What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis.

BACKGROUND: Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. OBJECTIVE AND RATIONALE: A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. SEARCH METHODS: The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included. OUTCOMES: The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. WIDER IMPLICATIONS: Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.

Prediction of delirium using data mining: A systematic review.

Delirium remains a significant cause of morbidity, mortality and economic burden to society. "Big data" refers to data of significantly large volume, obtained from a variety of resources, which is created and processed at high velocity. We conducted a systematic review and meta-analysis exploring whether big data could predict the incidence of delirium of patients in the inpatient setting. Medline, Embase, the Cochrane Library, Web of Science, CINAHL, clinicaltrials.gov, who.int and IEEE Xplore were searched using MeSH terms "big data", "data mining", "delirium" and "confusion" up to 30th September 2019. We included both randomised and observational studies. The primary outcome of interest was development of delirium and the secondary outcomes of interest were type of statistical methods used, variables included in the mining algorithms and clinically important outcomes such as mortality and length of hospital stay. The quality of studies was graded using the CHARMs checklist. Six retrospective single centre observational studies were included (n = 178,091), of which 17, 574 participants developed delirium. Studies were of generally of low to moderate quality. The most commonly studied method was random forest, followed by support vector machine and artificial neural networks. The model with best performance for delirium prediction was random forest, with area under receiver operating curve (AUROC) ranging from 0.78 to 0.91. Sensitivity ranged from 0.59 to 0.81 and specificity ranged from 0.73 to 0.92. Our systematic review suggests that machine-learning techniques can be utilised to predict delirium.

Age-related natural fertility outcomes in women over 35 years: a systematic review and individual participant data meta-analysis.

STUDY QUESTION: What is the rate of natural conception leading to ongoing pregnancy or livebirth over 6-12 months for infertile women of age ≥35 years? SUMMARY ANSWER: Natural conception rates were still clinically relevant in women aged 35 years and above and were significantly higher in women with unexplained infertility compared to those with other diagnoses. WHAT IS KNOWN ALREADY: In recent years, increasing numbers of women have attempted to conceive at a later age, resulting in a commensurate increase in the need for ART. However, there is a lack of data on natural fertility outcomes (i.e. no interventions) in women with increasing age. STUDY DESIGN, SIZE, DURATION: A systematic review with individual participant data (IPD) meta-analysis was carried out. PubMed, MEDLINE, EMBASE, the Cochrane Library, clinicaltrials.gov were searched until 1 July 2018 including search terms 'fertility service', 'waiting list', 'treatment-independent' and 'spontaneous conception'. Language restrictions were not imposed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were studies (at least partly) reporting on infertile couples with female partner of age ≥35 years who attended fertility services, underwent fertility workup (e.g. history, semen analysis, tubal status and ovulation status) and were exposed to natural conception (e.g. independent of treatment such as IVF, ovulation induction and tubal surgery). Studies that exclusively studied only one infertility diagnosis, without including other women presenting to infertility services for other causes of infertility, were excluded. For studies that met the inclusion criteria, study authors were contacted to provide IPD, after which fertility outcomes for women of age ≥35 years were retrieved. Time to pregnancy or livebirth and the effect of increasing age on fertility outcomes after adjustment for other prognostic factors were analysed. Quality of studies was graded with the Newcastle-Ottawa Scale (non-randomised controlled trials (RCTs)) or the Cochrane Risk of Bias tool (for RCTs). MAIN RESULTS AND THE ROLE OF CHANCE: We included nine studies (seven cohort studies and two RCTs) (n = 4379 women of at least age 35 years), with the observed composite primary outcome of ongoing pregnancy or livebirth occurring in 429 women (9.8%) over a median follow-up of 5 months (25th to 75th percentile: 2.5-8.5 months). Studies were of moderate to high quality. The probability of natural conception significantly decreased with any diagnosis of infertility, when compared with unexplained infertility. We found non-linear effects of female age and duration of infertility on ongoing pregnancy and tabulated the predicted probabilities for unexplained infertile women aged 35-42 years with either primary or secondary infertility and with a duration of infertility from 1 to 6 years. For a 35-year-old woman with 2 years of primary unexplained infertility, the predicted probability of natural conception leading to ongoing pregnancy or livebirth was 0.15 (95% CI 0.11-0.19) after 6 months and 0.24 (95% CI 0.17-0.30) after 12 months. For a 42-year-old woman, this decreased to 0.08 (95% CI 0.04-0.11) after 6 months and 0.13 (95% CI 0.07-0.18) after 12 months. LIMITATIONS, REASONS FOR CAUTION: In the studies selected, there were different study designs, recruitment strategies in different centres, protocols and countries and different methods of assessment of infertility. Data were limited for women above the age of 40 years. WIDER IMPLICATIONS OF THE FINDINGS: Women attending fertility services should be encouraged to pursue natural conception while waiting for treatment to commence and after treatment if it is unsuccessful. Our results may aid in counselling women, and, in particular, for those with unexplained infertility. STUDY FUNDING/COMPETING INTEREST(S): S.J.C. received funding from the University of Adelaide Summer Research Scholarship. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437), B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, iGenomix and Guerbet. B.W.M. reports research support by Merck and Guerbet. PROSPERO REGISTRATION NUMBER: CRD42018096552.

High Temperature Terahertz Detectors Realized by a GaN High Electron Mobility Transistor.

In this work, a high temperature THz detector based on a GaN high electron mobility transistor (HEMT) with nano antenna structures was fabricated and demonstrated to be able to work up to 200 °C. The THz responsivity and noise equivalent power (NEP) of the device were characterized at 0.14 THz radiation over a wide temperature range from room temperature to 200 °C. A high responsivity Rv of 15.5 and 2.7 kV/W and a low NEP of 0.58 and 10 pW/Hz0.5 were obtained at room temperature and 200 °C, respectively. The advantages of the GaN HEMT over other types of field effect transistors for high temperature terahertz detection are discussed. The physical mechanisms responsible for the temperature dependence of the responsivity and NEP of the GaN HEMT are also analyzed thoroughly.

Synthesis and phase evolutions in layered structure of Ga2S3 semiconductor thin films on epiready GaAs (111) substrates.

We report on synthesis and properties of p-type Ga2S3 semiconductor thin films that were prepared by sulfurizing epiready n-type GaAs (111) surface at elevated temperatures. Comparisons of structural and optical properties among the thin films, peeling-off resulted microtubes, and the remains after peeling-off give a clear clue to the crystal growth and phase evolutions of Ga2S3. Three layers of Ga2S3 are clearly identified in the thin films. They are layer i, cubic Ga2S3 epitaxially grown on the GaAs (111) substrate; layer ii, polycrystalline cubic Ga2S3 on top of layer-i; and layer iii, monoclinic and/or hexagonal Ga2S3 on top of layer ii. The onset of peeling-off occurred in layer i and/or at the interface between layer i and ii. Both the phase evolutions and the location of peeling-off are associated with a Ga out diffusion growth mechanism. Absorption spectroscopy revealed a direct bandgap of 3.0 eV, whereas photoluminescence spectra showed defects (excited Ga vacancies) related red (1.62 eV) and green (2.24 eV) emissions of the Ga2S3 films; both are qualitatively consistent with those reported values obtained at lower sample temperatures from Ga2S3 single crystals. These results, together with a large on/off current ratio (i.e., ∼14 at a bias of 4.0 V) of the resultant hetero p-Ga2S3/n-GaAs junction under a blue laser (405 nm, 3.0 mW) illumination, shed light on consequent integrations of Ga2S3- and GaAs-based optoelectronic devices, e.g., high-power laser radiation sensors.

Nano-antenna in a photoconductive photomixer for highly efficient continuous wave terahertz emission.

We report highly efficient continuous-wave terahertz (THz) photoconductive antenna based photomixer employing nano-gap electrodes in the active region. The tip-to-tip nano-gap electrode structure provides strong THz field enhancement and acts as a nano-antenna to radiate the THz wave generated in the active region of the photomixer. In addition, it provides good impedance matching to the THz planar antenna and exhibits a lower RC time constant, allowing more efficient radiation especially at the higher part of the THz spectrum. As a result, the output intensity of the photomixer with the new nano-gap electrode structure in the active region is two orders of magnitude higher than that of a photomixer with typical interdigitated electrodes. Significant improvement in the THz emission bandwidth was also observed. An efficient continuous wave THz source will greatly benefit compact THz system development for high resolution THz spectroscopy and imaging applications.

Phosphor-Free Apple-White LEDs with Embedded Indium-Rich Nanostructures Grown on Strain Relaxed Nano-epitaxy GaN.

Phosphor-free apple-white light emitting diodes have been fabricated using a dual stacked InGaN/GaN multiple quantum wells comprising of a lower set of long wavelength emitting indium-rich nanostructures incorporated in multiple quantum wells with an upper set of cyan-green emitting multiple quantum wells. The light-emitting diodes were grown on nano-epitaxially lateral overgrown GaN template formed by regrowth of GaN over SiO(2) film patterned with an anodic aluminum oxide mask with holes of 125 nm diameter and a period of 250 nm. The growth of InGaN/GaN multiple quantum wells on these stress relaxed low defect density templates improves the internal quantum efficiency by 15% for the cyan-green multiple quantum wells. Higher emission intensity with redshift in the PL peak emission wavelength is obtained for the indium-rich nanostructures incorporated in multiple quantum wells. The quantum wells grown on the nano-epitaxially lateral overgrown GaN has a weaker piezoelectric field and hence shows a minimal peak shift with application of higher injection current. An enhancement of external quantum efficiency is achieved for the apple-white light emitting diodes grown on the nano-epitaxially lateral overgrown GaN template based on the light -output power measurement. The improvement in light extraction efficiency, η(extraction,) was found to be 34% for the cyan-green emission peak and 15% from the broad long wavelength emission with optimized lattice period.

Fabrication of a nano-cone array on a p-GaN surface for enhanced light extraction efficiency from GaN-based tunable wavelength LEDs.

We report on the fabrication of a nano-cone structured p-GaN surface for enhanced light extraction from tunable wavelength light emitting diodes (LEDs). Prior to p-contact metallization, self-assembled colloidal particles are deposited and used as a mask for plasma etching to create nano-cone structures on the p-GaN layer of LEDs. A well-defined periodic nano-cone array, with an average cone diameter of 300 nm and height of 150 nm, is generated on the p-GaN surface. The photoluminescence emission intensity recorded from the regions with the nano-cone array is increased by two times as compared to LEDs without surface patterning. The light output power from the LEDs with surface nano-cones shows significantly higher electroluminescence intensity at an injection current of 70 mA. This is due to the internal multiple scattering of light from the nano-cone sidewalls. Furthermore, we have shown that with an incorporation of InGaN nanostructures in the quantum well, the wavelength of these surface-patterned LEDs can be tuned from 517 to 488 nm with an increase in the injection current. This methodology may serve as a practical approach to increase the light extraction efficiency from wavelength tunable LEDs.

Investigation of Semiconductor Quantum Dots for Waveguide Electroabsorption Modulator.

In this work, we investigated the use of 10-layer InAs quantum dot (QD) as active region of an electroabsorption modulator (EAM). The QD-EAM is a p-i-n ridge waveguide structure with intrinsic layer thickness of 0.4 mum, width of 10 mum, and length of 1.0 mm. Photocurrent measurement reveals a Stark shift of ~5 meV (~7 nm) at reverse bias of 3 V (75 kV/cm) and broadening of the resonance peak due to field ionization of electrons and holes was observed for E-field larger than 25 kV/cm. Investigation at wavelength range of 1,300-1320 nm reveals that the largest absorption change occurs at 1317 nm. Optical transmission measurement at this wavelength shows insertion loss of ~8 dB, and extinction ratio of ~5 dB at reverse bias of 5 V. Consequently, methods to improve the performance of the QD-EAM are proposed. We believe that QDs are promising for EAM and the performance of QD-EAM will improve with increasing research efforts.

Nanostructuring of InP surface by low-energy ion beam irradiation.

The InP nanodots of size 55 to 100 nm and height 25 to 30 nm have been synthesized by low-energy Ar+-ion irradiation with different ion energies. Sizes and size distributions of the dots strongly depend on growth conditions. Rapid thermal annealed (RTA) of the patterned surface shows cluster formation for annealing temperature 400 degrees C and above. Raman investigations reveal optical phonon softening due to correlation length shortening and broadening of the optical modes from the patterned surface. The softening is due to confinement of phonons in embedded nanocrystallites within the patterned surface along with surface nanodots, and broadening is attributed to their size distributions, which increases with increase in ion energy. The lattice damage recovery is observed from the patterned surface subjected to RTA, which exhibits upward shift of the LO and TO phonons due to the presence of complex interfacial stress, associated with the removal of crystal defects with RTA.