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This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [ 18 F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway., Competing Interests: A.E.L.W., M.P.H., L.J.D., E.M.-L., F.L.W.V.J.S., L.A.H., H.S. and K.L.B. have no competing interests to report. C.R.B. has recently served as a consultant for NeuraModix and Abbott and holds intellectual property related to neuromodulation therapy. J.S.A. has received honoraria from Medtronic. R.E.G. received research support from NeuroPace, Medtronic and Boston Scientific, and consulting payments from Medtronic, Boston Scientific, Abbott Labs and Nia Therapeutics, and holds equity interest in Nia Therapeutics; the arrangements are all approved by Emory University. L.J. and M.J.M. have equity ownership with NeuroPace and are employees of NeuroPace, Inc. J.D.R. has received consulting payments from Medtronic, Corlieve and NeuroPace., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Spaying female and castrating male dogs, hereinafter referred to as neutering, is a US convention for the first year in the dog's life. Research on 35 breeds of dogs revealed that early neutering increases risks of joint disorders, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament (CCL) tear, or cancers, such as lymphosarcoma (LSA), mast cell tumor (MCT), hemangiosarcoma (has), or osteosarcoma (OSA), for some breeds. Joint disorder risks are heightened for some larger breeds and for mixed-breed dogs weighing more than 20 kg. Some breeds had elevated risks for cancers. Several other research teams have reported health complications associated with neutering. The study goal includes using the same methodology for data collection and analyses as in the study on 35 breeds for five additional dog breeds weighing at least 20 kg. The breeds were: German Short/Wirehaired Pointer, Mastiff, Newfoundland, Rhodesian Ridgeback, and Siberian Husky. Major differences among breeds appeared in vulnerability to joint disorders and cancers with early neutering: male and female Pointer breeds had elevated joint disorders and increased cancers; male Mastiff breeds had increased CCL and LSA and females had non-significant elevated CCL risks; female Newfoundland breeds had heightened risks for joint disorders and males had non-significant elevated risks; female Ridgeback breeds had heightened MCT with very early neutering; and Siberian Huskies showed no significant effects on joint disorders or cancers, but female breeds showed a non-significant but elevated CCL. Updated guidelines cover 40 dog breeds. These results further emphasize the importance of personalized decisions regarding the neutering of dogs, considering the dog's breed, sex, and context., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hart, Thigpen, Hart, Willits, Lee, Babchuk, Lee, Ho, Clarkson and Chou.)

Progression through the profession of pharmacy is filled with many milestones that can contribute to feelings of stress, rejection, and isolation. For Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, and Asexual+(LGBTQIA+) students and practitioners, these feelings can be compounded by similar issues experienced by their sexual orientation or gender identity. Historically, LGBTQIA+ students, new practitioners, and seasoned professionals alike have lacked visible role models for how to intersect personal and professional identity in the pharmacy profession. In this paper, the authors describe experiences of intersecting personal queer identities with professional pharmacy identities; exploring barriers to integration and developing solutions to overcome these barriers. The authors also share how the formation of a collective of LGBTQIA+ practitioners and educators has led to a unified voice to advocate for the advancement of LGBTQIA+ healthcare in pharmacy education and practice. This manuscript will provide readers with a guide to navigate and address issues with the integration of personal and professional identity to lead to practice that validates personal identity as important, valuable, and affirmed., 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 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the association between number, timing, and type of Advanced Pharmacy Practice Experiences (APPEs) and likelihood of postgraduate year one (PGY1) residency match outcomes., Methods: A retrospective cohort study was performed among PGY1 residency-seeking pharmacy students from graduating years 2018-2021 as identified from the National Matching Services Inc. enrollee list. The number of APPEs of interest (AOI) most likely to align with general PGY1 residencies (acute care, ambulatory care, and elective rotations with significant direct patient care interactions) completed before January of the respective graduation year (GY) was compared between matched and unmatched students to a PGY1 program in any phase. Classification and regression tree (CART) analyses were performed to identify the AOI threshold associated with an increased likelihood of matching., Results: Among 155 students meeting inclusion criteria, 115 students (74%) matched during the study period. The probability of matching was 36%, 74%, and 83% for students completing two, three or four AOI, respectively. CART analyses identified three or more AOI completed prior to January of the GY as the threshold significantly associated with PGY1 residency matching., Conclusion: Completing at least three AOI before January of the GY was associated with a significantly increased probability of PGY1 residency matching. These findings may influence students' preferences for sequencing of APPEs to improve match results, but may be limited by institutional capacity., 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 Inc. All rights reserved.)

The number of pet cats in South Korea has sharply increased since 2010. Problems have arisen with feral or stray cats, creating conflict among residents, to such an extent that the government provides some sites for people to offer feeding stations for the stray cats. This study investigated hypotheses on people's attitudes toward feral cats in Seoul, South Korea: (i) dog and cat owners would show more positive attitudes than non-owners toward feral cats; (ii) females would have more positive attitudes toward feral cats than males; (iii) the number of Seoul-provided feeding stations by district would be correlated with people's positive attitudes toward feral cats. Responses from 7,394 participants were used for the final analyses with 3,179 males, 3,607 females, and 599 others (includes "decline to state"). Cat owners reported more extremely positive attitudes toward feral cats than people who had no cats. Females more often had cats than males, and they were more extremely positive toward pet and feral cats than males, and strongly opposed to culling as a management strategy. The attitudes toward feral cats of people with only dogs were intermediate between people with cats and people without pets, more resembling those of people without pets. There was a correlation between the number of city-provided feeding stations and people's attitudes toward feral cats, but only in the areas with at least 40 feeder stations; having many city-provided feeding stations was associated with very negative attitudes to feral cats. Whether the very large number of feeding stations were provided in the two neighborhoods due to a previously excessive number of feral cats in those neighborhoods, vs. those feeding stations attracting or provisioning an ever-growing number of feral cats, is unknown. These results show sharp differences in attitudes between cat owners and non-owners, and between males and females. Results resemble findings in other studies, perhaps with more extreme differences between sub-groups. The study revealed that attitudes toward pet and feral cats in Seoul were complex and varied with pet ownership, with sex, and with neighborhood context., 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 Kim, Kenyon, Cheong, Lee and Hart.)

Many dogs and cats were euthanized in US animal shelters through the 1940s, sharply declining in the 1980s. Early age neutering of young cats and dogs grew frequent in the 1990s; adoptions from shelters increased, leading to a decline in shelter euthanasia of dogs. Several publications, beginning in 2013, revealed heightened risks of joint disorders and some cancers for some dog breeds when neutered at young ages. These risks are breed-, gender-, and body-size specific and related to neutering age. Current guidelines suggest making a personalized decision for each dog's neutering age. Recommendations are presented for 40 breeds and mixed-breed weight classes., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In Korea, Institutional Animal Care and Use Committees (IACUCs) have been legally required to apply the Three Rs principles (i.e. replacement , reduction and refinement ) and undertake the ethical review of animal study protocols, since 2008. According to Korean law, each IACUC is required to appoint at least one lay member recommended by a non-governmental animal protection organisation, who participates in the ethical review process as part of this role. Despite the importance of the Three Rs and the ethical review process, limited information and practical resources are available for IACUC members in the Korean language, particularly for lay members who are inexperienced in animal experimentation. In January 2020, the Animal and Plant Quarantine Agency announced the funding for a six-month research project to develop guidance to assist IACUC members in carrying out effective and efficient protocol reviews in line with Korean legislative requirements. This funding was awarded for the production of two IACUC guidance documents - 'Guide for Animal Study Protocols' and 'Guide for the IACUC Lay Member' - which were published in December 2020. These guidance documents aim to foster the implementation of the Three Rs and provide practical resources for IACUC members, researchers and other relevant personnel. This paper describes the framework for animal use in Korea and the overall production of these two IACUC Guidance Documents.

For professionals caring for humans or non-human animals, many joys are to be found in working towards what an individual believes to be their calling, especially as they contribute to purposeful, meaningful work consistent with and intrinsic to their own values and beliefs. However, there can be downfalls. Empathic strain, conflict between co-workers, dissatisfaction with upper management, lack of opportunities to make positive changes, limited or no access to level and experience-appropriate professional development, and other stressors are all risks carried by organisations concerned with animal welfare. In the present study, a survey on job satisfaction and workplace stressors was completed by 311 zoo and aquarium professionals working in a range of roles from junior animal care staff to curator. Respondent profiles were created using Multiple Correspondence Analysis (MCA) and four distinct clusters were identified through Hierarchical Clustering on Principal Components (HCPC), highlighting common themes in different levels of experience and in job roles regarding stressors, satisfaction, and feelings about their work and workplaces. Overall, many zoo professionals were concerned with lacking the ability to feel empowered to do their best for animal welfare, and they described a link between the staff welfare and their perceptions of the welfare of the animals they cared for. Through identifying and understanding where organisations can better support their staff it is possible to target and reduce the number of common stressors faced by zoo professionals, leading to increased staff retention, higher job satisfaction, and an improved ability to perform at their best for animal welfare.

The veterinary profession has a unique responsibility to animals during the final stages of their lives. The veterinarian's obligations extend to humane endings, involving all species of animals in a range of circumstances including, but not limited to, euthanasia of individually owned animals, euthanasia of animals for research purposes, depopulation of animals during emergencies, and slaughter of animals raised for food. The veterinary profession continues to improve animal welfare through advances in end-of-life decision-making and humane killing techniques,1-3 but the psychological impacts on veterinarians have not received the same level of consideration. Building on the influential AVMA Humane Endings Guideline, the AVMA recognizes that support for the mental health of veterinarians engaged in such activities needs to be a priority. This article aims to provide the foundation and rationale for improved preparation and establishment of sustainable mental health resources and to offer recommendations on pragmatic solutions to support and prepare veterinary professionals as leaders impacted by participation in humane endings-related activities. While end-of-life decision-making and implementation may present mental health challenges to veterinarians, it is crucial to recognize that there are stressors specific to each situation and that every individual's experience is valid. Addressing the mental health issues surrounding the decision-making process and implementation of humane endings activities start with a comprehensive understanding of each activity's unique context and the veterinarian's leadership role. Therefore, this article highlights the psychological impact of depopulation and its similarities and exclusive challenges compared with euthanasia and humane slaughter.

The size of adult male giraffes ( Giraffa giraffa angolensis ) far exceeds the size of the females. At the Namutoni waterholes in Etosha National Park, bulls were seen many times each day screening adult females for their pending sexual receptivity by provoking them to urinate; this mainly involved sniffing their genitalia. If the female accedes to the male's invitation, she widens her hindleg stance, braces her body, and then urinates, usually for at least five seconds. The male places his muzzle and tongue in the urine stream, and then performs flehmen, often raising his head high in the air. Males never investigated urine on the ground. The bilateral papillae on the giraffe's hard palate connect with the nasopalatine ducts, which enter the bilateral vomeronasal organ (VNO). Unlike many mammals, the giraffe's VNO lacks a prominent connection to the nasal cavity and its connections to the oral cavity are primarily via the incisive papillae. Most days, some giraffes were observed searching for bones for extended periods, chewing them, and sometimes being troubled by a bone stuck in their mouth. A giraffe killed by lions was frequented for several days by a procession of giraffes investigating the carcass. A very dark-colored bull giraffe emitted loud pulsed growls that drove off most of the surrounding giraffes.

Polypharmacy in the emergency department (ED) presents additional challenges for older adults with acute illnesses but is also an opportunity for healthcare providers to prevent adverse drug events as well as the use of potentially inappropriate medications. Older patients have complex health-related needs and are at risk for medication-related complications during an ED visit. Implementing mitigating strategies of performing medication reconciliation and review, using existing implicit or explicit tools to evaluate medications, and deprescribing or de-escalating high-risk medications are critical to positive health outcomes. These practices can help to optimize pharmacologic interventions for older patients in the ED., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Doctor of Pharmacy (PharmD) students and faculty at University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) were highly motivated to support local and regional COVID-19 vaccination efforts, which began in January 2021. A system was created to streamline requests for SSPPS volunteers, maximize opportunities for student learning and engagement, and ensure adherence to pharmacy practice standards and laws in the process of assisting with vaccination efforts in the community. An existing model for approving student organized events was modified to fit additional needs for COVID-19 vaccination efforts by SSPPS students and faculty. For each event, students completed a standardized form containing event details including location, date, time, pharmacist preceptors, and duties. All requests were screened by designated SSPPS faculty to ensure student safety, availability, and feasibility. After each event, students and faculty completed a unique online form designed to track volunteer hours. Students received course credit for volunteering and completing a standardized self-reflection. Comments from students' reflections ( n = 74) were analyzed to identify common challenges. Between 11 January 2021 and 31 May 2021, SSPPS faculty and students volunteered for 245 shifts, totaling 1346 h. Students encountered several logistical challenges, such as availability of vaccines. The system utilized allowed for SSPPS students and faculty to play an integral role in COVID-19 vaccination efforts throughout the region.

Negative stress due to human handling has been reported for a number of domestic animals, including dogs. Many companion dogs display significant stress during routine care in the veterinary clinic, risking injury to staff and potentially compromising the quality of care that these dogs receive. On the other hand, positive interactions with humans can have a beneficial effect on dogs, particularly in stressful situations such as animal shelters. Research has shown that dogs can detect human emotions through visual, auditory, and chemical channels, and that dogs will exhibit emotional contagion, particularly with familiar humans. This study investigated relationships between emotional states of dogs and unfamiliar human handlers, using simultaneous measures of cardiac activity and behavior, during two sessions of three consecutive routine handling sets. Measures of cardiac activity included mean heart rate (HR mean ), and two measures of heart rate variability (HRV): the root mean square of successive differences between normal heartbeats (RMSSD); and the high frequency absolute power component of HRV, log transformed (HF log ). We also assessed human handlers' emotional state during handling sessions following an intervention designed to reduce stress, compared with sessions conducted on a different day and following a control activity. Polar H10 cardiac sensors were used to simultaneously record cardiac activity for both canine and human participants, and behavioral data were collected via digital video. The strongest influence on the dogs' stress levels in our study was found to be increasing familiarity with the setting and the handler; HR mean and SI decreased, and HRV (as RMSSD) increased, significantly from the first to the third handling set. Canine HRV (as HF log ) was also highest in set 3, although the difference was not statistically significant. There were no strong patterns found in the human cardiac data across handling set, session, or by pre-handling activity. We did not find consistent support for emotional contagion between the dogs and their handlers in this study, perhaps due to the brief time that the dogs spent with the handlers. Recommendations for application to dog handling, and limitations of our methods, are described., Competing Interests: DD owns company StressReductionPrograms.com. 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 © 2022 Grigg, Liu, Dempsey, Wong, Bain, Sollers, Haddock, Kogan, Barnhard, Tringali, Thigpen and Hart.)

Long-term HIV/AIDS survivors responded online concerning their experiences during the AIDS and COVID pandemics. Recruited from web-based organizations for AIDS survivors, 147 answered questions on: frequency of experiencing stigma, isolation, aloneness, or grief/sadness; pet ownership; and sources of human support during each pandemic. Conditional inference trees were run to identify relevant demographic factors. Post-hoc comparisons were conducted to compare dog owners and cat owners. AIDS survivors reported more frequent feelings of stigma, aloneness, and sadness/grief during the AIDS pandemic than during COVID. Cat owners' sadness/grief during AIDS was greater than non-owners. During COVID, older respondents unexpectedly were less often sad/grieving than younger ones; dog owners less often felt alone and isolated than non-dog owners. Support during the AIDS pandemic retrospectively was rated better for older respondents; young gays' support was greater than young straights. During COVID, support was better for men than women. Contrastingly, women with pets felt less support than those without; men with dogs felt more support than those without. Cat owners more often felt isolated and unsupported during COVID than dog owners. Few dog or cat owners received support from family members in either pandemic; during AIDS, family support was better for owners of dogs than cats.

Objectives: Improvement in the antenatal diagnosis of placenta accreta spectrum (PAS) would allow preparation for delivery in a referral center, leading to decreased maternal morbidity and mortality. Our objectives were to assess the performance of classic ultrasound signs and to determine the value of novel ultrasound signs in the detection of PAS., Methods: This was a retrospective cohort study of women with second-trimester placenta previa who underwent third-trimester transvaginal ultrasound and all women with PAS in seven medical centers. A retrospective image review for signs of PAS was conducted by three maternal-fetal medicine physicians. Classic signs of PAS were defined as placental lacunae, bladder-wall interruption, myometrial thinning and subplacental hypervascularity. Novel signs were defined as small placental lacunae, irregular placenta-myometrium interface (PMI), vascular PMI, non-tapered placental edge and placental bulge towards the bladder. PAS was diagnosed based on difficulty in removing the placenta or pathological examination of the placenta. Multivariate regression analysis was performed and receiver-operating-characteristics (ROC) curves were generated to assess the performance of combined novel signs, combined classic signs and a model combining classic and novel signs., Results: A total of 385 cases with placenta previa were included, of which 55 had PAS (28 had placenta accreta, 11 had placenta increta and 16 had placenta percreta). The areas under the ROC curves for classic markers, novel markers and a model combining classic and novel markers for the detection of PAS were 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.77-0.90) and 0.88 (95% CI, 0.82-0.94), respectively. A model combining classic and novel signs performed better than did the classic or novel markers individually (P = 0.03). An increasing number of signs was associated with a greater likelihood of PAS. With the presence of 0, 1, 2 and ≥ 3 classic ultrasound signs, PAS was present in 5%, 24%, 57% and 94% of cases, respectively., Conclusions: We have confirmed the value of classic ultrasound signs of PAS. The use of novel ultrasound signs in combination with classic signs improved the detection of PAS. These findings have clinical implications for the detection of PAS and may help guide the obstetric management of patients diagnosed with these placental disorders. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

This study explored the perspectives of elephant mahouts ( n = 55) and tiger caregivers ( n = 18) working in 4 private or 2 government facilities in Thailand to learn their experiences and viewpoints pertaining to use of animals in tourism. Interviews were conducted in Thailand at facilities in four cities. Mahouts working in private tourism facilities used one-to-one management and were significantly younger and more poorly compensated than those working at government-funded zoos, where some had shifted to group management. Tiger caregivers in tourism had direct contact with young tigers, with group management; these caregivers also were significantly younger than in government zoos, and with fewer benefits. Mahouts and tiger caregivers differed in how they viewed their relationships with their animals. Most mahouts considered their elephants as family members; a slight majority of these questioned the ethics of use of elephants in tourism. Tiger caregivers classified tigers as family or friend equally often; one-third of tiger caregivers declined answering on their approval of using tigers in tourism. What to do with aging tigers is a problem; this may explain some tiger caregivers' reticence to answer questions about using young tigers in tourism. While solving some problems, animal tourism creates several challenges.

Background: Central nervous system (CNS)-active medication use is an important modifiable risk factor for falls in older adults. A fall-related injury should prompt providers to evaluate and reduce CNS-active medications to prevent recurrent falls. We evaluated change in CNS-active medications up to 12 months following a fall-related injury in community-dwelling older adults compared with a matched cohort without fall-related injury., Methods: Participants were from the Adult Changes in Thought study conducted at Kaiser Permanente Washington. Fall-related injury codes between 1994 and 2014 defined index encounters in participants with no evidence of such injuries in the preceding year. We matched each fall-related injury index encounter with up to five randomly selected clinical encounters from participants without injury. Using automated pharmacy data, we estimated the average change in CNS-active medication use at 3, 6, and 12 months post-index according to the presence or absence of CNS-active medication use before index., Results: One thousand five hundred sixteen participants with fall-related injury index encounters (449 CNS-active users, 1067 nonusers) were matched to 7014 index encounters from people without fall-related injuries (1751 users, 5236 nonusers). Among CNS-active users at the index encounter, those with fall-related injury had an average decrease in standard daily doses (SDDs) at 12 months (-0.43; 95% CI: -0.63 to -0.23), and those without injury had a greater (p = 0.047) average decrease (-0.66; 95% CI: -0.78 to -0.55). Among nonusers at index, those with fall-related injury had a smaller increase than those without injury (+0.17, 95% CI: +0.13 to +0.21, vs. +0.24, 95% CI: +0.20 to +0.28, p = 0.005)., Conclusions: The differences in CNS-active medication use change over 12 months between those with and without fall-related injury were small and unlikely to be clinically significant. These results suggest that fall risk-increasing drug use is not reduced following a fall-related injury, thus opportunities exist to reduce CNS-active medications, a potentially modifiable risk factor for falls., (© 2021 The American Geriatrics Society.)