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'As the summer months bring warmer weather and. for the lucky ones, a time to relax away from desks, it also means a slight switch-up in our beauty routines and [...]

Multimodal artificial intelligence models using digital histopathology slides outperform clinical and pathological variables for prognostic prediction of distant metastasis and prostate cancer–specific mortality, and can be incorporated in clinical practice for personalized risk stratification.

In the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial, percutaneous coronary intervention (PCI) did not reduce the incidence of death or hospitalization for heart failure (HHF).

Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (Pvalue < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status.

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

IMPORTANCE: Combination androgen deprivation therapy (ADT) with radiotherapy is commonly used for patients with localized and advanced prostate cancer. OBJECTIVE: To assess the efficacy and safety of the oral gonadotropin-releasing hormone antagonist relugolix with radiotherapy for treating prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This multicenter post hoc analysis of patients with localized and advanced prostate cancer receiving radiotherapy in 2 randomized clinical trials (a phase 2 trial of relugolix vs degarelix, and a subset of the phase 3 HERO trial of relugolix vs leuprolide acetate) included men who were receiving radiotherapy and short-term (24 weeks) ADT (n = 103) from 2014 to 2015 and men receiving radiotherapy and longer-term (48 weeks) ADT (n = 157) from 2017 to 2019. The data were analyzed in November 2022. INTERVENTIONS: Patients receiving short-term ADT received relugolix, 120 mg, orally once daily (320-mg loading dose) or degarelix, 80 mg, 4-week depot (240-mg loading dose) for 24 weeks with 12 weeks of follow-up. Patients receiving longer-term ADT received relugolix, 120 mg, orally once daily (360-mg loading dose) or leuprolide acetate injections every 12 weeks for 48 weeks, with up to 90 days of follow-up. MAIN OUTCOMES AND MEASURES: Castration rate (testosterone level &lt;50 ng/dL [to convert to nmol/L, multiply by 0.0347) at all scheduled visits between weeks 5 and 25 for patients receiving short-term ADT and weeks 5 and 49 for patients receiving longer-term ADT. RESULTS: Of 260 patients (38 Asian [14.6%], 23 Black or African American [8.8%], 21 Hispanic [8.1%], and 188 White [72.3%] individuals), 164 (63.1%) received relugolix. Relugolix achieved castration rates of 95% (95% CI, 87.1%-99.0%) and 97% (95% CI, 90.6%-99.0%) among patients receiving short-term and longer-term ADT, respectively. Twelve weeks post–short-term relugolix, 34 (52%) achieved testosterone levels to baseline or more than 280 ng/dL. Ninety days post longer-term ADT, mean (SD) testosterone levels were 310.5 (122.4) (106.7) ng/dL (relugolix; n = 15) vs 53.0 ng/dL (leuprolide acetate; n = 8) among the subset assessed for testosterone recovery. Castration resistance-free survival was not statistically different between the relugolix and leuprolide acetate cohorts (hazard ratio, 0.97; 95% CI, 0.35-2.72; P = .62). Adverse events grade 3 or greater for short-term or longer-term relugolix (headache, hypertension, and atrial fibrillation) were uncommon (less than 5%). CONCLUSIONS AND RELEVANCE: The results of these 2 randomized clinical trials suggest that relugolix rapidly achieves sustained castration in patients with localized and advanced prostate cancer receiving radiotherapy. No new safety concerns were identified when relugolix was used with radiotherapy.

Background. Falls are the leading cause of injuries among older adults, and trips and slips are major contributors to falls. Objective. The authors sought to compare the effectiveness of adding a component of surface perturbation training to usual gait/balance training for reducing falls and fallrelated injury in high-risk older adults referred to physical therapy. Design. This was a multi-center, pragmatic, randomized, comparative effectiveness trial. Setting. Treatment took place within 8 outpatient physical therapy clinics. Patients. This study included 506 patients 65+ years of age at high fall risk referred for gait/balance training. Intervention. This trial evaluated surface perturbation treadmill training integrated into usual multimodal exercise-based balance training at the therapist's discretion versus usual multimodal exercise-based balance training alone. Measurements. Falls and injurious falls were assessed with a prospective daily fall diary, which was reviewed via telephone interview every 3 months for 1 year. A total of 211/253 (83%) patients randomized to perturbation training and 210/253 (83%) randomized to usual treatment provided data at 3-month follow-up. At 3 months, the perturbation training group had a significantly reduced chance of fall-related injury (5.7% versus 13.3%; relative risk 0.43) but no significant reduction in the risk of any fall (28% versus 37%, relative risk 0.78) compared with usual treatment. Time to first injurious fall showed reduced hazard in the first 3 months but no significant reduction when viewed over the entire first year. Limitations. The limitations of this trial included lack of blinding and variable application of interventions across patients based on pragmatic study design. Conclusion. The addition of some surface perturbation training to usual physical therapy significantly reduced injurious falls up to 3 months posttreatment. Further study is warranted to determine the optimal frequency, dose, progression, and duration of surface perturbation aimed at training postural responses for this population., In the United States, each year an estimated one-third of older adults fall. (1) In 2014, approximately 27,000 older adults in the United States died because of falls, 2.8 million [...]

The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement.

Benzylisoquinoline alkaloids are valuable active ingredients in medicines that are typically extracted from plants and subsequently derivatized. Buprenorphine is a member of this family of compounds and is an effective analgesic and is also used for the treatment of opioid use disorder. The commercial route of synthesis for buprenorphine starts from thebaine and uses toxic reagents and harsh reaction conditions for the N- and O-demethylation steps. Here, we propose an alternative approach for buprenorphine synthesis via enzymatic N-and O-demethylation reactions. Utilizing rational enzyme design and directed evolution, we identified and engineered two oxygenase enzymes. For the N-demethylation reaction, the best variant achieved a cumulative improvement in conversion of 567-fold, while for the O-demethylation, the best variant achieved 22-fold cumulative improvement in conversion. A separate variant was able to efficiently catalyze both the N-demethylation and the O-demethylation reactions.

Artificial intelligence (AI) applications have enabled remarkable advancements in healthcare delivery. These AI tools are often aimed to improve accuracy and efficiency of histopathology assessment and diagnostic imaging interpretation, risk stratification (i.e., prognostication), and prediction of therapeutic benefit for personalized treatment recommendations. To date, multiple AI algorithms have been explored for prostate cancer to address automation of clinical workflow, integration of data from multiple domains in the decision-making process, and the generation of diagnostic, prognostic, and predictive biomarkers. While many studies remain within the pre-clinical space or lack validation, the last few years have witnessed the emergence of robust AI-based biomarkers validated on thousands of patients, and the prospective deployment of clinically-integrated workflows for automated radiation therapy design. To advance the field forward, multi-institutional and multi-disciplinary collaborations are needed in order to prospectively implement interoperable and accountable AI technology routinely in clinic.

Objective: Ultrasound transient elastography (TE) technologies for liver stiffness measurement (LSM) utilize vibration of small, flat pistons, which generate shear waves that lack directivity. The most common cause for LSM failure in practice is insufficient shear wave signal at the needed depths. We propose to increase shear wave amplitude by focusing the waves into a directional beam. Here, we demonstrate the generation and propagation of focused shear wave beams (fSWBs) in gelatin. Methods: Directional fSWBs are generated by vibration at 200–400 Hz of a concave piston embedded near the surface of gelatin phantoms and measured with high-frame-rate ultrasound imaging. Five phantoms with a range of stiffnesses are employed. Shear wave speeds assessed by fSWBs are compared with those by radiation-force-based methods (2D SWE). fSWB amplitudes are compared to predictions using an analytical model. Results: fSWB-derived shear wave speeds are in good agreement with 2D SWE. The amplitudes of fSWBs are localized to the LSM region and are significantly greater than unfocused shear waves. Overall agreement with theory is observed, with some discrepancies in the theoretical source condition. Conclusion: Focusing shear waves can increase the signal in the LSM region for TE. Challenges for translation include coupling piston vibration with the patient skin and increased attenuation in vivo compared to the phantoms employed here. Significance: Fibrosis is the most predictive measure of patient outcome in non-alcoholic fatty liver disease. Increased shear wave amplitude in the LSM region can reduce fibrosis assessment failure rates by TE, thus reducing the need for invasive methods like biopsy.

Insulin binds the insulin receptor (IR) and regulates anabolic processes in target tissues. Impaired IR signalling is associated with multiple diseases, including diabetes, cancer and neurodegenerative disorders. IRs have been reported to form nanoclusters at the cell membrane in several cell types, even in the absence of insulin binding. Here we exploit the nanoscale spatial organization of the IR to achieve controlled multivalent receptor activation. To control insulin nanoscale spatial organization and valency, we developed rod-like insulin–DNA origami nanostructures carrying different numbers of insulin molecules with defined spacings. Increasing the insulin valency per nanostructure markedly extended the residence time of insulin–DNA origami nanostructures at the receptors. Both insulin valency and spacing affected the levels of IR activation in adipocytes. Moreover, the multivalent insulin design associated with the highest levels of IR activation also induced insulin-mediated transcriptional responses more effectively than the corresponding monovalent insulin nanostructures. In an in vivo zebrafish model of diabetes, treatment with multivalent—but not monovalent—insulin nanostructures elicited a reduction in glucose levels. Our results show that the control of insulin multivalency and spatial organization with nanoscale precision modulates the IR responses, independent of the insulin concentration. Therefore, we propose insulin nanoscale organization as a design parameter in developing new insulin therapies.

Venous thromboembolism (VTE) incidence after thoracic and fenestrated endovascular aortic repair (TEVAR/FEVAR) is high (up to 6–7%) relative to other vascular procedures; however, the etiology for this discrepancy remains unknown. Notably, patients undergoing TEVAR/FEVAR commonly receive cerebrospinal fluid drains (CSFDs) for neuroprotection, requiring interruption of perioperative anticoagulation and prolonged immobility. We hypothesized that CSFDs are a risk factor for VTE after TEVAR/FEVAR.

IMPORTANCE: Randomized clinical trials have demonstrated the noninferiority of shorter radiotherapy (RT) courses (termed hypofractionation) compared with longer RT courses in patients with localized prostate cancer. Although shorter courses are associated with cost-effectiveness, convenience, and expanded RT access, their adoption remains variable. OBJECTIVE: To identify the current practice patterns of external beam RT for prostate cancer in the US. DESIGN, SETTING, AND PARTICIPANTS: This cohort study obtained data from the National Cancer Database, which collects hospital registry data from more than 1500 accredited US facilities on approximately 72% of US patients with cancer. Patients were included in the sample if they had localized prostate adenocarcinoma that was diagnosed between 2004 and 2020 and underwent external beam RT with curative intent. Analyses were conducted between February and March 2023. EXPOSURES: Radiotherapy schedules, which were categorized as ultrahypofractionation (≤7 fractions), moderate hypofractionation (20-30 fractions), and conventional fractionation (31-50 fractions). MAIN OUTCOMES AND MEASURES: Longitudinal pattern in RT fractionation schedule was the primary outcome. Multivariable logistic regression was performed to evaluate the variables associated with shorter RT courses. Covariables included age, National Comprehensive Cancer Network risk group, rurality, race, facility location, facility type, median income, insurance type or status, and Charlson-Deyo Comorbidity Index. RESULTS: A total of 313 062 patients with localized prostate cancer (mean [SD] age, 68.8 [7.7] years) were included in the analysis. There was a temporal pattern of decline in the proportion of patients who received conventional fractionation, from 76.0% in 2004 to 36.6% in 2020 (P for trend &lt;.001). From 2004 to 2020, use of moderate hypofractionation increased from 22.0% to 45.0% (P for trend &lt;.001), and use of ultrahypofractionation increased from 2.0% to 18.3% (P for trend &lt;.001). By 2020, the most common RT schedule was ultrahypofractionation for patients in the low-risk group and moderate hypofractionation for patients in the intermediate-risk group. On multivariable analysis, treatment at a community cancer program (compared with academic or research program; odds ratio [OR], 0.54 [95% CI, 0.52-0.56]; P &lt; .001), Medicaid insurance (compared with Medicare; OR, 1.49 [95% CI, 1.41-1.57]; P &lt; .001), Black race (compared with White race; OR, 0.90 [95% CI, 0.87-0.92]; P &lt; .001), and higher median income (compared with lower median income; OR, 1.28 [95% CI, 1.25-1.31]; P &lt; .001) were associated with receipt of shorter courses of RT. CONCLUSIONS AND RELEVANCE: Results of this cohort study showed an increase in the use of shorter courses of RT for prostate cancer from 2004 to 2020; a number of social determinants of health appeared to be associated with reduced adoption of shorter treatment courses. Realignment of reimbursement models may be necessary to enable broader adoption of ultrahypofractionation to support technology acquisition costs.

The effects of Coronavirus disease 2019 (COVID-19) infection and altered processes of care on nonelective coronary artery bypass grafting (CABG) outcomes remain unknown. We hypothesized that patients with COVID-19 infection would have longer hospital lengths of stay and greater mortality compared with COVID-negative patients, but that these outcomes would not differ between COVID-negative and pre-COVID controls.

Endovascular repair of thoracoabdominal aortic aneurysms (TAAA) and juxtarenal aortic aneurysms (JAA) with fenestrated and/or branched endografts (B/FEVAR) has become common. Physician modified endografts for patients presenting with symptomatic or contained ruptures has made B/FEVAR a feasible option in nonelective settings. The purpose of this study was to describe our 10-year institutional experience with endovascular interventions for TAAA in elective and nonelective cases to evaluate differences in outcomes and the clinical risk factors associated with nonelective presentation.

I found the soon-to-be-retired tool of my trade in a dumpster nearly 15 years ago. Rescuing broken things is what good defence lawyers do. As a young criminal lawyer in [...]

THE SAME MEALS THAT KEEP YOUR BODY HEALTHY MIGHT ALSO CREATE A CALMER YOU. THE BEST GRUB? RIGHT THIS WAY.Hear the phrase 'emotional eating' and you might picture yourself scarfing [...]

Combined magnetic resonance imaging (MRI)-targeted and systematic biopsies are associated with less upgrading but more downgrading at radical prostatectomy. Our findings highlight a potential net harm of performing combined MRI-targeted and systematic biopsies if pathologic downgrading is considered more detrimental than upgrading at prostatectomy.

Objective. To examine the effects of facility-level acute-postacute continuity on probability of community discharge and 30-day rehospitalization following inpatient rehabilitation. Data Sources. We used national Medicare enrollment, claims, and assessment [...]

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Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.

Across the Australian continent, backed artefacts are produced in enormous numbers during the mid‐late Holocene. Previous examinations have revealed variation in the average shape of these artefacts, at both continental and regional scales. To better understand the factors creating this variability, we examine a large assemblage of backed artefacts from Ngungara (Weereewa/Lake George), in south‐eastern Australia. This is one of the few open sites in Australia which has high‐resolution evidence for spatially distinct, short‐term workshops. Within these well‐bounded workshops both locally manufactured and imported backed artefacts are present. However, across this landscape the shape of these artefacts is not uniform; rather, similarly shaped backed artefacts are concentrated in different workshop areas. Through the analysis of backed artefacts in different workshops, we suggest that “insert copying” or the replacement of spent inserts with similarly shaped, locally manufactured artefacts creates variability in backed artefact shape. À travers le continent australien, des artefacts à dos sont produits en grand nombre pendant le milieu et la fin de l'Holocène. Des examens antérieurs ont révélé une variation dans la forme moyenne de ces artefacts, à la fois à l'échelle continentale et régionale. Pour mieux comprendre les facteurs créant cette variabilité, nous examinons un grand ensemble d'artefacts à dos de Ngungara (Weereewa/Lake George), dans le sud‐est de l'Australie. Il s'agit de l'un des rares sites ouverts en Australie qui possède des preuves à haute résolution pour des ateliers spatialement distincts à court terme. Dans ces ateliers bien délimités, des artefacts à dos fabriqués localement et importés sont présents. Cependant, sur ce paysage, la forme de ces artefacts n'est pas uniforme; plutôt, des artefacts à dos de forme similaire sont concentrés dans différentes zones d'atelier. Grâce à l'analyse d'artefacts à dos dans différents ateliers, nous suggérons que la “copie d'insertion” ou le remplacement d'inserts usagés par des artefacts fabriqués localement de forme similaire crée de la variabilité dans la forme des artefacts à dos.

How does a blind person experience the broadening mouth and widening eyes of someone else's smile? How does a blind fiction writer like myself convey a blind character noticing that [...]

Detecting multiple enzyme activities simultaneously with high spatial specificity is a promising strategy to investigate complex biological phenomena, and Raman imaging would be an excellent tool for this purpose due to its high multiplexing capabilities. We previously developed activatable Raman probes based on 9CN-pyronins, but specific visualization of cells with target enzyme activities proved difficult due to leakage of the hydrolysis products from the target cells after activation. Here, focusing on rhodol bearing a nitrile group at the position of 9 (9CN-rhodol), we established a novel mechanism for Raman signal activation based on a combination of aggregate formation (to increase local dye concentration) and the resonant Raman effect along with the bathochromic shift of the absorption, and utilized it to develop Raman probes. We selected the 9CN-rhodol derivative 9CN-JCR as offering a suitable combination of increased stimulated Raman scattering (SRS) signal intensity and high aggregate-forming ability, resulting in good retention in target cells after probe activation. By using isotope-edited 9CN-JCR-based probes, we could simultaneously detect β-galactosidase, γ-glutamyl transpeptidase, and dipeptidyl peptidase-4 activities in live cultured cells and distinguish cell regions expressing target enzyme activity in Drosophilawing disc and fat body ex vivo.

Contrary to the perception of most women that breast cancer is the leading cause of death in women, it is heart disease and stroke that claim the most lives of women older than 35 years in the United States. The prevalence of cardiovascular disease is likely to increase as more women—notably the “baby boomers”— enter the menopausal period, a time of increased cardiac vulnerability. Primary care physicians should be on the forefront in taking an inventory of risk factors in their female patients and in educating them about the reality of heart disease in their gender and about the risk factors that these patients can modify to decrease their risk. To aid in their efforts, this article provides an overview of those risk factors that are modifiable, such as weight reduction, exercise, and smoking cessation. It also offers an evaluation of the benefit and nonbenefit of vitamin and herbal supplements in reduction of cardiac events.

Mikecoxite, ideally (CHg4)OCl2, is the first mercury-oxide-chloride-carbide containing a C4–anion coordinated by four Hg atoms (a permercurated methane derivative) to be described as a mineral species. It was found at the McDermitt open-pit mine on the eastern margin of the McDermitt Caldera, Humboldt County, Nevada, U.S.A. It is monoclinic, space group P21/n, Z = 4; a= 10.164(5), b= 10.490(4), c= 6.547(3) Å, V698.0(5) Å3. Chemical analysis by electron microprobe gave Hg 86.38, Cl 11.58, Br 0.46, C 1.81, sum = 100.23 wt%, and O was detected but the signal was too weak for quantitative chemical analysis. The empirical formula, calculated on the basis of Hg + Cl + Br = 6 apfu, is (C1.19Hg3.39)(Cl2.57Br0.05)Σ2.62, and the ideal formula based on the chemical analysis and the crystal structure is (CHg4)OCl2. The seven strongest lines in the X-ray powder diffraction pattern are [d(Å), I, (hkl)]: 2.884, 100, (230); 2.989, 81, (301, 301, 112, 112, 131, 131); 2.673, 79, (122, 122, 212, 212); 1.7443, 40, (060, 432, 432); 5.49, 34, (101, 101); 4.65, 32, (120); 2.300, 30, (312, 312). The Raman spectrum shows three bands at 638, 675, and 704 cm–1, well above the range characteristic of NHg4stretching vibrations between 540 and 580 cm–1, that are assigned to CHg4stretching vibrations. Mikecoxite forms intergrowths of bladed crystals up to 100 μm long that occur on granular quartz or in vugs associated with kleinite. It is black with a submetallic to metallic luster and strong specular reflections and does not fluoresce under short- or long-wave ultraviolet light. Neither cleavage nor parting were observed, and the calculated density is 8.58 g/cm3. In the crystal structure of mikecoxite, (C4−Hg42+)$(\mathrm C^{4-}\mathrm{Hg}_4^{2+})$groups link through O2–ions to form three-membered rings that polymerize into corrugated [CHg4OCl]+layers with near-linear C4––Hg2+–O and C4––Hg2+–Cl linkages. The layers link in the third direction directly via weak Hg2+–O2–and Hg2+–Cl–bonds to adjacent layers and also indirectly via interlayer Cl–. A bond-valence parameter has been derived for (Hg2+–C4–) bonds: Ro= 2.073 Å, b= 0.37, which gives bond-valence sums at the C4–ions in accord with the valence-sum rule. The source of carbon for mikecoxite in the volcanic high-desert environment of the type locality seems to be methane, with the reaction catalyzed by microbiota through full mercuration of carbon atoms, beyond the first stage that produces the volatile and highly mobile methylmercury, [CH3Hg]+, a potent neurotoxin that accumulates in marine food chains. Both the mineral and the mineral name have been approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA 2021-060). The mineral is named after Michael F. Cox (b. 1958), a founding member of the New Almaden Quicksilver County Park Association (NAQCPA) who was responsible for characterizing and remediating environmental mercury on-site and who recovered the rock containing the new mineral.

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors.Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (<80 years) using retrospective data from consecutive patients receiving EVT from four comprehensive stroke centres in New Zealand and Australia. We used propensity score matching or multivariable logistic regression to account for confounders.Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11–21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0–2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p< 0.01). There was no difference between the very elderly and the less-old in the proportion of patients who returned to baseline function at 90 days (56 (18.7%) vs 62 (20.7%), p= 0.54). All-cause 90-day mortality was higher in the very elderly (75 (25%) vs 49 (16.3%), p< 0.01), without a difference in symptomatic haemorrhage (very elderly 11 (3.7%) vs 6 (2.0%), p= 0.33). In the multivariable logistic regression models, the very elderly were significantly associated with reduced odds of good 90-day outcome (OR 0.49, 95% CI 0.34–0.69, p< 0.01) but not with return to baseline function (OR 0.85, 90% CI 0.54–1.29, p= 0.45) after adjusting for confounders.Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.

Background: Metastatic castrate sensitive prostate cancer (mCSPC) is a heterogeneous disease state with variable prognosis. Although several life-prolonging systemic agents are available, there is no robust multivariable model to predict prognosis and improve risk stratification in mCSPC. The objective of this study was to build and validate a multivariable prognostic model to predict overall survival (OS) in mCSPC. Methods: We used data from LATITUDE, a phase III randomized controlled trial in which men with de novo mCSPC were randomly allocated to either ADT plus abiraterone or ADT with placebo. Patients with non-missing data (n= 1,058) were randomly split in a 70:30 ratio to training (n= 743) and testing (n= 315) sets. Elastic net regression was used for variable selection. A multivariable Cox regression model for OS was then fitted using the selected variables. The predictive accuracy of the model was assessed on the testing set using the time-dependent area under curve (tAUC) with bootstrapped confidence intervals [CI] primarily for OS and secondarily for radiographic progression-free survival (rPFS). Results: The 11 prognostic variables in the final model were performance status, number of skeletal metastases, Gleason score, presence of liver metastasis, worst pain score, albumin, lactate dehydrogenase, prostate-specific antigen, hemoglobin, and treatment regimen. The tAUC for predicting OS at 2- and 3-years was 0.74 (95% CI, 0.67–0.80) and 0.72 (95% CI, 0.65–0.77), respectively. The tAUC for rPFS at 2- and 3-years was 0.72 (95% CI, 0.65–0.77) and 0.77 (95% CI, 0.70–0.82), respectively. Conclusions: A prognostic model for men with de novo mCSPC was developed and validated in an independent testing set. Our model had high accuracy for predicting OS and rPFS. The model includes commonly used clinical and laboratory parameters and can guide risk stratification of these patients for participation in future trials.

It is unclear whether cancer patients enrolled in clinical trials have improved outcomes compared with non-study patients. We compared prostate cancer-specific mortality (PCSM) in patients in a real-world setting (SEER-Medicare database) versus on a trial (NRG/RTOG 0521). The 7-year freedom from PCSM was superior in trial patients (92.4% vs. 88.1%, sHR = 1.77 [95% CI 1.05–2.97], P= 0.03). Black trial patients had significantly superior freedom from PCSM than Black real-world patients (sHR 6.52, 95% CI 1.43–29.72, P= 0.02), which was not seen among non-Black patients. Trial patients may have improved outcomes, and racial disparities are accentuated in the real world.

BackgroundNearly half of women experience unintended pregnancies. These are associated with increased risk of poor maternal physical and psychosocial health outcomes. Many pregnancies in the first year postpartum are unintended, further increasing risks of poor outcomes and complications. We undertook a qualitative evidence synthesis to evaluate qualitative research on women’s views and preferences for accessing postpartum contraception, and identify evidence gaps and opportunities for postpartum contraception provision.MethodsFive databases were searched to identify relevant qualitative studies. Included studies focused on views of, and preferences for, accessing postpartum contraception for women of reproductive age in high-income countries.ResultsOf 1854 studies identified, 28 full texts were assessed and 19 studies included. These were critically appraised using Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) and analysed using thematic synthesis. Included studies indicated the majority of women desire postpartum contraception, but face a range of financial, health system and personal barriers. Women felt unclear about the ideal interpregnancy interval (IPI) and the rationale for this. Women preferred contraceptive counselling at varying times both antenatally and postnatally, and commonly preferred to receive contraception in the immediate postpartum period before hospital discharge. Women commonly saw their obstetrician or general practitioner for contraceptive counselling, but welcomed midwifery involvement.ConclusionsMost women were interested in postpartum contraception and pregnancy spacing, but felt unclear about the optimal IPI, highlighting the need for further education and support around this issue. Contraceptive counselling was viewed as valuable antenatally and postnatally, and by varying maternal health providers, as was the provision of immediate postpartum contraception.

Here we present the genetic relationships of 26 specimens of the genus Breinlia (Nematoda: Filarioidea) from a range of Australian marsupials using markers in the small subunit of nuclear ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 (cox 1) genes and compare them with morphological determinations. The molecular data support the validity of most of the morpho-species included in the study and provide provisional insights into the phylogeny of the genus in Australian mammals, with dasyuroid marsupials appearing to be the original hosts. The recent discovery of Breinlia annulipapillata in the eye of a human brings this genus of parasites into the group of emerging infectious parasitic diseases. [ABSTRACT FROM AUTHOR]

Tomiolloite (IMA2021-019) is a new aluminum tellurite sulfite-sulfate mineral discovered at the Bambolla mine, Moctezuma, Sonora, Mexico, a well-known tellurium (Te) mineral locality. Tomiolloite forms roughly spherical clusters of crystals comprised of very thin, needle-like crystals (1 μm diameter, ~40 μm length) around a core of small, stubbier, broken crystals. Tomiolloite is generally found growing on tellurite or quartz. The strongest powder X‑ray diffraction lines are [dobsÅ (Iobs) (hkl)]: 11.667 (89) (100), 8.240 (38) (101), 4.107 (29) (202,211,121), 3.223 (100) (203,302,130), and 2.905 (37) (213,123,222,400). The empirical formula of tomiolloite, as determined by electron microprobe analysis, is (Al10.64Te61.01+Fe30.31+Zn0.04)Σ12(Te45.00+Pb0.02)Σ5.02(S40.49+S60.49+Si0.02)Σ1.00O21.53[(OH)20.86Cl0.11]Σ20.97, which is simplified to the ideal formula Al12(Te4+O3)5[(SO3)0.5(SO4)0.5](OH)24. Significant Te6+substitution for Al3+is observed in tomiolloite, verified by X‑ray photoelectron spectroscopy and crystal-structure analysis. The structure of tomiolloite was determined using synchrotron single-crystal X‑ray diffraction, showing that tomiolloite is hexagonal and crystallizes in the space-group P63/m, with the unit-cell parameters a= 13.3360(19) Å, c= 11.604(2) Å, V= 1787.3(6) Å3, and Z = 2. Tomiolloite has a unique microporous framework structure, which bears a slight similarity to that of zemannite, but it has a much larger cavity diameter (8.85 Å). The framework is built from edge-sharing Mφ6octahedra (M= Al3+and Te6+), Te4+O3trigonal pyramids, and Te4+O4disphenoids. Mφ6octahedra edge-share to form crankshaft-shaped chains along c, with Te4+Onpolyhedra filling notches in the crankshafts and providing linkages between adjacent chains. The framework has an overall positive charge, which is balanced by the presence of both sulfite (SO32−) trigonal pyramids and sulfate (SO42−) tetrahedra in the channels.

Background: Decipher Biopsy is a commercially available gene expression classifier used in risk stratification of newly diagnosed prostate cancer (PCa). Currently, there are no prospective data evaluating its clinical utility. We seek to assess the clinical utility of Decipher Biopsy in localized PCa patients. Methods: A multi-institutional study of 855 men who underwent Decipher Biopsy testing between February 2015 and October 2019. All patients were tracked through the prospective Michigan Urological Surgery Improvement Collaborative and linked to the Decipher Genomics Resource Information Database (GRID®; NCT02609269). Patient matching was performed by an independent third-party (ArborMetrix Inc.) using two or more unique identifiers. Cumulative incidence curves for time to treatment (TTT) and time to failure (TTF) were constructed using Kaplan–Meier estimates. Multivariable Cox proportional hazard models were used to evaluate the independent association of high-risk Decipher scores with the conversion from AS to radical therapy and treatment failure (biochemical failure or receipt of salvage therapy). Results and limitations: Eight hundred fifty-five patients underwent Decipher Biopsy testing during the study period. Of the 855 men, 264 proceeded to AS (31%), and 454 (53%) received radical therapy. In men electing AS, after adjusting for NCCN risk group, age, PSA, prostate volume, body mass index, and percent positive cores, a high-risk Decipher score was independently associated with shorter TTT (HR 2.51, 95% CI 1.52–4.13 p&lt; 0.001). Similarly, in patients that underwent radical therapy, a high-risk Decipher score was independently associated with TTF (HR 2.98, 95% CI 1.22–7.29, p= 0.01) on multivariable analysis. Follow-up time was a limitation. Conclusion: In a prospective statewide registry, high-risk Decipher Biopsy score was strongly and independently associated with conversion from AS to definitive treatment and treatment failure. These real-world data support the clinical utility of Decipher Biopsy. An ongoing phase 3 randomized trial (NCT04396808) will provide level 1 evidence of the clinical impact of Decipher biopsy testing.

1. In patients with intermediate-risk prostate cancer (IR PCa), the 10-yr treatment-free survival, metastasis-free survival, and cancer-specific survival ranged from 19.4% to 69%, 80.8% to 99%, and 88.2% to 99%, respectively.

Background: Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P). Methods: By using an established mutational signature, we created and validated HRD-P in six independent PCa cohorts (primary PCa, n= 8224; metastatic castration-resistant PCa [mCRPC], n= 328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations. Results: HRD-P+ tumors were more common than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%) and mCRPC (126/328, 38% vs 82/328, 25%) cases, and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with a shorter time to recurrence following surgery and shorter overall survival in men with mCRPC. In a prospective trial of mCRPC treated with olaparib (n= 10), all three men with HRD-P+ experienced prolonged (>330 days) PSA progression-free survival. Conclusion: These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application.

In this network meta-analysis of 11 randomized controlled trials, the triplet consisting of androgen deprivation therapy (ADT), androgen receptor axis–targeted therapy (ARAT), and docetaxel was found to be a somewhat more effective treatment strategy than ADT plus ARAT.