Bedside Calculation of Energy Expenditure Does Not Guarantee Adequate Caloric Prescription in Long-Term Mechanically Ventilated Critically Ill Patients: A Quality Control Study

Nutrition is essential in critically ill patients, but translating caloric prescriptions into adequate caloric intake remains challenging. Caloric prescriptions (P), effective intake (I), and caloric needs (N), calculated with modified Harris-Benedict formulas, were recorded during seven consecutive days in ventilated patients. Adequacy of prescription was estimated by P/N ratio. I/P ratio assessed accuracy of translating a prescription into administered feeding. I/N ratio compared delivered calories with theoretical caloric needs. Fifty patients were prospectively studied in a mixed medicosurgical ICU in a teaching hospital. Basal and total energy expenditure were, respectively, 1361 ± 171 kcal/d and 1649 ± 233 kcal/d. P and I attained 1536 ± 602 kcal/d and 1424 ± 572 kcal/d, respectively. 24.6% prescriptions were accurate, and 24.3% calories were correctly administered. Excessive calories were prescribed in 35.4% of patients, 27.4% being overfed. Caloric needs were underestimated in 40% prescriptions, with 48.3% patients underfed. Calculating caloric requirements by a modified standard formula covered energy needs in only 25% of long-term mechanically ventilated patients, leaving many over- or underfed. Nutritional imbalance mainly resulted from incorrect prescription. Failure of “simple” calculations to direct caloric prescription in these patients suggests systematic use of more reliable methods, for example, indirect calorimetry

Territorial rights and colonial wrongs

What is wrong with colonialism? The standard—albeit often implicit—answer to this question has been that colonialism was wrong because it violated the territorial rights of indigenous peoples, where territorial rights were grounded on acquisition theories. Recently, the standard view has come under attack: according to critics, acquisition based accounts do not provide solid theoretical grounds to condemn colonial relations. Indeed, historically they were used to justify colonialism. Various alternative accounts of the wrong of colonialism have been developed. According to some, colonialism involved a violation of territorial rights grounded on legitimate state theory. Others reject all explanations of colonialism's wrongfulness based on territorial rights, and argue that colonial practices were wrong because they departed from ideals of economic, social, and political association. In this article, we articulate and defend the standard view against critics: colonialism involved a procedural wrong; this wrong is not the violation of standards of equality and reciprocity, but the violation of territorial rights; and the best foundation for such territorial rights is acquisition based, not legitimacy based. We argue that this issue is not just of historical interest, it has relevant implications for the normative evaluation of contemporary inequalities

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Conceptualising slow tourism: a perspective from Latvia

Slow tourism is perceived as a new type of sustainable tourism and a promising alternative to mass tourism with which tourists, destination managers and tourism service providers are willing to engage. However, inconsistent interpretations impede the clarity of communication between tourism suppliers and consumers. This study re-examines the phenomenon of slow tourism to address this gap in the literature. The focus of the study is Latvia where slowness, until recently, was adopted in tourism branding. This qualitative study revealed that slow tourism is an approach to tourism underpinned by a slow mindset which enhances the core experiential aspect of the phenomenon within ethical boundaries. The environmental and economic aspects appear to be marginal and may fluctuate in intensity according to individuals’ perception. This study offers a theoretical perspective alongside some practical implications for slow tourism and enhances industry awareness of the phenomenon, satisfies consumers’ expectations and improves marketing communications

Septic AKI in ICU patients. diagnosis, pathophysiology, and treatment type, dosing, and timing: a comprehensive review of recent and future developments

Evidence is accumulating showing that septic acute kidney injury (AKI) is different from non-septic AKI. Specifically, a large body of research points to apoptotic processes underlying septic AKI. Unravelling the complex and intertwined apoptotic and immuno-inflammatory pathways at the cellular level will undoubtedly create new and exciting perspectives for the future development (e.g., caspase inhibition) or refinement (specific vasopressor use) of therapeutic strategies. Shock complicating sepsis may cause more AKI but also will render treatment of this condition in an hemodynamically unstable patient more difficult. Expert opinion, along with the aggregated results of two recent large randomized trials, favors continuous renal replacement therapy (CRRT) as preferential treatment for septic AKI (hemodynamically unstable). It is suggested that this approach might decrease the need for subsequent chronic dialysis. Large-scale introduction of citrate as an anticoagulant most likely will change CRRT management in intensive care units (ICU), because it not only significantly increases filter lifespan but also better preserves filter porosity. A possible role of citrate in reducing mortality and morbidity, mainly in surgical ICU patients, remains to be proven. Also, citrate administration in the predilution mode appears to be safe and exempt of relevant side effects, yet still requires rigorous monitoring. Current consensus exists about using a CRRT dose of 25 ml/kg/h in non-septic AKI. However, because patients should not be undertreated, this implies that doses as high as 30 to 35 ml/kg/h must be prescribed to account for eventual treatment interruptions. Awaiting results from large, ongoing trials, 35 ml/kg/h should remain the standard dose in septic AKI, particularly when shock is present. To date, exact timing of CRRT is not well defined. A widely accepted composite definition of timing is needed before an appropriate study challenging this major issue can be launched

Questions on causality and responsibility arising from an outbreak of Pseudomonas aeruginosa infections in Norway

In 2002, Norway experienced a large outbreak of Pseudomonas aeruginosa infections in hospitals with 231 confirmed cases. This fuelled intense public and professional debates on what were the causes and who were responsible. In epidemiology, other sciences, in philosophy and in law there is a long tradition of discussing the concept of causality. We use this outbreak as a case; apply various theories of causality from different disciplines to discuss the roles and responsibilities of some of the parties involved. Mackie's concept of INUS conditions, Hill's nine viewpoints to study association for claiming causation, deterministic and probabilistic ways of reasoning, all shed light on the issues of causality in this outbreak. Moreover, applying legal theories of causation (counterfactual reasoning and the "but-for" test and the NESS test) proved especially useful, but the case also illustrated the weaknesses of the various theories of causation

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigate relationships have been unsuitable for rare diseases. / Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, twelve clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. / Results: Disease severity at diagnosis measured by FEV1 z-score was (i) significantly worse in individuals with CCDC39 mutations compared to other gene mutations and (ii) better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. / Conclusions: This large scale multi-national study presents PCD as a syndrome with overlapping symptoms and variation in phenotype, according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutations), and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations

Shaping tourists’ wellbeing through guided slow adventures

Against the backdrop of the United Nations’ Sustainable Development Goal 3, good health and wellbeing, this paper reports on a study that examined how outdoor guides perceive their role in facilitating the psychological wellbeing of tourists who consume slow adventure experiences. These experiences, such as canoeing, stargazing or foraging, are characterised by a slower passage of time, immersion in the natural world and a sense of belonging to small social groups. Grounded in research on wellbeing from a positive psychology perspective, the study utilised semi-structured, in-depth, interviews with ten outdoor adventure guides in the Scottish Highlands and Islands. Following a hermeneutic interpretive approach to analyse the interview transcripts, the findings revealed how perceptions of time, meaningful moments and a sense of togetherness are choreographed by slow adventure guides to shape tourists’ psychological wellbeing through immersive guided experiences, ultimately helping tourists to re-establish a much-yearned-for connection with nature. The study adds to tourism, wellbeing and sustainability literature by providing new perspectives on psychological wellbeing through guided slow adventures. In particular the findings contribute to positive tourism, or tourism and positive psychology field of research, by revealing how mindful and eudaimonic visitor experiences are organised by adventure tour guides in natural settings

Functional Analysis of Ficolin-3 Mediated Complement Activation

The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway