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Abstract Parturition timing has long been a topic of interest in ungulate research. However, few studies have examined parturition timing at fine scale (e.g.,

Abstract Background Information on reproduction of harvested species such as mule deer (Odocoileus hemionus) is vital for conservation and management. Furthermore, parturition in ungulates may be detected using patterns of movement logged by GPS transmitters. Several movement-based methods have been developed to detect parturition in ungulates including the Peterson method, behavioral change point analysis (BCPA), rolling minimum convex polygons (rMCP), individual-based method (IBM), and population-based method (PBM). Our objectives were to (1) test the accuracy and the precision of each previously described method and (2) develop an improved method optimized for mule deer that incorporated aspects of the other methods. Methods We determined parturition timing and status for female mule deer fitted with GPS collars and implanted with vaginal implant transmitters (VITs). We used movement patterns before and after parturition to set movement thresholds for each movement-based method. Following model training, we used location and birth date data from an external dataset to test the effectiveness of each movement-based method. Additionally, we developed a novel method for detecting parturition called the analysis of parturition indicators (API). We used two regression analyses to determine the accuracy and precision of estimates generated by each method. Results The six methods we employed varied in accuracy, with the API, rMCP, and BCPA being most accurate. Precision also varied among methods, with the API, rMCP, and PBM generating the most precise estimates of parturition dates. The API and the rMCP performed similarly and better overall than any of the other existing methods. Conclusions We found that movement-based methods could be used to accurately and precisely detect parturition in mule deer. Further, we determined that the API and rMCP methods had the greatest overall success at detecting parturition in mule deer. The relative success of the API and rMCP may be attributed to the fact that both methods use home range size to detect parturition and are validated using known parturition dates of collared deer. We present the API as an efficient method of estimating birth status and timing of parturition of mule deer fitted with GPS transmitters, as well as affirm the effectiveness of a previously developed method, rMCP.

Background Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. Methods and Results The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta‐Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin‐like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47–0.7]; P=3.13E‐05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44–0.69]; P=0.0001), and DNASE1 (deoxyribonuclease‐1) (HR, 0.5704 [95% CI, 0.46–0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α‐1, collagen XV α‐1), metabolism (pancreatic α‐amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. Conclusions Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

Abstract Observed links between parasites, such as ticks, and climate change have aroused concern for human health, wildlife population dynamics, and broader ecosystem effects. The one‐host life history of the winter tick (Dermacentor albipictus) links each annual cohort to environmental conditions during three specific time periods when they are predictably vulnerable: spring detachment from hosts, summer larval stage, and fall questing for hosts. We used mixed‐effects generalized linear models to investigate the drivers of tick loads carried by moose (Alces alces) relative to these time periods and across 750 moose, 10 years, and 16 study areas in the western United States. We tested for the effects of biotic factors (moose density, shared winter range, vegetation, migratory behavior) and weather conditions (temperature, snow, humidity) during each seasonal period when ticks are vulnerable and off‐host. We found that warm climatic regions, warm seasonal periods across multiple partitions of the annual tick life cycle, and warm years relative to long‐term averages each contributed to increased tick loads. We also found important effects of snow and other biotic factors such as host density and vegetation. Tick loads in the western United States were, on average, lower than those where tick‐related die‐offs in moose populations have occurred recently, but loads carried by some individuals may be sufficient to cause mortality. Lastly, we found interannual variation in tick loads to be most correlated with spring snowpack, suggesting this environmental component may have the highest potential to induce change in tick load dynamics in the immediate future of this region.

Many of the larger US metropolitan regions promote polycentric development as a way of fostering livability, accessibility, and sustainability. Polycentric urban structures can increase transit ridership, promote active transportation, and decrease vehicle miles traveled (VMT) and CO2 emissions. Although many regions include ambitious polycentric aspirations in their plans, only a few follow up with rigorous implementation and see their efforts come to fruition. The topic of implementation is also widely omitted from scholarly inquiry. This research aims to explore three examples of successful implementation of urban polycentricity: Portland, Oregon; Seattle, Washington; and Denver, Colorado. Each region employs a very distinct polycentric development model, but each relies heavily on its regional governance organization for direction, guidance, and even command in the implementation process. To understand specific strategies and methods used by each region, the authors conducted interviews with metropolitan planning organizations, central cities, and transit agencies in the three regions and used qualitative techniques to analyze the interview transcripts and collected documents. As regional governance organizations play a crucial role in implementing regional plans, their policies and practices were also investigated by the authors. Based on collected data and insights, we conclude that the three regions are great examples of an advanced implementation of polycentric development. This research can be helpful to other US metropolitan regions that wish to promote polycentric development. The lessons learned from the three case studies can provide guidance and possible paths to successful implementation.

Nasal dermoid cysts are surgically treated using external incision, open rhinoplasty, transnasal endoscopy, or combined approaches. It is unclear how these approaches differ with regard to the incidence of adverse events. We conducted a systematic review of studies on the surgical management of midline nasal dermoids. Following data abstraction, we carried out a series of single-arm meta-analyses to estimate summary risks of recurrence and combined adverse events (recurrence, revision, infection, or readmission) according to the surgical approach. Forty-three eligible studies published between 1958 and 2020 reported on 439 cases of nasal dermoid cysts. Treatment approaches included external incision (25 studies), rhinoplasty (15 studies), and transnasal endoscopy (5 studies). To our knowledge, no study has compared outcome incidence between the surgical approaches. External incision had the lowest summary incidence of both recurrence (1.78% [95% CI: 0.57%, 3.65%]) and combined adverse events (4.94% [95% CI: 2.72%, 7.77%]). Rhinoplasty had a higher incidence of recurrence (4.81% [95% CI: 0.91%, 11.6%]) and combined adverse events (8.32% [95% CI: 2.77%, 16.5%]), and transnasal endoscopy had the highest incidence of recurrence (the only reported adverse event; 7.89% [95% CI: 0%, 28.9%]). Our results suggest that the incidence of adverse events was lowest among patients who were subjected to external incision for nasal dermoid removal. Incidence was higher for patients who underwent rhinoplasty and the highest for patients who underwent transnasal endoscopy. Future work on this topic should include well-designed prospective studies that compare rates of adverse events and cosmetic outcomes between surgical approaches. [ABSTRACT FROM AUTHOR]

Approximately 50% of melanoma patients fail to respond to immune checkpoint blockade (ICB), and acquired resistance hampers long-term survival in about half of initially responding patients. Whether targeting BET reader proteins, implicated in epigenetic dysregulation, can enhance ICB response rates and durability, remains to be determined. Here we show elevated BET proteins correlate with poor survival and ICB responses in melanoma patients. The BET inhibitor IBET151, combined with anti-CTLA-4, overcame innate ICB resistance however, sequential BET inhibition failed against acquired resistance in mouse models. Combination treatment response in the innate resistance model induced changes in tumor-infiltrating immune cells, reducing myeloid-derived suppressor cells (MDSCs). CD4+ and CD8+ T cells showed decreased expression of inhibitory receptors, with reduced TIM3, LAG3, and BTLA checkpoint expression. In human PBMCs in vitro, BET inhibition reduced expression of immune checkpoints in CD4+ and CD8+ T cells, restoring effector cytokines and downregulating the transcriptional driver TOX. BET proteins in melanoma may play an oncogenic role by inducing immune suppression and driving T cell dysfunction. The study demonstrates an effective combination for innately unresponsive melanoma patients to checkpoint inhibitor immunotherapy, yet highlights BET inhibitors' limitations in an acquired resistance context., (© 2024 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)