Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials.

BACKGROUND AND OBJECTIVE: Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy. METHODS: Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group. The outcome measures of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression estimated hazard ratios (HRs) for the three RFs and cN1 disease. KEY FINDINGS AND LIMITATIONS: A total of 3604 patients from ten trials were evaluated, with a median PSA value of 24 ng/ml. Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), cT3-4 disease (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with poorer outcomes. Adjusted 5-yr MFS rates were 83% and 78%, and 10-yr MFS rates were 63% and 53% for patients with one and two to three RFs, respectively; corresponding 10-yr adjusted OS rates were 67% and 60%, respectively. In cN1 patients, adjusted 5- and 10-yr MFS rates were 67% and 36%, respectively, and 10-yr OS was 47%. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRLPC patients with two to three RFs (and cN0) or cN1 disease had the poorest outcomes on RT and ltADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC. PATIENT SUMMARY: Radiotherapy and long-term hormone therapy are standard treatments for high-risk and locoregional prostate cancer. In this report, we defined prognostic groups within high-risk/locoregional prostate cancer and showed that outcomes to standard therapy are poorest in those with two or more "high-risk" factors or evidence of lymph node involvement. Such patients may therefore be the best candidates for intensification of treatment.

Application of Genomic Medicine in Africa: 14th Conference of the African Society of Human Genetics and the 2nd International Congress of the Moroccan Society of Genomics and Human Genetics, Rabat, Morocco 2022.

The 14th African Society of Human Genetics (AfSHG) Morocco Meeting and 2nd International Congress of the Moroccan Society of Genomics and Human Genetics (SM2GH), held in Rabat, Morocco, from December 12 through 17, 2022, brought together 298 attendees from 23 countries, organized by the AfSHG in collaboration with the SM2GH. The conference's overarching theme was "Applications of Genomics Medicine in Africa," covering a wide range of topics, including population genetics, genetics of infectious diseases, hereditary disorders, cancer genetics, and translational genetics. The conference aimed to address the lag in the field of genetics in Africa and highlight the potential for genetic research and personalized medicine on the continent. The goal was to improve the health of African populations and global communities while nurturing the careers of young African scientists in the field. Distinguished scientists from around the world shared their recent findings in genetics, immunogenetics, genomics, genome editing, immunotherapy, and ethics genomics. Precongress activities included a 2-day bioinformatics workshop, "NGS Analysis for Monogenic Disease in African Populations," and a Young Investigators Forum, providing opportunities for young African researchers to showcase their work. The vast genetic diversity of the African continent poses a significant challenge in investigating and characterizing public health issues at the genetic and functional levels. Training, research, and the development of expertise in genetics, immunology, genomics, and bioinformatics are vital for addressing these challenges and advancing genetics in Africa. The AfSHG is committed to leading efforts to enhance genetic research, coordinate training, and foster research collaborations on the continent.

Defining a Water-Soluble Formulation of Arachidonic Acid as a Novel Ferroptosis Inducer in Cancer Cells.

Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts.

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs). Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria. DEGs and DMPs between time points were detected using cell-type adjusted modeling with Cibersortx or IDOL, respectively. Results: Most major cell types and principal components had moderate to high correlation between the two deconvolution methods (r = 0.60-0.96). Estimates of cell-type proportions and DEGs or DMPs were largely unaffected by the method, with the greatest discrepancy in the estimation of neutrophils. Conclusion: Variation in cell-type proportions is captured similarly by both transcriptomic and methylome deconvolution methods for most major cell types.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

Late fall synthetic acaricide application is effective at reducing host-seeking adult and nymphal Ixodes scapularis (Ixodida: Ixodidae) abundances the following spring.

Based on increases in reported cases of tick-borne illnesses, expanding ranges of native ticks, and repeated documentation of arrivals of nonnative tick species, there is a clear need for their effective management in the United States. Synthetic acaricides have proven efficacious in tick management, but real/perceived negative impacts to the environment and nontarget, beneficial insects must be addressed. We sought to determine whether late fall synthetic acaricide application, when most susceptible beneficial insects are presumably dormant or have migrated, could effectively manage host-seeking spring Ixodes scapularis Say abundances as compared to traditional spring application. We compared results of delivery of Demand CS (lambda-cyhalothrin) via truck-mounted high-pressure spray and powered backpack blower as well as delivery of granular Demand G to experimental control (water) in peridomestic habitats in fall 2021, spring 2022, and combined fall 2021/spring 2022. High-pressure fall delivery of Demand CS and backpack delivery of Demand G significantly reduced host-seeking adult I. scapularis abundances within-season and the following spring combined by 100% and 94%, respectively. No host-seeking nymphal I. scapularis were documented in spring after fall only, spring only, or fall and spring combined delivery of Demand CS via high-pressure or powered backpack blower. No adult I. scapularis were documented at any time posttreatment on locations that received high-pressure delivery of Demand CS. We conclude that high-pressure delivery of Demand CS in late fall successfully eliminated multiple stages of host-seeking I. scapularis through the following spring while likely limiting exposure of beneficial insects to synthetic pyrethroids.

Mechanical and morphometric approaches to body mass estimation in rhesus macaques: A test of skeletal variables.

OBJECTIVES: Estimation of body mass from skeletal metrics can reveal important insights into the paleobiology of archeological or fossil remains. The standard approach constructs predictive equations from postcrania, but studies have questioned the reliability of traditional measures. Here, we examine several skeletal features to assess their accuracy in predicting body mass. MATERIALS AND METHODS: Antemortem mass measurements were compared with common skeletal dimensions from the same animals postmortem, using 115 rhesus macaques (male: n = 43; female: n = 72). Individuals were divided into training (n = 58) and test samples (n = 57) to build and assess Ordinary Least Squares or multivariate regressions by residual sum of squares (RSS) and AIC weights. A leave-one-out approach was implemented to formulate the best fit multivariate models, which were compared against a univariate and a previously published catarrhine body-mass estimation model. RESULTS: Femur circumference represented the best univariate model. The best model overall was composed of four variables (femur, tibia and fibula circumference and humerus length). By RSS and AICw, models built from rhesus macaque data (RSS = 26.91, AIC = -20.66) better predicted body mass than did the catarrhine model (RSS = 65.47, AIC = 20.24). CONCLUSION: Body mass in rhesus macaques is best predicted by a 4-variable equation composed of humerus length and hind limb midshaft circumferences. Comparison of models built from the macaque versus the catarrhine data highlight the importance of taxonomic specificity in predicting body mass. This paper provides a valuable dataset of combined somatic and skeletal data in a primate, which can be used to build body mass equations for fragmentary fossil evidence.

The frequency and presentation of upper thoracic spinous process deviations, their relationship to articular morphology, and the potential influence on static palpation techniques.

BACKGROUND: Static palpation of vertebral spinous process deviations from the midline are often utilized by manual therapists as a means to determine area for treatment of manipulable lesions. Previous research has discussed the diagnostic validity of this technique, but no correlation to vertebral morphology has been presented. AIM: To evaluate the frequency and presentation of vertebral spinous process deviations and their relationship with articular morphology, and the impact this may have in terms of static palpation techniques in the upper thoracic spine. SETTING: This study was conducted on human T1-T6 vertebrae. METHOD: A skeletal sample consisting of 58 humans T1-T6 vertebrae were photographed and linear and angular measurements taken utilizing ImageJ software and non-metric visual observations. RESULTS: Spinous process deviations in the entire sample group (n = 348) were found to occur in a frequency ranging from 19% (n = 11) at T1 to 41.4% (n = 24) at T3. However, when evaluated in terms of frequency within an individual's T1-T6, 83.3% (n = 25) of males and 67.86% (n = 19) of females demonstrated this feature, with an overall incidence of 77.59% (n = 45). Age of individuals did not show an increase in frequency, and no clear pattern could be identified regarding metric measurements and its presence. CONCLUSION: Spinous process deviations in the upper thoracic spine are most probably the result of random normal variations between individuals and are more frequent in males. Static palpation without pain criteria is not a reliable diagnostic technique to determine areas needing manual treatment, as these may be considered normal osseous anatomical variations.

Quantifying the relationship between bone and soft tissue measures within the rhesus macaques of Cayo Santiago.

OBJECTIVES: Interpretations of the primate and human fossil record often rely on the estimation of somatic dimensions from bony measures. Both somatic and skeletal variation have been used to assess how primates respond to environmental change. However, it is unclear how well skeletal variation matches and predicts soft tissue. Here, we empirically test the relationship between tissues by comparing somatic and skeletal measures using paired measures of pre- and post-mortem rhesus macaques from Cayo Santiago, Puerto Rico. MATERIALS AND METHODS: Somatic measurements were matched with skeletal dimensions from 105 rhesus macaque individuals to investigate paired signals of variation (i.e., coefficients of variation, sexual dimorphism) and bivariate codependence (reduced major axis regression) in measures of: (1) limb length; (2) joint breadth; and (3) limb circumference. Predictive models for the estimation of soft tissue dimensions from skeletons were built from Ordinary Least Squares regressions. RESULTS: Somatic and skeletal measurements showed statistically equivalent coefficients of variation and sexual dimorphism as well as high epiphyses-present ordinary least square (OLS) correlations in limb lengths (R2 >0.78, 0.82), joint breadths (R2 >0.74, 0.83) and, to a lesser extent, limb circumference (R2 >0.53, 0.68). CONCLUSION: Skeletal measurements are good substitutions for somatic values based on population signals of variation. OLS regressions indicate that skeletal correlates are highly predictive of somatic dimensions. The protocols and regression equations established here provide a basis for reliable reconstruction of somatic dimension from catarrhine fossils and validate our ability to compare or combine results of studies based on population data of either hard or soft tissue proxies.

Infection Control Measure Performance in Long-Term Care Hospitals and Their Relationship to Joint Commission Accreditation.

BACKGROUND: This study evaluated the relationship between Joint Commission accreditation and health care-associated infections (HAIs) in long-term care hospitals (LTCHs). METHODS: This observational study used Centers for Medicare & Medicaid Services (CMS) LTCH data for the period 2017 to June 2021. The standardized infection ratio (SIR) of three measures used by the Centers for Disease Control and Prevention's National Healthcare Safety Network were used as dependent variables in a random coefficient Poisson regression model (adjusting for CMS region, owner type, and bed size quartile): catheter-associated urinary tract infections (CAUTIs), Clostridioides difficile infections (CDIs), and central line-associated bloodstream infections (CLABSIs) for the periods 2017 to 2019 and July 1, 2020, to June 30, 2021. Data from January 1 to June 30, 2020, were excluded due to the COVID-19 pandemic. RESULTS: The data set included 244 (73.3%) Joint Commission-accredited and 89 (26.7%) non-Joint Commission-accredited LTCHs. Compared to non-Joint Commission-accredited LTCHs, accredited LTCHs had significantly better (lower) SIRs for CLABSI and CAUTI measures, although no differences were observed for CDI SIRs. There were no significant differences in year trends for any of the HAI measures. For each year of the study period, a greater proportion of Joint Commission-accredited LTCHs performed significantly better than the national benchmark for all three measures (p = 0.04 for CAUTI, p = 0.02 for CDI, p = 0.01 for CLABSI). CONCLUSION: Although this study was not designed to establish causality, positive associations were observed between Joint Commission accreditation and CLABSI and CAUTI measures, and Joint Commission-accredited LTCHs attained more consistent high performance over the four-year study period for all three measures. Influencing factors may include the focus of Joint Commission standards on infection control and prevention (ICP), including the hierarchical approach to selecting ICP-related standards as inputs into LTCH policy.

Evaluating the Prevalence of Four Recommended Practices for Suicide Prevention Following Hospital Discharge.

BACKGROUND: The Joint Commission's National Patient Safety Goal (NPSG) for suicide prevention (NPSG.15.01.01) requires that accredited hospitals maintain policies/procedures for follow-up care at discharge for patients identified as at risk for suicide. The proportion of hospitals meeting these requirements through use of recommended discharge practices is unknown. METHODS: This cross-sectional observational study explored the prevalence of suicide prevention activities among Joint Commission-accredited hospitals. A questionnaire was sent to 1,148 accredited hospitals. The authors calculated the percentage of hospitals reporting implementation of four recommended discharge practices for suicide prevention. RESULTS: Of 1,148 hospitals, 346 (30.1%) responded. The majority (n = 212 [61.3%]) of hospitals had implemented formal safety planning, but few of those (n = 41 [19.3%]) included all key components of safety planning. Approximately a third of hospitals provided a warm handoff to outpatient care (n = 128 [37.0%)] or made follow-up contact with patients (n = 105 [30.3%]), and approximately a quarter (n = 97 [28.0%]) developed a plan for lethal means safety. Very few (n = 14 [4.0%]) hospitals met full criteria for implementing recommended suicide prevention activities at time of discharge. CONCLUSION: The study revealed a significant gap in implementation of recommended practices related to prevention of suicide postdischarge. Additional research is needed to identify factors contributing to this implementation gap.

Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.

BACKGROUND AND OBJECTIVES: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories. METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics. RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers. DISCUSSION: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.

The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer.

Objectives: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT. Materials and methods: Men with mCRPC, with more than one prostate-specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with gallium68-Dota-exendin-4. We documented PET/CT PSMA-avid lesions, which were also PET/CT exendin avid, as evidence of in vivo GLP-1R expression. Results: Out of the 24 men referred, three did not meet the inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Among the four men imaged, three had no exendin-avid lesions, while one had six osseous PSMA-avid lesions, three of which were also exendin avid. Conclusions: We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and exendin, in one of four participants. GLP-1R expression may thus occur even in advanced-stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.

Evaluation of landscaping and vegetation management to suppress host-seeking Ixodes scapularis (Ixodida: Ixodidae) nymphs on residential properties in Connecticut, USA.

Ticks and tick-borne diseases are of increasing concern across the United States, particularly in the Northeast. Ixodes scapularis Say (Ixodida: Ixodidae) remains the primary vector for the Lyme disease spirochete, Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt, and Brenner). Prior studies established that I. scapularis can be found in greatest abundance in the 1-m forested ecotone surrounding the lawn edge in residential backyards. Our study was conducted on 42 properties in Guilford, CT, and sought to expand upon this premise by determining which key habitat features were associated with increased densities of host-seeking I. scapularis nymphs. We quantified nymphal abundances in 19 different habitat types that were posited to influence densities. We determined that nymphal I. scapularis densities were greatest in forested areas closest to lawn edges with leaf litter or understory vegetation present, as well as short lawns adjacent to woodland edges. Additionally, we determined that there were no significant declines in nymphal I. scapularis density where leaf litter was removed, lawns were left unmowed, or woodchip barriers were installed. Bird feeders and woodpiles were not associated with increased nymphal I. scapularis densities. However, areas adjacent to stone walls did have nearly 3 times the density of I. scapularis nymphs present compared with habitats without stone walls. The culmination of the results from this study can be utilized to create more targeted acaricide applications rather than broadcast spraying, as well as increase homeowner awareness for areas with heightened risk for exposure to nymphal I. scapularis, which are deemed the most epidemiologically important species and stage for pathogen transfer to humans.

Towards optimal heterogeneous prostate radiotherapy dose prescriptions based on patient-specific or population-based biological features.

BACKGROUND: Escalation of prescribed dose in prostate cancer (PCa) radiotherapy enables improvement in tumor control at the expense of increased toxicity. Opportunities for reduction of treatment toxicity may emerge if more efficient dose escalation can be achieved by redistributing the prescribed dose distribution according to the known heterogeneous, spatially-varying characteristics of the disease. PURPOSE: To examine the potential benefits, limitations and characteristics of heterogeneous boost dose redistribution in PCa radiotherapy based on patient-specific and population-based spatial maps of tumor biological features. METHOD: High-resolution prostate histology images, from a cohort of 63 patients, annotated with tumor location and grade, provided patient-specific "maps" and a population-based "atlas" of cell density and tumor probability. Dose prescriptions were derived for each patient based on a heterogeneous redistribution of the boost dose to the intraprostatic lesions, with the prescription maximizing patient tumor control probability (TCP). The impact on TCP was assessed under scenarios where the distribution of population-based biological data was ignored, partially included, or fully included in prescription generation. Heterogeneous dose prescriptions were generated for three combinations of maps and atlas, and for conventional fractionation (CF), extreme hypo-fractionation (EH), moderate hypo-fractionation (MH), and whole Pelvic RT + SBRT Boost (WPRT + SBRT). The predicted efficacy of the heterogeneous prescriptions was compared with equivalent homogeneous dose prescriptions. RESULTS: TCPs for heterogeneous dose prescriptions were generally higher than those for homogeneous dose prescriptions. TCP escalation by heterogeneous dose prescription was the largest for CF. When only using population-based atlas data, the generated heterogeneous dose prescriptions of 55 to 58 patients (out of 63) had a higher TCP than for the corresponding homogeneous dose prescriptions. The TCPs of the heterogeneous dose prescriptions generated with the population-based atlas and tumor probability maps did not differ significantly from those using patient-specific biological information. The generated heterogeneous dose prescriptions achieved significantly higher TCP than homogeneous dose prescriptions in the posterior section of the prostate. CONCLUSION: Heterogeneous dose prescriptions generated via biologically-optimized dose redistribution can produce higher TCP than the homogeneous dose prescriptions for the majority of the patients in the studied cohort. For scenarios where patient-specific biological information was unavailable or partially available, the generated heterogeneous dose prescriptions can still achieve TCP improvement relative to homogeneous dose prescriptions.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.

BACKGROUND: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown. STUDY DESIGN: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial. ENDPOINTS: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness. ELIGIBILITY CRITERIA: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT. PATIENTS AND METHODS: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707).