On defining the Hamiltonian beyond quantum theory

Energy is a crucial concept within classical and quantum physics. An essential tool to quantify energy is the Hamiltonian. Here, we consider how to define a Hamiltonian in general probabilistic theories, a framework in which quantum theory is a special case. We list desiderata which the definition should meet. For 3-dimensional systems, we provide a fully-defined recipe which satisfies these desiderata. We discuss the higher dimensional case where some freedom of choice is left remaining. We apply the definition to example toy theories, and discuss how the quantum notion of time evolution as a phase between energy eigenstates generalises to other theories.Comment: Authors' accepted manuscript for inclusion in the Foundations of Physics topical collection on Foundational Aspects of Quantum Informatio

PART I: MINIMUM QUALITY THRESHOLD IN PRECLINICAL SEPSIS STUDIES (MQTiPSS) FOR STUDY DESIGN AND HUMANE MODELING ENDPOINTS

The Austrian Science Fund T707-B13 (SD, MFO)The William Harvey Research Foundation (CT)NWO VIDI (no.: 91716475)MC-ITN ‘‘European Sepsis Academy’’ (WJW)National Institutes of Health R01 GM067202 and GM115973 (BZ)The National Institute of General Medical Sciences GM072808, GM104323, GM109779, and GM113228 (CMC)

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

IMPORTANCE: Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE: To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS: A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROM EVIDENCE SYNTHESIS: Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS: Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE: These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis

Intensivist supervision of resident-placed central venous catheters decreases the incidence of catheter-related blood stream infections

Catheter-related blood stream infections (CRBSI) cause significant morbidity and mortality. A retrospective study of a performance improvement project in our teaching hospital's surgical intensive care unit (SICU) showed that intensivist supervision was important in reinforcing maximal sterile barriers (MSB) use during the placement of a central venous catheter (CVC) in the prevention of CRBSI. A historical control period, 1 January 2001–31 December 2003, was established for comparison. From 1 January 2003–31 December 2007, MSB use for central venous line placement was mandated for all operators. However, in 2003 there was no intensivist supervision of CVC placements in the SICU. The use of MSB alone did not cause a significant change in the CRBSI rate in the first year of the project, but close supervision by an intensivist in years 2004–2007, in conjunction with MSB use, demonstrated a significant drop in the CRBSI rate when compared to the years before intensivist supervision (2001–2003), p < .0001. A time series analysis comparing monthly rates of CRBSI (2001–2007) also revealed a significant downward trend, p = .028. Additionally, in the first year of the mandated MSB use (2003), 85 independently observed resident-placed CVCs demonstrated that breaks in sterile technique (34/85), as compared those placements that had no breaks in technique (51/85), had more CRBSI, 6/34 (17.6%) vs. 1/51 (1.9%), p < .01. Interventions to reduce CRBSI in our SICU needed emphasis on adequate supervision of trainees in CVC placement, in addition to use of MSB, to effect lower CRBSI rates

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Fragmentation of care threatens patient safety in peripheral vascular catheter management in acute care--a qualitative study.

BACKGROUND: The use of peripheral vascular catheters (PVCs) is an extremely common and necessary clinical intervention, but inappropriate PVC care poses a major patient safety risk in terms of infection. Quality improvement initiatives have been proposed to reduce the likelihood of adverse events, but a lack of understanding about factors that influence behaviours of healthcare professionals limits the efficacy of such interventions. We undertook qualitative interviews with clinical staff from a large group of hospitals in order to understand influences on PVC care behaviors and subsequent patient safety. METHODS: Ten doctors, ten clinical pharmacists, 18 nurses and one midwife at a National Health Service hospital group in London (United Kingdom) were interviewed between December 2010 and July 2011 using qualitative methods. Responses were analysed using a thematic framework. RESULTS: FOUR KEY THEMES EMERGED: 1) Fragmentation of management and care, demonstrated with a lack of general overview and insufficient knowledge about expected standards of care or responsibility of different professionals; 2) feelings of resentment and frustration as a result of tensions in the workplace, due to the ambiguity about professional responsibilities; 3) disregard for existing hospital policy due to perceptions of flaws in the evidence used to support it; and 4) low-risk perception for the impact of PVC use on patient safety. CONCLUSION: Fragmentation of practice resulted in ill-defined responsibilities and interdisciplinary resentment, which coupled with a generally low perception of risk of catheter use, appeared to result in lack of maintaining policy PVC standards which could reduced patient safety. Resolution of these issues through clearly defining handover practice, teaching interdisciplinary duties and increasing awareness of PVC risks could result in preventing thousands of BSIs and other PVC-related infections annually

Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats

PURPOSE:To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline.METHODS:It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3.RESULTS:The values of sO2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR).CONCLUSION:The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion.São Paulo University Medical SchoolUSP Medical SchoolFederal University of São Paulo Medical SchoolUSP School of MedicineUSP School of Medicine Department of SurgeryUSP Medical School Department of SurgeryUNIFESP, Medical SchoolSciEL

Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO) to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1) TNF-α production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice