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High-speed top-illuminated avalanche photodiodes (APDs) with large diameters (25 μm) are demonstrated for the application of 4-channels 100 Gb/s data rate. They achieve a bandwidth of 17 GHz at low-gain (MG = 6.2; 3.6 A/W) and large-gain bandwidth (responsivity bandwidth) product (410 GHz (237.8 GHz-A/W); 55% external efficiency at the unit gain) while maintaining invariant high speed (14 GHz) under high power (0.5 mW) and 0.9 Vbr operations. By packaging the demonstrated APD with a 25 Gb/s transimpedance amplifier in a 100 Gb/s ROSA package, a good sensitivity of around –20.6 dBm optical modulation amplitude (OMA) at the data rate of 25.78 Gb/s has been successfully demonstrated. The achieved sensitivity not only meets the required receiver sensitivity (–18.5 dBm OMA) in 100 GbE-ER-4 Lite (40 km) system, it is also comparable with that of the high-performance 100 Gb/s ROSA incorporated with the back-side illuminated APD design. Overall, our novel APD structure can eliminate the costly flip-chip bonding package in the 100 Gb/s ROSA without sacrificing its sensitivity performance. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sedation is not required to perform a technically adequate gastroscopy (EGDE), but does improve patient satisfaction, comfort, and willingness to repeat particularly in the elderly and those with decreased pharyngeal sensitivity. The comparative cost-efficacy of sedationversusno sedation remains poorly characterized.AIM: To compare the cost-efficacy of diagnostic EGDE with and without sedation in an adult ambulatory Canadian population.METHODS: A double-blind randomized controlled trial assigned patients to sedationversusplacebo.“Successful endoscopy” was considered an EGDE rated 4/4 in technical adequacy (1= inadequate to 4= totally adequate), and 1–2/5 in patient self-reported comfort (1= acceptable to 5= unacceptable). Secondary outcomes included recovery room time, patient satisfaction alone, and willingness to repeat the procedure. Cost data were obtained using a published, institutional activity-based costing methodology. Analysis was intention to treat using standard univariate and multivariate methods.RESULTS: 419 patients (mean age 54.5, 48% male) were randomized (N= 210 activevsN= 209 placebo). Among patients randomized to active medication 76% of procedures were“successful” (placebo 46%), 79% were satisfied with their level of comfort (placebo 47%), and willingness to repeat was 81% (placebo 65%). We observed a 10% crossover rate from placebo to active medications. The use of sedation was the major determinant of successful endoscopy (OR= 3.8; 95% CI: 2.5–5.7), but contributed to an increased recovery room time (29vs15 min;p<0.0001). The expected cost of an additional successful endoscopy using sedation was$90.06 (CDN). In a planned subgroup analysis, among the elderly (>75; N= 53) unsedated endoscopy became the dominant approach. Indeed, in this population, a trend was observed favoring the effectiveness of placebo (63%)versusactive medication (57%) (OR= 0.75; 95% CI: 0.25–2.3) and was less costly resulting in$450 savings/unsedated EGDE.CONCLUSIONS: In the average Canadian ambulatory adult population, sedated diagnostic EGDE is more costly but remains an efficacious strategy by increasing the rate of successful endoscopies, patient satisfaction, and willingness to repeat. However, among the elderly (>75 yr), an unsedated strategy may be more cost-efficacious.(Am J Gastroenterol 2004;99:1692-1699) [ABSTRACT FROM AUTHOR]

In this work, we demonstrate In0.52Al0.48As top/backside-illuminated avalanche photodiodes (APD) with dual multiplication layers for high-speed and wide dynamic range performances. Our fabricated top-illuminated APDs, with a partially depleted p-type In0.53Ga0.47As absorber layer and thin In0.52Al0.48As dual multiplication (M-) layer (60 and 88 nm), exhibit a wide optical-to-electrical bandwidth (16 GHz) with high responsivity (2.5 A/W) under strong light illumination (around 1 mW). The measured bias dependent 3-dB O-E bandwidth was pinned at 16 GHz without any serious degradation near the saturation current output. To further increase the speed, we downscaled the active diameter and adopted a back-side illuminated structure with flip-chip bonding for batter optical alignment tolerance. A significant improvement in maximum bandwidth was demonstrated (25 versus 18 GHz). On the other hand, we adopted a thick dual M-layer (200 and 300 nm) and 2 μm absorber layer in the APD design to circumvent the problem of serious bandwidth degradation under high gain (>100) and high-power operation which significantly enhanced the dynamic range. Due to dual M-layer, the carriers could be energized in the first M-layer then propagate to the second M-layer to trigger the avalanche process. In both cases, despite variation in thickness of the absorber and M-layer, the cascade avalanche process leads to values close to the ultra-high gain bandwidth product (GBP) of around 460 GHz with a responsivity of 0.4 and 1 A/W at unit gain for the thin and thick M-layer devices, respectively. We successfully achieved a good sensitivity of around −20.6 dBm optical modulation amplitude (OMA) at a data rate of 25.78 Gb/s, by packaging the fabricated APDs (thin dual M-layer (60 and 88 nm) version) with a 25 Gb/s trans-impedance amplifier in a 100 Gb/s ROSA package. The results show that, the incorporation of a dual multiplication (M) layer structure in the APD opens a new window to obtaining the higher GBP in order to meet the requirements for high-speed transmission without the need of further downscaling the multiplication layer. [ABSTRACT FROM AUTHOR]

Cryopreservation of oocytes by vitrification is a promising new technique for assisted human reproduction. Any new technical development must be accompanied with data concerning obstetric and perinatal outcome. This study analysed the obstetric and perinatal outcomes in 165 pregnancies and 200 infants conceived following oocyte vitrification cycles in three assisted reproduction centres. The results indicate that the mean birth weight and the incidence of congenital anomalies are comparable to that of spontaneous conceptions in fertile women or infertile women undergoing in-vitro fertilization treatment. These preliminary findings may provide reassuring evidence that pregnancies and infants conceived following oocyte vitrification are not associated with increased risk of adverse obstetric and perinatal outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The purposes of this study were to determine whether biomechanical properties of mature oocytes could predict usable blastocyst formation better than morphological information or maternal factors, and to demonstrate the safety of the aspiration measurement procedure used to determine the biomechanical properties of oocytes. Methods: A prospective split cohort study was conducted with patients from two IVF clinics who underwent in vitro fertilization. Each patient's oocytes were randomly divided into a measurement group and a control group. The aspiration depth into a micropipette was measured, and the biomechanical properties were derived. Oocyte fertilization, day 3 morphology, and blastocyst development were observed and compared between measured and unmeasured cohorts. A predictive classifier was trained to predict usable blastocyst formation and compared to the predictions of four experienced embryologists. Results: 68 patients and their corresponding 1252 oocytes were included in the study. In the safety analyses, there was no significant difference between the cohorts for fertilization, while the day 3 and 5 embryo development were not negatively affected. Four embryologists predicted usable blastocyst development based on oocyte morphology with an average accuracy of 44% while the predictive classifier achieved an accuracy of 71%. Retaining the variables necessary for normal fertilization, only data from successfully fertilized oocytes were used, resulting in a classifier an accuracy of 81%. Conclusions: To date, there is no standard guideline or technique to aid in the selection of oocytes that have a higher likelihood of developing into usable blastocysts, which are chosen for transfer or vitrification. This study provides a comprehensive workflow of extracting biomechanical properties and building a predictive classifier using these properties to predict mature oocytes' developmental potential. The classifier has greater accuracy in predicting the formation of usable blastocysts than the predictions provided by morphological information or maternal factors. The measurement procedure did not negatively affect embryo culture outcomes. While further analysis is necessary, this study shows the potential of using biomechanical properties of oocytes to predict embryo developmental outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to establish reference values for fetal aortic isthmus blood flow velocity and associated indices during the first trimester, utilizing a novel ultrasonographic technique known as high-definition flow imaging (HDFI). Additionally, the correlation between Doppler profiles of aortic blood flow and key fetal parameters, including nuchal thickness (NT), crown-rump length (CRL), and fetal heartbeat (FHB), was investigated. Methods: A total of 262 fetuses were included in the analysis between December 2022 and December 2023. Utilizing 2D power Doppler ultrasound images, aortic blood flow parameters were assessed, including aortic peak systolic velocity (PS), aortic end-diastolic velocity (ED), aortic time average maximal velocity (TAMV), and various indices such as aortic systolic velocity/diastolic velocity (S/D), aortic pulsatile index (PI), aortic resistance index (RI), aortic isthmus flow velocity index (IFI), and aortic isthmic systolic index (ISI). Concurrently, fetal FHB, NT, and CRL were evaluated during early trimester Down syndrome screening. Results: Significant findings include a positive correlation between gestational age (GA) and PS (PS = 3.75 × (GA) − 15.4, r2 = 0.13, p < 0.01), ED (ED = 0.42 × (GA) − 0.61, r2 = 0.04, p < 0.01), PI (PI = 0.07 × (GA) + 1.03, r2 = 0.04, p < 0.01), and TAMV (TAMV = 1.23 × (GA) − 1.66, r2 = 0.08, p < 0.01). In contrast, aortic ISI demonstrated a significant decrease (ISI = −0.03 × (GA) + 0.57, r2 = 0.05, p < 0.05) with gestational age. No significant correlation was observed for aortic RI (p = 0.33), S/D (p = 0.39), and IFI (p = 0.29) with gestational age. Aortic PS exhibited positive correlations with NT (0.217, p = 0.001) and CRL (0.360, p = 0.000) but a negative correlation with FHB (−0.214, p = 0.001). Aortic PI demonstrated positive correlations with CRL (0.208, p = 0.001) and negative correlations with FHB (−0.176, p = 0.005). Aortic TAMV showed positive correlations with NT (0.233, p = 0.000) and CRL (0.290, p = 0.000) while exhibiting a negative correlation with FHB (−0.141, p = 0.026). Aortic ISI demonstrated negative correlations with NT (−0.128, p = 0.045) and CRL (−0.218, p = 0.001) but a positive correlation with FHB (0.163, p = 0.010). Conclusions: Power Doppler angiography with Doppler ultrasound demonstrates the ability to establish accurate reference values for fetal aortic blood flow during the first trimester of pregnancy. Notably, aortic PS, TAMV, and ISI exhibit significant correlations with NT, CRL, and FHB, with ISI appearing more relevant than IFI, PS, TAMV, and FHB. The utilization of HDFI technology proves advantageous in efficiently detecting the site of the aortic isthmus compared to traditional color Doppler mode in early second trimesters. [ABSTRACT FROM AUTHOR]

Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than −1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses. [ABSTRACT FROM AUTHOR]

Male infertility is a pervasive global reproductive challenge, primarily attributed to a decline in semen quality. Addressing this concern, there has been a growing focus on spermatozoa sorting in assisted reproductive technology. This study introduces a groundbreaking development in the form of a thermotaxis and rheotaxis microfluidic (TRMC) device designed for efficient motile spermatozoa sorting within a short 15-min timeframe. The TRMC device mimics the natural sperm sorting mechanism of the oviduct, selecting spermatozoa with superior motility and DNA integrity. The experimental outcomes demonstrate a remarkable enhancement in the percentage of progressive spermatozoa following sorting, soaring from 3.90% to an impressive 96.11% when subjected to a temperature decrease from 38 °C to 35 °C. Notably, sperm motility exhibited a substantial 69% improvement. The TRMC device exhibited a commendable recovery rate of 60.93%, surpassing current clinical requirements. Furthermore, the sorted spermatozoa displayed a notable reduction in the DNA fragmentation index to 6.94%, signifying a substantial 90% enhancement in DNA integrity. This remarkable advancement positions the TRMC device as highly suitable for applications in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), offering a promising solution to male infertility challenges. [ABSTRACT FROM AUTHOR]

We have conducted cervical imaging of uterine and micro-vessel flow velocity waveforms in acute pelvic inflammatory disease (PID) by transvaginal power Doppler ultrasound (TVPDU) in order to explore the associations of sonographic parameters with simple and complex cervicitis. Thirty-eight patients with acute PID (26 with acute simple cervicitis and 12 with complex cervicitis) were enrolled for an assessment of vascular grading of cervix and micro-vessel flow velocity using TVPDU before treatment. Seven parameters, including vascular grading (VG), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end diastolic velocity (ED), time average maximum velocity (TAMV), and vascular index (VI = PS/ED), were measured and recorded. Forty-one healthy patients were assessed as the control group. Vascular grading (VG) was significantly higher in the study group than the control group (p < 0.0001). The PI, RI, and VI were significantly lower in the study group than control group (p < 0.0001). No significant associations were observed between seven sonographic parameters and acute simple or/and complex cervicitis. For acute simple cervicitis, a PI cutoff of 1.1 had a sensitivity of 85.4% and a specificity of 92.1% (area under ROC curve [AUC], 93.2%). A RI of 0.6 had a sensitivity of 85.4% and a specificity of 78.9% (AUC, 86.1%). A VI of 2.6 had a sensitivity of 85.4% and a specificity of 78.9% (AUC, 84.9%). Power Doppler angiography of micro-vessel flow velocity waveforms in the cervix could represent a practical method to assist the diagnosis of pelvic inflammatory disease presented as acute cervicitis detected on transvaginal ultrasound before medical or surgical treatment. Cervical PI may be a useful index to detect micro-vessel flow velocity waveforms in acute cervicitis and differentiate acute simple cervicitis from complex cervicitis. [ABSTRACT FROM AUTHOR]

Objective: To identify predictor microRNAs (miRNAs) from patients with repeated implantation failure (RIF).Design: Systemic analysis of miRNA profiles from the endometrium of patients undergoing in vitro fertilization (IVF).Setting: University research institute, private IVF center, and molecular testing laboratory.Patient(s): Twenty five infertile patients in the discovery cohort and 11 patients in the validation cohort.Interventions(s): None.Main Outcome Measure(s): A signature set of miRNA associated with the risk of RIF.Result(s): We designed a reproductive disease-related PanelChip to access endometrium miRNA profiles in patients undergoing IVF. Three major miRNA signatures, including hsa-miR-20b-5p, hsa-miR-155-5p, and hsa-miR-718, were identified using infinite combination signature search algorithm analysis from 25 patients in the discovery cohort undergoing IVF. These miRNAs were used as biomarkers in the validation cohort of 11 patients. Finally, the 3-miRNA signature was capable of predicting patients with RIF with an accuracy >90%.Conclusion(s): Our findings indicated that specific endometrial miRNAs can be applied as diagnostic biomarkers to predict RIF. Such information will definitely help to increase the success rate of implantation practice. [ABSTRACT FROM AUTHOR]