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Background: Carbapenem-resistant Gram-negative organism (CRO) infection is a critical clinical disease with high mortality rates. The 30-day mortality rate following antibiotic treatment serves as a benchmark for assessing the quality of care. Colistin sulfate is currently considered the last resort therapy against infections caused by CRO. Nevertheless, there is a scarcity of reliable tools for personalized prognosis of CRO infections. This study aimed to develop and validate a nomogram to predict the 30-day all-cause mortality in patients with CRO infection who underwent colistin sulfate treatment. Methods: A prediction model was developed and preliminarily validated using CRO-infected patients treated with colistin sulfate at Tongji Hospital in Wuhan, China, who were hospitalized between May 2018 and May 2023, forming the study cohort. Patients admitted to Xianning Central Hospital in Xianning, China, between May 2018 and May 2023 were considered for external validation. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of 30-day allcause mortality. The receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and the calibration curve were used to evaluate model performance. The decision curve analysis (DCA) was used to assess the model clinical utility. Results: A total of 170 patients in the study cohort and 65 patients in the external validation cohort were included. Factors such as age, duration of combination therapy, nasogastric tube placement, history of previous surgery, presence of polymicrobial infections, and occurrence of septic shock were independently associated with 30-day all-cause mortality and were used to construct the nomogram. The AUC of the nomogram constructed from the above six factors was 0.888 in the training set. The Hosmer-Lemeshow test showed that the model was a good fit (p = 0.944). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the reliability of the prediction nomogram. Conclusion: A nomogram was developed and validated to predict the occurrence of 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate. This nomogram offers healthcare providers a precise and efficient means for early prediction, treatment management, and patient notification in cases of CRO infection treated with colistin sulfate. [ABSTRACT FROM AUTHOR]

Laboratory animal professionals (LAP) may experience situations that contribute to compassion fatigue (CF). The goal of this research was to better understand CF in LAP in and across employment categories. Surveys were distributed through LAP organizational listservs in the European Union (EU), China, and Japan, and results were analyzed to identify CF prevalence, personal and work-related factors, coping mechanisms, and beneficial work-support programs. Independent χ²-tests compared personal and work-related factors and feelings of CF. Feelings of CF and coping mechanisms were compared with personality scores using independent sample t tests. There were 302 respondents from the EU, 39 from China, and 77 from Japan. Over half of respondents from the EU (52%) and China (56%) reported experiencing CF (52%), with fewer (32%) reporting CF in Japan. No major differences were found based on employer type. Personality scores were significantly related to feelings of CF and preferred coping mechanisms. Work-related factors that contributed to feelings of CF in over half of respondents included staffing levels, workplace relationships, and availability of programs geared to address CF. Across regions, talking to someone, physical activity, getting away from work, and self-care were effective coping mechanisms in over 50% of respondents. Fewer than 30% of respondents indicated that their place of employment had CF support programs, and even fewer (8% to 28%) indicated that these programs were helpful. The study results suggest that to be effective, employer CF programs for LAP should consider providing quiet places at work and programs for self-care, promoting physical and mental health and social support systems, and establishing opportunities to memorialize animals.

The emergence of carbapenem-resistant organisms (CROs) has become a great challenge alarming the public health community. Thus, the current study was conducted to investigate the occurrence of CROs among pet animals suffering from respiratory illness. Nasal swabs from 100 pet animals (51 dogs and 49 cats) showing respiratory illness were screened for CROs. The obtained swabs were streaked onto CHROMagar mSuper CARBATM medium followed by sub-culturing on MacConkey agar. Colonies were identified by cultural characteristics, Gram staining, and biochemical tests as well as molecular techniques. Then, the identified isolates were confirmed to be CROs after being non-susceptible to at least one of four carbapenem antibiotics using the Kirby-Bauer method. The confirmed CRO isolates were also investigated on molecular basis for carbapenemase-encoding genes (blaNDM, blaKPC, blaOXA-48, blaVIM, blaIMP). Out of 100 pet animals, 6 yielded CROs with an overall occurrence rate 6% (3.9% for all tested dogs and 8.2% for all tested cats). The obtained CRO isolates were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter cloacae with the following distribution among the examined animals 3%, 1%, 1%, and 1%, respectively. BlaNDM was the only detected carbapenemase-encoding gene among the isolates and it was detected in two cat isolates. In conclusion, the results of the current study highlight the emergence of carbapenem-resistant organisms among pet animals suffering from respiratory illness which may have a possible public health risk. [ABSTRACT FROM AUTHOR]

To improve the quality of services provided to their customers, cloud service providers move some of their resources closer to the users. Proper server placement, considering the volume of service demands in different parts of the network, plays an important role in providing better services to users, more effective use of resources, and reducing the server's energy consumption. However, designing a model that can meet the requirements of both the users and the service providers has received less attention. Most researchers use discrete models to select candidate locations for resource deployment and servers can only be placed in these predefined locations. The proposed method explores the entire search area to find optimal locations for server placement with a continuous approach. To reduce the complexity of the problem and faster convergence in reaching the optimal solution, the resource deployment area is divided into smaller subregions. In the first step of the proposed method, the Butterfly optimization algorithm is used to find the best local locations for resource deployment. To avoid falling into the local optimum and to converge the subregions, the coral reefs optimization algorithm is used. The experiments show that the proposed method can effectively save energy and reduces network latency. [ABSTRACT FROM AUTHOR]

Kaili Li, Sanle Jiang, Hongxue Fu, Yingting Hao, Shijing Tian, Fachun Zhou Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shijing Tian; Fachun Zhou, Emergency Department, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, 17th Floor, Building 1, Chongqing, People’s Republic of China, Tel +86 023-89011756, Email doctortianshijing@163.com; cyzfc1966@126.com; zfc88@126.comBackground: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis.Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis.Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11– 45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11– 35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475– 17.595, P=0.01) by Cox proportional-hazards regression.Conclusion: Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.Keywords: CRO, acute cholangitis, risk factors, prognosis

Pharmaxi (hereinafter CRO) is a Ukrainian group of companies providing full service in clinical trials. At the beginning of the massive military Russian invasion of Ukraine on the 24th of February 2022, it was the biggest CRO in Ukraine with 17 full-time employees and 8 contractors.Founded in 2013, it has grown up increasingly while building resilience to repeated crises in Ukraine, sustaining continuity of operations. The company evolved through political instability during the Revolution of Dignity, the subsequent beginning of the Russian occupation of Crimea, the beginning of hybrid armed conflict in the Eastern part of Ukraine in 2014, and the COVID-2019 crisis. In the sixth month of the active Russian-Ukrainian war, the company continues business operations and is ready for further development.This case study investigates the strategy and best practices for ensuring business stability through contingency, resilience, and recovery actions analysis, expert interviews with management, and the SWOT analysis of the study findings. In particular, the organisational continuity framework features financial policy, human resources management, organisational behaviour practices, internal communication, and diversification.While investigating the case of company's continuity of operations, it appeared that the company had a crosscutting orientation on stability. The core domains ensuring resilient company's activity over repeated crises were the diversification, utilization tools for financial stability, distinct human capital management and design of operations.Study's results might be relevant to small and middle-sized service companies.

Objective: Dermatology and aesthetic medicine has experienced significant growth in recent years, driven by industry-sponsored research performed by clinical investigators. Contract research organizations (CROs) play an important role to ensure clinical trials are run efficiently, ethically, and according to Good Clinical Practice. An advisory group of dermatologists and aesthetic researchers was assembled to obtain feedback about CRO experiences for developing a "next-generation" specialty CRO for dermatology and aesthetic medicine.Methods: Experienced dermatologists and aesthetic physician researchers convened during the 2022 Winter Dermatology Annual Meeting in Kauai, Hawaii, to discuss experiences and make suggestions regarding CROs. Topics included positive and negative aspects of CRO experiences, desirable CRO services, and how CROs can be improved.Results: Benefits of working with CROs include project, data, and resource management and availability of technology. Desired functions include rapid study start-up, subject recruitment, and accurate and organized site-related documentation. Other qualities include access to large subject populations close to study locations, use of CRO-based clinical research assistants to support principal investigators across study sites, and scientific consultation, protocol development, medical writing, project management, clinical and medical monitoring, data management, biostatistics, and pharmacovigilance.Conclusion: CROs serve a vital role in the development process of drug, device, and therapeutics; however, it is important that changes to traditional CRO models are made to provide improved interactions with researchers in dermatology and aesthetic medicine. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Gram-negative organism (CRO) infection is a critical clinical disease with high mortality rates. The 30-day mortality rate following antibiotic treatment serves as a benchmark for assessing the quality of care. Colistin sulfate is currently considered the last resort therapy against infections caused by CRO. Nevertheless, there is a scarcity of reliable tools for personalized prognosis of CRO infections. This study aimed to develop and validate a nomogram to predict the 30-day all-cause mortality in patients with CRO infection who underwent colistin sulfate treatment., Methods: A prediction model was developed and preliminarily validated using CRO-infected patients treated with colistin sulfate at Tongji Hospital in Wuhan, China, who were hospitalized between May 2018 and May 2023, forming the study cohort. Patients admitted to Xianning Central Hospital in Xianning, China, between May 2018 and May 2023 were considered for external validation. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of 30-day all-cause mortality. The receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and the calibration curve were used to evaluate model performance. The decision curve analysis (DCA) was used to assess the model clinical utility., Results: A total of 170 patients in the study cohort and 65 patients in the external validation cohort were included. Factors such as age, duration of combination therapy, nasogastric tube placement, history of previous surgery, presence of polymicrobial infections, and occurrence of septic shock were independently associated with 30-day all-cause mortality and were used to construct the nomogram. The AUC of the nomogram constructed from the above six factors was 0.888 in the training set. The Hosmer-Lemeshow test showed that the model was a good fit ( p = 0.944). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the reliability of the prediction nomogram., Conclusion: A nomogram was developed and validated to predict the occurrence of 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate. This nomogram offers healthcare providers a precise and efficient means for early prediction, treatment management, and patient notification in cases of CRO infection treated with colistin sulfate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Liu, Xiao, Cai, Gao, Xu, Han and He.)

El objetivo de este artículo fue verificar cómo la gestión de riesgos se materializa en las organizaciones. Para ello, se realizó una investigación descriptiva con un enfoque cuantitativo por medio de encuesta. El instrumento de recolección de datos consistía en un cuestionario estructurado enviado a Chief risk officers (CROs) de empresas brasileñas, auditores y consultores de gestión de riesgos. Un total de 22 respuestas fueron obtenidas. El análisis de los datos revela que entre los entrevistados existe poco conocimiento acerca de los trabajos relacionados con la gestión de riesgos presentados en la investigación, lo cual indica un uso escaso de estos trabajos como estrategias de capacitación para los CROs. En cuanto a las herramientas y técnicas de gestión de riesgos, se constató que las técnicas señaladas por el COSO (2007) son poco utilizadas por los encuestados, mientras que las más utilizadas son las que son menos complicadas en su aplicación. Con respecto a los motivos detrás de la adopción de GRC en una empresa, el más común fue su exigencia por parte de órganos reguladores.

This paper analyzes the profile required by a chief risk officer (CRO) in large companies in Colombia, based on knowledge of the traits, skills, aptitudes and knowledge that are necessary to achieve adequate performance, so that it contributes the achievement of objectives. The study is carried out under a qualitative methodology of descriptive scope. Semi-structured interviews were conducted with risk managers of large Colombian companies in different sectors, and experts. In the results found it can be evidenced the importance to the chief risk officer and as well as to develop their profile both in technical aspects and in the soft skills they require. This is due to the fact that from their performance they add value to the company with their expertise and provide a prospective vision on the risk situations to which they may be exposed. This paper contributes to the knowledge about CRO that requires further academic research. [ABSTRACT FROM AUTHOR]

This study investigates the influence of CFO roles on the implementation of ERM initiatives in a sample of Nigerian financial institutions (between 2013-2017). We develop three distinct factors representing the CFO roles namely CFO power, CFO experience and CFO knowledge using principal component factoring. Like prior work, we measure ERM components simultaneously to capture the extent of sophisticated ERM system. Our findings pose that the CFO involvement in ERM implementation remains minimal while the CRO is solely responsible for ERM implementation, which could undermine cost-benefit effectiveness. Our empirical evidence reports that the sophisticated ERM only promote the market evaluation while the accounting performance is undermined. The result then contravenes the expectation that effective ERM enhances accounting performance by mitigating risk exposure. While the sophisticated ERM is significantly positive with leverage, which reveals that ERM implementation does not necessarily reduce the firm risk. This indicates that the ERM implementation remains ineffective to mitigate risks, where the CFO involvement in the ERM initiative is limited. We then advocate that CFOs should be allowed to contribute strongly on some specific aspects of ERM initiatives namely identification and analysis of key risk indicators, the financial implication of risks and integration of ERM into traditional finance activities.

Copyright of Revista Facultad de Ciencias Economicas: Investigacion y Reflexion is the property of Revista Facultad de Ciencias Economicas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Temperate bacteriophages possess a molecular switch, which regulates the lytic and lysogenic growth. The genomes of the temperate telomere phages N15, PY54 and ɸKO2 harbor a primary immunity region (immB) comprising genes for the prophage repressor, the lytic repressor and a putative antiterminator. The roles of these products are thought to be similar to those of the lambda proteins CI, Cro and Q, respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ɸKO2 are also reminiscent of lambda-like phages. By contrast, in silico analyses revealed the presence of only one operator (O\(_{\rm{R}}\)3) in PY54. The purified PY54 Cro protein was used for EMSA studies demonstrating that it exclusively binds to a 16-bp palindromic site (O\(_{\rm{R}}\)3) upstream of the prophage repressor gene. The O\(_{\rm{R}}\)3 operator sequences of PY54 and ɸKO2/N15 only differ by their peripheral base pairs, which are responsible for Cro specificity. PY54 cI and cro transcription is regulated by highly active promoters initiating the synthesis of a homogenious species of leaderless mRNA. The location of the PY54 Cro binding site and of the identified promoters suggests that the lytic repressor suppresses cI transcription but not its own synthesis. The results indicate an unexpected diversity of the growth regulation mechanisms in lambda-related phages.

Background: We determined the prevalence of antimicrobial resistance (AMR) in polymicrobial pathogens in Pakistan. Methods: A total of 70,518 clinical samples were collected aseptically and confirmation of isolates and antibiogram were performed by the VITEK 2 system. Results: Of 70,518 samples, 441 (0.62%) were polymicrobial samples, with 882 (1.2%) polymicrobial pathogens with 689 (78.1%) Gram-negative rods (GNRs), 166 (18.8%) Gram-positive cocci and 27 (3.1%) Candida albicans . Among GNRs, 28.8% were Escherichia coli and 25.9% were Klebsiella pneumoniae. Majority, 15.1% of Pseudomonas aeruginosa and K. pneumoniae were found in combination. 30.1% of isolates were ESBL producers, 9.7% carbapenem-resistant organisms, 35.5% MRSA and 6.0% VRE. 100% of E. coli were resistant to ampicillin and 98% of K. pneumoniae were resistant to piperacillin. Conclusion: A high prevalence of AMR in polymicrobial pathogens was observed.

Despite the existence of good clinical practice guidelines, the way in which they are applied to the bioanalytical laboratory remains unclear. Aspects of patient confidentiality, informed consent and subject withdrawal; addressing unblinding associated with sample analysis, including repeat analysis and incurred sample reanalysis; or the differences in responsibilities between the sponsor and contract research organization are not articulated by the US FDA within the bioanalytical setting, and for most bioanalytical laboratories this remains a gap in their standard operating procedures. The aim of this article is to identify and clarify the aspects of the good clinical practices that are applicable to the bioanalytical laboratory when conducting bioanalysis with clinical samples, and to address potential gaps in the bioanalytical laboratory when it comes to clinical sample bioanalysis.

Purpose: This article presents a novel design of a cranial remodeling orthosis (CRO) helmet developed through a three-dimensional (3D) scanning and 3D printing process to correct an infantile plagiocephaly. Materials and Methods: This research merges a handheld scanner, computer-aided engineering (CAE), and fused deposition modeling (FDM) technologies to propose an alternative to traditional plaster casting. The study finds out all criteria that will merge with requirements, 3D scanning, topological optimization into the CAE, and 3D printing to implement the design for manufacturing (DFM) approach to get a reproducible process that is less invasive for the child. Results: The project identifies the current limitations and creates design requirements and acceptance criteria to define a design and manufacturing process using a topological optimization method. Based on a child's skull 3D scan, the application aims to manufacture a CRO helmet due to clinical criteria by 3D printing. The new design aims to reduce the time from assessment to initial fitting and to reduce the temperature within the CRO. The project has manufactured a CRO helmet by fused depositing modeling in 3D printing to characterize its mechanical behavior and analyze the possible improvements. Conclusions: Limitations were found in the material used in the 3D printing, and some recommendations are made to improve the method. The DFM approach is useful for improving the final product by considering manufacturing and use constraints as soon as possible in the design stage, such as part orientation, infill density, and topological optimization parameters as well as the practitioner' skills. The main novelty is to have developed a 3D scanning and 3D printing process to correct an infantile plagiocephaly to obtain a CRO helmet responding to use and manufacturing constraints while proposing a suitable organic shape. [ABSTRACT FROM AUTHOR]

In recent years, the number and scope of outsourced activities in the pharmaceutical industry have increased heavily. In addition, also the type of outsourcing has changed significantly in that time. This raises the question of whether and how sponsors retain the capability to select and to control the contract research organizations (CROs) involved and what expertise still has to be present in the development department as well as other relevant departments to ensure adequate oversight, also in line with the expectations of regulators and health authorities. In order to answer these questions, a survey was conducted among the German vfa member companies. The survey describes the latest developments and experiences in outsourcing by 18 German vfa member companies. It concentrates on measures how to implement Quality Assurance (QA) when performing outsourced clinical studies.This study shows that the majority of companies apply a full-outsourcing, preferred-provider model of clinical trial services, with the clinical research department playing the major role in this process. A large amount of guiding documents, processes and tools are used to ensure an adequate oversight of the services performed by the CRO(s).Finally the guiding principles for all oversight processes should be transparent communication, a clearly established expectation for quality, a precise definition of accountability and responsibility while avoiding silo mentality, and a comprehensive documentation of the oversight’s evidence. For globally acting and outsourcing sponsors, oversight processes need to be aligned with regards to local and global perspectives. This survey shows that the current implementation of oversight processes in the participating companies covers all relevant areas to ensure highest quality and integrity of the data produced by the outsourced clinical trial.

Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different organisations. Here we outline the computational chemistry skills within Sygnature Discovery, along with the software and hardware at our disposal, and briefly discuss the methods that are not employed and why. The goal of the group is to provide support for design and analysis in order to improve the quality of compounds synthesised and reduce the timelines of drug discovery projects, and we reveal how this is achieved at Sygnature. Impact on medicinal chemistry is vital to demonstrating the value of computational chemistry, and we discuss the approaches taken to influence the list of compounds for synthesis, and how we recognise success. Finally we touch on some of the areas being developed within the team in order to provide further value to the projects and clients. [ABSTRACT FROM AUTHOR]

In this paper, an application of a hybrid Chemical Reaction Optimization (CRO) algorithm with adaptive Differential Evolution (DE) mutation strategies for training Higher Order Neural Networks (HONNs), especially the Pi-Sigma Network (PSN) is presented. Contrasting to traditional CRO algorithms, the reactant size (population size) remains fixed throughout all iterations, which makes it easier to implement. In addition, four DE mutation strategies (DE/rand/1, DE/best/1, DE/rand/2 and DE/best/2) with adaptive selection of control parameters as inter-molecular reactions and one intra-molecular reaction have been used. The proposed algorithm combines the diversification property of inter-molecular reactions following DE/rand mutation strategies and intensification property of intra-molecular reaction as well as inter-molecular reactions following DE/best mutation strategies, thereby glorifying the chances of reaching the global optima in less iteration. The performance of the proposed algorithm for HONN training is evaluated through a well-known neural network training benchmark i.e., to classify the parity-p problems. The results obtained from the proposed algorithm to train HONN have been compared with results from the following algorithms: Basic CRO algorithm, CRO-HONN Training (HONNT) and the most popular variants of DE algorithm (DE/rand/1/bin, DE/best/1/bin). It is observed that the application of the proposed hybridized algorithm to (DE-CRO-HONNT) performs statistically better than that of other algorithms considering both classification accuracy and number of generation taken to attain the solutions. [ABSTRACT FROM AUTHOR]

Drug development is a complicated and lengthy process requiring a significant amount of intellectual and capital input, as well as extensive collaborations among various organizations and institutions. Contract research organizations play important roles at some or even all stages of the drug development process. To provide better service in in vitro drug absorption, disposition, metabolism and excretion studies, maintain data accuracy and promote work efficiency, we developed an integrated information system termed the 'Drug Metabolism Information System', and it is being used routinely by our drug metabolism department. The Drug Metabolism Information System assists scientists with assay design, data analysis and report drafting and thus reduces human error.

The resistive switching memory characteristics of 100 randomly measured devices were observed by reducing device size in a Cr/CrO/TiO/TiN structure for the first time. Transmission electron microscope image confirmed a via-hole size of 0.4 µm. A 3-nm-thick amorphous TiO with 4-nm-thick polycrystalline CrO layer was observed. A small 0.4-µm device shows reversible resistive switching at a current compliance of 300 µA as compared to other larger size devices (1-8 µm) owing to reduction of leakage current through the TiO layer. Good device-to-device uniformity with a yield of >85 % has been clarified by weibull distribution owing to higher slope/shape factor. The switching mechanism is based on oxygen vacancy migration from the CrO layer and filament formation/rupture in the TiO layer. Long read pulse endurance of >10 cycles, good data retention of 6 h, and a program/erase speed of 1 µs pulse width have been obtained. [ABSTRACT FROM AUTHOR]

Temperate bacteriophages possess a molecular switch, which regulates the lytic and lysogenic growth. The genomes of the temperate telomere phages N15, PY54 and ΦKO2 harbor a primary immunity region (immB) comprising genes for the prophage repressor, the lytic repressor and a putative antiterminator. The roles of these products are thought to be similar to those of the lambda proteins CI, Cro and Q, respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ΦKO2 are also reminiscent of lambda-like phages. By contrast, in silico analyses revealed the presence of only one operator (OR3) in PY54. The purified PY54 Cro protein was used for EMSA studies demonstrating that it exclusively binds to a 16-bp palindromic site (OR3) upstream of the prophage repressor gene. The OR3 operator sequences of PY54 and ΦKO2/N15 only differ by their peripheral base pairs, which are responsible for Cro specificity. PY54 cI and cro transcription is regulated by highly active promoters initiating the synthesis of a homogenious species of leaderless mRNA. The location of the PY54 Cro binding site and of the identified promoters suggests that the lytic repressor suppresses cI transcription but not its own synthesis. The results indicate an unexpected diversity of the growth regulation mechanisms in lambda-related phages. [ABSTRACT FROM AUTHOR]

Copyright of Index.Comunicación is the property of Index.comunicacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses the role of alliances between pharmaceutical companies for research and development and production. Topics discussed include competition in generic drugs market, novel therapeutics and drug development and short-term outsourcing research. It also discusses public-private partnerships, and the role of technology in production and traditional biotechnology partnerships.

Pharmaxi (hereinafter CRO) is a Ukrainian group of companies providing full service in clinical trials. At the beginning of the massive military Russian invasion of Ukraine on the 24 th of February 2022, it was the biggest CRO in Ukraine with 17 full-time employees and 8 contractors. Founded in 2013, it has grown up increasingly while building resilience to repeated crises in Ukraine, sustaining continuity of operations. The company evolved through political instability during the Revolution of Dignity, the subsequent beginning of the Russian occupation of Crimea, the beginning of hybrid armed conflict in the Eastern part of Ukraine in 2014, and the COVID-2019 crisis. In the sixth month of the active Russian-Ukrainian war, the company continues business operations and is ready for further development. This case study investigates the strategy and best practices for ensuring business stability through contingency, resilience, and recovery actions analysis, expert interviews with management, and the SWOT analysis of the study findings. In particular, the organisational continuity framework features financial policy, human resources management, organisational behaviour practices, internal communication, and diversification. While investigating the case of company's continuity of operations, it appeared that the company had a crosscutting orientation on stability. The core domains ensuring resilient company's activity over repeated crises were the diversification, utilization tools for financial stability, distinct human capital management and design of operations. Study's results might be relevant to small and middle-sized service companies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The first author, Mariia Yashchenko, declare being the Head of Biometrics at Pharmaxi group of companies (“Pharmaxi” LLC, “Pharmaxi-Ukraine” LLC, “Pharmaxi Clinical Research” LLC, “Pharmaxi Clinical Solutions” LLC, “OnlineCRF” LLC, Pharmaxi Poland sp. Z o. o.), Postgraduate student and Senior lecturer at National University of Kyiv-Mohyla Academy, National Consultant at the World Health Organisation (Ukraine). The author, Yurii Lebid, declare being the CEO at Pharmaxi group of companies (“Pharmaxi” LLC, “Pharmaxi-Ukraine” LLC, “Pharmaxi Clinical Research” LLC, “Pharmaxi Clinical Solutions” LLC, “OnlineCRF” LLC, Pharmaxi Poland sp. Z o. o.). The author, Andrii Zaremba, declare being the СОО at Pharmaxi group of companies (“Pharmaxi” LLC, “Pharmaxi-Ukraine” LLC, “Pharmaxi Clinical Research” LLC, “Pharmaxi Clinical Solutions” LLC, “OnlineCRF” LLC, Pharmaxi Poland sp. Z o. o.). The author, Svitlana Bolman, declare being the Junior Statistician at Pharmaxi group of companies (“Pharmaxi” LLC, “Pharmaxi-Ukraine” LLC, “Pharmaxi Clinical Research” LLC, “Pharmaxi Clinical Solutions” LLC, “OnlineCRF” LLC, Pharmaxi Poland sp. Z o. o.). The author, Iryna Hoi, declare being the Head of Business Development Department at Pharmaxi group of companies (“Pharmaxi” LLC, “Pharmaxi-Ukraine” LLC, “Pharmaxi Clinical Research” LLC, “Pharmaxi Clinical Solutions” LLC, “OnlineCRF” LLC, Pharmaxi Poland sp. Z o. o.), Student of Master Program Public Policy and Administration at Kyiv School of Economics. The author, Roman Bystrov, declare being the Head of Data Management Department at Pharmaxi group of companies (“Pharmaxi” LLC, “Pharmaxi-Ukraine” LLC, “Pharmaxi Clinical Research” LLC, “Pharmaxi Clinical Solutions” LLC, “OnlineCRF” LLC, Pharmaxi Poland sp. Z o. o.)., (© 2022 The Authors.)

Parallel computing problems of multiphysical coupling applications based on discrete grids can be equivalently transformed into parallel computing problems based on a directed acyclic graph (DAG). Due to the problem of the discrete high-dimensional grids of the multiphysical coupling application, the directed data dependencies usually have parallelism. Moreover, this kind of scheduling problem based on DAG is NP-hard problem. Heuristic algorithms are often used to achieve optimal execution order scheduling of tasks and mapping between tasks and processors. In this paper, we propose an improved chemical reaction optimization algorithm based on adaptive search strategy (ASSCRO), which is used to solve the DAG task scheduling problem of discrete multiphysical coupling applications. ASSCRO is divided into two phases. The first phase is used to search the directed execution order of the tasks, and the second phase aims to use the heuristic strategy to map the tasks to the processors efficiently. In the four basic reactions of CRO, the algorithm can cover a larger search solution space by using an adaptive search strategy, it can obtain a better solution, and achieve less overhead and superior performance than the state-of-the-art. We conducted the experiment that applied our ASSCRO to deal with the multiphysical coupling applications. The experimental results showed that the proposed algorithm outperforms other algorithms in multiple metrics when dealing with DAG scheduling problems. • We propose the ASSCRO to solve the DAG issue with directed data dependencies. • The ASSCRO obtains the solution faster in the entire feasible solution space. • We propose a greedy strategy in the ASSCRO during the mapping process. • The strategy reduces inefficient mapping and maintains computational load-balancing. [ABSTRACT FROM AUTHOR]

Contract research organization (CRO) outsourcing has become a critical strategy for multinational biopharmaceutical companies looking to reduce costs, time-to-market and expanding their pipelines as blockbuster patents expire. Much of the growth in the CRO industry is coming from emerging markets, such as China and India. China's CRO industry began in 1996 and is still relatively young and fragmented. However, it is growing quickly at an annual rate of 30%. Global CRO giants such as Quintiles, PPD, Covance, Parexel and ICON have invested in facilities in China and some Chinese CROs have grown to become global players. This paper will provide a detailed analysis on CROs in China, including the characterization of companies and services provided, recent IPO/M&A deal activity, trends in the sector, and intellectual property and regulatory issues to consider. Readers will be able to obtain a clear picture of China's CRO landscape. This paper should serve as a guide for companies considering outsourcing R&D to China and investors looking for opportunities in China's CRO industry. [ABSTRACT FROM AUTHOR]

In order to generate synthesis gas or hydrogen free from nitrogen by partial oxidation of methane using air as an oxidant, gas-solid reactions of methane and a metal oxide and/or mixed metal oxides were carried out. The background of the gas-solid reaction was briefly reviewed and then a series of the present author's studies was described. As metal oxides FeO and NiO were active, but the reaction with methane and these oxides afforded complete oxidation to give HO and CO. To both oxides, addition of Cr- and Mg- oxides promoted the following reaction to give synthesis gas. After the reaction with methane, mixed oxides were reduced to lower valence state oxides and they were regenerated by the oxidation with air. Up to 10 repeated reaction and regeneration cycles did not or only slightly decreased the activity of the mixed oxides. By switching two or more reactors, the reaction and the regeneration were carried out to give synthesis gas continuously. [ABSTRACT FROM AUTHOR]

Abstract: The lysogeny region of the Lactobacillus delbrueckii bacteriophage mv4 contains two divergently oriented ORFs coding for the Rep (221 aa) and Tec (64 aa) proteins. The transcription of these two genes was analysed by primer extension and Northern blot experiments on lysogenic strains. The location of the transcription initiation sites of rep and tec in the intergenic region allowed the identification of the divergently oriented non overlapping promoters P rep and P tec. Transcriptional fusions analysis showed that Rep negatively regulates the P tec promoter and activates its own transcription, and that Tec is a negative regulator of the two promoters. As demonstrated by gel mobility shift assays, the repressor Rep binds to a single specific 17 bp site located between the P tec −10 and −35 regions whereas Tec binds to a single specific 40 bp long complex operator site located between the two promoters. The presence of a single specific operator site for each repressor in the intergenic region is an unusual feature. [Copyright &y& Elsevier]

Abstract: Tuc2009 is a temperate bacteriophage of Lactococcus lactis subsp. cremoris UC509 which encodes a CI- and Cro-type lysogenic–lytic switch region. A helix-swap of the α3 helices of the closely related CI-type proteins from the lactococcal phages r1t and Tuc2009 revealed the crucial elements involved in DNA recognition while also pointing to conserved functional properties of phage CI proteins infecting different hosts. CI-type proteins have been shown to bind to specific sequences located in the intergenic switch region, but to date, no detailed binding studies have been performed on lactococcal Cro analogues. Experiments shown here demonstrate alternative binding sites for these two proteins of Tuc2009. CI2009 binds to three inverted repeats, two within the intergenic region and one within the cro 2009 gene. This DNA-binding pattern appears to be conserved among repressors of lactococcal and streptococcal phages. The Cro2009 protein appears to bind to three direct repeats within the intergenic region causing distortion of the bound DNA. [Copyright &y& Elsevier]