Search Results (35)

Objectives: This study aimed to evaluate the implementation of a formalized fertility preservation (FP) program for transgender and nonbinary patients assigned male at birth (TGNB-AMAB) at our institution. Methods: We reviewed TGNB-AMAB patients who were referred to the FP program at our academic institution between 2016 and September 2023. We compared the number of referrals and the percentage of patients who underwent FP per year. Clinical and demographic information including age at referral, time from referral to banking, semen parameters, and serum hormone values were evaluated. Results: In total, 154 TGNB-AMAB patients were referred to the FP program since 2016; 131 (85.1%) met with a reproductive urologist or advanced practice provider for FP consultation; and 124 (94.7%) completed sperm cryopreservation. The number of annual referrals significantly increased over time (p = 0.001). The average age (±standard deviation) at referral was 20.5 ± 5.7 years. The median time from referral to sperm cryopreservation was 14 days. The average semen parameters among all the patients were volume 2.7 ± 1.7 mL, sperm concentration 36.0 ± 31.6 M/mL, sperm motility 56.8 ± 19.0%, and sperm morphology 4.7 ± 2.9%. There was no significant difference in semen parameters between TGNB-AMAB patients previously on gender-affirming hormonal therapy prior to banking and those not on prior hormonal treatment (p > 0.05). Conclusions: Our fertility preservation program significantly increased the number of TGNB-AMAB patients who received consultation and underwent sperm cryopreservation. The institution of a formalized FP program can be used to increase access for TGNB-AMAB patients who desire future fertility. Full article

Objective: We aimed to characterize the impact of body mass index (BMI) on stroke in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). Methods: We queried the Extracorporeal Life Support Organization registry for patients receiving ECPR (2020–2024). Patients were categorized into five BMI groups: underweight (<18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), class 1 obesity (30–34.9 kg/m²), and class 2 obesity or above (≥35 kg/m²). A generalized additive model (GAM) analysis was used to identify the BMI range with the greatest stroke risk. Multivariable regression was used to compare odds of stroke between standard BMI groups and normal weight. Propensity score matching was used to compare stroke and mortality between normal weight and the BMI group with the highest predicted stroke risk. Results: Of 6390 patients (median age = 57.5, 68.6% male), 470 (7.4%) had a stroke during ECMO support (4.5% ischemic; 3.4% hemorrhagic). A total of 9.6% (n = 131) of class 1 obesity patients experienced stroke compared with 6.6% (n = 111) of normal weight, 6.9% (n = 79) of class 2 obesity or above, 6.9% (n = 143) of overweight, and 5.4% (n = 6) of underweight patients (p = 0.01). The GAM analysis showed a highest predicted stroke risk for class 1 obesity patients (n = 1366), which was confirmed by multivariable regression (adjusted odds ratio (aOR) = 1.63, 95%CI = 1.01–2.62, p = 0.045). After propensity matching (n = 357 each), class 1 obesity was associated with ischemic (aOR = 2.01, 95%CI = 1.02–4.08, p = 0.047) but not hemorrhagic stroke. Odds of hospital mortality were higher in both class 1 and 2 obesity patients compared with normal weight. Conclusions: Class 1 obesity was associated with increased odds of ischemic but not hemorrhagic stroke compared with normal weight patients. Full article

Ovine pulmonary adenocarcinoma (OPA) is an infectious, neoplastic lung disease of sheep that causes significant animal welfare and economic issues throughout the world. Understanding OPA pathogenesis is key to developing tools to control its impact. Central to this need is the availability of model systems that can monitor and track events after Jaagsiekte sheep retrovirus (JSRV) infection. Here, we report the development of an experimentally induced OPA model intended for this purpose. Using three different viral dose groups (low, intermediate and high), localised OPA tumour development was induced by bronchoscopic JSRV instillation into the segmental bronchus of the right cardiac lung lobe. Pre-clinical OPA diagnosis and tumour progression were monitored by monthly computed tomography (CT) imaging and trans-thoracic ultrasound scanning. Post mortem examination and immunohistochemistry confirmed OPA development in 89% of the JSRV-instilled animals. All three viral doses produced a range of OPA lesion types, including microscopic disease and gross tumours; however, larger lesions were more frequently identified in the low and intermediate viral groups. Overall, 31% of JSRV-infected sheep developed localised advanced lesions. Of the sheep that developed localised advanced lesions, tumour volume doubling times (calculated using thoracic CT 3D reconstructions) were 14.8 ± 2.1 days. The ability of ultrasound to track tumour development was compared against CT; the results indicated a strong significant association between paired CT and ultrasound measurements at each time point (R² = 0.799, p < 0.0001). We believe that the range of OPA lesion types induced by this model replicates aspects of naturally occurring disease and will improve OPA research by providing novel insights into JSRV infectivity and OPA disease progression. Full article

For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes. Full article

Rainwater runoff samples from a range of roofing materials were temporally collected from 19 small-scale roof structures and two commercial buildings through simulated and actual storm events, and the concentrations of polycyclic aromatic hydrocarbons (PAHs), phosphorus flame retardants (PFLs), and pyrethroid insecticides and other water quality parameters were analyzed. In Part I of this research, the concentrations of these contaminants in roof runoff and soils receiving runoff from a range of roofing materials were evaluated. In Part II, recommendations have been developed for a first-flush exclusion to improve the quality of water harvesting for nonpotable uses. Recommendations focus on a first-flush diversion based on mass removals of total suspended solids (TSS) and PAHs linked to conductivity measurements throughout a storm event. Additionally, an upper-confidence limit (UCL) was constructed to determine the minimum diversion required to obtain 50, 75, 90, and 95% mass removal of TSS and PAH contaminants. The majority of TSS were produced during the initial 1.2 mm of runoff. Likewise, the majority of PAHs were removed during the initial 1.2 mm of runoff, except for the asphalt shingle roofs, where high PAHs were observed after 6 mm of runoff. The Texas Water Development Board (TWDB)-recommended first-flush diversion of one gallon for every 100 square feet of rooftop was not always adequate for removing 50% of TSS and PAHs from the roofs. Rainwater runoff conductivity decreased drastically between 1.2 to 2.4 mm of rainwater runoff. Diverting the first flush based on conductivity has the potential to also divert the majority of TSS and PAHs in roof runoff. Full article

Rainfall runoff may be captured and stored for later use, but the quality of this water can be detrimental in some uses without the use of appropriately designed first-flush diverters. The rainfall runoff water quality was measured on nineteen new small-scale and two aged commercial roofs located near high traffic highways. Roof coverings included asphalt shingles, sheet metal, clay tiles, and tar and gravel. Runoff samples were evaluated for polycyclic aromatic hydrocarbons (PAHs), phosphorus flame retardants (PFRs), and pyrethroid insecticides. Eighteen small-scale roofs were subjected to a range of simulated rainfall events, while natural runoff was sampled on the commercial roofs and one small-scale roof. Runoff was analyzed for pH, conductivity, turbidity, total suspended solids, boron, iron, copper, zinc, manganese, sodium adsorption ratio, nitrate-nitrogen, seventeen PAHs, tris(2-chloroethyl) phosphate, tris(1,3-dichloro-2-propyl)phosphate, bifenthrin, cypermethrin, and lambda-cyhalothrin. Samples from four natural storm events were also analyzed for total coliforms and Escherichia coli. In addition, soils below seventeen existing gutter downspouts were sampled to determine long-term pollutant accumulation. Atmospheric deposition was the main contributor of pollutants in the roof runoff. A majority of samples fell within the U.S. EPA guidelines for non-potable urban and agricultural water reuse. Trace levels of PAHs, PFRs, and insecticides were detected, but all detections were three orders of magnitude below the USGS health-based screening level benchmark concentrations. Results indicate that diverting the first flush, based on turbidity, total suspended solids, or conductivity, can improve the overall water quality and reduce the concentrations of PAHs in harvested rainwater. Downspout soil sampling showed potential for the long-term accumulation of PAHs at concentrations exceeding the minimum human-health risk-based screening levels at these high runoff-loading locations. Full article

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures. Full article

To align with climate initiatives, multiple reporting programs are transitioning from generic activity-based emission factors to site-specific measured emissions data to estimate greenhouse gas emissions at oil and gas facilities. This study contemporaneously deployed two top-down (TD) aerial methods across 14 midstream facilities, building upon previous research in the field. The methods produced multiple whole-facility estimates at each facility, resulting in 773 individual paired estimates (same facility, same day), and robust mean estimates for each facility. Mean estimates for each facility, aggregated across all facilities, differed by nearly 2:1 (49% [32% to 69%]). At 6 of 14 facilities, the methods produced mean estimates that differed by more than a factor of two. These data suggest that one or both methods did not produce accurate facility-level estimates at a majority of facilities and in aggregate across all facilities. The overall results are augmented with two case studies where TD estimates at two pre-selected facilities were coupled with comprehensive onsite measurements to understand the factors driving the divergence between TD and bottom-up (BU) emissions estimates. In 3 of 4 paired comparisons between the intensive onsite estimates and one of the TD methods, the intensive onsite surveys did not conclusively diagnose the difference in estimates. In these cases, our work suggests that the TD methods mis-estimate emissions an unknown fraction of the time, for unknown reasons. While two methods were selected for this study, it is unlikely that the issues identified here are confined to these two methods; similar issues may exist for other similar whole-facility methods on midstream and/or other facility types. These findings have important implications for the construction of voluntary and regulatory reporting programs that rely on emission estimates for reporting fees or penalties, or for studies using whole-facility estimates to aggregate TD emissions to basin or regional estimates. Full article

A reduction in wake effects in large wind farms through wake-aware control has considerable potential to improve farm efficiency. This work examines the success of several emerging, empirically derived control methods that modify wind turbine wakes (i.e., the pulse method, helix method, and related methods) based on Strouhal numbers on the $\mathcal{O}\left(0.3\right)$. Drawing on previous work in the literature for jet and bluff-body flows, the analyses leverage the normal-mode representation of wake instabilities to characterize the large-scale wake meandering observed in actuated wakes. Idealized large-eddy simulations (LES) using an actuator-line representation of the turbine blades indicate that the $n=0$ and $\pm 1$ modes, which correspond to the pulse and helix forcing strategies, respectively, have faster initial growth rates than higher-order modes, suggesting these lower-order modes are more appropriate for wake control. Exciting these lower-order modes with periodic pitching of the blades produces increased modal growth, higher entrainment into the wake, and faster wake recovery. Modal energy gain and the entrainment rate both increase with streamwise distance from the rotor until the intermediate wake. This suggests that the wake meandering dynamics, which share close ties with the relatively well-characterized meandering dynamics in jet and bluff-body flows, are an essential component of the success of wind turbine wake control methods. A spatial linear stability analysis is also performed on the wake flows and yields insights on the modal evolution. In the context of the normal-mode representation of wake instabilities, these findings represent the first literature examining the characteristics of the wake meandering stemming from intentional Strouhal-timed wake actuation, and they help guide the ongoing work to understand the fluid-dynamic origins of the success of the pulse, helix, and related methods. Full article

As part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed. In AGMs, the impact of bamlanivimab pretreatment on viral loads and clinical and histological pathology was assessed to evaluate enhanced SARS-CoV-2 replication or pathology. Bamlanivimab did not increase viral replication in vitro, despite a demonstrated effector function. In vivo, no significant differences were found among the AGM groups for weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Bamlanivimab did not induce ADE of SARS-CoV-2 infection in vitro or in an AGM model of infection at any dose evaluated. The findings suggest that high-affinity monoclonal antibodies pose a low risk of mediating ADE in patients and support their safety profile as a treatment of COVID-19 disease. Full article

The survival of Escherichia coli (E. coli) bacteria, the most common faecal indicator bacteria (FIB), may be significantly affected by cyanobacteria present during a harmful algal bloom (HAB). Therefore, the effect of Microcystis on the survival of FIB E.coli and coliforms was investigated. Microcosms containing two species of Microcystis (M. aeruginosa and M. smithii) were established and then inoculated with four reference strains of E. coli (ATCC 25922, 8739, 51813, and 11775) to explore the cyanobacteria-bacteria dynamics at a laboratory setting. Monitoring over several days showed normal growth of Microcystis, with or without the presence of E. coli. However, Microcystis was shown to dramatically decrease the survival of E. coli over time. Analysis of microcystin production by Microcystis was found to correlate with loss of E. coli, suggesting a toxic effect of microcystins on E. coli bacteria. This phenomenon was also demonstrated for a natural consortium of E. coli and coliform bacteria by inoculating with contaminated lake water. The results indicate that the use of E. coli as FIB may be greatly compromised in the presence of Microcystis spp. such as during a HAB when associated toxins are produced. Full article

Background: Relugolix is an oral GnRH receptor antagonist approved for men with advanced prostate cancer. Relugolix treatment has demonstrated an ability to lower testosterone to sustained castration levels in the phase 4 HERO study. Herein, we describe the results of a secondary endpoint of castration resistance-free survival (CRFS) during 48 weeks of treatment and profile patients with castration-resistant prostate cancer (CRPC). Methods: Subjects were 2:1 randomized to either relugolix 120 mg orally once daily (after a single 360 mg loading dose) or 3-monthly injections of leuprolide for 48 weeks. CRFS, defined as the time from the date of first dose to the date of confirmed prostate-specific antigen progression while castrated or death due to any reason was conducted in the metastatic disease population and the overall modified intention-to-treat (mITT) populations. Results: The CRFS analysis (mITT population) included 1074 men (relugolix: n = 717; leuprolide: n = 357) with advanced prostate cancer as well as 434 men (relugolix: n = 290; leuprolide: n = 144) with metastatic prostate cancer. In the metastatic disease populations, CRFS rates were 74.3% (95% CI: 68.6%, 79.2%) and 75.3% (95% CI: 66.7%, 81.9%) in the relugolix and leuprolide groups, respectively (hazard ratio: 1.03 [0.68, 1.57]; p = 0.84) at week 48. Results in the overall mITT population were similar to the metastatic population. No new safety findings were identified. Conclusions: In men with metastatic disease or in the overall population of the HERO study, CRFS assessed during the 48-week treatment with relugolix was not significantly different than standard-of-care leuprolide. Relugolix had similar efficacy for men with/without CRFS progression events. Full article

Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men reported at twice the rate for women. Using a controlled, cross-sectional, age-matched (18–56 y) design to better understand the cognitive neuroscience of OUD, we evaluated the electroencephalographic (EEG) responses of male and female participants with OUD vs. age- and gender-matched non-OUD controls during a simple visual object recognition Go/No-Go task. Overall, women had significantly slower reaction times (RTs) than men. In addition, EEG N200 and P300 event-related potential (ERP) amplitudes for non-OUD controls were significantly larger for men, while their latencies were significantly shorter than for women. However, while N200 and P300 amplitudes were not significantly affected by OUD for either men or women in this task, latencies were also affected differentially in men vs. women with OUD. Accordingly, for both N200 and P300, male OUD participants exhibited longer latencies while female OUD participants exhibited shorter ones than in non-OUD controls. Additionally, robust oscillations were found in all participants during a feedback message associated with performance in the task. Although alpha and beta power during the feedback message were significantly greater for men than women overall, both alpha and beta oscillations exhibited significantly lower power in all participants with OUD. Taken together, these findings suggest important gender by OUD differences in cognitive processing and reflection of performance in this simple visual task. Full article

Here we present a case study for using visual stratigraphy to date a shallow firn core from coastal West Antarctica. The Mount Siple ice core has the potential to reconstruct climate in this data-sparse region over recent decades. Line scanned images of the 24 m firn core were used to generate a grey-scale, which displays variability consistent with annual cycles. The resulting Mount Siple age scale spans from 1998 ± 1 to 2017 CE. This study demonstrates that the seasonal changes in the grey-scale record provide an independent method of dating firn cores. However, the presence of melt layers at this site has introduced an error of ±1 year. Visual line stratigraphy has the unique advantage over traditional annual layer counting, based on chemical or isotopic species, of being non-destructive and relatively inexpensive. Visual line stratigraphy has proved to be an effective dating method for this site. Full article