Response Plateau Research Articles

EANM expert opinion: How can lessons from radiobiology be applied to the design of clinical trials? Part I: back to the basics of absorbed dose-response and threshold absorbed doses.

This study by the EANM radiobiology working group aims to analyze the efficacy and toxicity of targeted radionuclide therapy (TRT) using radiopharmaceuticals approved by the EMA and FDA for neuroendocrine tumors and prostate cancer. It seeks to understand the correlation between physical parameters such as absorbed dose and TRT outcomes, alongside other biological factors. We reviewed clinical studies on TRT, focusing on the relationship between physical parameters and treatment outcomes, and applying basic radiobiological principles to radiopharmaceutical therapy to identify key factors affecting therapeutic success. The analysis revealed that mean absorbed dose alone is insufficient to predict treatment response or toxicity. For absorbed doses below a certain threshold, outcomes are unpredictable, while doses above this threshold improve the likelihood of biological responses. However, even at higher absorbed doses, response plateaus indicate the need for additional parameters to explain outcome variability, including heterogeneity in target expression, anatomical disease location, (epi)genetics, DNA repair capacity, and the tumor microenvironment, aspects that will be discussed in Part II of this analysis. Understanding radiobiology is crucial for optimizing TRT. More dosimetric data is needed to refine treatment protocols. While absorbed dose is critical, it alone does not determine TRT outcomes. Future research should integrate biological parameters with physical dosimetry to enhance efficacy and minimize toxicity.

Winter Grazing, Not Fencing or Unicast, Promotes Stability of Microbial Community and Function in the Qilian Mountains of Qinghai‐Xizang Plateau

ABSTRACTIn alpine meadows, microorganisms are essential to sustain the stability of terrestrial geochemical processes and vegetation–soil–microbial systems. The present study in order investigate how various management measures impact the microbial communities' composition and functionality, we utilize metagenomic sequencing techniques to examinate the composition and function of soil microbial communities in the southern Qilian Mountains of the Qinghai‐Xizang Plateau in response to the management practices of fencing enclose (FE), winter grazing (WG), transition zone between natural and artificial grasslands (TZ), and artificial unicast oats (AU). Vegetation diversity and soil physicochemical characteristics were dramatically altered by the management measures. The prokaryotic community structure was considerably similar in FE and WG, as well as in TZ and AU. Near‐natural (FE) and artificial establishment (AU) disturbances changed the fungal community structure. Enzymes related to carbon metabolism did not respond significantly to the management measures, whereas those related to nitrogen metabolism did not respond significantly in TZ and AU. The relative abundance of enzymes participating in nitrogen metabolism was higher under TZ and AU than under FE and WG. We concluded that grassland management measures altered the structure of aboveground graminoid and leguminous vegetation communities and belowground biomass allocation, resulting in changes in K uptake, causing striking changes in the structure of fungal communities and nitrogen‐metabolizing enzymes; moderate disturbance (WG) was beneficial for maintaining the stability of microbial communities in alpine grasslands.

Dopamine release plateau and outcome signals in dorsal striatum contrast with classic reinforcement learning formulations

We recorded dopamine release signals in centromedial and centrolateral sectors of the striatum as mice learned consecutive versions of visual cue-outcome conditioning tasks. Dopamine release responses differed for the centromedial and centrolateral sites. In neither sector could these be accounted for by classic reinforcement learning alone as classically applied to the activity of nigral dopamine-containing neurons. Medially, cue responses ranged from initial sharp peaks to modulated plateau responses; outcome (reward) responses during cue conditioning were minimal or, initially, negative. At centrolateral sites, by contrast, strong, transient dopamine release responses occurred at both cue and outcome. Prolonged, plateau release responses to cues emerged in both regions when discriminative behavioral responses became required. At most sites, we found no evidence for a transition from outcome signaling to cue signaling, a hallmark of temporal difference reinforcement learning as applied to midbrain dopaminergic neuronal activity. These findings delineate a reshaping of striatal dopamine release activity during learning and suggest that current views of reward prediction error encoding need review to accommodate distinct learning-related spatial and temporal patterns of striatal dopamine release in the dorsal striatum.

Miocene Alkaline Basaltic Magmatism in Northeastern Tibetan Plateau: Implications for Mantle Evolution and Plateau Outward Growth

AbstractThe widespread Cenozoic alkaline magmatism within and around the Tibetan Plateau offers a prime opportunity to probe the nature of the mantle at the depths where basalt magmas originate. The close temporal and spatial relationship between volcanism and regional strike‐slip fault systems also helps better understand the geodynamics of outward growth of the plateau in response to the continued India‐Asia convergence. We present a comprehensive study of the deeply sourced alkaline basalts formed along the Kunlun strike‐slip fault with the aim of understanding their petrogenesis and the composition of mantle sources beneath the northeastern Tibetan Plateau. High Nb/U and Ce/Pb ratios and relatively depleted bulk‐rock Sr‐Nd‐Pb isotope compositions corroborate the mantle origin of these alkaline basalts. Homogeneous and low 87Sr/86Sr of clinopyroxene indicates negligible crustal contamination during magmatic evolution. Low δ26Mg in the alkaline basalts and positive correlations with Hf/Sm and Ti/Ti* indicate that the basalts were derived from mantle that was metasomatized by melts derived from sedimentary carbonates during the Paleo‐Tethyan seafloor subduction. Based on 40Ar/39Ar dating results, it appears that the alkaline basaltic magmatism in the northeastern Tibetan Plateau occurred simultaneously with Kunlun strike‐slip faulting. These observations suggest that the India‐Asia convergence must have reactivated ancient subduction plate boundaries and resulted in strike‐slip faulting along these suture zones within and around the Tibetan Plateau. The eruption of low‐volume and deeply rooted alkaline basalts may have been controlled by fractures associated with the strike‐slip fault systems.

Seismic Evidence of Basin Development in NE Tibetan Plateau in Response to Deep Crustal Dynamics From Joint Inversion of Rayleigh Wave Ellipticity and Phase Velocity

Seismic Evidence of Basin Development in NE Tibetan Plateau in Response to Deep Crustal Dynamics From Joint Inversion of Rayleigh Wave Ellipticity and Phase Velocity

Multi-stage perfect load-bearing behavior for tandem honeycomb by face-centered hierarchical strategy

Tandem design is promising to improve the undesired compressive behavior of honeycomb for the long-stroke demand. Therefore, a novel tandem honeycomb, named tandem face-centered hierarchical honeycomb (TFCHH), is developed to achieve the perfect load-bearing process. The deformation mechanism of TFCHH is revealed by the compressive experiments, which dissipates energy by progressive folding and demonstrates a multi-stage plateau response. The numerical research is conducted to explore the compressive properties of TFCHH. It is observed that the energy absorption and load-bearing stability of TFCHH is 23.04 % and 38.24 % higher than those of integrated face-centered hierarchical honeycomb. To approach the perfect load-bearing behavior of TFCHH, the matching strategy of hierarchy order and relative density is investigated to fully exploit the compressive potential of hierarchical honeycomb components. As a result, the optimal load-bearing capacities of hierarchical honeycomb components with the hierarchy order from 1 to 3 are obtained when the relative densities are 16.6 %, 15.0 %, and 11.2 %. The customized design on the load-bearing behavior of TFCHH demonstrates that altering the stacking sequence can control the deformation sequence of hierarchical honeycomb components, and adjusting the composition proportion can tailor the effective stroke of the desired plateau stress. By establishing the theoretical relationship between the plateau force and configuration parameters, it is found that the load-bearing behavior of TFCHH is accurately predicted with the dynamic correction coefficient of 1.4.

Sexuality & Mental Health: Sexual Responses of Young Blind Females Experienci A Romantic Relationship

The study presented herein delves into the sexual responses of young blind females involved in romantic relationships. More specifically, it focuses on the four stages of sexual response—Excitement/Arousal Response, Plateau Response, Orgasm Response, and Resolution Response—within the context of mental health. The primary objective of this research endeavor is to garner insights into the navigation and response of these individuals to sexual experiences within the framework of romantic relationships, as well as to comprehend the impact of said experiences on their mental well-being. To achieve this objective, a qualitative exploratory approach was employed, with the participants being seven adolescent blind females ranging in age from 16 to 19 years old. It is noteworthy that these individuals were interviewed at a specialized school for the visually impaired in West Java. The findings unveiled that sensory experiences, communication with partners, and societal misconceptions significantly influence the sexual response experiences of young Blind females, which in turn are intertwined with their mental well-being. This research aims to understand how young blind women's sexuality and mental health intersect in romantic relationships.

Changes in Late Pleistocene Dust Activity in the Southern Tibetan Plateau in Response to Orbital Precession and Mountain Glaciers

AbstractThe Tibetan Plateau (TP) serves not only as the “water tower” of Asia but also as an important source in the global atmospheric dust cycle. While our knowledge of modern dust activity and its impacts and interactions with climate change in the TP has greatly advanced in the past decades, the emission, transport, and deposition of dust on the geological time scale remains unclear. This study analyzed a 7.6‐m thick sedimentary sequence consisting of loess and sand from the Yarlung Tsangpo River (YTR) valley in the southern TP. The sequence chronology was established using nineteen K‐feldspar post‐infrared infrared stimulated luminescence (pIRIR) ages, which ranged from 47.11 ± 1.95 to 116.65 ± 5.55 ka in a general stratigraphical order. The dust sedimentation rate and sorting coefficient of grain size were used to reflect dust activity and near‐surface wind, respectively. The results indicated that dust activity in the southern TP is mainly regulated by the near‐surface wind intensity and follows the variation pattern of precession, although the waxing and waning of mountain glaciers also affect the amplitude of dust activity. This pattern is not consistent with the Greenland dust record, which follows the variation pattern of obliquity. Therefore, dust accumulation in the southern TP is concluded to be primarily controlled by the South Asian winter monsoon (SAWM) forced by precession, whereas dust accumulation in Greenland is closely related to the intensity of the high‐level westerlies forced by obliquity.

17β-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca2+-ATPase

High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca2+ regulatory mechanisms; however, its effect on the plasma membrane Ca2+-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca2+-ATPases.In guinea pig ASM, Ca2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca2+ ATPases.In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17β-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.

Physiology of the weight-loss plateau in response to diet restriction, GLP-1 receptor agonism, and bariatric surgery.

The objective of this study was to investigate why different weight-loss interventions result in varying durations of weight loss prior to approaching plateaus. A validated mathematical model of energy metabolism and body composition dynamics was used to simulate mean weight- and fat-loss trajectories in response to diet restriction, semaglutide 2.4 mg, tirzepatide 10 mg, and Roux-en-Y gastric bypass (RYGB) surgery interventions. Each intervention was simulated by adjusting two model parameters affecting energy intake to fit the mean weight-loss data. One parameter represented the persistent shift of the system from baseline equilibrium, and the other parameter represented the strength of the feedback control circuit relating weight loss to increased appetite. RYGB surgery resulted in a persistent intervention magnitude more than threefold greater than diet restriction and about double that of tirzepatide and semaglutide. All interventions except diet restriction substantially weakened the appetite feedback control circuit, resulting in an extended period of weight loss prior to the plateau. These preliminary mathematical modeling results suggest that both glucagon-like peptide 1 (GLP-1) receptor agonism and RYGB surgery interventions act to weaken the appetite feedback control circuit that regulates body weight and induce greater persistent effects to shift the body weight equilibrium compared with diet restriction.

A meta-analysis of the relationship between milk protein production and absorbed amino acids and digested energy in dairy cattle

Milk protein production is the largest draw on AA supplies for lactating dairy cattle. Prior NRC predictions of milk protein production have been absorbed protein (MP)-based and used a first-limiting nutrient concept to integrate the effects of energy and protein, which yielded poor accuracy and precision (root mean squared error [RMSE] >21%). Using a meta-data set gathered, various alternative equation forms considering MP, absorbed total EAA, absorbed individual EAA, and digested energy (DE) supplies as additive drivers of production were evaluated, and all were found to be superior in statistical performance to the first limitation approach (RMSE = 14%-15%). Inclusion of DE intake and a quadratic term for MP or absorbed EAA supplies were found to be necessary to achieve intercept estimates (nonproductive protein use) that were similar to the factorial estimates of the National Academies of Sciences, Engineering, and Medicine (2021). The partial linear slope for MP was found to be 0.409, which is consistent with the observed slope bias of -0.34 g/g when a slope of 0.67 was used for MP efficiency in a first-limiting nutrient system. Replacement of MP with the supplies of individual absorbed EAA expressed in grams per day and a common quadratic across the EAA resulted in unbiased predictions with improved statistical performance as compared with MP-based models. Based on Akaike's information criterion and biological consistency, the best equations included absorbed His, Ile, Lys, Met, Thr, the NEAA, and individual DE intakes from fatty acids, NDF, residual OM, and starch. Several also contained a term for absorbed Leu. These equations generally had RMSE of 14.3% and a concordance correlation of 0.76. Based on the common quadratic and individual linear terms, milk protein response plateaus were predicted at approximately 320 g/d of absorbed His, Ile, and Lys; 395 g/d of absorbed Thr; 550 g/d of absorbed Met; and 70 g/d of absorbed Leu. Therefore, responses to each except Leu are almost linear throughout the normal in vivo range. De-aggregation of the quadratic term and parsing to individual absorbed EAA resulted in nonbiological estimates for several EAA indicating over-parameterization. Expression of the EAA as g/100 g total absorbed EAA or as ratios of DE intake and using linear and quadratic terms for each EAA resulted in similar statistical performance, but the solutions had identifiability problems and several nonbiological parameter estimates. The use of ratios also introduced nonlinearity in the independent variables which violates linear regression assumptions. Further screening of the global model using absorbed EAA expressed as grams per day with a common quadratic using an all-models approach, and exhaustive cross-evaluation indicated the parameter estimates for BW, all 4 DE terms, His, Ile, Lys, Met, and the common quadratic term were stable, whereas estimates for Leu and Thr were known with less certainty. Use of independent and additive terms and a quadratic expression in the equation results in variable efficiencies of conversion. The additivity also provides partial substitution among the nutrients. Both of these prevent establishment of fixed nutrient requirements in support of milk protein production.

A Comparative Study of the Efficacy of Platelet-rich Plasma Therapy versus Topical Application of 0.1% Tretinoin Gel in the Management of Striae Gravidarum

Abstract Aim: To determine the relative efficacy of platelet rich plasma therapy versus topical 0.1% tretinoin gel in the management of striae gravidarum. Objectives: To determine the degree of response to platelet rich plasma therapy in comparison with topical 0.1% tretinoin gel in striae gravidarum and to determine the treatment of choice amongst platelet rich plasma and topical 0.1% tretinoin gel. Material and Methods: Study design - A randomised control cross sectional comparative study among the female patients with striae gravidarum was carried out at department of Dermatology, Venereology & Leprosy, Base Hospital, Delhi Cantt, New Delhi. Results: There was early and fast clinical improvement in PRP group with continuous clinical improvement noticed in successive sittings although degree of improvement was lower in 5th and 6th sittings. There was also an earlier plateau of response, in tretinion group after 04 sittings with mild or little improvement in the last 02 sittings in comparison to the PRP group. Conclusion: Platelet Rich Plasma therapy was effective as compared to topical 0.1% Tretinoin gel in the management of Striae gravidarum. PRP had better treatment outcome as well as patient satisfaction.

Crystalloid Fluid Management of Non-Traumatic Hypotension by New South Wales Ambulance

Introduction Shock is circulatory insufficiency, inadequate oxygen delivery, and cellular hypoxia. Intravenous fluids are essential for shock management. Despite treatment, patients can face persistent shock with ongoing hypotension, contributing to higher mortality. This analysis aims to quantify hypotensive non-traumatic cases in an Australian ambulance service, determine persistent hypotension prevalence, and assess paramedic-administered intravascular fluids’ impact on blood pressure changes. Methods This study is a retrospective analysis of prehospital fluid resuscitation by New South Wales Ambulance paramedics during 2022. Hypotension is defined as a systolic blood pressure of ≤ 90 mmHg, and persistent hypotension is a systolic blood pressure consistently below 90 mmHg across all observations, with a final blood pressure below 90 mmHg. This study aimed to determine the volume of fluid resuscitation at which a plateau in population-level systolic blood pressure response is observed, by calculating the derivative of the fitted logistic regression model. Moreover, this analysis identified the relative contribution of factors influencing the probability of an attempt at intravenous or intraosseous access using machine learning. Results Among 796,865 attendances, 23,049 (2.9%) involved non-traumatic patients with hypotension. In total 7,388 (32.1%) of the hypotensive cases resulted in persistent hypotension, of which 3,235 (43.8%) received Hartmann’s solution and 1,745 (53.9%) received at least 500 ml of fluids but still had hypotension. The model showed that systolic blood pressure tends to stop increasing after 500–600 milliliters of fluid are given. This suggests that, on average, giving more fluid than this may not raise blood pressure further in a prehospital setting, though individual patient needs can differ. The top four factors from the machine learning shows that as initial respiratory rate goes up, the probability of intravascular access rises. Transport times less than 20 min are associated with a smaller chance of access and younger patients are less likely to receive an attempt. Finally, extremes of systolic blood pressure are more likely to receive access attempts. Conclusion This study found that three percent of non-traumatic attendances have at least one episode of hypotension, and that more than half of these have persistent hypotension. Only 44% of persistently hypotensive received fluids, and half of persistently hypotensive patients stayed hypotensive despite a reasonable volume of prehospital crystalloids.

Optimal treatment placement for on-farm experiments: pseudo-Bayesian optimal designs with a linear response plateau model

Optimal treatment placement for on-farm experiments: pseudo-Bayesian optimal designs with a linear response plateau model

Exposure-Response Relationships between the Factor B Inhibitor Iptacopan and Complement Biomarkers in Healthy Volunteers and Patients (Pts) with Paroxysmal Nocturnal Hemoglobinuria (PNH), C3 Glomerulopathy (C3G) or IgA Nephropathy (IgAN)

Background: Iptacopan is the first oral proximal complement inhibitor that targets factor B to selectively inhibit the alternative pathway (AP) of the complement system. Iptacopan is currently being investigated in Phase III trials in PNH, C3G and IgAN. AP biomarkers can be used to evaluate the inhibitory effect of iptacopan. Wieslab ® ex vivo assay measures the amount of soluble C5b-9 (sC5b-9) formation in serum after AP activation. Plasma sC5b-9 is the final product of complement activation and is also known as the membrane attack complex. Plasma Bb levels increase following AP activation. Aim: To characterize exposure-response relationships between iptacopan and AP biomarkers Wieslab ®, Bb and sC5b-9 to rationalize the iptacopan dose selection. Methods: This analysis was based on final data from a Phase I clinical trial enrolling healthy volunteers (X2101 [EUDRACT2015-005567-16]) and 4 Phase II trials enrolling pts with PNH (X2201 [NCT03439839] and X2204 [NCT03896152]), C3G (X2202 [NCT03832114]) and IgAN (X2203 [NCT03373461]). In these trials, oral iptacopan was administered in doses ranging from 5-400 mg single dose and from 10-200 mg twice daily (bid). A longitudinal mixed-effects modeling approach was applied to the AP biomarkers used in this study: serum Wieslab ® assay, plasma Bb and plasma sC5b-9. Direct response sigmoid Emax models were considered as most appropriate and biologically plausible for all biomarkers, reflecting the rapid biomarker response following exposure to iptacopan. The exposure metric driving the response was the observed time-matching pharmacokinetic (PK) data. A population PK (popPK) model built on bid dose levels (10-200 mg) using data from pts (not healthy volunteers) simulated steady state exposure over 6 months of iptacopan bid dosing in each population. Results: The modeling dataset contained 247 participants, of which 88 (36%) were healthy volunteers, 29 (12%) were pts with PNH, 27 (11%) were pts with C3G, and 103 (42%) were pts with IgAN. Overall, 69 (28%) participants were female, and the median age (range) was 38 (18-78) years. A total of 2317, 2296 and 2279 samples for Wieslab ®, Bb and C5b-9, respectively, were used in the modeling, with the same number of time-matched PK samples. The biomarker responses decreased monotonically with saturation of effect and without apparent time lag, which was expected based on the mechanism of iptacopan. An exposure-dependent decrease in Wieslab ® was seen in pts and healthy volunteers, with estimated iptacopan concentrations required to achieve 90% of the maximum response (EC 90) being 1281 ng/mL (90% confidence interval [CI] 1207, 1418) and 706 ng/mL (90% CI 653, 788), respectively. Based on simulations from the popPK model, this exposure was expected to be reached at steady state trough concentration (C trough) by an estimated 74% of pts at 200 iptacopan mg bid, compared with 44% and 18% receiving 100 mg bid and 50 mg bid, respectively ( Table). The interindividual variability of Wieslab ® response decreased as iptacopan dose increased to 200 mg bid and C trough to ≥1300g/mL. A clear decrease from baseline in plasma Bb was seen following iptacopan treatment, with an EC 90 value of 521 ng/mL (90% CI 268, 912). Based on simulations from the popPK model, this exposure was expected to be reached by 97% of pts treated with iptacopan 200 mg bid, compared with 91% and 79% receiving 100 mg bid and 50 mg bid, respectively ( Table). For sC5b-9, the EC 90 value was 682 ng/mL (90% CI 503, 894) across all participants. This exposure was expected to be achieved by 94%, 83% and 64% of pts receiving iptacopan 200 mg bid, 100 mg bid and 50 mg bid, respectively ( Table). Age, weight, sex and ethnicity did not affect the biomarker responses. Conclusions: In this analysis, iptacopan 200 mg bid was the dose at which the highest proportion of participants achieved EC 90 values for the AP biomarkers Wieslab ®, Bb and sC5b9. Other than pts having higher EC 90 values than healthy volunteers for Wieslab ®, no differences were found in EC 90 values between the trial populations, demonstrating that no dose adjustment is needed between them. A response plateau was achieved by the iptacopan 200 mg bid dose for Wieslab ® and lower doses for Bb and C5b-9, suggesting higher doses would not lead to greater responses. In summary, these data support the use of oral iptacopan at 200 mg bid to achieve rapid, substantial and sustained inhibition of the complement AP in pts with PNH, C3G or IgAN.

PSI-16 Too Late to Catch up? Parity Order and Baseline Overall Claw Quality Impact on the Responsiveness of Sows to Mineral-Amino Acid-Complex Supplementation: A Case Study

Abstract Poor claw quality can predispose sows to lameness, which may be counteracted by mineral-amino acid-complex (ZPM) supplementation. The objective was to investigate the effects of parity order (PO) and baseline overall claw quality (BCW) on the time required to achieve optimal response to ZPM in sows. A total of 15,500 sows (PO 1-6) supplemented with ZPM for different periods of time (months) were randomly selected and scored from 0 (no lesions) to 3 (severe lesions) for claw lesions: heel overgrowth and erosion, heel-sole crack, separation along the white line, horizontal and vertical wall cracks, and overgrown toes, or dewclaws. A lesion index (L-Index) was calculated as the sum of the greater scores from each lesion, per animal. Sows were grouped by similarity (BCW) in claw lesions in two clusters (C1 and C2). The effects of cluster and PO were investigated. A quadratic response plateau (QRP) model was fitted to assess the interrelationships between the change in L-Index and the duration of ZPM supplementation within parity and cluster. Sows from C1 had greater L-Index compared with C2 sows (6.57 vs. 2.55; SEM = 0.08; P < 0.05). Sows from PO4 (4.12), 5 (4.23), and 6 (4.34) had greater L-Index compared with sows from PO1 (3.44) and 2 (3.71), with PO3 being intermediate (3.94; SEM = 0.15; P < 0.05). Sows from PO1-C1, PO1-C2, PO2-C1, and PO2-C2 had breakpoints (duration of ZPM supplementation) of 10.36 ± 3.83, 12.41 ± 2.77, 14.85 ± 4.28, and 16.02 ± 3.85 months, respectively (P < 0.05). The breakpoints for PO3, 4, 5, and 6 from C2 were 15.02 ± 4.24, 14.08 ± 4.87, 14.28 ± 4.58, and 10.50 ± 4.30, respectively (P < 0.05). There was no breakpoint achieved for PO3, 4, 5, and 6 from C1 (P > 0.05). Our results indicate that ZPM supplementation should start early (PO1 and PO2) as the potentially negative aging effects on healing capacity may decrease the ability of sows to optimally respond to the supplementation.

206 Development and Validation of an Indigestible Protein Index to Investigate the Effects of Protein Content in Weaned Pigs: A Multivariate Approach

Abstract Increased proteolytic fermentation may lead to negative effects on gastrointestinal health and function, which ultimately impact on performance. The objective was to develop and validate, by investigating performance and gut structure outcomes, an index of indigestible protein content (IDP) in weaned pigs. Ninety-four studies reporting growth performance [average daily gain (ADG), average daily feed intake (ADFI), gain: feed (GF), initial (IBW) and final body weight (FBW)] and duodenal histomorphometries [villus height (VH), crypt depth([CD), and villus height: crypt depth ratio (VCR)] variables of pigs fed different protein content (CP) and sources in the diet were included. Diets were recalculated using a common database to generate the IDP from each study. Studies were grouped by similarity in performance in two clusters (C1 and C2) by hierarchical clustering on principal components (HCPC). The effects of cluster were investigated. Quadratic response plateau (QRP) models were fitted to assess the interrelationships between ADG, ADFI, GF, VH, CD, and VCR with the dietary CP or calculated IDP content within cluster. Pigs from C2 had greater IBW (6.3 vs. 8.8 ± 0.2kg), FBW (10.2 vs. 17.2 ± 0.7kg), ADG (0.2 vs. 0.4 ± 0.0kg/d), and ADFI (0.3 vs. 0.6 ± 0.1kg/d) compared with C1 (P < 0.05). There was no effect of cluster (P > 0.05) on VH (405.5 vs. 405.5 ± 15.8μm), CD (232.5 vs. 220.7 ± 10.1μm), or VCR (1.9 vs. 2.0 ± 0.3μm). Pigs from C1 achieved break point (BP) and plateau (Pl) for VH (BP = 24.25%, Pl = 96.32μm; P < 0.05) when fed increasing CP content and for ADG (BP = 2.32%, Pl = 0.28kg/d; P < 0.05) and GF (BP = 2.18%, Pl = 0.83kg/kg; P < 0.05) when fed increasing calculated IDP content. Pigs from C2 fed increasing content of calculated IDP achieved BP and Pl for ADG (BP = 3.04%, Pl = 0.54kg/d; P < 0.05). Our findings suggest that calculated IDP might be a reliable index to investigate the effects of proteolytic fermentation on pig performance, particularly in the immediate post-weaning phase.

Sensitive temperature changes on the Tibetan Plateau in response to global warming

In recent years, rapid global warming has led to a dramatic cryosphere retreat and caused environmental disasters on the Tibetan Plateau (TP). To better understand the near-surface air temperature variation on the TP in response to global warming in the 21st century, we systematically detected temperature changes on the TP relative to global warming regarding warming time, warming amplitude, and elevation-dependent warming (EDW) using the multi-model ensemble (MME) means of 24 CMIP6 models. The results showed that the warming rate on the TP is 1.3–1.45 times more than that of mean global warming from 2015 to 2100, with the TP having already warmed by 1.5 °C above the pre-industrial levels in 2016/2015 and will warm by 2 °C by 2028/2027 under the Shared Socioeconomic Pathway (SSP) scenarios, SSP2–4.5 and SSP5–8.5. In addition, the warming amplitude on the TP in response to global warming levels of 1.5 and 2 °C would be 1.97 and 2.69 °C under the SSP2–4.5 scenario and 1.94 and 2.68 °C under the SSP5–8.5 scenario. Furthermore, EDW amplifies the warming amplitude at high elevations, mainly because of the decrease in surface albedo. The most sensitive warming amplitude in the cryosphere region, with an elevation of 5–5.5 km, would exceed 2.06, 2.79, 4.29, and 5.73 °C when global warming reaches 1.5, 2, 3, and 4 °C under the SSP5–8.5 scenario. This additional 0.56–1.73 °C warming in the high elevation relative to the global mean will intensify the cryosphere ablation on the TP. Thus, considering the projected larger warming trend and amplitude, the high-elevation region on the TP would be particularly sensitive and vulnerable, which is unfavorable for the TP from the perspective of the Paris Agreement warming target.

Projecting future aboveground carbon sequestration rate of alpine forest on the eastern Tibetan Plateau in response to climate change.

The aboveground carbon sequestration rate (ACSR) of forests serves as an indicator of their carbon sequestration capacity over time, providing insights into the potential carbon sequestration capacity of forest ecosystems. To explore the long-term Spatiotemporal variation of ACSR in the transitional ecotone of theeastern Tibetan Plateau under climate change scenarios, we utilized a forest landscape model that was parameterized with forest inventory data from the eastern Tibetan Plateau to simulate this ecological function changes. The study found that climate warming had significant effect on forests ACSR in different types of forests. ACSR was significantly reduced (p<0.05) in cold temperate coniferous and temperate coniferous forests, whereas it was significantly increased in deciduous broad-leaved forests. However, the impact of climate warming on evergreen broad-leaved forests was found to be negligible. At the species level, climate warming has mostly suppressed the ACSR of coniferous trees, except for Chinese hemlock. The main dominant species, spruce and fir, have been particularly affected. Conversely, the ACSR of most broad-leaved trees has increased due to climate warming. In addition, at the landscape scale, the ACSR within this region is expected to experience a steady decline after 2031s-2036s. Despite the effects of climate warming, this trend is projected to persist. In conclusion, the forests ACSR in this region will be significantly affected by future climate warming. Our research indicates that climate warming will have a noticeable suppressive effect on conifers. It is imperative that this factor be taken into account when devising forest management plans for the future in this region.

Use of statistical models to determine the optimal concentration of metabolizable energy for growth performance of broiler chickens

The formulation of diets that adequately meet energy requirements in the different phases of broiler chicken production is of the utmost importance. The objective of this study was to determine the optimal content of metabolizable energy (ME) for broiler chickens in various production phases using different statistical models. A total of 900 broiler chickens were assigned to 5 treatments with 9 replicates of 20 broiler chickens each from 21 to 42 d of age in a completely randomized design. Experimental diets were based on corn and soybean meal and formulated to meet the nutritional requirements of broiler chickens, except for ME requirements. Dietary treatments consisted of 5 pelleted/crushed diets with increasing levels of ME: T1 to T5 (2,850 to 3,250 kcal/kg), divided into grower (21 to 35 d) and finisher (35 to 42 d) phases. Feed intake (FI), body weight gain (BWG), feed conversion ratio (FCR), total energy intake, efficiency of energy use for BWG, and carcass and cuts yields were determined. The ideal ME content for best FCR was determined with the use of quadratic polynomial (QP), segmented, and linear response plateau models (LRP). In all evaluated periods, BWG was not influenced by ME, whereas FI and FCR decreased linearly with increasing ME. Total energy intake increased and the energy use efficiency for BWG decreased with greater ME (P < 0.05). Neither carcass nor cuts yields were influenced by dietary ME. The ideal dietary ME content differed between statistical models. In conclusion, based on FCR results, the QP regression model presented the best fit of the data in the grower phase, indicating an optimal content of metabolizable energy for feed conversion of 3,264 kcal/kg, whereas LRP presented the best data adjustment in the finisher phase, indicating 3,224 kcal/kg of ME as optimal.