Search

Background The extent to which sex, racial, and ethnic groups receive advanced heart therapies equitably is unclear. We estimated the population rate of left ventricular assist device (LVAD) and heart transplant (HT) use among (non‐Hispanic) White, Hispanic, and (non‐Hispanic) Black men and women who have heart failure with reduced ejection fraction (HFrEF). Methods and Results We used a retrospective cohort design combining counts of LVAD and HT procedures from 19 state inpatient discharge databases from 2010 to 2018 with counts of adults with HFrEF. Our primary outcome measures were the number of LVAD and HT procedures per 1000 adults with HFrEF. The main exposures were sex, race, ethnicity, and age. We used Poisson regression models to estimate procedure rates adjusted for differences in age, sex, race, and ethnicity. In 2018, the estimated population of adults aged 35 to 84 years with HFrEF was 69 736, of whom 44% were women. Among men, the LVAD rate was 45.6, and the HT rate was 26.9. Relative to men, LVAD and HT rates were 72% and 62% lower among women (P0.05) or higher (P

The article focuses on the Beyceğiz Tumulus, located 11.5 km east of Gordion, which was subjected to multiple looting attempts, leading to a salvage excavation conducted between 2013 and 2017. It reveals that the tumulus, identified as a cenotaph, contained no burial or ritual deposits but rather a stone platform at its center, surrounded by guide walls, highlighting the architectural and planning expertise involved in its construction.

While typically thought of as an illicit substance, oxybate salts or gamma-hydroxybutyrate (GHB) has more recently been prescribed to treat narcolepsy by enhancing nighttime sleep resulting in decreased daytime drowsiness. This case involves a college-aged female with prescribed GHB for narcolepsy who took her second nightly dose too early. This resulted in mental depression, respiratory failure, intubation and mechanical ventilation. The patient was successfully extubated in the intensive care unit several hours later with no residual morbidity. We were unable to identify any prior reports of mixed-salt oxybate toxicity following mistimed drug administration. This case should serve as a warning to emergency physicians to be on the lookout for GHB as part of the differential diagnosis for patients with narcolepsy presenting with altered mental status. It should also serve as a warning to patients and prescribers that this medication can have outcomes that require immediate medical intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preeclampsia, a pregnancy-specific condition associated with new-onset hypertension after 20-weeks gestation, is a leading cause of maternal and neonatal morbidity and mortality. Predictive tools to understand which individuals are most at risk are needed. METHODS: We identified a cohort of N=1125 pregnant individuals who delivered between May 2015 and May 2022 at Mass General Brigham Hospitals with available electronic health record data and linked genetic data. Using clinical electronic health record data and systolic blood pressure polygenic risk scores derived from a large genome-wide association study, we developed machine learning (XGBoost) and logistic regression models to predict preeclampsia risk. RESULTS: Pregnant individuals with a systolic blood pressure polygenic risk score in the top quartile had higher blood pressures throughout pregnancy compared with patients within the lowest quartile systolic blood pressure polygenic risk score. In the first trimester, the most predictive model was XGBoost, with an area under the curve of 0.74. In late pregnancy, with data obtained up to the delivery admission, the best-performing model was XGBoost using clinical variables, which achieved an area under the curve of 0.91. Adding the systolic blood pressure polygenic risk score to the models did not improve the performance significantly based on De Long test comparing the area under the curve of models with and without the polygenic score. CONCLUSIONS: Integrating clinical factors into predictive models can inform personalized preeclampsia risk and achieve higher predictive power than the current practice. In the future, personalized tools can be implemented to identify high-risk patients for preventative therapies and timely intervention to improve adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Abstract We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR’s potential for use in molecular tumour boards, clinician-patient communication, and education. XR serves as a universal language, fostering collaborative decision-making in oncology.

Abstract Fentanyl test strips (FTS) are lateral flow immunoassays that were originally designed and validated for detecting low concentrations of fentanyl in urine. Some FTS are now being marketed for the harm reduction purpose of testing street drugs for the presence of fentanyl. This manuscript provides a simple protocol to assess whether different brands and lots of fentanyl test strips perform adequately for use in drug checking. The results gathered from this protocol will document problems with particular lots or brands of FTS, help buyers choose from among the array of products, provide feedback to manufacturers to improve their products, and serve as an early warning system for ineffective products.

This study represents a pioneering effort in establishing normative benchmarking for countermovement jump (CMJ) metrics on Hawkin Dynamics dual wireless force plate within a substantial cohort (n = 96) of NCAA Division-I (DI) Power Five Men’s College Basketball (MCBB) players. This cohort comprised four centers (age = 20.01 ± 1.31 years, height on website = 216.32 ± 5.27 cm, body mass on plates = 115.11 ± 16.13 kg), 37 forwards (age = 21.09 ± 1.68 years, height on website = 203.84 ± 5.45 cm, body mass on plates = 103.67 ± 10.42), and 55 guards (age = 20.92 ± 1.54 years, height on website = 190.49 ± 7.44 cm, body mass on plates = 87.04 ± 6.98 kg) from seven teams that performed three CMJ trials with hands on hips during the pre-season period of the 2023-2024 season over a span of 26 days and seven testing sites. All data was uniformly collected by a single designated tester who implemented consistent instructions, procedures, and equipment at all test sites. Comparing forwards and guards, 45% (18/40) of the reported metrics showed significance (p < 0.05) and 35% (14/40) yielded moderate-large effect sizes (e.g., > 0.50). Additionally, percentiles (3-97th) with qualitative descriptors and a traffic light system were provided. Such normative data can serve as a valuable reference point for coaches, scouts, and players alike, facilitating the evaluation of both individual and team performance while also guiding the development of tailored strength and conditioning strategies specific to the demands of NCAA DI MCBB.

[Display omitted] Survival analysis is widely utilized in healthcare to predict the timing of disease onset. Traditional methods of survival analysis are usually based on Cox Proportional Hazards model and assume proportional risk for all subjects. However, this assumption is rarely true for most diseases, as the underlying factors have complex, non-linear, and time-varying relationships. This concern is especially relevant for pregnancy, where the risk for pregnancy-related complications, such as preeclampsia, varies across gestation. Recently, deep learning survival models have shown promise in addressing the limitations of classical models, as the novel models allow for non-proportional risk handling, capturing nonlinear relationships, and navigating complex temporal dynamics. We present a methodology to model the temporal risk of preeclampsia during pregnancy and investigate the associated clinical risk factors. We utilized a retrospective dataset including 66,425 pregnant individuals who delivered in two tertiary care centers from 2015 to 2023. We modeled the preeclampsia risk by modifying DeepHit, a deep survival model, which leverages neural network architecture to capture time-varying relationships between covariates in pregnancy. We applied time series k-means clustering to DeepHit's normalized output and investigated interpretability using Shapley values. We demonstrate that DeepHit can effectively handle high-dimensional data and evolving risk hazards over time with performance similar to the Cox Proportional Hazards model, achieving an area under the curve (AUC) of 0.78 for both models. The deep survival model outperformed traditional methodology by identifying time-varied risk trajectories for preeclampsia, providing insights for early and individualized intervention. K-means clustering resulted in patients delineating into low-risk, early-onset, and late-onset preeclampsia groups—notably, each of those has distinct risk factors. This work demonstrates a novel application of deep survival analysis in time-varying prediction of preeclampsia risk. Our results highlight the advantage of deep survival models compared to Cox Proportional Hazards models in providing personalized risk trajectory and demonstrating the potential of deep survival models to generate interpretable and meaningful clinical applications in medicine. [ABSTRACT FROM AUTHOR]

Abstract Pyroclastic density currents (PDCs) are the most lethal volcanic process on Earth. Forecasting their inundation area is essential to mitigate their risk, but existing models are limited by our poor understanding of their dynamics. Here, we explore the role of evolving grain-size distribution in controlling the runout of the most common PDCs, known as block-and-ash flows (BAFs). Through a combination of theory, analysis of deposits and experiments of natural mixtures, we show that rapid changes of the grain-size distribution transported in BAFs result in the reduction of pore volume (compaction) within the first kilometres of their runout. We then use a multiphase flow model to show how the compressibility of granular mixtures leads to fragmentation-induced fluidisation (FIF) and excess pore-fluid pressure in BAFs. This process dominates the first ~2 km of their runout, where the effective friction coefficient is progressively reduced. Beyond that distance, transport is modulated by diffusion of the excess pore pressure. Fragmentation-induced fluidisation provides a physical basis to explain the decades-long use of low effective friction coefficients used in depth-averaged simulations required to match observed flow inundation.

The objective of this study was to investigate the effects of dietary supplementation of Bacillus (B.) amyloliquefaciens on growth performance, diarrhea, systemic immunity, and intestinal microbiota of weaned pigs experimentally infected with F18 enterotoxigenic Escherichia coli (ETEC). A total of 50 weaned pigs (7.41 ± 1.35 kg BW) were individually housed and randomly allotted to one of the following five treatments: sham control (CON-), sham B. amyloliquefaciens (BAM-), challenged control (CON+), challenged B. amyloliquefaciens (BAM+), and challenged carbadox (AGP+). The experiment lasted 28 days, with 7 days of adaptation and 21 days after the first ETEC inoculation. ETEC challenge reduced (P < 0.05) average daily gain (ADG) of pigs. Compared with CON+, AGP+ enhanced (P < 0.05) ADG, while B. amyloliquefaciens supplementation tended (P < 0.10) to increase ADG in pigs from days 0 to 21 post-inoculation (PI). The ETEC challenge increased (P < 0.05) white blood cell (WBC) count on days 7 and 21 PI, while BAM+ pigs tended (P < 0.10) to have low WBC on day 7 PI and had lower (P < 0.05) WBC on day 21 PI compared with CON+. In comparison to AGP+ fecal microbiota, BAM+ had a lower (P < 0.05) relative abundance of Lachnospiraceae on day 0 and Clostridiaceae on day 21 PI, but a higher (P < 0.05) relative abundance of Enterobacyeriaceae on day 0. In ileal digesta, the Shannon index was higher (P < 0.05) in BAM+ than in AGP+. Bray-Curtis PCoA displayed a difference in bacterial community composition in ileal digesta collected from sham pigs vs. ETEC-infected pigs on day 21 PI. Pigs in BAM+ had a greater (P < 0.05) relative abundance of Firmicutes, but a lower (P < 0.05) relative abundance of Actinomycetota and Bacteroidota in ileal digesta than pigs in AGP+. Ileal digesta from AGP+ had a greater (P < 0.05) abundance of Clostridium sensu stricto 1 but lower (P < 0.05) Bifidobacterium than pigs in BAM+. In conclusion, supplementation of B. amyloliquefaciens tended to increase ADG and had limited effects on the diarrhea of ETEC-infected pigs. However, pigs fed with B. amyloliquefaciens exhibit milder systemic inflammation than controls. B. amyloliquefaciens differently modified the intestinal microbiota of weaned pigs compared with carbadox.

Purpose: Adenosquamous carcinoma (ASC) of the head and neck, specifically sinonasal ASC, is a rare and aggressive malignancy with metastasis occurring in 80% of patients in its initial reporting; sinonasal ASC with orbital extension has rarely been reported in literature. Despite treatment, ASC carries a poor prognosis with a 5-year survival of approximately 22%, with 50% dying within 23 months.10 Mucoepidermoid carcinoma (MEC) and ASC have similar morphologic features. It is imperative to distinguish these two entities apart as the biologic behavior and prognosis of ASC is much worse than that of poorly differentiated MEC and squamous cell carcinoma. This case provides a rare presentation of a secondary orbital tumor, ASC with orbital extension, that manifests with ocular symptoms and is therefore relevant to practitioners in the field of ophthalmology while reviewing the histology of ASC with the goal of distinguishing the entity from its differential diagnoses. Observation: To further understand the natural history of this unusual tumor, we report a case of adenosquamous carcinoma in a 76-year-old female who presented with a three-day history of left-sided: vision loss (worse centrally and nasally), afferent pupillary defect, esotropia and abduction deficit, cervical lymphadenopathy and an extraconal mass on MRI producing a compressive optic neuropathy. We provide photography that demonstrates the patient's presentation, histologic slides provided via biopsy of the malignancy, and radiologic findings on magnetic resonance imaging, all of which support the diagnosis. Conclusions/Importance: This case adds to the limited literature of sinonasal adenosquamous carcinoma while exploring orbitotomy techniques for adequate extraconal mass biopsies of the entity. Our manuscript reviews key histological findings of ASC provided by the patient's biopsies and details how to differentiate the cancer from other pathologies, like MEC; A differentiation that proves vital for practitioners due to the widely differing prognosis of the two pathologies. We present the first case of sinonasal ASC with orbital extension causing ophthalmologic symptoms.

Stu2 in S. cerevisiae is a member of the XMAP215/Dis1/CKAP5/ch-TOG family of MAPs and has multiple functions in controlling microtubules, including microtubule polymerization, microtubule depolymerization, linking chromosomes to the kinetochore, and assembly of γ-TuSCs at the SPB. Whereas phosphorylation has been shown to be critical for Stu2 localization at the kinetochore, other regulatory mechanisms that control Stu2 function are still poorly understood. Here, we show that a novel form of Stu2 regulation occurs through the acetylation of three lysine residues at K252, K469, and K870, which are located in three distinct domains of Stu2. Alteration of acetylation through acetyl-mimetic and acetyl-blocking mutations did not impact the essential function of Stu2. Instead, these mutations lead to a decrease in chromosome stability, as well as changes in resistance to the microtubule depolymerization drug, benomyl. In agreement with our in silico modeling, several acetylation-mimetic mutants displayed increased interactions with γ-tubulin. Taken together, these data suggest that Stu2 acetylation can govern multiple Stu2 functions, including chromosome stability and interactions at the SPB.

The objective of this study was to investigate supplementation of botanical blends (BB) comprised of 0.3% capsicum oleoresin and 12% garlic oil on gut microbiota and metabolomic profiles in serum and ileal mucosa of Escherichia coli infected pigs. Sixty weaned pigs were assigned to one of five treatments: negative control (CON−), positive control (CON+), dietary supplementation of 100 ppm BB1, 50 or 100 ppm BB2. All pigs, except CON−, were orally inoculated with 1010 CFU F18 ETEC/3-mL dose for 3 consecutive days after 7 d adaption. Feces, ileal digesta and cecal content were collected for 16S rRNA amplicon sequencing. Serum and ileal mucosa underwent primary metabolomics analysis. Supplementing 100 ppm BB1 increased (p < 0.05) relative abundances of Enterobacteriaceae and Escherichia–Shigella in ileum, and the relative abundances of Bacteroidota and Prevotellaceae in cecum than CON+ on d 5 post-inoculation (PI). Supplementing 100 ppm BB2 upregulated serum pinitol on d 4 PI and serum cholesterol and aminomalonic acids on d 21 PI, while supplementing 50 ppm BB2 reduced asparagine in ileal mucosa on d 5 PI than CON+. Supplementation with botanical blends modulated ileal and cecal microbiota and serum metabolomics profiles in weaned pigs under Escherichia coli challenge.

Lahar monitoring on active volcanoes is challenging, and the ever changing environment leads to inconsistent results that hamper a warning systems ability to characterize the flow event properly. Therefore, more data, new methods, and the use of different sensors needs to be tested, which could lead to improvements in warning capabilities. Here, we present data from a 3-component broadband seismometer and video camera installed 3 m from the Lumbre channel on Volcán de Colima, Mexico to understand rheology differences within multiple lahar events that occurred in late 2016. We examine differences in frequency and directionality from each seismic component. Results indicate an increase in peak frequency above background in each component when a lahar nears the sensor, and a decrease in overall peak frequency when transitioning from a streamflow to a higher concentration flow. The seismic frequency distribution for the cross-channel component for the streamflow has a wider range compared with the lahar events. In contrast, the peak spectral frequency of the streamflow is narrower in comparison to the lahar events in the flow parallel and vertical directions. Estimated directionality ratios (cross-channel signal divided by flow parallel signal) yielded further evidence for a rheologic change between streamflow and lahars. Directionality ratios >1 were calculated for each lahar, and

Abstract At approximately 09:36 UTC on 27 April 2016, a phreatic eruption occurred on Whakaari Island (White Island) producing an eruption sequence that contained multiple eruptive pulses determined to have occurred over the first 30 min, with a continuing tremor signal lasting ~ 2 h after the pulsing sequence. To investigate the eruption dynamics, we used a combination of cross-correlation and coherence methods with acoustic data. To estimate locations for the eruptive pulses, seismic data were collected and eruption vent locations were inferred through the use of an amplitude source location method. We also investigated volcanic acoustic–seismic ratios for comparing inferred initiation depths of each pulse. Initial results show vent locations for the eruptive pulses were found to have possibly come from two separate locations only ~ 50 m apart. These results compare favorably with acoustic lag time analysis. After error analysis, eruption sources are shown to conceivably come from a single vent, and differences in vent locations may not be constrained. Both vent location scenarios show that the eruption pulses gradually increase in strength with time, and that pulses 1, 3, 4, and 5 possibly came from a deeper source than pulses 2 and 6. We show herein that the characteristics and locations of volcanic eruptions can be better understood through joint analysis combining data from several data sources.

Emulsification-diffusion method is often used to produce polymeric nanoparticles. However, their numerous and/or lengthy steps make it difficult to use widely. Thus, a modified method using solvent blends (miscible/partially miscible in water, 25–100%) as the organic phases to overcome these disadvantages and its design space were investigated. To further simplify the process, no organic/aqueous phase saturation and no water addition after the emulsification step were performed. Biodegradable (PLGA) or pH-sensitive (Eudragit® E100) nanoparticles were robustly produced using low/medium shear stirring adding dropwise the organic phase into the aqueous phase or vice versa. Several behaviors were also obtained: lowering the partially water-miscible solvent ratio relative to the organic phase or the poloxamer-407 concentration; or increasing the organic phase polarity or the polyvinyl alcohol concentration produced smaller particle sizes/polydispersity. Nanoparticle zeta potential increased as the water-miscible solvent ratio increased. Poloxamer-407 showed better performance to decrease the particle size (~50 nm) at low concentrations (≤1%, w/v) compared with polyvinyl alcohol at 1–5% (w/v), but higher concentrations produced bigger particles/polydispersity (≥600 nm). Most important, an inverse linear correlation to predict the particle size by determining the solubility parameter was found. A rapid method to broadly prepare nanoparticles using straightforward equipment is provided.