HIV Prevalence and HIV Screening History Among a Veterans Association Cohort of People with Opioid and Alcohol Use Disorders.

BACKGROUND: Veterans face high risk for HIV and substance use, and thus could be disproportionately impacted by the HIV and substance use disorder (SUD) "syndemic." HIV prevalence among veterans with SUD is unknown. OBJECTIVE: To project HIV prevalence and lifetime HIV screening history among US veterans with alcohol use disorder (AUD), opioid use disorder (OUD), or both. DESIGN: We conducted a retrospective cohort analysis using national Veterans Health Administration (VHA) data. PARTICIPANTS: We selected three cohorts of veterans with SUD: (1) AUD, (2) OUD, and (3) AUD/OUD. Included veterans had ICD codes for AUD/OUD from 2016 to 2022 recorded in VHA electronic medical records, sourced from the VA Corporate Data Warehouse (CDW). MAIN MEASURES: We estimated HIV prevalence by dividing the number of veterans who met two out of three criteria (codes for HIV diagnosis, antiretroviral therapy, or HIV screening/monitoring) by the total number of veterans in each cohort. We also estimated lifetime HIV screening history (as documented in VHA data) by cohort. We reported HIV prevalence and screening history by cohort and across demographic/clinical subgroups. KEY RESULTS: Our sample included 669,595 veterans with AUD, 63,787 with OUD, and 57,015 with AUD/OUD. HIV prevalence was highest in the AUD/OUD cohort (3.9%), followed by the OUD (2.1%) and AUD (1.1%) cohorts. Veterans of Black race and Hispanic/Latinx ethnicity, with HCV diagnoses, and aged 50-64 had the highest HIV prevalence in all cohorts. Overall, 12.8%, 29.1%, and 33.1% of the AUD/OUD, OUD, and AUD cohorts did not have history of HIV screening, respectively. CONCLUSIONS: HIV prevalence was high in all SUD cohorts, and was highest among veterans with AUD/OUD, with disparities by race/ethnicity and age. A substantial portion of veterans had not received HIV screening in the VHA. Findings highlight room for improvement in HIV prevention and screening services for veterans with SUD.

Nickel-Catalyzed Electrochemical Cross-Electrophile C(sp2)-C(sp3) Coupling via a NiII Aryl Amido Intermediate.

Cross-electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp2)-C(sp3) bond construction, which is highly valuable in medicinal chemistry. Based on a key NiII aryl amido intermediate, we developed a highly selective and scalable Ni-catalyzed electrochemical XEC reaction between (hetero)aryl halides and primary and secondary alkyl halides. Experimental and computational mechanistic studies indicate that an amine secondary ligand slows down the oxidative addition process of the Ni-polypyridine catalyst to the aryl bromide and a NiII aryl amido intermediate is formed in situ during the reaction process. The relatively slow oxidative addition is beneficial for enhancing the selectivity of the XEC reaction. The NiII aryl amido intermediate stabilizes the NiII-aryl species to prevent the aryl-aryl homo-coupling side reactions and acts as a catalyst to activate the alkyl bromide substrates. This electrosynthesis system provides a facile, practical, and scalable platform for the formation of (hetero)aryl-alkyl bonds using standard Ni catalysts under mild conditions. The mechanistic insights from this work could serve as a great foundation for future studies on Ni-catalyzed cross-couplings.

Electro/Ni Dual-Catalyzed Decarboxylative C(sp3)-C(sp2) Cross-Coupling Reactions of Carboxylates and Aryl Bromide.

Paired redox-neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non-toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C-C cross-coupling reactions. Here, we report the electro/Ni dual-catalyzed redox-neutral decarboxylative C(sp3)-C(sp2) cross-coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar-Br bond by a NiI-bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2-phenoxy propionic acid, undergo oxidative decarboxylation to form carbon-based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)-C(sp2) cross-coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual-catalyzed cross-coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)-C(sp2) cross-coupling and represent a promising method for the construction of the C(sp3)-C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow-synthesis technology.

Understanding Formation and Roles of NiII Aryl Amido and NiIII Aryl Amido Intermediates in Ni-Catalyzed Electrochemical Aryl Amination Reactions.

Ni-catalyzed electrochemical aryl amination (e-amination) is an attractive, emerging approach to building C-N bonds. Here, we report in-depth experimental and computational studies that examined the mechanism of Ni-catalyzed e-amination reactions. Key NiII-amine dibromide and NiII aryl amido intermediates were chemically synthesized and characterized. The combination of experiments and DFT calculations suggest (1) there is coordination of an amine to the NiII catalyst before the cathodic reduction and oxidative addition steps, (2) a stable NiII aryl amido intermediate is produced from the cathodic half-reaction, a critical step in controlling the selectivity between cross-coupling and undesired homo-coupling reaction pathways, (3) the diazabicycloundecene additive shifts the aryl halide oxidative addition mechanism from a NiI-based pathway to a Ni0-based pathway, and (4) redox-active bromide in the supporting electrolyte functions as a redox mediator to promote the oxidation of the stable NiII aryl amido intermediate to a NiIII aryl amido intermediate. Subsequently, the NiIII aryl amido intermediate undergoes facile reductive elimination to provide a C-N cross-coupling product at room temperature. Overall, our results provide new fundamental understandings about this e-amination reaction and guidance for further development of other Ni-catalyzed electrosynthetic reactions such as C-C and C-O cross-couplings.

Mechanistic studies of Ni-catalyzed electrochemical homo-coupling reactions of aryl halides.

Ni-catalyzed electrochemical arylation is an attractive, emerging approach for molecular construction as it uses air-stable Ni catalysts and efficiently proceeds at room temperature. However, the homo-coupling of aryl halide substrates is one of the major side reactions. Herein, extensive experimental and computational studies were conducted to examine the mechanism of Ni-catalyzed electrochemical homo-coupling of aryl halides. The results indicate that an unstable NiII(Ar)Br intermediate formed through oxidative addition of the cathodically generated NiI species with aryl bromide and a consecutive chemical reduction step. For electron-rich aryl halides, homo-coupling reaction efficiency is limited by the oxidative addition step, which can be improved by negatively shifting the redox potential of the Ni-catalyst. DFT computational studies suggest a NiIII(Ar)Br2/NiII(Ar)Br ligand exchange pathway for the formation of a high-valent NiIII(Ar)2Br intermediate for reductive elimination and production of the biaryl product. This work reveals the reaction mechanism of Ni-catalyzed electrochemical homo-coupling of aryl halides, which may provide valuable information for developing cross-coupling reactions with high selectivity.

Directing-Group-Free Arene C(sp2)-H Amination Using Bulky Aminium Radicals and DFT Analysis of Regioselectivity.

A hydroxylamine-derived electrophilic aminating reagent produces a transient and bulky aminium radical intermediate upon in situ activation by either TMSOTf or TFA and a subsequent electron transfer from an iron(II) catalyst. Density functional theory calculations were used to examine the regioselectivity of arene C-H amination reactions on diversely substituted arenes. The calculations suggest a simple charge-controlled regioselectivity model that enables prediction of the major C(sp2)-H amination product.

Long-term outcomes of anastomotic urethroplasty for radiation-induced strictures.

PURPOSE: To present our experience with excision and primary anastomosis (EPA) of radiation-induced urethral strictures (RUS) in men, including risk factors for stricture recurrence and long-term recurrence rates. METHODS: A retrospective review was performed of patients who underwent EPA of RUS between 2007 and 2018 at a single tertiary referral center. Demographic information, stricture location and length, complications, and stricture recurrence were analyzed. Univariate and multivariate Cox regression analyses were performed to identify variables impacting recurrence. RESULTS: EPA was performed in 116 patients with RUS. The majority of patients (86.2%, 100/116) underwent at least one prior urologic intervention. Mean stricture length was 2.3 cm. Stricture recurrence occurred in 19.0% (22/116) at a mean of 8.6 months. For patients with at least 1 year of postoperative follow-up (mean 30.7 months), stricture recurrence significantly increased to 36.6% (15/41; p = 0.03). On univariate and multivariate analyses, postoperative complications were associated with stricture recurrence (p < 0.001). CONCLUSION: EPA remains a viable option for men with RUS. Nearly two-thirds of RUS patients remain recurrence-free with long-term follow-up following EPA.

Strong correlation between standing cough test and 24-hour pad weights in the evaluation of male stress urinary incontinence.

AIMS: We sought to compare in-office physical exam findings via standing cough test (SCT) versus 24-hour pad weights among men seeking treatment for postprostatectomy stress urinary incontinence (SUI). METHODS: A retrospective review of a single surgeon database of incontinence procedures was performed. Documentation of SUI severity (grades 0-4) was completed by SCT preoperatively utilizing the Male Stress Incontinence Grading Scale (MSIGS). All patients had pads per day (PPD) and 24-hour pad weights obtained. We determined the Spearman's correlation coefficient between these variables. RESULTS: We identified 104 men who underwent anti-incontinence surgery (AdVance Sling or artificial urinary sphincter [AUS]). In the sling group (65 patients), nearly all (97%) had minimal incontinence with SCT (MSIGS = 0-2). In the AUS group (39 patients), most patients (69%) had an MSIGS 3 or 4 with SCT. Spearman's coefficient between quantification of SCT and pad weight for the overall group was ρ = .68 (P < .0001) demonstrating a strong positive correlation. PPD was also strongly correlated with pad weight (ρ = .55, P < .0001). As seen previously, SCT and PPD were correlated (ρ = .47, P < .0001). In a multivariable model predicting pad weight, the effect of SCT was greater than PPD (ß = 83 [54-111], P < .0001 vs 45 [2169], P = .0004). CONCLUSIONS: SCT findings strongly correlate to 24-hour pad weights in the evaluation of male SUI. The SCT shows promise as a rapid, reliable, noninvasive measure of SUI severity before anti-incontinence surgery.

Heterogeneous silicon photonics sensing for autonomous cars.

Heterogeneous silicon photonics is uniquely positioned to address the photonic sensing needs of upcoming autonomous cars and provide the necessary cost reduction for widespread deployment. This is because it allows for wafer-scale active/passive integration, including optical sources. We present our recent research and the development of interferometric optical gyroscopes and LiDAR sensors. More specifically, we show a fully integrated gyroscope front-end occupying an area of only 4.5 mm2. We also show the first dense pitch optical phased array using heterogeneous phase shifters. The 4 µm pitch heterogeneous phase shifters provide very low V2π of only 0.35-1.4 V across 200 nm, low residual amplitude modulation of only 0.1-0.15 dB for 2π phase shift, extremely low static power consumption (<3 nW), and high speed (> 1 GHz). All of these factors make them ideal for next-generation LiDAR systems that employ optical phased arrays.

Synchronous Urethral Repair During Prosthetic Surgery: Safety of Planned and Damage Control Approaches Using Suprapubic Tube Urinary Diversion.

BACKGROUND: Urethral injury during inflatable penile prosthesis (IPP) or artificial urinary sphincter (AUS) placement is rare, and traditionally most prosthetic surgeons abort prosthetic implantation when urethral repair is necessary. AIM: To report our experience with synchronous urethroplasty (SU) as a planned or damage control surgery during urologic prosthetic surgery, to evaluate the safety and outcomes of the procedure. METHODS: A retrospective review of our IPP and AUS database was completed to identify patients who underwent an SU between 2007 and 2018. We included patients who underwent an SU during prosthetic surgery in either a planned procedure for known stricture or diverticulum or a "damage control" procedure after intraoperative injury. OUTCOME: Patient characteristics and surgical outcomes were assessed, with success defined as the absence of urethral stricture and revision surgery. RESULTS: From our database of 1,508 prosthetic cases, we identified 7 patients (0.46%) who had an SU in the same setting as complete prosthesis placement (4 AUS and 3 IPP [1 combined IPP/AUS], and 1 sling). Three patients underwent planned repair of a known urethral abnormality (urethral diverticulum, urethrocutaneous fistula, and urethral stricture), and 4 underwent repair of an intraoperative urethral injury. Among the patients who experienced an intraoperative urethral injury, contributing etiologies included previous anti-incontinence surgery with periurethral fibrosis (n = 2), severe corporal fibrosis from priapism, and previous urethral disruption from pelvic fracture. Nearly all of the urethroplasties (6 of 7; 86%) were completed with a primary closure. The average indwelling duration of suprapubic tube (SPT) catheters was 4.1 weeks (range, 7 to 47 days). The average duration of follow-up was 21.5 months, and all patients were continent at follow-up. No device infections or urethral complications were identified. CLINICAL IMPLICATIONS: Our study illustrates the safety of concomitant urethral repair at time of prosthetic placement as an option to avoid the use of 2 anesthetics and prevent further scarring in high-risk patients. STRENGTHS & LIMITATIONS: This is the first study to address definitive urethral reconstruction during anti-incontinence procedures along with planned concomitant urethroplasty during IPP placement. This promising initial experience is relevant for surgeons who may encounter concomitant urethral pathology in the setting of complex reoperative prosthetic cases. The need for SU is rare, and thus our cohort size was limited in this retrospective, single-institution experience. CONCLUSION: SU with prolonged SPT urinary diversion offers a safe damage control approach for men with concomitant urethral pathology during prosthetic surgery without conferring an increased risk of infection or stricture. Yi YA, Fuchs JS, Davenport MT, et al. Synchronous Urethral Repair During Prosthetic Surgery: Safety of Planned and Damage Control Approaches Using Suprapubic Tube Urinary Diversion. J Sex Med 2019;16:1106-1110.

Total Synthesis of Clavatadine B.

The first total synthesis of clavatadine B (2), a natural product found to be a selective human blood coagulation factor XIa inhibitor, is described. A convergent approach that exemplifies the advantages of direct, early stage guanidinylation provided an immediate clavatadine B precursor, which was assembled in an efficient manner using known synthetic precursors of the structurally related natural product clavatadine A (1). Global deprotection cleanly provided clavatadine B in only four steps from a known derivative of homogentisic acid lactone (longest linear sequence, 75% overall yield).

Reflection sensitivity of 1.3 µm quantum dot lasers epitaxially grown on silicon.

We present measurements of relative intensity noise versus various levels of optical feedback for 1.3 µm quantum dot lasers epitaxially grown on silicon for the first time. A systematic comparison is made with heterogeneously integrated 1.55 µm quantum well lasers on silicon. Our results indicate up to 20 dB reduced sensitivity of the quantum dot lasers on silicon compared to the quantum wells.

Stabilization of heterogeneous silicon lasers using Pound-Drever-Hall locking to Si3N4 ring resonators.

Recent results on heterogeneous Si/III-V lasers and ultra-high Q Si3N4 resonators are implemented in a Pound-Drever-Hall frequency stabilization system to yield narrow linewidth characteristics for a stable on-chip laser reference. The high frequency filtering is performed with Si resonant mirrors in the laser cavity. To suppress close in noise and frequency walk off, the laser is locked to an ultra-high Q Si3N4 resonator with a 30 million quality factor. The laser shows high frequency noise levels of 60 × 103 Hz2/Hz corresponding to 160 kHz linewidth, and the low frequency noise is suppressed 33 dB to 103 Hz2/Hz with the PDH system.

Integrated chip-scale Si3N4 wavemeter with narrow free spectral range and high stability.

We designed, fabricated, and characterized an integrated chip-scale wavemeter based on an unbalanced Mach-Zehnder interferometer with 300 MHz free spectral range. The wavemeter is realized in the Si3N4 platform, allowing for low loss with ∼62 cm of on-chip delay. We also integrated an optical hybrid to provide phase information. The main benefit of a fully integrated wavemeter, beside its small dimensions, is increased robustness to vibrations and temperature variations and much improved stability over fiber-based solutions.

Unidirectional hybrid silicon ring laser with an intracavity S-bend.

We demonstrate a hybrid silicon ring laser with an internal amplifying S-bend that couples a fraction of the counter-clockwise circulating light into the the clockwise direction. The device supported single-mode, unidirectional laser oscillation at certain bias conditions. A spatial field distribution model is derived to describe the unidirectional operation. A unidirectional clockwise laser output with a suppression ratio up to 18.6 dB over the counter-clockwise mode was achieved.

Heterogeneously integrated 2.0 µm CW hybrid silicon lasers at room temperature.

Here we experimentally demonstrate room temperature, continuous-wave (CW), 2.0 µm wavelength lasers heterogeneously integrated on silicon. Molecular wafer bonding of InP to Si is employed. These hybrid silicon lasers operate CW up to 35°C and emit up to 4.2 mW of single-facet CW power at room temperature. III-V tapers transfer light from a hybrid III-V/silicon optical mode into a Si waveguide mode. These lasers enable the realization of a number of sensing and detection applications in compact silicon photonic systems.

Low threshold and high speed short cavity distributed feedback hybrid silicon lasers.

In this paper we investigate reducing threshold and improving the efficiency and speed of distributed feedback hybrid silicon lasers. A low threshold current of 8.8 mA was achieved for a 200 µm cavity at 20 °C. A 3 dB bandwidth of 9.5 GHz as well as 12.5 Gb/s direct modulation of DFB laser diode was achieved on the hybrid silicon platform for the first time.

The influence of preexisting lower extremity edema and venous stasis disease on body contouring outcomes.

BACKGROUND: While a cause and effect relationship is traditionally thought to exist between thigh surgery and postoperative lymphedema, the link between obesity-related lymphatic and/or venous disease and post-body contouring lower extremity edema has not been investigated. We hypothesize that patients who experience prolonged lower extremity edema following thigh surgery are predisposed to developing this complication due to unrecognized preoperative lymphovascular disease. METHODS: Fifty-five patients who had undergone body contouring surgery were identified from our prospective registry. Twenty-eight patients completed the Venous Clinical Severity Score (VCSS), a validated outcome measure of venous disease. Three time points were assessed: pre-weight loss (T1), post-weight loss but pre-body contouring (T2), and post-body contouring (T3). Based on T3 VCSS, patients were divided into 2 groups-a T3 VCSS ≤3 (group 1; N = 13) and a T3 VCSS ≥4 (group 2; N = 15). RESULTS: VCSS for group 1 at T1, T2, and T3 were 3.31 ± 0.55, 1.85 ± 0.27, and 1.54 ± 0.35 (mean ± SEM), respectively, versus 6.3 ± 1.10, 4.33 ± 0.8, and 6.8 ± 0.63 for group 2 (P < 0.05, P < 0.05, and P < 0.0001). Pain scores at T1 was 0.46 ± 0.21 for group 1 versus 1.1 ± 0.24 for group 2 (P < 0.05). Edema scores for group 1 at T1, T2, and T3 were 0.69 ± 0.29, 0.08 ± 0.08, and 0.15 ± 0.10 versus 1.87 ± 0.35, 1.13 ± 0.31, and 2.13 ± 0.24 for group 2 (P < 0.05, P < 0.001, and P < 0.0001, respectively). CONCLUSIONS: Using VCSS, post-bariatric patients with prolonged lower extremity edema experienced clinically identifiable signs of disease prior to weight loss and body contouring surgery. Thus, careful preoperative evaluation may help identify at-risk patients and aid in managing postoperative expectations.

Gender differences in receipt of telehealth versus in person behavioral therapy, medication for opioid use disorder (MOUD), and 90-day MOUD retention during the pandemic: A retrospective veteran cohort study.

BACKGROUND: COVID-19 significantly negatively impacted access to care among patients with opioid use disorder (OUD). The Veterans Health Administration (VHA) enacted policies to expand telehealth and medication for OUD (MOUD) during the public health emergency, which offset risk of treatment disruption. In this study, we evaluated gender differences in utilization of behavioral therapy in person and via telehealth, MOUD utilization, and achieving 90-day MOUD retention pre-post pandemic onset, given known gender differences in treatment utilization between men and women. Secondarily, we examined MOUD receipt and retention as a function of in-person vs. telehealth behavioral therapy received over time. METHODS: Using VHA's nationwide electronic health record data, we compared outcomes between men and women veterans, pre- to post-pandemic onset (January 2019-February 2020 vs. March 2020-April 2021). Primary outcomes included receipt of behavioral therapy (in person or telehealth), number of appointments attended, any MOUD, and whether patients achieved 90-day MOUD retention post-induction. RESULTS: Veterans with OUD were less likely to receive behavioral therapy post-pandemic onset, which was driven by marked decreases in in-person care; these effects were strongest among women. The odds of receiving MOUD also decreased pre- to post-pandemic onset, particularly among men. Receipt of or achieving 90-day MOUD retention was differentially related to receipt of behavioral therapy via in person vs. telehealth; telehealth was more strongly associated with these utilization indicators post-pandemic onset-an effect that was more pronounced for men. CONCLUSION: The likelihood of receiving behavioral therapy and MOUD were lower during COVID-19 and varied by gender, with men being less likely to receive MOUD over time and women being less likely to receive in-person behavioral therapy. Behavioral therapy received via telehealth was generally associated with improved MOUD utilization compared to in-person behavioral therapy, but this was less true for women than for men regarding utilization of or achieving 90-day MOUD retention. In addition to the need for further telehealth expansion for veterans with OUD, more research should explore how to better engage men in MOUD treatment and improve adherence to MOUD among women engaged in behavioral therapy.

Risk factors for renal cell carcinoma in the VITAL study.

PURPOSE: The incidence of renal cell carcinoma is increasing worldwide. Cited risk factors include obesity, smoking and hypertension but few others have been confirmed in prospective studies. We used a prospective cohort to validate established renal cell carcinoma risk factors and evaluate more controversial risk factors for incident renal cell carcinoma. MATERIALS AND METHODS: A total of 77,260 residents of Washington 50 to 76 years old completed a questionnaire between 2000 and 2002 on demographic, lifestyle and health data. Incident renal cell carcinoma cases were determined by linkage to the regional cancer registry through December 31, 2009. Multivariate methods using covariates and cutoffs selected a priori were applied to analyze the association between renal cell carcinoma and previously studied factors related to lifestyle (body mass index, smoking and alcohol/fruit/vegetable consumption) and health (hypertension, diabetes, kidney disease and viral hepatitis). RESULTS: There were 249 incident cases of renal cell carcinoma. Independent renal cell carcinoma risk factors in the fully adjusted model were body mass index (35 or greater vs less than 25 kg/m2 HR 1.71, 95% CI 1.06-2.79), smoking (greater than 37.5 pack-years vs never HR 1.58, 95% CI 1.09-2.29), hypertension (HR 1.70, 95% CI 1.30-2.22), kidney disease (HR 2.58, 95% CI 1.21-5.50) and viral hepatitis (HR 1.80, 95% CI 1.03-3.14). Diabetes was associated with renal cell carcinoma (HR 1.83, 95% CI 1.26-2.65) in a base model adjusting for age and gender but not in the multivariate model. We found no association between alcohol, fruit or vegetable intake and renal cell carcinoma. CONCLUSIONS: We identified a significant association of renal cell carcinoma with obesity, smoking, hypertension, renal disease and viral hepatitis. Identifying risk factors offers an opportunity for targeted education and intervention.