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The Inflation Reduction Act (IRA) is regarded as the most prominent piece of federal climate legislation in the U.S. thus far. This paper investigates potential impacts of IRA on the power sector, which is the focus of many core IRA provisions. We summarize a multi-model comparison of IRA to identify robust findings and variation in power sector investments, emissions, and costs across 11 models of the U.S. energy system and electricity sector. Our results project that IRA incentives accelerate the deployment of low-emitting capacity, increasing average annual additions by up to 3.2 times current levels through 2035. CO 2 emissions reductions from electricity generation across models range from 47%–83% below 2005 in 2030 (68% average) and 66%–87% in 2035 (78% average). Our higher clean electricity deployment and lower emissions under IRA, compared with earlier U.S. modeling, change the baseline for future policymaking and analysis. IRA helps to bring projected U.S. power sector and economy-wide emissions closer to near-term climate targets; however, no models indicate that these targets will be met with IRA alone, which suggests that additional policies, incentives, and private sector actions are needed.

It is important to understand the reasons for companion animal relinquishment to help reduce the financial and ethical problems arising from too many dogs and cats in shelters. This study investigates the socioeconomic factors and reasons behind companion animal relinquishment in Australia, utilizing data from five animal shelters, over a five-year period (Financial Year 2018/19 to 2022/23). Descriptive statistics reveal that the median Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD) decile of companion animal guardians who relinquished their companion animal was decile 4 out of 10, indicating that they live in areas of lower-than-average socioeconomic status. Cats accounted for 59.4% and dogs for 40.6% of all relinquishments, with more relinquishments from lower socioeconomic deciles (1–5) (cats: 62.6%, dogs: 65.8%). The median age of relinquished cats was 5 months and dogs 16 months, with human factor-related issues (e.g., Housing, Financial Constraints, Human Healthcare) cited in 86% of cases. Descriptive analysis for the five financial years shows a declining trend in numbers of relinquishments, with housing issues (31.2%) identified as the primary reason, followed by ownership decisions (16.2%), financial constraints (11.2%), and human health issues (10.4%). Comparing the reasons for relinquishment between lower (decile 1–5) and higher (decile 6–10) socioeconomic status demonstrated that financial difficulties were a more common reason in lower vs. higher socioeconomic groups, while human health and family-related issues are more common in higher vs. lower socioeconomic groups. These findings highlight the critical role of socioeconomic factors in understanding why people relinquish their companion animals, which can inform targeted interventions to support companion animal welfare across different socioeconomic backgrounds.

Vulvovaginal melanomas are rare tumors that account for a small fraction of all vulvovaginal cancers. Biologically, they seem to be similar to mucosal and acral melanomas of other sites. There are limited data specific to vulvovaginal melanomas, especially regarding systemic therapies. Most treatment decisions are based on extrapolation from data regarding cutaneous melanomas of other sites. It is reasonable to follow already established guidelines from other professional groups and societies. Outcomes tend to be worse compared with cutaneous melanomas likely because of the later presentation and physical biological characteristics of these tumors.

Background The Franches-Montagnes (FM) is the last native horse breed of Switzerland, established at the end of the 19th century by cross-breeding local mares with Anglo-Norman stallions. We collected high-density SNP genotype data (Axiom™ 670 K Equine genotyping array) from 522 FM horses, including 44 old-type horses (OF), 514 European Warmblood horses (WB) from Sweden and Switzerland (including a stallion used for cross-breeding in 1990), 136 purebred Arabians (AR), 32 Shagya Arabians (SA), and 64 Thoroughbred (TB) horses, as introgressed WB stallions showed TB origin in their pedigrees. The aim of the study was to ascertain fine-scale population structures of the FM breed, including estimation of individual admixture levels and genomic inbreeding (F ROH ) by means of Runs of Homozygosity. Results To assess fine-scale population structures within the FM breed, we applied a three-step approach, which combined admixture, genetic contribution, and F ROH of individuals into a high-resolution network visualization. Based on this approach, we were able to demonstrate that population substructures, as detected by model-based clustering, can be either associated with a different genetic origin or with the progeny of most influential sires. Within the FM breed, admixed horses explained most of the genetic variance of the current breeding population, while OF horses only accounted for a small proportion of the variance. Furthermore, we illustrated that FM horses showed high TB admixture levels and we identified inconsistencies in the origin of FM horses descending from the Arabian stallion Doktryner. With the exception of WB, FM horses were less inbred compared to the other breeds. However, the relatively few but long ROH segments suggested diversity loss in both FM subpopulations. Genes located in FM- and OF-specific ROH islands had known functions involved in conformation and behaviour, two traits that are highly valued by breeders. Conclusions The FM remains the last native Swiss breed, clearly distinguishable from other historically introgressed breeds, but it suffered bottlenecks due to intensive selection of stallions, restrictive mating choices based on arbitrary definitions of pure breeding, and selection of rare coat colours. To preserve the genetic diversity of FM horses, future conservation managements strategies should involve a well-balanced selection of stallions (e.g., by integrating OF stallions in the FM breeding population) and avoid selection for rare coat colours.

High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive behavior and poor prognosis. Cyclin D1 has been reported as a diagnostic immunomarker for high-grade endometrial stromal sarcoma with an YWHAE-FAM22 rearrangement. YWHAE-FAM22 endometrial stromal sarcomas (ESS) represent a clinically aggressive subtype of ESS classified as high-grade endometrial sarcomas, and its distinction from the usual low-grade ESS with JAZF1 rearrangement and from HGUS with no identifiable molecular aberration may be important in guiding clinical management. Median age of the patients is between 55 and 60 years. The most common symptoms are vaginal bleeding, abdominal pain, and increasing abdominal girth. Disease is usually advanced with approximately 70% of the patients staged III to IVaccording to the International Federation of Gynecology and Obstetrics classification. Preferential metastatic locations include peritoneum, lungs, intra-abdominal lymph nodes, and bone. Median progression-free survival ranged from 7 to 10 months, and median overall survival ranged from 11 to 23 months. There is no clear prognostic factor identified for HGUS, not even stage. The standard management for HGUS consists of total hysterectomy and bilateral salpingooophorectomy. Systematic lymphadenectomy is not recommended. Adjuvant therapies, such as chemotherapy and radiotherapy, have to be discussed in multidisciplinary staff meetings.

The social determinants of health (SDH) focus on the social, physical and economic factors that impact human health. Studies have revealed that animal guardians face a range of challenges in attaining positive welfare outcomes for their companion animals, which can be influenced by socioeconomic and environmental factors. Despite this, there is a lack of research specifically exploring the relationship between SDH and animal welfare outcomes. Given that the SDH impact on humans, which in turn directly impacts on their companion animal, it is important to adapt an SDH framework for companion animal welfare by characterising the impact of the SDH on companion animal guardians in their attempts to care for their animals and, by extension, the associated welfare outcomes. This paper explores how these human health determinants may impact animal welfare and the possible challenges that may arise for the guardian when attempting to meet their companion animal’s welfare needs. By integrating the SDH with other key frameworks, including the five domains model of animal welfare, through multidisciplinary collaboration, this framework can be used to inform future programs aiming to improve animal welfare.

Background Cell therapies present an exciting potential but there is a long history of expensive translational failures in stroke research. Researchers engaged in cell therapy research would benefit from a practical framework that can help in planning research and development of investigational cell therapies into viable medical products. Methods We developed a checklist using a mixed methodology approach to evaluate the impact of study design, regulatory policy, ethical, and health economic considerations for efficient implementation of early phase cell therapy studies. Results The checklist comprises a series of questions arranged under four domains: the first concerns study design such as characterization of target study population, trial design, endpoints and operational fit of dosage, time, and route of administration to target populations. A second domain addresses the data package required for regulatory approval relevant to the intended use (allogeneic/autologous; homologous/non-homologous; nature of cell processing). The third domain comprises patient involvement to ensure relevant data is collected via targeted study design. The final domain requires the team to determine the critical data elements that could be built into study design to enable health economic data collection to be started at an early phase of the study. Conclusions The CT2S checklist can help to determine areas of expertise gaps and enable research groups to appropriately allocate resources for capacity building. Use of this checklist will allow identification of key areas where trial planning needs to be optimized, as well as helping to identify resources that need to be secured. The CT2S checklist can also serve as a general cell therapy research decision aid to improve research output and accelerate new cell therapy development.

OBJECTIVESThe Gynecologic Cancer InterGroup aimed to provide an overview of uterine and ovarian leiomyosarcoma management. METHODSPublished articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the Gynecologic Cancer InterGroup for review and comment, and appropriate revisions were made. RESULTSThe approach to management of uterine and ovarian leiomyosarcoma management is reviewed. CONCLUSIONSUterine and ovarian leiomyosarcomas are rare and aggressive cancers that require specialized expertise for optimal management.

Background Desmoid tumors (DT) are rare, locally aggressive neoplasms that affect a young population and have a tendency for recurrence. There is sparse contemporary real‐world data to guide practice for DT. Here, we report on a large cohort of DT patients, describing patterns of care and clinical outcomes. Methods Data on DT patients first seen between 2010 and 2021 were extracted from a prospective database and supplemented with a retrospective review of hospital records. Trends in treatment use were analyzed using the Cochran‐Armitage test. Time‐to‐next intervention (TTNI) was estimated with the Kaplan–Meier method. Imaging response was categorized using the RECIST v1.1 criteria. Results A total of 135 patients, 265 treatment episodes were analyzed. Median follow‐up was 4.3 years. The common tumor sites were abdominal wall (27%), upper limb (20%), lower limb (16%), and intra‐abdominal (15%). Over time, the proportion of patients receiving no upfront treatment was stable (2010–2013: 31%, 2014–2017: 35%, 2018–2021: 29%; p = 0.5), but there was increasing first‐line use of NSAID/tamoxifen (7%, 41%, 47%; p < 0.001), and decreasing first‐line use of radiotherapy (35%, 14%, 4%; p < 0.001) and surgery (28%, 8%, 18%; p < 0.05). At 5 years, the proportion not requiring treatment switch was highest following surgery (72%), radiotherapy (66%), and no upfront therapy (52%). 12% and 5% of patients without treatment achieved partial and complete imaging responses at 2 years. Conclusion We highlight the heterogeneity and trends in DT management over a 12‐year period, affirming the role of active surveillance, radiotherapy, and surgery in selected patients. Medical therapies are evolving and may significantly influence the DT management paradigm.