits and trade-offs in nano-photonic antenna design is essential for devising compact antenna structures with improved performance. In this paper, the fundamental electromagnetic limits, as well as fabrication imposed constraints on improving antenna effective aperture and FOV are studied, and approximated performance upper limits are derived and quantified. By deviating from the conventional assumptions leading to these limits, high-performance multi-mode antenna structures with performance characteristics beyond the conventional perceived limits are demonstrated. Finally, the application of a pillar multi-mode antenna in a dense array is discussed, an antenna array with more than 95% collection efficiency and 170∘ FOV is demonstrated, and a coherent receiving system utilizing such an aperture is presented

Breaking FOV-Aperture Trade-Off with Multi-Mode Nano-Photonic Antennas

Nano-photonic antennas are one of the key components in integrated photonic transmitter and receiver systems. Conventionally, grating couplers, designed to couple into an optical fiber, suffering from limitations such as large footprint and small field-of-view (FOV) have been used as on-chip antennas. The challenge of the antenna design is more pronounced for the receiver systems, where both the collected power by the antenna and its FOV often need to be maximized. While some novel solutions have been demonstrated recently, identifying fundamental limits and trade-offs in nano-photonic antenna design is essential for devising compact antenna structures with improved performance. In this paper, the fundamental electromagnetic limits, as well as fabrication imposed constraints on improving antenna effective aperture and FOV are studied, and approximated performance upper limits are derived and quantified. By deviating from the conventional assumptions leading to these limits, high-performance multi-mode antenna structures with performance characteristics beyond the conventional perceived limits are demonstrated. Finally, the application of a pillar multi-mode antenna in a dense array is discussed, an antenna array with more than 95% collection efficiency and 170∘ FOV is demonstrated, and a coherent receiving system utilizing such an aperture is presented

Molecular diversity of Symbiodinium spp. within six coral species in Larak Island, the Persian Gulf

Reef-building coral harbor communities of photosynthetic taxa of the genus Symbiodinium (zooxanthellae). The genus Symbiodinium is currently classified into nine genetic clades (A–I). Various corals harbor different Symbiodinium clades; some show specificity to a single strain. Coral and their zooxanthellae are sensitive to environmental stresses. In the Persian Gulf, coral reefs are subject to harsh environmental conditions including extreme temperatures and high salinity. This is the first study to use clade specific primers to clarify the diversity of Symbiodinium in each coral species of Larak Island. For this purpose six coral species were collected at two different locations in Larak Island. After DNA extraction, PCR amplification was performed using clade specific primers. The results showed that multiple Symbiodinium clades are hosted by most coral species. In addition, among thirteen obtained Symbiodinium sequences, the frequency of either tree [sic] clades, A, C and D was almost the same. Corals species may contain different clades of Symbiodinium depending on the region and on the tolerance characteristics of each clade. Thus, knowledge of zooxanthellae diversity associated with scleractinian can contribute to a better understanding of the sensitivity of corals to environmental conditions

Evaluation of lysosomal stability and red blood cell membrane fragility in mudskipper (Boleophthalmus dussumieri) as a biomarker of poly aromatic hydrocarbons

This research was carried out to study some physiological responses of mudskipper (i.e., Boleophthalmus dussumieri) as a biomarker Poly Aromatic Hydrocarbons (PAHs). Fish specimens were obtained 5 stations (Arvand, Jafari, Zangi, Samayeli, Bahrakan) along north western coast of the Persian Gulf (Khuzestan Coast). PAHs concentration was measured by HPLC method. Lysosomal membrane change was measured by NRR time method and stability of red blood cell membrane was evaluated by EOF test. Total PAH concentrations in the sediments and the liver tissue ranged between 113.50-3384.34 ng g-1dw, 3.99-46.64ng g-1 dw, respectively. Highest PAHs pollution was found at Jafari while the lowest was detected at Bahrakan, with significant between these 2 stations. Values of mean RT of the dye ranged from 34 (for the blood samples of mudskipper collected from Jafari site) to 78 minutes (for the blood samples of mudskipper collected from Bahrakan). Preliminary results showed a significant difference among stations except between Arvand and Zangi. Osmotic fragility curves indicated that erythrocytes collected from mudskippers at Jafari were the most fragile followed by Zangi> Arvand> Samayeli> and Bahrakan. The results suggest that lysosomal membrane change and red blood cell membrane stability in B. dussumieri could be extended as a biomarker of oil pollution in marine biomonitoring programs

Idleness-aware dynamic power mode selection on the i.Mx 7ULP iot edge processor

Power management is a crucial concern in micro-controller platforms for the Internet of Things (IoT) edge. Many applications present a variable and difficult to predict workload profile, usually driven by external inputs. The dynamic tuning of power consumption to the application requirements is indeed a viable approach to save energy. In this paper, we propose the implementation of a power management strategy for a novel low-cost low-power heterogeneous dual-core SoC for IoT edge fabricated in 28 nm FD-SOI technology. Ss with more complex power management policies implemented on high-end application processors, we propose a power management strategy where the power mode is dynamically selected to ensure user-specified target idleness. We demonstrate that the dynamic power mode selection introduced by our power manager allows achieving more than 43% power consumption reduction with respect to static worst-case power mode selection, without any significant penalty in the performance of a running application