Heat stress from current and predicted increases in temperature impairs lambing rates and birth weights in the Australian sheep flock.

Livestock heat stress threatens production, particularly in semi-arid, arid and tropical regions. Using established temperature thresholds for sheep, we modelled +1 °C and +3 °C temperature increases over the historical baseline, estimating that 2.1 million potential lambs are lost annually due to heat stress alone, increasing to 2.5 and 3.3 million, respectively, as temperatures rise. Heat stress poses risks at key periods of the reproductive cycle, with consequences across the Australian sheep flock.

Tracking Cancer: Exploring Heart Rate Variability Patterns by Cancer Location and Progression.

Reduced heart rate variability (HRV) is an autonomic nervous system (ANS) response that may indicate dysfunction in the human body. Consistent evidence shows cancer patients elicit lower HRV; however, only select cancer locations were previously evaluated. Thus, the aim of the current study was to explore HRV patterns in patients diagnosed with and in varying stages of the most prevalent cancers. At a single tertiary academic medical center, 798 patients were recruited. HRV was measured via an armband monitor (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA) equipped with electrocardiographic capabilities and was recorded for 5 to 7 min with patients seated in an upright position. Three time-domain metrics were calculated: SDNN (standard deviation of the NN interval), rMSSD (the root mean square of successive differences of NN intervals), and the percentage of time in which the change in successive NN intervals exceeds 50ms within a measurement (pNN50). Of the 798 patients, 399 were diagnosed with cancer. Cancer diagnoses were obtained via medical records one week following the measurement. Analysis of variance models were performed comparing the HRV patterns between different cancers, cancer stages (I-IV), and demographic strata. A total of 85% of the cancer patients had breast, gastrointestinal, genitourinary, or respiratory cancer. The cancer patients were compared to a control non-cancer patient population with similar patient size and distributions for sex, age, body mass index, and co-morbidities. For all HRV metrics, non-cancer patients exhibited significantly higher rMSSDs (11.1 to 13.9 ms, p < 0.0001), SDNNs (22.8 to 27.7 ms, p < 0.0001), and pNN50s (6.2 to 8.1%, p < 0.0001) compared to stage I or II cancer patients. This significant trend was consistently observed across each cancer location. Similarly, compared to patients with stage III or IV cancer, non-cancer patients possessed lower HRs (-11.8 to -14.0 bpm, p < 0.0001) and higher rMSSDs (+31.7 to +32.8 ms, p < 0.0001), SDNNs (+45.2 to +45.8 ms), p < 0.0001, and pNN50s (19.2 to 21.6%, p < 0.0001). The HR and HRV patterns observed did not significantly differ between cancer locations (p = 0.96 to 1.00). The depressed HRVs observed uniformly across the most prevalent cancer locations and stages appeared to occur independent of patients' co-morbidities. This finding highlights the potentially effective use of HRV as a non-invasive tool for determining common cancer locations and their respective stages. More studies are needed to delineate the HRV patterns across different ages, between sexes and race/ethnic groups.

Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.

Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.

Internal or External Training Load Metrics: Which Is Best for Tracking Autonomic Nervous System Recovery and Function in Collegiate American Football?

Sport coaches increasingly rely on external load metrics for designing effective training programs. However, their accuracy in estimating internal load is inconsistent, and their ability to predict autonomic nervous system (ANS) deterioration is unknown. This study aimed to evaluate the relationships between internal and external training load metrics and ANS recovery and function in college football players. Football athletes were recruited from a D1 college in the southeastern US and prospectively followed for 27 weeks. Internal load was estimated via exercise cardiac load (ECL; average training heartrate (HR) × session duration) and measured with an armband monitor equipped with electrocardiographic capabilities (Warfighter MonitorTM (WFM), Tiger Tech Solutions, Miami, FL, USA). External load was estimated via the summation and rate of acceleration and decelerations as measured by a triaxial accelerometer using the WFM and an accelerometer-based (ACCEL) device (Catapult Player Load, Catapult Sports, Melbourne, Australia) worn on the mid-upper back. Baseline HR, HR variability (HRV) and HR recovery served as the indicators for ANS recovery and function, respectively. For HRV, two, time-domain metrics were measured: the standard deviation of the NN interval (SDNN) and root mean square of the standard deviation of the NN interval (rMSSD). Linear regression models evaluated the associations between ECL, ACCEL, and the indicators of ANS recovery and function acutely (24 h) and cumulatively (one- and two-week). Athletes (n = 71) were male and, on average, 21.3 ± 1.4 years of age. Acute ECL elicited stronger associations for 24 h baseline HR (R2 0.19 vs. 0.03), HR recovery (R2 0.38 vs. 0.07), SDNN (R2 0.19 vs. 0.02) and rMSSD (R2 0.19 vs. 0.02) compared to ACCEL. Similar results were found for one-week: 24 h baseline HR (R2 0.48 vs. 0.05), HR recovery (R2 0.55 vs. 0.05), SDNN (R2 0.47 vs. 0.05) and rMSSD (R2 0.47 vs. 0.05) and two-week cumulative exposures: 24 h baseline HR (R2 0.52 vs. 0.003), HR recovery (R2 0.57 vs. 0.05), SDNN (R2 0.52 vs. 0.003) and rMSSD (R2 0.52 vs. 0.002). Lastly, the ACCEL devices weakly correlated with ECL (rho = 0.47 and 0.43, p < 0.005). Our findings demonstrate that ACCEL poorly predicted ANS deterioration and underestimated internal training load. ACCEL devices may "miss" the finite window for preventing ANS deterioration by potentially misestimating training loads acutely and cumulatively.