Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase/Visfatin Enzymatic Activity Identifies a New Inflammatory Pathway Linked to NAD

Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFα levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders

Perceived risk of infection and death from COVID-19 among community members of low- and middle-income countries: A cross-sectional study [version 1; peer review: awaiting peer review]

Background: Risk perceptions of coronavirus disease 2019 (COVID-19) are considered important as they impact community health behaviors. The aim of this study was to determine the perceived risk of infection and death due to COVID-19 and to assess the factors associated with such risk perceptions among community members in low- and middle-income countries (LMICs) in Africa, Asia, and South America. Methods: An online cross-sectional study was conducted in 10 LMICs in Africa, Asia, and South America from February to May 2021. A questionnaire was utilized to assess the perceived risk of infection and death from COVID-19 and its plausible determinants. A logistic regression model was used to identify the factors associated with such risk perceptions. Results: A total of 1,646 responses were included in the analysis of the perceived risk of becoming infected and dying from COVID-19. Our data suggested that 36.4% of participants had a high perceived risk of COVID-19 infection, while only 22.4% had a perceived risk of dying from COVID-19. Being a woman, working in healthcare-related sectors, contracting pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, as well as seeing or reading about individuals infected with COVID-19 on social media or TV were all associated with a higher perceived risk of becoming infected with COVID-19. In addition, being a woman, elderly, having heart disease and pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, and seeing or reading about individuals infected with COVID-19 on social media or TV had a higher perceived risk of dying from COVID-19. Conclusions: The perceived risk of infection and death due to COVID-19 are relatively low among respondents; this suggests the need to conduct health campaigns to disseminate knowledge and information on the ongoing pandemic

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Optimal sensor location for improved multifixture assembly system fault diagnosis: A methodology.

This thesis presents a multi-sensor placement methodology developed and implemented for dimensional fault diagnosis, and the process control of assembly lines such as those in sheet metal assembly. An assembly line is defined as consisting of a sequence of fixtures. Sensors are used to measure dimensional characteristics of the subassemblies as they move from fixture to fixture in the sequence. Fault diagnosis involves identifying the specific fixture and the functional part of the fixture at fault, if the assembly does not meet dimensional acceptance criteria. Fixture fault diagnosis is a critical component of techniques aimed at assembly variation reduction. The effectiveness of the diagnosis is contingent on the effectiveness of the sensor measurements of assembled parts. A novel means of enhancing diagnosability is proposed for multi-fixture sheet-metal assembly, using in-line measurement sensors, through a methodology which develops an optimized configuration of sensor locales for measurement. The methodology incorporates specifications (representations) of fixtures, assemblies, and sensor locations. Sensor placement optimization techniques are provided for three levels of system complexity in the development of the multi-sensor methodology: (i) for a single fixture assembly system, (ii) an enhancement for a multi-fixture assembly system with sensing at a measurement station in a single end-of-line location, and (iii) an enhancement to deal with multi-fixture assembly systems with sensing distributed at multiple locations in the assembly sequence. For a single fixture assembly system, the methodology involves optimization carried out on sensor location and number to achieve optimal diagnosability for that fixture. For a multi-fixture assembly system, a hierarchical group description of the assembly is used to build a state-transition representation which, with CAD fixture information, is used in multi-level hierarchical optimization to arrive at the optimal for the overall assembly. In the end-of-line sensing system, this can then optimally diagnose faults caused by failures anywhere in the multi-fixture assembly line upstream of the measurement station. The distributed sensing enhancement allows for enhanced fault diagnosis in an assembly line by finding an optimal locale of sensor positions at multiple, distributed, measurement stations. In each case, a configured optimal locale provides an optimally distinctive signature for each fault in the assembly, and optimally discriminates among all possible faults. The developed approach has significant utility in automotive body assembly, where system complexity makes the choice of sensor location vital to fault isolation. Examples using simulated and industrial automotive body assembly sequences are provided to help illustrate and validate the proposed methodology.Ph.D.Applied SciencesAutomotive engineeringIndustrial engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131687/2/9929861.pd

Konsten att balansera: Revisorns integritet och klientrelationer i fokus

Titel: The Art of Balancing: The Auditor’s Integrity and Client Relationships in Focus   Level: Final Assignment for bachelor’s degree in business administration   Author: Danait Bri and Mahir Khan   Supervisor: Fredrik Hartwig   Date: 2024 – May   Aim: The study aims to create an understanding of how accountants balance in negotiation situations between maintaining good relationships with their clients while maintaining their independence and integrity.   Method: In this study, we have used a qualitative method where the data collection took place through semi-structured interviews with five authorized accountants. A deductive approach together with an interpretive perspective has been used in data collection and analysis. A thematic content analysis has been used to answer the purpose of the study.   Results and conclusions: The study shows that a long-term relationship does not lead to emotional involvement with the clients, but to a certain comfort. A higher degree of self-realization and taking an outside perspective helps the accountant resist external pressures. The auditor's independence can be threatened in long-term client relationships or by the prvision of non-audit-related services. Direct negotiations are unusual, instead there are discussions with elements of negotiation.   Contribution of the thesis: The work highlights accountants' challenges in balancing the relationship with clients. The study shows that auditors usually have discussions with elements of negotiation rather than direct negotiations. The study has contributed with a new strategy which involves lowering the clients' expectations from the start to arrive at a reasonably good solution.   Suggestions for further research: In future studies, it may be interesting to examine wheither the clients perceive that there are direct negotiations or discussions with negotiation elements that occur.    Titel: Konsten att balansera: Revisorns integritet och klientrelationer i fokus   Nivå: Examensarbete på grundnivå (kandidatexamen) i ämnet företagsekonomi   Författare: Danait Bri och Mahir Khan   Handledare: Fredrik Hartwig   Datum: 2024 – maj   Syfte: Studien ämnar skapa förståelse för hur revisorer balanserar i förhandlingssituationer mellan att upprätthålla goda relationer med sina klienter samtidigt som de behåller sitt oberoende och sin integritet.    Metod: I denna studie har vi använt en kvalitativ metod där datainsamlingen skett via semistrukturerade intervjuer med fem auktoriserade revisorer. En deduktiv ansats tillsammans med tolkande perspektiv har använts vid datainsamling och analys. En tematisk innehållsanalys har använts för att besvara studiens syfte.   Resultat och slutsats: Studien visar att en långvarig relation inte leder till känslomässig inblandning med klienterna, dock till en viss bekvämlighet. Högre grad av självförverkligande och intagning av utomstående perspektiv hjälper revisorn att motstå externa påtryckningar. Revisorns oberoende kan hotas vid långvariga kundrelationer eller vid tillhandahållandet av icke-revisionsrelaterade tjänster. Direkta förhandlingar är ovanliga, istället är det diskussioner med förhandlingsinslag som förekommer.   Examensarbetets bidrag: Arbetet belyser revisorers utmaningar med att balansera relationen till klienter. Studien visar att revisorer oftast har diskussioner med förhandlingsinslag snarare än direkta förhandlingar. Studien har bidragit med en ny strategi som innebär att sänka klienternas förväntningar från början för att i slutändan kunna komma fram till en rimligt bra lösning.   Förslag till fortsatt forskning: I framtida studier kan det vara intressant att undersöka om klienterna upplever att det är direkta förhandlingar eller diskussioner med förhandlingsinslag som förekommer