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After the ejection of viral DNA into the host cytoplasm, the temperate bacteriophage (phage) lambda integrates a cascade of expressions from various regulatory genes, coupled with DNA replication, to commit to a decision between lysis and lysogeny. Higher multiplicity of infection (MOI) greatly shifts the decision toward the lysogenic pathway. However, how the phage separates the MOI from replicated viral DNA during lysis-lysogeny decision-making is unclear. To quantitatively understand the role of viral DNA replication, we constructed a reporter system facilitating the visualization of individual copies of phage DNA throughout the phage life cycle, along with the lysis-lysogeny reporters. We showed that intracellular viral DNA diverges between the lytic and lysogenic pathways from the early phase of the infection cycle, mostly due to the synchronization and success of DNA injection, as well as the competition for replication resources, rather than the replication rate. Strikingly, we observed two distinct replication patterns during lysogenization and surprisingly heterogeneous integration kinetics, which advances our understanding of temperate phage life cycles. We revealed that the weak repression function of Cro is critical for an optimal replication rate and plays a crucial role in establishing stable lysogens. IMPORTANCE Temperate bacteriophages, such as lambda, incorporate environmental cues including host abundance and nutrient conditions to make optimal decisions between propagation and dormancy. A higher phage-to-host ratio or multiplicity of infection (MOI) during λ infection strongly biases toward lysogeny. However, a comprehensive understanding of this decision-making process and the impact of phage replication prior to the decision is yet to be achieved. Here, we used fluorescence microscopy to quantitatively track the spatiotemporal progression of viral DNA replication in individual cells with different cell fates. The implementation of this fluorescent reporter system and quantitative analysis workflow opens a new avenue for future studies to delve deeper into various types of virus-host interactions at a high resolution. [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 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]

Financial disasters can have catastrophic consequences for economies that extend beyond the organisational walls. This case study will examine the downfall of Silicon Valley Bank by exploring ineffective risk management practices and the absence of the Chief Risk Officer (CRO). It will begin by establishing a basic understanding of the bank's history and client base before diving into the events that led up to the third-largest bank run in US history. In our upcoming discussion, we will delve into the risk management standards that financial organisations typically employ to avoid insolvency. Additionally, we will emphasise the pivotal importance of the CRO role within such institutions. Finally, the study will conclude by emphasising the critical role of robust risk management practices, effective regulatory oversight and organisational reforms in mitigating the risks associated with financial disasters and safeguarding the resilience of the banking ecosystem. Understanding the impacts and lessons of past financial disasters is essential to build a more stable and resilient economic landscape as the financial system evolves. [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.

Purpose of Review: Over 50% of the infections in most ICUs in tertiary care centres in India are caused by difficult to treat (DTR) gram-negative bacteria. The options available for the treatment of these infections are quite limited. This review discusses the epidemiology of these DTR infections in India and explores the various treatment strategies for these infections which are relevant in an Indian setting. Recent Findings: The most common organisms causing DTR infections in India are Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa. The mechanisms of resistance in these organisms are not the same as those in DTR organisms prevalent in the western world. Treatment strategies recommended by western guidelines may not work in India. Management of these DTR organisms needs to be tailored to the situation in India. Summary: Overuse of antibiotics has led to an alarming rate of DTR infections in Indian ICUs. The polymyxins are often the only drugs which are effective against many of these infections. Physicians in India and the government need to take urgent measures to control the spread of these organisms. Key points: Antibiotic overuse has led to a situation where over 50% of infections in Indian ICUs are caused by DTR organisms. Carbapenemase production is the primary mechanism of resistance in carbapenem-resistant Enterobacterales (CRE). Efflux pumps, altered outer membrane porin and production of carbapenemases are all implicated in DTR Pseudomonas aeruginosa and Acinetobacter baumannii. KPC production is very uncommon in the CRE prevalent in India. Western guidelines may therefore not be relevant in India. The polymyxins (in combination) and ceftazidime/avibactam with aztreonam are the drugs most often used to deal with DTR gram-negative bacteria in India. Local delivery of antibiotics may be indicated in the management of these DTR infections in special sites like meningitis and pneumonia. [ABSTRACT FROM AUTHOR]

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.

After the ejection of viral DNA into the host cytoplasm, the temperate bacteriophage (phage) lambda integrates a cascade of expressions from various regulatory genes, coupled with DNA replication, to commit to a decision between lysis and lysogeny. Higher multiplicity of infection (MOI) greatly shifts the decision toward the lysogenic pathway. However, how the phage separates the MOI from replicated viral DNA during lysis-lysogeny decision-making is unclear. To quantitatively understand the role of viral DNA replication, we constructed a reporter system facilitating the visualization of individual copies of phage DNA throughout the phage life cycle, along with the lysis-lysogeny reporters. We showed that intracellular viral DNA diverges between the lytic and lysogenic pathways from the early phase of the infection cycle, mostly due to the synchronization and success of DNA injection, as well as the competition for replication resources, rather than the replication rate. Strikingly, we observed two distinct replication patterns during lysogenization and surprisingly heterogeneous integration kinetics, which advances our understanding of temperate phage life cycles. We revealed that the weak repression function of Cro is critical for an optimal replication rate and plays a crucial role in establishing stable lysogens., Importance: Temperate bacteriophages, such as lambda, incorporate environmental cues including host abundance and nutrient conditions to make optimal decisions between propagation and dormancy. A higher phage-to-host ratio or multiplicity of infection (MOI) during λ infection strongly biases toward lysogeny. However, a comprehensive understanding of this decision-making process and the impact of phage replication prior to the decision is yet to be achieved. Here, we used fluorescence microscopy to quantitatively track the spatiotemporal progression of viral DNA replication in individual cells with different cell fates. The implementation of this fluorescent reporter system and quantitative analysis workflow opens a new avenue for future studies to delve deeper into various types of virus-host interactions at a high resolution., Competing Interests: The authors declare no conflict of interest.

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]

Random search algorithms have been widely applied in practice to solve optimization problems. In the field of automatic control, there has been much research applying random search algorithms to optimize the parameter of Proportional -- Integral - Derivative (PID) controller. The content of this research mainly stops at comparing the performance of the PID controller using the traditional tuning method with the optimization algorithm-based tuning method. Therefore, there is a need for research to compare the performance among random search algorithms for finding optimal parameters of the PID controller. In this paper, authors simulate five well-known and modern stochastic search algorithms including Genetic Algorithm (GA), Particle Swarm Optimization (PSO), Whale Optimization Algorithm (WOA), Chemical Reaction Optimization (CRO), Teaching Learning Based Optimization (TLBO) to find optimal parameters of the PID controller for controlling the speed of the DC motor. The simulation results showed that the CRO algorithm is the most suitable to optimize PID controller parameters for the proposed problem. [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.

In today's e-commerce industry, conversion rate optimization is often considered essentially the same as user experience optimization. In addition, there is a strong focus on quantitative experimentation, which some deem a jack-of-all-trades solution, often at the expense of qualitative user experience research. Both are worrying developments. This essay elaborates on why it is harmful to consider conversion rate optimization and user experience optimization to be the same thing in the context of growth marketing, and how the three concepts are interrelated. [ABSTRACT FROM AUTHOR]

The 16th GCC Closed Forum was held in Orlando, FL, USA, on 23 June 2023. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: IS response, flow cytometry, changes to the bioanalytical industry, NGS assays, biomarker assay for tissues, dPCR validation, immunogenicity harmonization and ICH M10 implementation. Conclusions and consensus from discussions of these topics are included in this article.