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In this paper, an on-chip optical circulator on the InP-membrane-on-Si (IMOS) platform is demonstrated. The circulator is composed of two multi-mode interferometers (MMIs), four polarization converters (PCs), and a Cerium-doped Yttrium Iron Garnet (Ce:YIG) die. The Ce:YIG die is adhesively bonded on the InP membrane via a 125-nm thin bonding layer. Nonreciprocal phase shift (NRPS) is employed in the presence of a transverse magnetic field. The device works as a 4-port optical circulator with a maximum optical isolation of 27.0 dB and a minimum optical isolation of 18.6 dB for the TE mode. The measured optical isolation bandwidth is 0.12 nm. Two methods are proposed in order to improve the optical isolation bandwidth.

We report a versatile method for improving post-bonding wafer alignment accuracy and BCB thickness uniformity in stacks bonded with soft-baked BCB. It is based on novel BCB-based micro-pillars that act as anchors during bonding. The anchor structures become a natural part of the bonding interface therefore causing minimal interference to the optical, electrical and mechanical properties of the bonded stack. We studied these properties for fixed anchor density and various anchor heights with respect to the adhesive BCB thickness. We demonstrated that the alignment accuracy can be improved by approximately an order of magnitude and approach the fundamental pre-bond alignment accuracy by the tool. We also demonstrated that this technique is effective for a large range of BCB thicknesses of 2–16 μm. Furthermore we observed that the thickness non-uniformities were reduced by a factor of 2–3 × for BCB thicknesses in the 8–16 μm range.

In photonic integrated circuits (PICs), optical isolators and circulators are essential to prevent lasers from backreflections and to reroute the light flow. In this paper, an integrated polarization-independent device that can be operated as an optical isolator or an optical circulator, based on an InP membrane on silicon platform, is demonstrated. A cerium-doped yttrium iron garnet die is adhesively bonded on a Mach–Zehnder interferometer, in combination with four polarization converters. The device shows maximum optical isolations of 27.0 dB for transverse-electric (TE)-mode input and 34.0 dB for transverse-magnetic TM-mode input. The device also works as a four-port optical circulator. Optical isolations of at least 18.6 dB and 16.4 dB are measured between each circulator port pair for TE- and TM-mode input, respectively. This work could remove the optical interfaces between laser and isolator for robust production. It also provides a step forward toward a multifunctional and high-density PIC.

Reconfigurable waveguide components are promising building blocks for photonic neural networks and as an optical analogue to field-programmable gate arrays. By changing the effective index of the waveguide, reconfigurable waveguide components can achieve on-chip light routing and modulation. In this paper, we design and demonstrate an Sb2S3-reconfigurable InP membrane Mach–Zehnder interferometer (MZI) on a silicon substrate. Sb2S3, which has tunable refractive index and low absorption in the near-infrared spectrum, was patterned on the InP waveguide MZIs to make an optical switch in the telecoms conventional-band. By laser induced crystallisation of the Sb2S3, it was possible to control interference in the MZI and achieve 18 dB on/off switching at 1540 nm. Laser reamorphisation and reversible switching of the Sb2S3layer resulted in damage to the waveguide structure. However, simulations show that transition metal di-chalcogenide two-dimensional crystal layers can act as efficient thermal barriers that prevent thermal damage to the waveguide during laser amorphisation. Therefore, combining Sb2S3with InP waveguides seems to be a feasible approach to achieve low-loss reprogrammable waveguide components for on-chip photonics routing and neural networks.

Multipurpose prevention technologies (MPT) have been increasingly researched for their dual-purpose preventative properties against HIV and other STIs. The acceptability of PC-1005, a topical MPT candidate, was explored among men and women participating in the MTN-037 Phase I trial at two U.S. sites (Pittsburgh, PA, and Birmingham, AL). We triangulated quantitative and qualitative assessments of the acceptability of three volumes (4 mL, 16 mL, 32 mL) of PC-1005 administered rectally (N = 12; 6 males, 6 females). Participants rated overall gel acceptability on a scale of 1–10, with a median of 7.17 (SD = 2.04) and had positive feelings about all three dose volumes, citing them to be very comfortable or comfortable (dose 1 = 91.7%; dose 2 = 91.7%; dose 3 = 83.3%). High acceptability of and comfort with all three dose volumes shows promise for PC-1005 as an MPT to prevent HIV and STIs, warranting future clinical development.

Butt-joint regrowth is widely used in photonic integration, but it has been challenging to break the density-quality tradeoff due to the edge growth rate enhancement (GRE) effect. In this work, we propose a scheme to circumvent this tradeoff by using large regrowth masks whose centers are exposed to epi-growth for neutralization of the excessive species. With the GRE under control, epi-stacks with arbitrarily large sizes supporting dense arrays can be butt-joint integrated with minimal compromise to their epitaxy quality. In our experiment, multi-quantum-well-based material of an exceptionally large area of 0.5 × 1.7 mm2 was epitaxially integrated with passive InP material on the same wafer. A more than 20 × reduction in edge topology compared to conventional methods was achieved.

We present a characterization method for polarization converters which improves the accuracy of traditional characterization methods significantly. An experimental demonstration of the method is presented on the InP-membrane-on-silicon (IMOS) platform. The design and fabrication of the polarization converter is discussed, as well as the simulated polarization conversion efficiency. A device of only 4 microns is shown to achieve 97.5%±0.5% polarization conversion, corresponding to an extinction ratio of -16± 0.9 dB. The traditional characterization method is compared to the new 4-port method, and the accuracy is improved from up to 20% to 0.5%.

A V-band Vivaldi antenna design for beyond-5G base station applications operating within V-band is demonstrated. The device can be used for interfacing with radio-over-fibre links and optoelectronic components through a coplanar waveguide to slotline transition. Simulations show an end-fire radiation with a 3 dB gain bandwidth ranging between 46.9-77.4 GHz combined with the reflection coefficients remaining below-10dB for the same frequency range. A comb structure inspired by optical grating couplers is added providing an increased maximum gain of 12.6 dBi at 68.5 GHz. Measurement results validate the promising characteristics of the planar antenna.

Background To identify the association between tricuspid annular circumference and secondary tricuspid regurgitation and analyze the risk factors of recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery. Methods From October 2018 to June 2019, a total of 117 patients receiving concomitant tricuspid annuloplasty within left heart surgery were enrolled. Severity of tricuspid regurgitation was classified as 4 subtypes: normal, mild, moderate and severe. Perioperative data and mid-term outcome were collected. Tricuspid annular circumference (TAC) was measured under cardiac arrest during surgery procedure by cardioplegia. Optimal TAC and TAC index (TAC/body surface area, BSA) cutoffs of significant tricuspid annulus dilatation (moderate and severe) were obtained. Univariable and multivariable logistic regression analyses were performed to identify the risk factors of postoperative recurrent tricuspid regurgitation. The follow up period is 13–19 months (mean 15.5 ± 3.2 months). Results There was 1 patient was excluded who died after surgery. A total of 116 patients receiving tricuspid annuloplasty were included. Optimal cutoffs of significant tricuspid annulus dilatation were recommended (TAC 11.45 cm, Sensitivity 82.89%, Specificity 73.68%, AUC 0.915; TAC index 7.09 cm/m2, Sensitivity 73.68%, Specificity 85%, AUC 0.825, respectively). Based on findings of multivariable logistic regression, it has been showed that TAC index and postoperative atrial fibrillation were the independent risk factors of recurrent regurgitation after surgery. Optimal TAC index cutoff to predict recurrent tricuspid regurgitation was 7.86 cm/m2 Conclusions The severity of secondary tricuspid regurgitation is associated with the tricuspid annular circumference. The cut-offs of significant tricuspid regurgitation (more than moderate) were TAC 11.45 cm and TAC index 7.09 cm/m2, respectively. Clinically, concomitant tricuspid annuloplasty is relative safe and effective. TAC index ≥ 7.86 cm/m2 and postoperative atrial fibrillation are the risk factors of recurrent significant tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery.

Background Many comparative studies of percutaneous balloon mitral valvuloplasty (PBMV) and surgical mitral commissurotomy (SMC) in rheumatic mitral stenosis (MS) were done in the last few decades. With the development of valve repair techniques, various surgical rheumatic valve repair techniques have been applied in clinic, but there is a lack of comparison with PBMV. Our study was designed to compare the perioperative and mid-term outcomes of PBMV and mitral valve repair with "four-step" procedure in the treatment of rheumatic MS. Methods Patients with MS were treated with PBMV or rheumatic mitral valve repair (rMVP) at Beijing Anzhen Hospital between January 1, 2013 and September 30, 2018 were selected. By using propensity score matching (PSM) method, we compared the changes in post-operation clinical outcomes between the two matched groups. Kaplan-Meier analyses was used for survival analysis and drawing the curve, and log-rank test were used to compare intergroup differences. Results A total of 252 cases were enrolled after selection, 74 cases in PBMV and 178 cases in rMVP. Seventy-four pairs were matched successfully after PSM. There were 53 females in PBMV and 54 in rMVP. The mean age of two groups was 46.95±12.50 and 47.55±11.91 years respectively. There was no significantly differences in mitral valve orifice area (MVOA) (1.05±0.32 vs. 0.97±0.24 cm2, P=0.12) and left ventricular ejection fraction (EF) (62.36%±5.17% vs. 62.52%±4.94%, P=0.76) between two groups preoperatively. Baseline characteristics were basically balanced after PSM. In each group, there was one case transferred to surgical mitral valve replacement due to the failure of valvuloplasty before discharge. All patients survived the interventions and no severe complications were found. MVOA were significantly increased in rMVP compared with PBMV postoperatively, as well as grading of MS and tricuspid regurgitation (TR) were significantly improved in rMVP. Three cases in PBMV were lost during the follow-up. Mitral replacement was performed in 11 patients and one of them died in PBMV, while none of patients underwent re-intervention in rMVP, but one patient died of pneumonia. Conclusions For selected patients with rheumatic MS in China, our study shows that there are comparable clinical outcomes in terms of operative, mid-term mortality and complications between PBMV and surgical rMVP with "four-step" procedure. Surgical rMVP shows more advantageous in the correction of valve stenosis and the management of concomitant tricuspid valve lesions and atrial fibrillation (AF).

Integrated optical true time delay lines attract lots of attention for optically controlled mm-wave beam steering due to its low-loss/broadband performance and stable/compact system architecture. However, for remotely-controlled networks, the techniques that require local-site actively-tuned elements would make the network control more complicated. A passive design using wavelength-tuning is regarded as a promising candidate. In this paper, an integrated wavelength-tuned optical mm-wave beamformer with doubled delay resolution is proposed and demonstrated in a generic InP platform. A bidirectional looped-back arrayed waveguide grating (AWG) module acts as the stepwise tunable delay unit. By introducing an extra AWG router for delay mode (positive/negative) selection and a bidirectional optical interface, a pure λ-tuned, resolution-doubled optical delay network is realized without using any active component (e.g. heaters, current injection) at the local site. This photonic passive design is more beneficial to the remotely-controlled mm-wave beam steering system. Furthermore, the AWG router potentially allows multi-port wavelength switching to support the scaling-up of the network. The fabrication-caused delay error of

In this work we have demonstrated a waveguide integrated uni-traveling carrier photodiode on an InP-membrane-on-silicon platform with 3 dB bandwidth beyond 110 GHz. With design optimization and an improved process, devices as small as $ \text{3}\times \text{2}\;\mu \text{m}^2$ are successfully realized. An electrical equivalent circuit model based on measured S-parameters revealed ultra-small series resistance and junction capacitance as low as 6.5 $\Omega$ and 4.4 fF, respectively, in the diodes. The model also provided insight in the photocurrent dependent characteristics in the bandwidth and resonsivity of the devices. Finally, data transmission measurements are demonstrated, showcasing the high speed telecommunication abilities of the UTC-PD.

Targeting BRCA-deficient tumors with PARP inhibitors has improved the progression-free survival of ovarian and breast cancer patients in the clinic. However, the majority of patients develop acquired resistance. PARP inhibitor (PARPi) resistance in tumors can occur by restoration of homologous recombination (HR) or replication fork stability and/or by suppression of single-stranded DNA (ssDNA) gaps at replication forks. USP1 is a ubiquitin specific protease which deubiquitinates PCNA and FANCD2. We have previously shown that USP1 deficiency causes replication fork instability and is synthetic lethal with BRCA1 deficiency, suggesting USP1 as a potential therapeutic target for overcoming PARPi resistance (Lim et al, Mol Cell, 2018). Accordingly, USP1 inhibitors are now undergoing preclinical and clinical development. Here, we evaluated the activity of the novel USP1 inhibitors such as I-138 (Simoneau et al, Mol Cancer Ther, 2022) and TNG-6132 in preclinical models of BRCA1-deficient tumors. I-138 preferentially killed BRCA1-deficient ovarian and breast cancer cells and increased the cellular level of ubiquitinated PCNA. An aniPOND analysis demonstrated an accumulation of ubiquitinated PCNA specifically at the replication fork in I-138-treated cells. Consistent with our previous study (Lim et al, Mol Cell, 2018), I-138 treatment led to replication fork instability and DNA damage in BRCA1-deficient cancer cells. I-138 exposure also resulted in the accumulation of ssDNA gaps, as detected by an S1 nuclease assay. Interestingly, the induction of ssDNA gaps was detected in I-138-sensitive but not in I-138-resistant BRCA1-deficient cells, suggesting a mechanism of cytotoxicity by USP1 inhibition. Persistent monoubiquitinated PCNA accumulation was the cause of cell killing after USP1 inhibition. Knockdown of RAD18, the E3 ubiquitin ligase known to ubiquitinate PCNA, in BRCA1-deficient ovarian cancer cells resulted in reduced PCNA-Ub levels, resistance to I-138, and suppression of ssDNA gaps. Notably, I-138 exhibited monotherapy activity in ovarian and breast cancer cell lines with acquired PARPi resistance and re-sensitized the cells to PARP inhibition. Similarly, PARPi-resistant BRCA1-mutated organoids, derived from patient-derived xenograft (PDX)-derived models of ovarian cancer, were also sensitized by USP1 inhibition by TNG-6132. Interestingly, the ssDNA gap accumulation induced by I-138 strongly correlated with the drug sensitivity of both PARPi-sensitive and PARPi-resistant cells. In conclusion, I-138 exhibits monotherapy activity in both PARPi-sensitive and -resistant preclinical models of BRCA1-deficient cancer, induces ssDNA gaps and overcomes PARP inhibitor resistance. Taken together, these data support use of a USP1 inhibitor, with or without a PARP inhibitor, as a therapeutic strategy for a subset of PARP-inhibitor-resistant BRCA1-deficient tumors. Citation Format: Alexandre Andre B. A. Da Costa, Arindam Bose, David Martignetti, Cecilia Ayala-Zambrano, Ramya Ravindranathan, Golbahar Sadatrezaei, Yuqing Jiao, Bose Kochupurakkal, Huy Nguyen, Jean-Bernard Lazaro, Kalindi Parmar, Geoffrey I. Shapiro, Alan D. D’Andrea. The USP1 inhibitor I-138 kills BRCA1-deficient tumor cells and overcomes PARP inhibitor resistance. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5725.

PARP inhibitors are being used in maintenance treatment of BRCA-mutated high-grade serous ovarian cancer (HGSOC). However, de novo and acquired resistance to PARP inhibitors, resulting from restoration of homologous recombination repair or stabilization of replication forks, is a pressing clinical problem. ATR inhibitors are known to reverse both of these mechanisms of PARP inhibitor resistance and are currently in clinical development. In this study, we assessed the activity of a novel ATR inhibitor, M1774, as a monotherapy and in combination with PARP inhibition in HGSOC preclinical models. M1774 exhibited single-agent activity across a panel of ovarian cancer cell lines with induction of DNA damage. We used a panel of BRCA1-mutated patient-derived xenograft (PDX) models of HGSOC with acquired PARP inhibitor resistance and identified two M1774-sensitive models and one M1774-resistant model. M1774 monotherapy demonstrated anti-tumor activity in mice bearing sensitive PDX models of HGSOC with PARP inhibitor resistance. In the M1774-sensitive models, the combination of M1774 and niraparib augmented the degree and durability of response compared with M1774 monotherapy. The combination of M1774 and niraparib also demonstrated synergistic anti-tumor activity in the M1774-resistant model, indicating that the combination could overcome monotherapy resistant to either agent. We also generated organoid cultures from these PDX models. Treatment of the organoid models with M1774, niraparib or the combination faithfully recapitulated the anti-tumor activities seen in vivo. Mechanistically, M1774-resistant organoid cultures demonstrated stable replication forks and an absence of replication stress. The combination of M1774 with niraparib resulted in destabilization of the replication forks. In contrast, M1774-sensitive organoids exhibited unstable replication forks, which were further destabilized by the niraparib combination. In addition, the sensitive models demonstrated higher basal levels of replication stress, as detected by increased levels of phospho-RPA. Collectively, these results indicate that the combination of M1774 and niraparib can overcome PARP inhibitor resistance and ATR inhibitor resistance in BRCA1-mutant ovarian cancer PDX models and demonstrate the utility of organoid cultures for discerning mechanisms of resistance and strategies to restore drug sensitivity. Combined M1774-mediated ATR inhibition and PARP inhibition may be a promising therapeutic strategy for the treatment of ovarian cancer. Citation Format: Jie Hao, Arindam Bose, Golbahar Sadatrezaei, David B. Martignetti, Yuqing Jiao, Alexandre André B. da Costa, Jean-Bernard Lazaro, Bose Kochupurakkal, Huy Nguyen, Kalindi Parmar, Alan D. D’Andrea, Geoffrey I. Shapiro. Combination of M1774 and niraparib can overcome ATR and PARP inhibitor resistance in BRCA1 mutated ovarian cancer models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6210.

We present waveguide photonic crystal reflectors on the InP-membrane-on-silicon (IMOS) platform, and a method to accurately measure the reflectivity of those reflectors. The photonic crystal holes are patterned on a waveguide using electron-beam lithography and etched through the waveguiding layer to create a broadband distributed Bragg reflector. We show simulations of these reflectors and experimental results of fabricated devices, both showing a high, free-to-choose reflectivity, and high quality factor Fabry-Pérot cavities. We experimentally show reflectivities higher than 95% for the reflectors and a quality factor as high as 15,911±511 for a Fabry-Pérot cavity, using reflectors with a length of only 4 microns. For the first time, to our knowledge, two methods for measuring the reflectivity are used for characterization of on-chip reflectors to accurately determine the reflection. The first method is based on analysis of the transmission through a Fabry-Pérot cavity, the second is based on a direct four-port measurement of the reflector. A systematic error is made in both methods, resulting in an upper and lower boundary for the actual reflection coefficient.

In this letter, a reflection-type arrayed waveguide grating (AWG) (de)multiplexer using high-reflection photonic crystal reflector (PCR) in the Indium-phosphide Membrane on Silicon (IMOS) platform is proposed and experimentally demonstrated for the first time. This reflection-type AWG enables a 35% size-reduced footprint compared with the traditional transmission-type AWG having the same spectral parameters. Considering the realized performance of silicon-nanowire R-AWGs, an acceptable performance ( $680\,\times \,190\,\mu \text {m}^{2}$ size, 6.7-dB loss, and 10-dB crosstalk) is obtained. By using the ultra-small $5.4\,\times \,0.7\,\mu \text {m}^{2}$ PCR, merely 1.1-dB power loss higher than the corresponding transmission-type AWG is implemented. The PCR is a standard building block with a reflectivity of >90%. Besides, the length reduction of the arrayed waveguide will contribute to minimize the accumulated phase error in fabrication.

A five-channel mode division multiplexed on-chip optical bus is designed and demonstrated on a submicron-thick InP membrane wafer bonded on a Si substrate. Dual-core adiabatic tapers are leveraged for realization of the mode (de)multiplexers. The optimized device shows low excess optical loss of maximum 0.14 dB compared to a reference waveguide and low cross talk of maximum −18.5 dB for all five channels over a broad optical bandwidth of 1510–1600 nm. High fabrication tolerance to width variations is also demonstrated, where a low excess loss of less than 1 dB and a low cross talk of less than −14 dB are maintained in the range of 1530–1585 nm, covering the C-band, when the width varies by up to 50 nm. The demonstrated results show an essential step toward a monolithic photonic layer on top of electronic chips for high-capacity on-chip optical interconnects.

Despite being one of the few chronic secondary heart diseases that can be prevented, current epidemiological data on rheumatic heart disease (RHD) in China are unavailable. This study examined mitral valve (MV) surgery trends in a large Chinese cardiovascular center over the last 10 years and provided insight into the distribution of RHDs and their changes.Medical records of patients who underwent cardiac surgery, MV surgery, and MV surgery for rheumatic MV (rMV) disease at Beijing Anzhen Hospital between January 2010 and December 2019 were retrospectively reviewed. Patients' demographic and clinical characteristics were statistically analyzed among age groups.Overall, 7,736 patients underwent rMV surgery and 87.5% were aged 40-70 years. The proportion of patients aged60 years increased annually (P0.05), and the proportion of patients in all other age groups decreased. The proportion of patients with rMV diseases among those with cardiac or mitral valve diseases decreased each year, but the absolute number of patients with rMV disease remained stable. Approximately 90% of patients who underwent rMV surgery were from northern China. The incidence of rMV disease among patients with mitral valve disease moderately correlated with the per capita gross regional product (Per-GRP), an indicator of living standards (r=-0.517, P0.05).RHD still exists in northern China and requires adequate resources for its management. The number of older patients with rMV disease presents a challenge for mitral valve surgery.

Optical beam steerers on InP integrated photonics have not been able to offer high angular resolution, due to the technological challenges in realizing a large emission aperture. In this paper, we propose the creation of waveguide-based grating antennas fabricated in SiO2 super-cladding on InP membrane on silicon (IMOS) to achieve simultaneously high resolution and good compatibility with InP-based active devices. By exploiting the high dry etch selectivity between SiO2 and InP, a tolerant fabrication process is proposed and demonstrated, allowing for high controllability in the process. Device parameters including buffer thickness and pitch have been explored to obtain an optimized design. A 2-mm long grating antenna is fabricated and shows a record narrow full-width-half-maximum angular beam width of 0.05° and a high spatial resolution of more than 250 points when the wavelength is tuned over a range of 100 nm.

BACKGROUND: The elevation of troponin after coronary artery bypass grafting (CABG) is common This study aimed to investigate the association between very early cardiac troponin I (cTnI) concentration and its longitudinal change within 24 hours after CABG and 30-day adverse events. METHODS: This study prospectively enrolled 633 patients who underwent isolated off-pump CABG from January 2019 to May 2019. Serum cTnI levels were measured in all patients at two examinations within 24 hours postoperatively (1 hour and 12–18 hours), and a proportional hazards model was used to determine the association between cTnI levels and their change with adverse events, which were defined as a composite of 30-day mortality, stroke, heart failure, myocardial infarction (MI), and ventricular fibrillation. RESULTS: cTnI levels of the two examinations and absolute change of cTnI levels were significantly higher in the event group than in the non-event group (P

Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037.Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR.High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa.The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

Photonic integration in a micrometer-thick indium phosphide (InP) membrane on silicon (IMOS) offers intrinsic and high-performance optoelectronic functions together with high-index-contrast nanophotonic circuitries. Recently demonstrated devices have shown competitive performances, including high side-mode-suppression ratio (SMSR) lasers, ultrafast photodiodes, and significant improvement in critical dimensions. Applications of the IMOS devices and circuits in optical wireless, quantum photonics, and optical cross-connects have proven their performances and high potential.

We present an improved calculation for reflection and transmission coefficients in the context of a mode-matching method with optimization, which makes the results more reliable and accurate as the number of modes employed in the mode-matching method is increased. This method is successfully demonstrated in a series of waveguide structures.

Mobility and flexibility of anterior mitral leaflet (AML) are considered to be the important factor for mitral valve (MV) repair in rheumatic population, we try to use the bending angle of AML to quantify its' mobility and flexibility and investigate whether it can predict the success of rheumatic MV repair or not.Total 54 patients underwent rheumatic MV surgeries with mild lesions of subvalvular apparatus from August, 2017 to November, 2017 at the author institution, we divided the patients into MV repair and MV replacement groups which included directly MV replacement and repair attempt but failed repairing transfer to replacement intraoperatively. Patients' MV structure was carefully evaluated on transthoracic echocardiography (TTE) and scored by the Wilkins score (WS) preoperatively. The bending angle of AML was measured during systole and diastole at different level before surgery.The differences of patients' demographic characteristics between repair group and replacement group were not statistically significant (P value0.05) and the differences among B-angle, T-angle, Bs-angle, C-angle of AML between repair group and replacement groups were not statistically significant (P value0.05). Only BT-angle in repair group was significantly larger than that of replacement group (21.56°±3.84°, 10.29°±6.02°, respectively, P0.001), therefore the BT-angle was tested as a predictor of reparability by observing the receiver operating characteristic (ROC) curve (ROC area: 0.944, standard error: 0.06, 95% CI: 0.826-1), BT-angle of AML on preoperative transthoracic echo of 15.5° or more predicts feasibility of rheumatic MV repair with 100% sensitivity and 85.7% specificity in patients with mild lesions of subvalvular apparatus. Logistic regression for a single area of calcification (diameter0.8 cm) at commissure were shown that: β: 0.08, Exp (β): 1.083, P: 0.7770.05, the minor single calcified area at commissure had no effect on reparability of rheumatic MV disease. The differences of total WS and each component score between repair group and replacement group were not statistically significant (P value0.05). By observing the ROC curve for total WS (ROC area: 0.508), the WS cannot be a predictor for the rheumatic MV repair.The bending angle of AML which was considered as quantification of mobility and flexibility of AML can be a predictor for MV repair in patients with rheumatic heart disease (RHD). The small single area of commissural calcification had no effect on reparability of rheumatic MV disease. WS cannot appropriately predict the outcome of rheumatic MV repair.

The polyethylene glycol (PEG-1000) was selected as phase change material (PCM) and the expanded perlite (EP), the granular activated carbon（GAC）, the powdered activated carbon (PAC) and the expanded graphite (EG) were selected as porous adsorption materials. The composite phase change material (CPCM) was prepared by the physical adsorption method. The composite phase change materials compound with the polyethylene glycol and the expanded graphite were picked by comparing and analyzing the adsorption capacity of such four types of porous materials. And then the composite building material for thermal storage mixed with the CPCM and the cement, water-reducer, early strength agent was prepared in the pressure condition of -0.05Mpa and the constant temperature condition of 70℃. Its thermal physical properties, the structural stability and the compression resistance capability of different quality proportion specimens were experimental researched. The results show that such composite building materials with CPCM appears light density, high thermal conductivity, large heat storage capacity and good stability, and its compression resistance capability can satisfy the requirement of ordinary mortar building material.

The ancient architectures of tower buildings type are representative in ancient architectures in Beijing, and compared with other types of ancient architectures, they are characterized by long distance from ground, high height of building itself, and large inner space. For the ancient architectures of tower buildings type, a proposal using floor-type fan coil air-conditioner for control of physical environment is suggested, and simulation calculation for indoor temperature field for one ancient architecture of tower building in Beijing is done using CFD software, with calculation content comprising the indoor temperature field and velocity field when the system is used in summer. The result shows that: adopting floor-type fan coil air-conditioner for summer conditions and adjusting blast amount of fan coil and blasting parameters can make air temperature agreeable and comfortable.

InP membranes have appeared in the last decade as a viable integrated photonics platform, suitable for adding photonic functions to silicon electronics. It combines the strengths of silicon photonics (high index contrasts and therefore small footprint devices) with those of generic InP-platforms (monolithic integration of active and passive devices). A range of functionalities has been developed on this platform, which goes by the name of Indium phosphide membrane on silicon (IMOS). Competitive performances have been demonstrated for lasers, fast detectors, waveguides, filters, couplers, modulators, and more. Here, we provide an overview of IMOS and describe recent developments regarding technology and devices. This includes record low propagation losses, plasmonic waveguides, a variety of laser structures, and improved wavelength demuliplexers. These developments demonstrate that IMOS has potential to deliver photonic integrated circuits to a wide variety of application fields, e.g. telecom, datacom, sensing, terahertz, and many others.

Recently a novel photonic integration technology, based on a thin InP-based membrane, is emerging. This technology offers monolithic integration of active and passive functions in a sub-micron thick membrane. The enhanced optical confinement in the membrane results in ultracompact active and passive devices. The membrane also enables approaches to converge with electronics. It has shown high potential in breaking the speed, energy and density bottlenecks in conventional photonic integration technologies. This paper explains the concept of the InP membrane, discusses the versatility of various technology approaches and reviews the recent advancement in this field.

In this paper, an optical switch based on a microelectromechanical phase modulator is presented. Phase tuning is achieved by tuning the vertical gap between two vertically coupled waveguides through the application of a reverse bias on a p-i-n junction. An effective refractive index tuning Δneff of 0.03 and a phase shift of more than 3π rad at telecom wavelengths are measured with an on-chip Mach–Zehnder interferometer (MZI), with a phase-tuning length of only 140 μm. With a bias voltage of 5.1 V, a half-wave-voltage-length product (Vπ L) of 5.6 × 10−3 V·cm is achieved. Furthermore, optical crossbar switching in a MZI is demonstrated with a 15 dB extinction ratio using an actuation voltage of only 4.2 V. Our work provides a solution to on-chip, low-voltage phase modulation and optical switching. The switch is fabricated on an indium-phosphide membrane on a silicon substrate, which enables the integration with active components (e.g., amplifiers, lasers, and detectors) on a single chip.In this paper, an optical switch based on a microelectromechanical phase modulator is presented. Phase tuning is achieved by tuning the vertical gap between two vertically coupled waveguides through the application of a reverse bias on a p-i-n junction. An effective refractive index tuning Δneff of 0.03 and a phase shift of more than 3π rad at telecom wavelengths are measured with an on-chip Mach–Zehnder interferometer (MZI), with a phase-tuning length of only 140 μm. With a bias voltage of 5.1 V, a half-wave-voltage-length product (Vπ L) of 5.6 × 10−3 V·cm is achieved. Furthermore, optical crossbar switching in a MZI is demonstrated with a 15 dB extinction ratio using an actuation voltage of only 4.2 V. Our work provides a solution to on-chip, low-voltage phase modulation and optical switching. The switch is fabricated on an indium-phosphide membrane on a silicon substrate, which enables the integration with active components (e.g., amplifiers, lasers, and detectors) on a single chip.

In this paper, we experimentally verify the antibunching properties of multiple single photons located at distinct optical modes in a quantum frequency comb generated by cavity-enhanced spontaneous four-wave mixing in an InP membrane micro-ring resonator. The experimentally measured single photon conditional self-correlation parameter gH 2 =0.08 ± 0.008, well below the classical regime (0.5) with the corresponding detector corrected Klyshko efficiency η k of 3%-4.2%.

BACKGROUND: We compared and analyzed differences between repair vs. replacement of mitral valves on severe rheumatic mitral stenosis by looking at mid-term clinical outcomes. METHODS: Patients with severe rheumatic mitral stenosis (mitral valve area ≤1.5 cm(2), with or without mitral valve regurgitation) from January 2011 to September 2017 were divided into two groups: a mitral valve repair group (MVP) and a mitral valve replacement group (MVR). After propensity score matching between the two groups, we compared changes in post-operation clinical outcomes. We also monitored changes in left ventricular longitudinal and circumferential strain in successfully matched patients (20 pairs) by echocardiography speckle tracing. RESULTS: A total of 921 patients were recruited (221 in MVP and 700 in MVR). After a propensity score matching, 216 cases were selected with 108 patients in each group. With a follow-up period of 3 months to 7.1 years, the incidence of heart failure was observed to be significantly higher in the MVR group than in the MVP group (P

Objective Whether mitral valve repair is superior to replacement in the population with rheumatic heart disease has been debated. This study aims to compare outcomes of repair with replacement by the propensity score method. Methods This observational, prospective study enrolled patients with rheumatic heart disease who underwent mitral valve repair and replacement from January 2011 to April 2019. The propensity score method was used to select 2 groups with similar baseline characteristics. Baseline, clinical, and follow-up data were collected. Clinical outcomes included death from any cause, reoperation, and valve-related complications. Results The overall population before matching (N = 1644) included 612 patients who underwent repair and 1032 patients who underwent replacement. The propensity score analysis generated matches for 1058 patients (529 pairs). The median follow-up time was 4.12 years. Early mortality and death from any cause during follow-up were significantly lower in the repair group compared with the replacement group (hazard ratio, 0.19; 95% confidence interval [CI], 0.05-0.64; P = .003; hazard ratio, 0.38; 95% CI, 0.19-0.74; P = .003, respectively). Patients in the repair group had a lower risk of valve-related complications compared with patients in the replacement group (subhazard ratio, 0.44; 95% CI, 0.21-0.90; P = .025). In terms of reoperation, no significant difference was observed between the repair and replacement groups (subhazard ratio, 2.54; 95% CI, 0.89-7.22; P = .081). Conclusions The results suggest that rheumatic mitral valve repair in select patients is superior to mitral valve replacement with regard to lower mortality and fewer valve-related complications; meanwhile, it has a comparable risk of reoperation compared with replacement.

Ever-increasing data traffic demands higher-speed and lower-cost PICs for the access network. Nanophotonic ICs on a thin membrane is a promising solution providing high density, enhanced speed and reduced assembly cost through electronics co-integration. We present our recent developments on an InP nanophotonic membrane. (TuB4.2)

We present an integrated Vernier laser with two-ring filter in the cavity. Tuning of the rings shows 21 nm range. Laser has 39 mA threshold current, SMSR better than 35.7 dB and 1.3 mW power.