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Background and Aim: Zoonotic diseases are naturally transmissible infections between animals and humans. To address these cross-sectoral health issues holistic, transdisciplinary health approaches are required. The legalization of the game meat trade in Tanzania in 2020 has created a new value chain from wild habitats to registered game meat selling facilities in human settlements, thus creating new human-animal interfaces associated with potential risks of zoonotic disease transmission among wildlife, livestock, and human populations. This study aimed to apply a simple, collaborative prioritization process to identify important zoonotic pathogens associated with wild animal taxa harvested and traded for game meat consumption in northern Tanzania. Materials and Methods: A prioritization process was conducted to identify and rank zoonotic diseases associated with wildlife in the Arusha, Kilimanjaro, and Manyara regions of northern Tanzania to help determine the zoonotic disease risks associated with the game meat value chain. Two districts from each region were selected for this study. The prioritization process was conducted through an expert workshop that involved 41 participants, including a District Veterinary Officer, Public Health Officer, and District Game Officer from each district, as well as national One Health focal persons, zonal Veterinary and Laboratory Officers, scientific researchers, and a representative from the national Game Meat Selling Advisory Committee. Results: Experts identified 11 common zoonotic diseases reported in these regions, of which anthrax, rabies, brucellosis, Rift Valley fever, and bovine tuberculosis were considered the most important. This finding is broadly consistent with the national priority list for zoonotic diseases. Conclusions: This approach was time-efficient and cost-effective. In Tanzania, multi-sectoral planning, communication, and cooperation among human health, domestic animal health, wildlife health, and environmental protection have been strengthened. In the future, we recommend regular exercises using such an approach to update the information on important diseases and promote information sharing for epidemic and pandemic preparedness associated with the wild animal trade. [ABSTRACT FROM AUTHOR]

The Zirconium (Z = 40) isotopic chain has attracted interest for more than four decades. The abrupt lowering of the energy of the first 2 + state and the increase in the transition strength B(E2; 2 1 + → 0 1 +) going from 98 Zr to 100 Zr has been the first example of “quantum phase transition” in nuclear shapes, which has few equivalents in the nuclear chart. Although a multitude of experiments have been performed to measure nuclear properties related to nuclear shapes and collectivity in the region, none of the measured lifetimes were obtained using the Recoil Distance Doppler Shift method in the γ γ -coincidence mode where a gate on the direct feeding transition of the state of interest allows a strict control of systematical errors. This work reports the results of lifetime measurements for the first yrast excited states in 98 - 104 Zr carried out to extract reduced transition probabilities. The new lifetime values in γ γ -coincidence and γ -single mode are compared with the results of former experiments. Recent predictions of the Interacting Boson Model with Configuration Mixing, the Symmetry Conserving Configuration Mixing model based on the Hartree–Fock–Bogoliubov approach and the Monte Carlo Shell Model are presented and compared with the experimental data. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds (CMBs) are a possible sequela in human brain tumor patients treated with radiation therapy (RT). No such association is reported in dogs., Objectives: To investigate whether CMBs occur in dogs after radiotherapy, and if there is an association between number and dose, and an increase over time., Animals: Thirty-four client-owned dogs irradiated for primary intracranial neoplasia. ≥2 magnetic resonance imaging (MRI) scans including susceptibility-weighted imaging (SWI) were required., Methods: Retrospective, observational, single-center study. Cerebral microbleeds identified on 3 T SWI were counted within the entire brain, and within low- (<20 Gy), intermediate- (20-30 Gy), and high- (>30 Gy) dose regions. A generalized linear mixed-effects model was used to analyze the relationship between the CMBs count and the predictor variables (irradiation dose, time after treatment)., Results: Median follow-up time was 12.6 months (range, 1.8-37.6 months). Eighty-three MR scans were performed. In 4/15 dogs (27%, 95% CI, 10%-52%) CMBs were present at baseline. ≥1 CMBs after RT were identified in 21/34 dogs (62%, 95% CI, 45%-77%). With each month, the number of CMBs increased by 14% (95% CI, 11%-16%; P < .001). The odds of developing CMBs in the high-dose region are 4.7 times (95% CI, 3.9-5.6; P < .001) greater compared with the low-dose region., Conclusion and Clinical Importance: RT is 1 possible cause of CMBs formation in dogs. Cerebral microbleeds are most likely to occur in the peritumoral high-dose volume, to be chronic, and to increase in number over time. Their clinical relevance remains unknown., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Importance: Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME)., Objective: To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME., Design, Setting, and Participants: This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021., Interventions: Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52., Main Outcomes and Measures: The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs)., Results: A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms., Conclusions and Relevance: MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept., Trial Registration: ClinicalTrials.gov Identifier: NCT03610646.

Objective: To translate and communicate outcomes data for prostate cancer from a clinical registry data into a consumer-friendly resource., Methods: First, we analyzed real-world data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) registry for men diagnosed from 2008 to 2018 including clinical and functional outcomes following surgery, external beam radiotherapy, brachytherapy, hormone therapy, active surveillance and watchful waiting. These outcomes included overall survival, cancer specific survival, biochemical recurrence, decline in functional outcomes, and transition to active treatment following active surveillance. Second, we translated outcomes into a summary text and pictographic format and present in one document that consumers found easy to understand and interpret. This "Prostate Cancer Outcomes Report Card" was developed in consultation with a consumer advisory group and further improved through exploratory interviews with people affected by prostate cancer, an online survey among the general public, and clinician feedback., Results: The 5-year prostate cancer-specific survival rate was 97%. There is a reasonably high chance of cancer returning within 5 years (17% after surgery and 14% after radiotherapy) while 1 in 3 men on active surveillance transitioned to other treatments within 5 years. Sexual function was negatively affected following all treatment types. Men with higher risk disease had a worse prognosis, a higher chance of recurrence and greater decline in physical function. Consumers required trustworthy, comprehensive, simple and up-to-date information collated in one place, and valued having access to this resource. Data on high survival rates were considered reassuring. There were high levels of unmet psychosocial and supportive care needs, especially in relation to mental health and sexual function. The report card was well received by patients and health care workers., Conclusions: This relatively simple and easily understandable consumer-oriented outcome report serves to better inform men with prostate cancer and facilitate patient-provider communication and shared decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To assess the impact of comorbidities on prostate cancer mortality., Methods: We studied 15,695 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked data sets. Comorbidity was measured 1-year before prostate cancer diagnosis using Rx-Risk, a medication-based comorbidity index. Flexible parametric competing risk regression was used to estimate the independent association between comorbidities and prostate cancer-specific mortality. Specific common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and pain) were also assessed to determine their association with mortality. All models were adjusted for sociodemographic variables, tumor characteristics, and treatment type., Results: Prostate cancer-specific mortality was higher for patients with a Rx-Risk score ≥3 versus 0 (adjusted sub-hazard ratio (sHR) 1.34, 95% CI: 1.15-1.56). Lower comorbidity scores (Rx-Risk score 2 vs. 0 and Rx-Risk score 1 vs. 0) were not significantly associated with prostate cancer-specific mortality. Men who were using medications for cardiac disorders (sHR 1.31, 95% CI: 1.13-1.52), chronic airway disease (sHR 1.20, 95% CI: 1.01-1.44), depression and anxiety (sHR 1.17, 95% CI: 1.02-1.35), and thrombosis (sHR 1.21, 95% CI: 1.04-1.42) were at increased risk of dying from prostate cancer compared with men not on those medications. Use of medications for diabetes and chronic pain were not associated with prostate cancer-specific mortality. All Rx-Risk score categories and the specific comorbidities were also associated with increased risk of all-cause mortality., Conclusion: The findings showed that ≥3 comorbid conditions and specific comorbidities including cardiac disease, chronic airway disease, depression and anxiety, and thrombosis were associated with poor prostate cancer-specific survival. Appropriate management of these comorbidities may help to improve survival in prostate cancer patients., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Objective: Despite available support, sexuality needs are the most frequently reported unmet need among men with prostate cancer, which may be due to low help-seeking rates. Using the Ecological Systems Framework as a theoretical foundation, we conducted a scoping review of the available literature to understand what factors impact help-seeking behaviour for sexual issues after prostate cancer treatment among men who had received treatment., Methods: Following PRISMA guidelines, a systematic search on Medline, PsychInfo, Embase, Emcare, and Scopus was conducted to identify studies of adult prostate cancer patients post-treatment, which reported barriers and/or facilitators to help-seeking for sexual health issues. Quality appraisals were conducted using Joanna Briggs Institute appraisal tools, and results were qualitatively synthesised., Results: Of the 3870 unique results, only 30 studies met inclusion criteria. In general, studies were considered moderate to good quality, though only six used standardised measures to assess help-seeking behaviour. Barriers and facilitators for sexual help-seeking were identified across all five levels of the Ecological Systems Framework, including age, treatment type, and previous help seeking experience (individual level), healthcare professional communication and partner support (microsystem), financial cost and accessibility of support (meso/exosystem), and finally embarrassment, masculinity, cultural norms, and sexuality minority (macrosystem)., Conclusions: Addressing commonly reported barriers (and inversely, enhancing facilitators) to help-seeking for sexual issues is essential to ensure patients are appropriately supported. Based on our results, we recommend healthcare professionals include sexual wellbeing discussions as standard care for all prostate cancer patients, regardless of treatment received, age, sexual orientation, and partnership status/involvement., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Objective: Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5 years before and 5 years after prostate cancer diagnosis., Methods: Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n = 13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns., Results: Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5 years before to 40.3% 5 years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2 years following prostate cancer diagnosis., Conclusion: There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Introduction: Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation., Methods: We reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models., Results: We first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model., Discussion: Altogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19., Competing Interests: KB was employed by MAB Discovery GmbH, Germany. UP and DP were employed by MAB Discovery GmbH and IcanoMAB GmbH, Germany. SF is the CEO of MAB Discovery GmbH and IcanoMAB GmbH. JF received consulting fees from MAB Discovery GmbH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Lunding, Webber, Beckmann, Azam, Falkesgaard Højen, Amo-Aparicio, Dinarello, Nguyen, Pessara, Parera, Orlicky, Fischer, Wegmann, Dinarello and Li.)

The oxygen diffusion rate in hafnia (HfO 2 )-based resistive memory plays a pivotal role in enabling nonvolatile data retention. However, the information retention times obtained in HfO 2 resistive memory devices are many times higher than the expected values obtained from oxygen diffusion measurements in HfO 2 materials. In this study, we resolve this discrepancy by conducting oxygen isotope tracer diffusion measurements in amorphous hafnia (a-HfO 2 ) thin films. Our results show that the oxygen tracer diffusion in amorphous HfO 2 films is orders of magnitude lower than that of previous measurements on monoclinic hafnia (m-HfO 2 ) pellets. Moreover, oxygen tracer diffusion is much lower in denser a-HfO 2 films deposited by atomic layer deposition (ALD) than in less dense a-HfO 2 films deposited by sputtering. The ALD films yield similar oxygen diffusion times as experimentally measured device retention times, reconciling this discrepancy between oxygen diffusion and retention time measurements. More broadly, our work shows how processing conditions can be used to control oxygen transport characteristics in amorphous materials without long-range crystal order.

Secondary brain injury (SBI) occurs with a lag of several days post-bleeding in patients with aneurysmal subarachnoid hemorrhage (aSAH) and is a strong contributor to mortality and long-term morbidity. aSAH-SBI coincides with cell-free hemoglobin (Hb) release into the cerebrospinal fluid. This temporal association and convincing pathophysiological concepts suggest that CSF-Hb could be a targetable trigger of SBI. However, sparse experimental evidence for Hb's neurotoxicity in vivo defines a significant research gap for clinical translation. We modeled the CSF-Hb exposure observed in aSAH patients in conscious sheep, which allowed us to assess neurological functions in a gyrencephalic species. Twelve animals were randomly assigned for 3-day bi-daily intracerebroventricular (ICV) injections of either Hb or Hb combined with the high-affinity Hb scavenger protein haptoglobin (Hb-Hp, CSL888). Repeated CSF sampling confirmed clinically relevant CSF-Hb concentrations. This prolonged CSF-Hb exposure over 3 days resulted in disturbed movement activity, reduced food intake, and impaired observational neuroscores. The Hb-induced neurotoxic effects were significantly attenuated when Hb was administered with equimolar haptoglobin. Preterminal magnetic resonance imaging (MRI) showed no CSF-Hb-specific structural brain alterations. In both groups, histology demonstrated an inflammatory response and revealed enhanced perivascular histiocytic infiltrates in the Hb-Hp group, indicative of adaptive mechanisms. Heme exposure in CSF and iron deposition in the brain were comparable, suggesting comparable clearance efficiency of Hb and Hb-haptoglobin complexes from the intracranial compartment. We identified a neurological phenotype of CSF-Hb toxicity in conscious sheep, which is rather due to neurovascular dysfunction than structural brain injury. Haptoglobin was effective at attenuating CSF-Hb-induced neurological deterioration, supporting its therapeutic potential., (© 2024. The Author(s).)

The activation of CD40-mediated signaling in antigen-presenting cells is a promising therapeutic strategy to promote immune responses against tumors. Most agonistic anti-CD40 antibodies currently in development require the Fcγ-receptor (FcγR)-mediated crosslinking of CD40 molecules for a meaningful activation of CD40 signaling but have limitations due to dose-limiting toxicities. Here we describe the identification of CD40 antibodies which strongly stimulate antigen-presenting cells in an entirely FcγR-independent manner. These Fc-silenced anti-CD40 antibodies induce an efficient upregulation of costimulatory receptors and cytokine release by dendritic cells. Finally, the most active identified anti-CD40 antibody shows activity in humanized mice. More importantly, there are no signs of obvious toxicities. These studies thus demonstrate the potent activation of antigen-presenting cells with anti-CD40 antibodies lacking FcγR-binding activity and open the possibility for an efficacious and safe combination therapy for cancer patients.

Introduction: We aimed to assess the association between comorbidities and prostate cancer management., Patients and Methods: We studied 12,603 South Australian men diagnosed with prostate cancer between 2003 and 2019. Comorbidity was measured one year prior to prostate cancer diagnosis using a medication-based comorbidity index (Rx-Risk). Binomial logistic regression analyses were used to assess the association between comorbidities and primary treatment selection (active surveillance, radical prostatectomy (RP), external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT), brachytherapy, ADT alone, and watchful waiting (WW)). Certain common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and chronic pain) were also assessed. All models were adjusted for sociodemographic and tumor characteristics., Results: Likelihood of receiving RP was lower among men with Rx-Risk score ≥3 (odds ratio (OR) 0.62, 95%CI:0.56-0.69) and Rx-Risk 2 (OR 0.80, 95%CI:0.70-0.92) compared with no comorbidity (Rx-Risk ≤0). Men with high comorbidity (Rx-Risk ≥3) were more likely to have received ADT alone (OR 1.76, 95%CI:1.40-2.21), EBRT (OR 1.30, 95%CI:1.17-1.45) or WW (OR 1.49, 95%CI:1.19-1.88) compared with Rx-Risk ≤0. Pre-existing cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with lower likelihood of selecting RP and higher likelihood of EBRT (except chronic airway disease) or WW (except diabetes and depression and anxiety). Cardiac disorders and thrombosis were associated with higher likelihood of selecting ADT alone. Furthermore, age had greater effect on treatment choice than the level of comorbidity., Conclusion: High comorbidity burden was associated with primary treatment choice, with significantly less RP and more EBRT, WW and ADT alone among men with higher levels of comorbidity. Each of the individual comorbid conditions also influenced treatment selection., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Memristors, non-volatile switching memory platform, has recently attracted significant interest, offering unique potential to enable the realization of human brain-like neuromorphic computing efficiency. Memristors also demonstrate excellent temperature tolerance, long-term durability, and high tunability with nanosecond pulses, making them highly attractive for neuromorphic computing applications. To better understand the material processing, microstructure, and property relationship of switching mechanisms in memristor devices, computational methodologies, and tools are developed to predict the I-V characteristics of memristor devices based on tantalum oxide (TaO x ) resistive random-access memory (ReRAM) integrated with an n-channel metal-oxide-semiconductor (NMOS) transistor. A multiphysics model based on coupled partial differential equations for electrical and thermal transport phenomena is solved for the high- and low-resistance states during the formation, growth, and destruction of a conducting filament through SET and RESET stages. These stages effectively represent the migration of oxygen vacancies within an oxide exchange layer. A series of parametric studies and energy minimization calculations are conducted to determine probable ranges for key material and model parameters accounting for the experimental data. The computational model successfully predicted the measured I-V curves across various gate voltages applied to the NMOS transistor in the one transistor one resistance (1T1R) configuration., (© 2024 Wiley VCH GmbH. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The use of polygenic risk score (PRS) models has transformed the field of genetics by enabling the prediction of complex traits and diseases based on an individual's genetic profile. However, the impact of genotype-environment interaction (GxE) on the performance and applicability of PRS models remains a crucial aspect to be explored. Currently, existing genotype-environment interaction polygenic risk score (GxE PRS) models are often inappropriately used, which can result in inflated type 1 error rates and compromised results. In this study, we propose novel GxE PRS models that jointly incorporate additive and interaction genetic effects although also including an additional quadratic term for nongenetic covariates, enhancing their robustness against model misspecification. Through extensive simulations, we demonstrate that our proposed models outperform existing models in terms of controlling type 1 error rates and enhancing statistical power. Furthermore, we apply the proposed models to real data, and report significant GxE effects. Specifically, we highlight the impact of our models on both quantitative and binary traits. For quantitative traits, we uncover the GxE modulation of genetic effects on body mass index by alcohol intake frequency. In the case of binary traits, we identify the GxE modulation of genetic effects on hypertension by waist-to-hip ratio. These findings underscore the importance of employing a robust model that effectively controls type 1 error rates, thus preventing the occurrence of spurious GxE signals. To facilitate the implementation of our approach, we have developed an innovative R software package called GxEprs, specifically designed to detect and estimate GxE effects. Overall, our study highlights the importance of accurate GxE modeling and its implications for genetic risk prediction, although providing a practical tool to support further research in this area., (© 2024 The Authors. Genetic Epidemiology published by Wiley Periodicals LLC.)

Background: Drug prescription registries has become an alternative data source to hospital admission databases for measuring comorbidities. However, the predictive validity of prescription-based comorbidity measures varies based on the population under investigation and outcome of interest. We aimed to determine which prescription-based index of comorbidity has most utility in Australian men with prostate cancer., Methods: We studied 25,414 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked datasets. The Rx-Risk index, Chronic Disease Score (CDS), Drug Comorbidity Index (DCI) and Pharmaceutical Prescribing Profile (P3) with one year lookback period from prostate cancer diagnosis were evaluated. The predictive ability of each index to determine all-cause deaths within two and five years of prostate cancer diagnosis was compared using the c-statistic from flexible parametric survival models, adjusting for age, socioeconomic status and year of prostate cancer diagnosis., Results: The Rx-Risk index performed better in predicting two-year (c-statistic = 0.818) and five-year (c-statistic = 0.784) all-cause mortality than P3, CDS and DCI. Including comorbidity measures as continuous scores resulted in a better performance than including them as categories. Grouping scores into four categories (≤0, >0 - ≤1, >1 - ≤2, and >2) resulted in better performance and calibration than using fewer categories., Conclusion: Rx-Risk was validated in Australia and reflects Australian prescribing patterns. It showed better predictive performance for mortality in our study, with a modest improvement over P3, CDS and DCI. For research with prostate cancer populations, we recommend the use of drug-based comorbidity indices that have been validated in a similar population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Key Message: Simulation planned pre-breeding can increase the efficiency of starting a hybrid breeding program. Starting a hybrid breeding program commonly comprises a grouping of the initial germplasm in two pools and subsequent selection on general combining ability. Investigations on pre-breeding steps before starting the selection on general combining ability are not available. Our goals were (1) to use computer simulations on the basis of DNA markers and testcross data to plan crosses that separate genetically two initial germplasm pools of rapeseed, (2) to carry out the planned crosses, and (3) to verify experimentally the pool separation as well as the increase in testcross performance. We designed a crossing program consisting of four cycles of recombination. In each cycle, the experimentally generated material was used to plan the subsequent crossing cycle with computer simulations. After finishing the crossing program, the initially overlapping pools were clearly separated in principal coordinate plots. Doubled haploid lines derived from the material of crossing cycles 1 and 2 showed an increase in relative testcross performance for yield of about 5% per cycle. We conclude that simulation-designed pre-breeding crossing schemes, that were carried out before the general combining ability-based selection of a newly started hybrid breeding program, can save time and resources, and in addition conserve more of the initial genetic variation than a direct start of a hybrid breeding program with general combining ability-based selection., (© 2024. The Author(s).)

Introduction: This study evaluated the effect of a surgical opioid-avoidance protocol (SOAP) on postoperative pain scores. The primary goal was to demonstrate that the SOAP was as effective as the pre-existing non-SOAP (without opioid restriction) protocol by measuring postoperative pain in a diverse, opioid-naive patient population undergoing inpatient surgery across multiple surgical services., Methods: This prospective cohort study was divided into SOAP and non-SOAP groups based on surgery date. The non-SOAP group had no opioid restrictions (n=382), while the SOAP group (n=449) used a rigorous, opioid-avoidance order set with patient and staff education regarding multimodal analgesia. A non-inferiority analysis assessed the SOAP impact on postoperative pain scores., Results: Postoperative pain scores in the SOAP group compared with the non-SOAP group were non-inferior (95% CI: -0.58, 0.10; non-inferiority margin=-1). The SOAP group consumed fewer postoperative opioids (median=0.67 (IQR=15) vs 8.17 morphine milliequivalents (MMEs) (IQR=40.33); p<0.01) and had fewer discharge prescription opioids (median=0 (IQR=60) vs 86.4 MMEs (IQR=140.4); p<0.01)., Discussion: The SOAP was as effective as the non-SOAP group in postoperative pain scores across a diverse patient population and associated with lower postoperative opioid consumption and discharge prescription opioids., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

We investigated whether prostate cancer patients treated with external beam radiation therapy (EBRT) have a higher cumulative incidence of secondary cancer compared with patients treated with radical prostatectomy (RP). We used state-wide linked data from South Australia to follow men with prostate cancer diagnosed from 2002 to 2019. The cumulative incidence of overall and site-specific secondary cancers between 5 and 15 years after treatment was estimated. Fine-Gray competing risk analyses were performed with additional sensitivity analyses to test different scenarios. A total of 7625 patients were included (54% underwent RP and 46% EBRT). Characteristics of the two groups differed significantly, with the EBRT group being older (71 vs. 64 years), having higher comorbidity burden and being more likely to die during follow-up than the RP group. Fifteen-year cumulative incidence for all secondary cancers was 27.4% and 22.3% in EBRT and RP groups, respectively. In the adjusted models, patients in the EBRT group had a significantly higher risk of genitourinary (adjusted subhazard ratio (aSHR), 2.29; 95%CI 1.16-4.51) and lung (aSHR, 1.93; 95%CI 1.05-3.56) cancers compared with patients in the RP group. However, there was no statistically significant difference between the two groups for risk of any secondary cancer, gastro-intestinal, skin or haematologic cancers. No statistically significant differences in overall risk of secondary cancer were observed in any of the sensitivity analyses and patterns for risk at specific cancer sites were relatively consistent across different age restriction and latency/time-lag scenarios. In conclusion, the increased risk of genitourinary and lung cancers among men undergoing EBRT may relate partly to treatment effects and partly to unmeasured residual confounding., (© 2023. The Author(s).)

Background: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location., Hypothesis/objectives: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade., Animals: Forty-four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation., Methods: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board-certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board-certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis., Results: Forty-four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low-grade), 19 were PNSTs Grade 2 (medium-grade), and 9 were PNSTs Grade 3 (high-grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade., Conclusions and Clinical Importance: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high-grade PNSTs including tumor size and peripheral contrast enhancement., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Aim: To compare the utility of various admission-based comorbidity indices in men diagnosed with non-metastatic prostate cancer., Methods: The study cohort consisted of men diagnosed with prostate cancer between January 2002 and December 2020 according to the state-wide South Australian Cancer Registry. Comorbid conditions were captured for 11,470 men through linkage to public hospital admission data 5-years prior to prostate cancer diagnosis. The comorbidity indices evaluated included the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), National Cancer Institute (NCI) comorbidity index, and Cancer, Care and Comorbidity (C3) index. The predictive performance of the four indices for 5-year overall mortality was compared using the C-statistic from Cox proportional hazard models adjusted for age, socioeconomic status, and year of prostate cancer diagnosis., Results: Approximately 31 %, 45 %, 28 % and 47 % of patients had at least one comorbid condition captured by CCI, ECI, NCI and C3, respectively. Regarding the prediction of 5-year overall survival, CCI (c-index = 0.763) slightly higher predictive performance than ECI (0.758), NCI (0.755), and C3 (0.754). Indices in their continuous score resulted in better predictive performance than them being used categorically (0, 1, and 2 +). The NCI (continuous score) showed a stronger association with overall mortality (hazard ratio (HR) 2.47, 95%CI:2.29-2.67) than the other indices, despite its predictive performance being lower than the CCI and ECI., Conclusion: There were only slight differences in the predictive accuracy among the indices, with the CCI having a slightly better prognostic value than the other indices. All four indices demonstrated a strong association with mortality in men diagnosed with prostate cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To describe real-world clinical and functional outcomes in an Australian cohort of men with localised prostate cancer according to treatment type and risk category., Subjects and Methods: Men diagnosed from 2008 to 2018 who were enrolled in South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a multi-institutional prospective clinical registry-were studied. The main outcome measures were overall survival, cancer-specific survival, decline in functional outcomes, biochemical recurrence and transition to active treatment following active surveillance. Multivariable adjusted models were applied to estimate outcomes., Results: Of the 8513 eligible men, majority of men (46%) underwent radical prostatectomy (RP) followed by external beam radiation therapy with or without androgen deprivation therapy (EBRT +/- ADT) in 22% of the cohort. Five-year overall survival was above 91%, and 5-year prostate cancer-specific survival was above 97% in the low- and intermediate-risk categories across all treatments. Five-year prostate cancer-specific survival in the active surveillance group was 100%. About 37% of men with high-risk disease treated with RP and 17% of men treated with EBRT +/- ADT experienced biochemical recurrence within 5 years of treatment. Of men on active surveillance, 15% of those with low risk and 20% with intermediate risk converted to active treatment within 2 years. The decline in urinary continence and sexual function 12 months after treatment was greatest among men who underwent RP while the decline in bowel function was greatest for men who received EBRT +/- ADT., Conclusion: This contemporary real-world evidence on risk-appropriate treatment outcomes helps inform treatment decision-making for clinicians and patients., Competing Interests: No conflicts of interest., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Analog hardware-based training provides a promising solution to developing state-of-the-art power-hungry artificial intelligence models. Non-volatile memory hardware such as resistive random access memory (RRAM) has the potential to provide a low power alternative. The training accuracy of analog hardware depends on RRAM switching properties including the number of discrete conductance states and conductance variability. Furthermore, the overall power consumption of the system inversely correlates with the RRAM devices conductance. To study material dependence of these properties, TaOx and HfOx RRAM devices in one-transistor one-RRAM configuration (1T1R) were fabricated using a custom 65 nm CMOS fabrication process. Analog switching performance was studied with a range of initial forming compliance current (200-500 µA) and analog switching tests with ultra-short pulse width (300 ps) was carried out. We report that by utilizing low current during electroforming and high compliance current during analog switching, a large number of RRAM conductance states can be achieved while maintaining low conductance state. While both TaOx and HfOx could be switched to more than 20 distinct states, TaOx devices exhibited 10× lower conductance, which reduces total power consumption for array-level operations. Furthermore, we adopted an analog, fully in-memory training algorithm for system-level training accuracy benchmarking and showed that implementing TaOx 1T1R cells could yield an accuracy of up to 96.4% compared to 97% for the floating-point arithmetic baseline, while implementing HfOx devices would yield a maximum accuracy of 90.5%. Our experimental work and benchmarking approach paves the path for future materials engineering in analog-AI hardware for a low-power environment training., (© 2023. Springer Nature Limited.)

Background: Chemotherapy Induced Peripheral Neuropathy (CIPN) is the most common presenting side effect of chemotherapy. As a sensory based neuropathy, this condition can persist for a long time after cessation of chemotherapy and impact the quality of life of cancer survivors. Podiatrists in Australia have been managing people with CIPN related lower limb complications, however guidelines on management of CIPN do not exist. The aim of this study was to achieve consensus and agreement of Australian podiatrists on strategies to best manage people presenting with symptoms of CIPN., Methods: An online three-round modified Delphi survey of Australian podiatrists with expertise in CIPN was conducted in line with recommendations for conducting and reporting of Delphi studies (CREDES). Panellists responded to open-ended questions in Round 1, whereupon their responses were themed into statements and analysed for existing consensus. Statements not reaching consensus were returned during Round 2 to seek agreement from responders using a five-point Likert scale and to allow responders to make further comments. For a statement to reach consensus or agreement, 70% or more of panellists needed to make the same comment or agree or strongly agree with the same themed statement. Statements reaching 50 to 69% consensus or agreement were returned to panellists in Round 3 for them to consider their responses in the light of group outcomes., Results: Round one resulted in 229 comments from 21 of 26 podiatrists who agreed to participate. These comments were themed into 53 statements with 11 consensus statements accepted. Round 2 resulted in 22 statements reaching agreement, and 15 new statements being generated from 18 comments made by 17 respondents. Round 3 resulted in 11 statements reaching agreement. Outcomes were developed into a set of clinical recommendations for diagnosis and management of people presenting with CIPN. These recommendations provide guidance on 1) identifying common signs and symptoms of CIPN including sensory, motor and autonomic symptoms; 2) diagnosis and assessment of CIPN including neurological, motor and dermatological assessment modalities; and 3) best clinical practice and management strategies for CIPN identified by podiatrists including both podiatry and non-podiatry specific care., Conclusions: This is the first study in podiatry literature to develop expert-informed consensus-based recommendations for clinical presentation, diagnosis and assessment and management of people with CIPN. These recommendations aim to help guide podiatrists in the consistent care of people with CIPN., (© 2023. The Author(s).)

Background: Currently, follow-up protocols are applied equally to men on active surveillance (AS) for prostate cancer (PCa) regardless of findings at their initial follow-up biopsy. To determine whether less intensive follow-up is suitable following negative biopsy findings, we assessed the risk of converting to active treatment, any subsequent upgrading, volume progression (>33% positive cores), and serious upgrading (grade group >2) for negative compared with positive findings on initial follow-up biopsy., Methods: 13,161 men from 24 centres participating in the Global Action Plan Active Surveillance Prostate Cancer [GAP3] consortium database, with baseline grade group ≤2, PSA ≤ 20 ng/mL, cT-stage 1-2, diagnosed after 1995, and ≥1 follow-up biopsy, were included in this study. Risk of converting to treatment was assessed using multivariable mixed-effects survival regression. Odds of volume progression, any upgrading and serious upgrading were assessed using mix-effects binary logistic regression for men with ≥2 surveillance biopsies., Results: 27% of the cohort (n = 3590) had no evidence of PCa at their initial biopsy. Over 50% of subsequent biopsies in this group were also negative. A negative initial biopsy was associated with lower risk of conversion (adjusted hazard ratio: 0.45; 95% confidence interval [CI]: 0.42-0.49), subsequent upgrading (adjusted odds ratio [OR]: 0.52; 95%CI: 0.45-0.62) and serious upgrading (OR: 0.74; 95%CI: 0.59-92). Radiological progression was not assessed due to limited imaging data., Conclusion: Despite heterogeneity in follow-up schedules, findings from this global study indicated reduced risk of converting to treatment, volume progression, any upgrading and serious upgrading among men whose initial biopsy findings were negative compared with positive. Given the low risk of progression and high likelihood of further negative biopsy findings, consideration should be given to decreasing follow-up intensity for this group to reduce unnecessary invasive biopsies., (© 2022. The Author(s).)

Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed with surgical colic ( n = 11), peritonitis ( n = 5), typhlocolitis ( n = 2), pneumonia, and pyometra (each n = 1) were included. Antimicrobial treatment was randomized to GENTA (gentamicin 10 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV) or NO GENTA (marbofloxacin 2 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV). The duration of PolyB treatment ranged from 1 to 4 days. Clinical and neurological examinations were performed, and serum PolyB concentrations were measured daily during and three days following PolyB treatment. Urinary analysis, plasma creatinine, urea and SDMA were assessed every other day. Video recordings of neurological examinations were graded by three blinded observers. All horses showed ataxia during PolyB treatment in both groups (median maximum ataxia score of 3/5, range 1-3/5). Weakness was detected in 15/20 (75%) horses. In 8/14 horses, the urinary γ-glutamyltransferase (GGT)/creatinine ratio was elevated. Plasma creatinine was mildly elevated in 1/16 horses, and SDMA in 2/10 horses. Mixed-model analysis showed a significant effect of time since last PolyB dose ( p = 0.0001, proportional odds: 0.94) on the ataxia score. Ataxia and weakness should be considered as reversible adverse effects in hospitalized horses receiving PolyB. Signs of tubular damage occurred in a considerable number of horses; therefore, the nephrotoxic effect of polymyxins should be considered and urinary function monitored.

Background: Active surveillance (AS) aims to reduce overtreatment and minimize the negative side effects of radical therapies (i.e., prostatectomy or radiotherapy) while preserving quality of life. However, a substantial proportion of men can experience a decline in sexual function during AS follow-up. The aim of this study was to identify predictors of declining sexual function among men on AS., Methods: Men enrolled from 2008 to 2018 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a prospective clinical registry-were studied. Sexual function outcomes were measured using expanded prostate cancer index composite (EPIC-26) at baseline and 12-months postdiagnosis. Multivariable regression models adjusted for baseline score and other sociodemographic and clinical factors were applied to identify predictors of sexual function score at 12-months., Results: A total of 554 men were included. Variables that showed significant association with decline in sexual function score at 12-months were: having two or more biopsies after diagnosis (mean change score (MCS): -16.3, p < 0.001) compared with no biopsy, higher number of positive biopsy cores (MCS: -1.6, p = 0.004), being in older age category (above 70 vs. below 60: MCS: -16.7, p < 0.001; 65-70 vs. below 60: MCS: -9.7, p = 0.024), having had depression (MCS: -9.0, p = 0.020), and impaired physical function (MCS: -10.0, p = 0.031). Greater socioeconomic advantage (highest vs. lowest quintile: MCS: 15.7, p = 0.022) and year of diagnosis (MCS: 2.6 for every year, p < 0.001) were positively associated with 12-months sexual function score. Neither biopsy type, biopsy timing nor PSA velocity were associated with declines in sexual function., Conclusions: Our findings suggest that multiple factors affected sexual function during AS. Interventions toward reducing the number of biopsies through less invasive monitory approaches, screening for physical and mental well-being, and targeted emotional support and counseling services may be helpful for men on AS., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Introduction: A variety of treatment options have been described for canine meningoencephalitis of unknown origin (MUO). Few studies focused on radiation therapy as a second line immunomodulating treatment, implicating its effective use. However, a standard radiation therapy protocol is lacking, and further research will help to evaluate the effect of different dose regimens., Methods: Ten dogs diagnosed with MUO based on MRI and CSF findings were prospectively enrolled. The dogs were treated with a shortened whole brain radiation therapy protocol (5 × 4 Gy) in combination with prednisolone. Neurologic changes were quantified using an established scoring scheme. Follow-up MRI and CSF examination was scheduled three months after radiation therapy. Overall survival and time to progression were calculated. Histopathology of the brain was performed in case of death., Results: Seven dogs were diagnosed de novo and three had a history of relapsing MUO. Neurological status improved in all 10 dogs during radiation therapy, with 4/10 returning to normal shortly after radiation therapy. Three dogs died within the first three months after radiation therapy. At follow-up MRI lesions completely resolved in two dogs, partially resolved in five dogs, and progressed in one dog. After follow-up MRI, dogs were further treated with prednisolone monotherapy (two dogs) and additional immunosuppressant drugs (five dogs). Overall, four dogs showed disease progression, with a mean time to progression of 691 days (95%CI: 396-987) and mean overall survival for all dogs was 723 days (95%CI: 436-1011) (both medians not reached). Histopathology confirmed MUO in three dogs but was suggestive for oligodendroglioma in one dog. Radiation induced side effects were not seen., Conclusion: Shortened whole-brain radiation therapy could be an additional treatment option for MUO in conjunction to prednisolone, specifically for cases that require rapid relief of symptoms and with relapsing history., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herzig, Beckmann, Körner, Steffen and Rohrer Bley.)

Objectives: To study how handling missing data on M stage in a clinical cancer register affects estimates of incidence of metastatic prostate cancer., Study Design and Setting: Estimates of age-standardized incidence of metastatic prostate cancer were obtained by the use of data in a population-based clinical cancer register in Sweden and using four methods for imputation of missing M stage. Adjusted survival was used to compare men with known and imputed M stage., Results: The proportion of men with missing M stage was high (66%) and varied according to the risk group and over calendar time. The estimated incidence of metastatic disease varied depending on imputation method, with all methods indicating a decreasing incidence over time. A combination of deterministic imputation (DI) and multiple imputation (MI) produced adjusted survival curves for men with imputed M stage that best resembled the survival for men with known M stage., Conclusions: Plausible estimates of incidence of metastatic prostate cancer in clinical cancer registers can be obtained by the use of a combination of DI of missing M stage and MI., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Induced mutations are an essential source of genetic variation in plant breeding. Ethyl methanesulfonate (EMS) mutagenesis has been frequently applied, and mutants have been detected by phenotypic or genotypic screening of large populations. In the present study, a rapeseed M 2 population was derived from M 1 parent cultivar 'Express' treated with EMS. Whole genomes were sequenced from fourfold (4×) pools of 1988 M 2 plants representing 497 M 2 families. Detected mutations were not evenly distributed and displayed distinct patterns across the 19 chromosomes with lower mutation rates towards the ends. Mutation frequencies ranged from 32/Mb to 48/Mb. On average, 284 442 single nucleotide polymorphisms (SNPs) per M 2 DNA pool were found resulting from EMS mutagenesis. 55% of the SNPs were C → T and G → A transitions, characteristic for EMS induced ('canonical') mutations, whereas the remaining SNPs were 'non-canonical' transitions (15%) or transversions (30%). Additionally, we detected 88 725 high confidence insertions and deletions per pool. On average, each M 2 plant carried 39 120 canonical mutations, corresponding to a frequency of one mutation per 23.6 kb. Approximately 82% of such mutations were located either 5 kb upstream or downstream (56%) of gene coding regions or within intergenic regions (26%). The remaining 18% were located within regions coding for genes. All mutations detected by whole genome sequencing could be verified by comparison with known mutations. Furthermore, all sequences are accessible via the online tool 'EMSBrassica' (http://www.emsbrassica.plantbreeding.uni-kiel.de), which enables direct identification of mutations in any target sequence. The sequence resource described here will further add value for functional gene studies in rapeseed breeding., (© 2022 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Objectives: Hypertensive encephalopathy in cats is an important entity but is underestimated in clinical practice. This could be explained, in part, by non-specific clinical signs. The objective of this study was to characterise the clinical manifestations of hypertensive encephalopathy in cats., Methods: Cats with systemic hypertension (SHT) recognised by routine screening, associated with underlying predisposing disease or a clinical presentation suggestive of SHT (neurological or non-neurological), were prospectively enrolled over a 2-year period. Confirmation of SHT was based on at least two sets of measurements of systolic blood pressure >160 mmHg by Doppler sphygmomanometry., Results: Fifty-six hypertensive cats with a median age of 16.5 years were identified; 31 had neurological signs. In 16/31 cats, neurological abnormalities were the primary complaint. The other 15 cats were first presented to the medicine or ophthalmology service, and neurological disease was recognised based on the cat's history. The most common neurological signs were ataxia, various manifestations of seizures and altered behaviour. Individual cats also showed paresis, pleurothotonus, cervical ventroflexion, stupor and facial nerve paralysis. In 28/30 cats, retinal lesions were detected. Of these 28 cats, six presented with a primary complaint of visual deficits, and neurological signs were not the primary complaint; nine presented with non-specific medical issues, without suspicion of SHT-induced organ damage; in 13 cats, neurological issues were the primary complaint and fundic abnormalities were detected subsequently., Conclusions and Relevance: SHT is common in older cats and the brain is an important target organ; however, neurological deficits are commonly ignored in cats with SHT. Gait abnormalities, (partial) seizures and even mild behavioural changes should prompt clinicians to consider the presence of SHT. A fundic examination in cats with suspected hypertensive encephalopathy is a sensitive test to support the diagnosis.

Background: Intraventricular tumors are rare, optimal treatment is not defined. Symptomatic patients often exhibit life-threatening hydrocephalus. With several months time-to-effect after radiotherapy (RT), increased intracranial pressure is concerning. This increase in pressure can be overcome by ventriculoperitoneal shunting (VPS)., Objectives: Retrospective evaluation of outcome and complications in dogs and cats with intracranial tumors treated with either RT or VPS/RT., Animals: Twelve client-owned cats and dogs., Methods: Dogs and cats with symptomatic intraventricular tumors treated with definitive-intent RT or VPS/RT were included in a retrospective, descriptive case series. Complications, tumor volume evolution, time-to-progression, and survival time were determined., Results: Twelve animals were included: 1 cat and 5 dogs treated with single-modality RT and 4 cats and 2 dogs treated with VPS/RT. Neurological worsening seen in 4/6 animals during single-modality RT and 2/6 died during RT (suspected brain herniation). All dogs with VPS normalized clinically by the end of RT or earlier. Complications occurred in 4/6 animals, all but 1 were successfully managed surgically. Imaging follow-up in 8 animals surviving RT showed a marked decrease in tumor volume. Median survival time was 162 days (95% confidence interval [CI]: 16; infinity) for animals treated with RT and 1103 days (95%CI: 752; infinity) for animals treated with VPS/RT. Median time-to-progression was 71 days (95%CI: 7; infinity) and 895 days (95%CI: 704; infinity) for each group, respectively. Two dogs died because of intraventricular metastasis 427 and 461 days after single-modality RT., Conclusions and Clinical Importance: Ventriculoperitoneal shunting led to rapid normalization of neurological signs and RT had a measurable effect on tumor volume. Combination of VPS/RT seems to be beneficial., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)