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The cost of being early or late: Biological and economic outcomes of age at first calving in dairy buffaloes
No full textAge at first calving (AFC) is a key determinant of lifetime productivity and profitability in dairy herds, yet its long-term effects in dairy buffaloes remain poorly documented. This study evaluated the influence of AFC on milk yield and composition, reproductive performance, and economic outcomes in Italian Mediterranean buffaloes reared under commercial conditions. Data included 576,028 test-day records from 27,744 buffaloes across 110 herds, collected over a 10-yr period (2013–2023). Animals were grouped into 8 AFC classes and stratified by parity order, namely: primiparous, mid-parity (second–third parities), and greater parity (≥4). Productive traits comprised daily milk yield, fat and protein content, SCS, and cumulative yields of milk, fat, and protein per lactation, whereas reproductive traits included calving interval (CIN) and days open (DO). Mixed-model analysis indicated that mid- and greater-parity buffaloes calving between 35 and 38 mo achieved higher daily milk yield, whereas daily milk yield increased progressively with AFC in primiparous buffaloes. Milk fat content was unaffected by AFC, whereas the highest protein percentages were observed in mid-parity buffaloes calving at AFC between 32 and 34 mo. Somatic cell score significantly decreased as AFC increased across all parity groups, except in primiparous buffaloes, where an increase in SCS was observed in buffaloes with AFC between 37 and 38 mo. Moreover, CIN and DO were shortest in buffaloes calving the first time between 32 and 37 mo. The economic analysis integrated model-based estimates of milk yield with farm-level cost data from the Farm Accountancy Data Network covering the same 10-yr period. Production costs were organized into 3 categories: direct costs, overheads, and imputed costs. Based on this structure, the average production cost was estimated at €1.38/L of milk. Total production costs per lactation were calculated as the unit cost multiplied by the estimated cumulative milk yield for each AFC class and parity group. Revenues were obtained in the same way, by applying the actual farm-gate milk price (€1.50/L) to the estimated cumulative milk yields, providing a standardized framework for comparison across AFC classes. Net profit was calculated as the difference between total revenues and production costs, yielding an overall average of €314 per lactation across all AFC and parity groups. The highest net profit was recorded in mid-parity buffaloes whose first calving occurred between 37 and 38 mo of age, with an average net return of €339 per lactation. Overall, buffaloes calving the first time between 34 and 42 mo achieved significantly higher net profit compared with other AFC classes. Conversely, both early (42 mo) AFC values were associated with reduced net profits, driven by lower milk yields. Overall, these results indicate that targeting an AFC of 35 to 38 mo provides the most favorable balance between biological performance, udder health, reproductive efficiency, and farm profitability
Julius Lucas Becker, The Global Impact of the First Sino-Japanese War of 1894-95. European Imperialism, Diplomacy and Perception of an East Asian Conflict
No full textSynergy Between BIM and e-Procurement: A New Paradigm for Digital Procurement Management
No full textThe Architecture, Engineering and Construction (AEC) sector is undergoing a digital transformation thanks to Construction 4.0 technologies. Among these, e-procurement represents a key element for the optimisation of tendering procedures and the improvement of administrative transparency, through the dematerialisation of documents and the rationalisation of workflows, resulting in time and cost reductions in procurement. In parallel, Building Information Modeling (BIM), stimulated by national and international regulations, allows a more integrated management of design information, improving the quality of decisions and reducing errors and inefficiencies. However, the integration between BIM and e-procurement is still limited, as e-procurement mainly focuses on document digitisation without fully exploiting the potential of BIM for advanced data management. With this in mind, this research aims to analyse the state of the art regarding the joint application of BIM and e-procurement in the public procurement sector. Through an in-depth bibliographical analysis, the main scientific studies and existing application experiences will be examined in order to identify best practices, still existing criticalities and phases of tendering procedures where BIM can bring the greatest added value. Furthermore, in order to concretely understand the potential and limits of this integration, an application to a case study will be developed, analysing in detail the achievable advantages and the problems encountered in the operational implementation. The analysis conducted also aims to outline possible evolutionary scenarios and strategies to overcome the technological, organisational and regulatory barriers that currently hinder full interoperability between these two technologies. The final objective is to provide a comprehensive picture of the opportunities arising from the joint adoption of BIM and e-procurement, highlighting how this synergy can improve efficiency, transparency and economic sustainability in public procurement
Arnold Toynbee, Turning the Tide of Terror (1973).pdf (https://www.academia.edu/145737374/Arnold_Toynbee_Turning_the_Tide_of_Terror_1973_)
No full textADDITIONS, INTEGRATIONS, CORRECTIONS AND SUPPLEMENTS TO THE BIBLIOGRAPHY OF ARNOLD JOSEPH TOYNBEE,
No. 560, Addition to Part I, Works by Arnold J. Toynbe
Thyroid hormone inactivation sustains cancer stem cell maintenance and tumorigenesis in basal cell carcinoma
No full text: A hierarchical organization within a tumor underlies the varying capacities of cancer cells to proliferate, metastasize, and drive relapse. Cancer stem cells (CSCs) are resistant to conventional therapies, making them critical targets for cancer treatment. Thyroid hormone (TH), a key regulator of proliferation and differentiation, is tightly controlled by the deiodinase enzymes. By integrating in vivo animal studies in a genetic mouse model of basal cell carcinoma (BCC) with analyses of human BCC specimens, we demonstrate that deiodinase type 3 (D3), the TH-inactivating enzyme, is expressed in the most tumorigenic CSC subpopulation. D3 genetic ablation significantly reduces the CSC population within protumorigenic niches and downregulates key stemness markers, including the transcription factor Sox9. Similarly, systemic induction of hyperthyroidism leads to a reduction of the CSC pool. Importantly, analysis of human BCC specimens revealed that D3 is highly enriched in the CSC niche. Mechanistically, we found that TH treatment suppresses Sox9 expression. These findings demonstrate that D3 sustains the tumorigenic potential of BCC CSCs by protecting them from TH-induced apoptosis and differentiation. Targeting the D3/TH axis may represent a promising therapeutic strategy to reduce the ability to self-renew of CSCs and inhibit tumor progression in BCC
Tumor-Derived LIF Promotes GDF15-Driven Cachexia and Adverse Outcomes in Gastric Cancer
No full textCancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle and adipose tissue loss, systemic inflammation, and poor clinical outcomes, and represents a major unmet clinical need in gastric cancer. Growth Differentiation Factor 15 (GDF15) is a key mediator of cachexia-associated anorexia and tissue wasting; however, the upstream mechanisms regulating its expression in gastric cancer remain poorly defined. Leukemia Inhibitory Factor (LIF), a pleiotropic cytokine implicated in tumor progression and metabolic dysregulation, has emerged as a potential regulator of cachexia-related pathways. Here, we investigated the association between LIF in regulating GDF15 expression and its relationship with metabolic, inflammatory, and body composition alterations in gastric cancer. Transcriptomic profiling of paired neoplastic and non-neoplastic gastric mucosa from 61 gastric cancer patients revealed a significant upregulation of both LIF and GDF15 in tumor tissue, with a strong positive correlation between their expression levels. High GDF15 expression was associated with reduced overall survival, a finding validated in independent TCGA-STAD and ACRG cohorts. Intratumoral bile acid profiling uncovered a marked enrichment of primary bile acids and a depletion of secondary bile acids, resulting in reduced levels of bile acids with endogenous LIF receptor (LIFR) antagonist activity; elevated primary, LIFR non-antagonist bile acids were associated with worse survival outcomes. Clinically, increased LIF and GDF15 expression correlated with weight loss, heightened inflammatory burden, reduced serum protein and albumin levels, and impaired body composition in a sub-cohort of 19 patients. Notably, LIF expression showed a significant inverse association with both lumbar skeletal muscle index (L3SMI) and subcutaneous adipose tissue index (SATI). Mechanistically, experimental models demonstrated that LIF enhances proliferative activity in gastric cancer spheroids and exerts paracrine effects that impair myogenic differentiation and suppress hepatic metabolic gene expression. Collectively, these findings identify the LIF/GDF15 axis as a central driver of cancer-associated cachexia in gastric cancer and highlight LIF signaling as a potential therapeutic target
