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This study presents an application of a measure of learner involvement developed by Paas, Tuovinen, van Merrienboer, and Darabi (2005). These authors combined learners' performance scores with their perceived mental effort invested in instruction and used it to assess learner involvement in instructional conditions. The present study examines the differentiating attributes of the Paas et al. learner involvement measure by using data collected in an experiment that investigated the effectiveness of three computer-based instructional strategies: (a) conventional problem solving, (b) product-oriented worked examples, and (c) process-oriented worked examples. As hypothesized, learners using worked example strategies showed higher involvement scores than those in conventional problem solving. However, no differences in learner involvement were found between the two worked-example strategies. The implications of these findings for designing instructional strategies and suggestions for further research are discussed. (Contains 2 figures and 1 table.)

In order to develop an expert-like mental model of complex systems, causal reasoning is essential. This study examines the differences between forward and backward instructional strategies in terms of efficiency, students' learning and progression of their mental models of the electronic transport chain in an undergraduate metabolism course (n = 151). Additionally, the participants' cognitive flexibility, prior knowledge, and mental effort in the learning process are also investigated. The data were analyzed using a series of general linear models to compare the strategies. Although the two strategies did not differ significantly in terms of mental model progression and learning outcomes, both groups' mental models progressed significantly. Mental effort and prior knowledge were identified as significant predictors of mental model progression. An interaction between instructional strategy and cognitive flexibility revealed that the backward instruction was more efficient than the conventional (forward) strategy for students with lower cognitive flexibility, whereas the conventional instruction was more efficient for students with higher cognitive flexibility. The results are discussed and suggestions for future research on the possible moderating role of cognitive flexibility in the area of health education are presented.

This study investigated the effect of two instructional strategies, segmented and holistic, on the progression over time of learners' mental models toward that of an expert with the moderator of cognitive flexibility. Sixty-four juniors and seniors in a college metabolism course were randomly assigned to one of the two strategies for instruction on the electron transport chain. The data were analyzed with a repeated measures general linear model. Mental models progressed significantly for both strategies (p less than 0.001), and a significant interaction was found between cognitive flexibility and instructional strategy on mental model progression (p = 0.02). The segmented strategy was superior for learners with higher cognitive flexibility but inferior to the holistic strategy for lower cognitive flexibility learners. Results have important implications for differentiating instruction on the basis of learner characteristics. (Contains 4 tables and 3 figures.)

In a diagnostic problem solving operation of a computer-simulated chemical plant, chemical engineering students were randomly assigned to two groups: one studying product-oriented worked examples, the other practicing conventional problem solving. Effects of these instructional strategies on the progression of learners' mental models were examined by comparing representations of their mental models with those of experts at three segments of the instruction. Progression of mental models for the worked example group was significantly greater than those using the problem-solving strategy. However, this progression did not manifest itself in learners' troubleshooting performance measured by number of correct diagnosis and first time correct diagnosis. The implications of these results for designing instruction tailored to learners' domain knowledge are discussed. (Contains 4 figures, 2 tables, and 1 footnote.)

The purpose of this study was to investigate the effects of two types of maps (generative vs. completed) and the amount of prior knowledge (high vs. low) on well-structured and ill-structured problem-solving performance. Forty-four undergraduates who were registered in an introductory instructional technology course participated in the study. Participants were randomly assigned to two treatments that used generative and completed concept maps. Within those treatment groups, participants were differentiated by prior domain knowledge, high or low. Although the high knowledge-generative group outperformed the other three groups on well-structured problem-solving performance, it did not have an effect on ill-structured problem-solving performance.

The purpose of this article is to provide five empirically-derived guidelines for knowledge map construction tools that facilitate problem solving. First, the combinational representation principle proposes that conceptual and corresponding procedural knowledge should be represented together (rather than separately) within the knowledge map. Second, the contextual enhancement principle proposes that the learner should provide information regarding the context of the problem within the knowledge map. Third, the spatial flexibility principle proposes that the space where learners represent concepts should be flexible and not artificially constrained. Fourth, the property association principle proposes that the magnitude of association between the concept and associated processes should be classified by the learner within the knowledge map. Fifth, the multiple representation principle proposes that the knowledge map construction tool should have the capacity to represent concepts through multiple modalities. The article presents a prototype of a new knowledge map construction tool that incorporates each of these principles. (Contains 4 figures.)

The articles published in four prominent distance education journals between 1997 and 2002 were categorized and the references cited were tallied. The study provides an opportunity to examine research topics, methods, and citation trends. The results can be used to review current research trends and to explore potential research directions.

When a patient is admitted to the intensive care unit (ICU) after a traumatic brain injury (TBI), an early prognosis is essential for baseline risk adjustment and shared decision making. TBI outcomes are commonly categorised by the Glasgow Outcome Scale–Extended (GOSE) into eight, ordered levels of functional recovery at 6 months after injury. Existing ICU prognostic models predict binary outcomes at a certain threshold of GOSE (e.g., prediction of survival [GOSE > 1]). We aimed to develop ordinal prediction models that concurrently predict probabilities of each GOSE score. From a prospective cohort (n = 1,550, 65 centres) in the ICU stratum of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) patient dataset, we extracted all clinical information within 24 hours of ICU admission (1,151 predictors) and 6-month GOSE scores. We analysed the effect of two design elements on ordinal model performance: (1) the baseline predictor set, ranging from a concise set of ten validated predictors to a token-embedded representation of all possible predictors, and (2) the modelling strategy, from ordinal logistic regression to multinomial deep learning. With repeated k-fold cross-validation, we found that expanding the baseline predictor set significantly improved ordinal prediction performance while increasing analytical complexity did not. Half of these gains could be achieved with the addition of eight high-impact predictors to the concise set. At best, ordinal models achieved 0.76 (95% CI: 0.74–0.77) ordinal discrimination ability (ordinal c-index) and 57% (95% CI: 54%– 60%) explanation of ordinal variation in 6-month GOSE (Somers' Dxy). Model performance and the effect of expanding the predictor set decreased at higher GOSE thresholds, indicating the difficulty of predicting better functional outcomes shortly after ICU admission. Our results motivate the search for informative predictors that improve confidence in prognosis of higher GOSE and the development of ordinal dynamic prediction models. [ABSTRACT FROM AUTHOR]

Background: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID‐19, relating post‐intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID‐19 pandemic has posed enormous health challenges to individuals and health‐care systems worldwide. An emerging feature of severe COVID‐19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. Methods: In this study, we aim to investigate patients treated for severe COVID‐19 in the ICU, as to describe and relate serum‐, plasma‐ and cerebrospinal fluid‐borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3–12 months after ICU discharge. Results: To date, we have performed 51 3‐month follow‐up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. Conclusion: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation. [ABSTRACT FROM AUTHOR]

Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I mRNA, and ileal proglucagon mRNA. Plasma IGF-I concentration was restored to fed levels with 2 days of ad libitum refeeding but not with 4 days of intravenous or intragastric refeeding. Administration of an inhibitor of endogenous GLP-2 (rat [GLP-2.sup.3-33]) during ad libitum refeeding partially attenuated mucosal growth and prevented the increase in plasma IGF-I to fed levels; however, plasma GLP-2 and jejunal IGF-I mRNA were restored to fed levels. Intragastric refeeding restored intestinal cellularity and functional capacity (sucrase activity and sodium-glucose transporter-1 expression) to fed levels, whereas intravenous refeeding had no effect. Intestinal regeneration after 4 days of intragastric or 2 days of ad libitum refeeding was positively associated with increases in plasma concentrations of GLP-2 and jejunal IGF-I mRNA. These data suggest that luminal nutrients stimulate intestinal growth, in part, by increased expression of both GLP-2 and IGF-I. parenteral nutrition; proglucagon; sodium-glucose linked transporter-1; [GLP-2.sup.3-33]

Background Traumatic brain injury (TBI) is a major contributor to morbidity and mortality. Computerized tomography (CT) scanning of the brain is essential for diagnostic screening of intracranial injuries in need of neurosurgical intervention, but may also provide information concerning patient prognosis and enable baseline risk stratification in clinical trials. Novel CT scoring systems have been developed to improve current prognostic models, including the Stockholm and Helsinki CT scores, but so far have not been extensively validated. The primary aim of this study was to evaluate the Stockholm and Helsinki CT scores for predicting functional outcome, in comparison with the Rotterdam CT score and Marshall CT classification. The secondary aims were to assess which individual components of the CT scores best predict outcome and what additional prognostic value the CT scoring systems contribute to a clinical prognostic model. Methods and findings TBI patients requiring neuro-intensive care and not included in the initial creation of the Stockholm and Helsinki CT scoring systems were retrospectively included from prospectively collected data at the Karolinska University Hospital (n = 720 from 1 January 2005 to 31 December 2014) and Helsinki University Hospital (n = 395 from 1 January 2013 to 31 December 2014), totaling 1,115 patients. The Marshall CT classification and the Rotterdam, Stockholm, and Helsinki CT scores were assessed using the admission CT scans. Known outcome predictors at admission were acquired (age, pupil responsiveness, admission Glasgow Coma Scale, glucose level, and hemoglobin level) and used in univariate, and multivariable, regression models to predict long-term functional outcome (dichotomizations of the Glasgow Outcome Scale [GOS]). In total, 478 patients (43%) had an unfavorable outcome (GOS 1-3). In the combined cohort, overall prognostic performance was more accurate for the Stockholm CT score (Nagelkerke's pseudo-R.sup.2 range 0.24-0.28) and the Helsinki CT score (0.18-0.22) than for the Rotterdam CT score (0.13-0.15) and Marshall CT classification (0.03-0.05). Moreover, the Stockholm and Helsinki CT scores added the most independent prognostic value in the presence of other known clinical outcome predictors in TBI (6% and 4%, respectively). The aggregate traumatic subarachnoid hemorrhage (tSAH) component of the Stockholm CT score was the strongest predictor of unfavorable outcome. The main limitations were the retrospective nature of the study, missing patient information, and the varying follow-up time between the centers. Conclusions The Stockholm and Helsinki CT scores provide more information on the damage sustained, and give a more accurate outcome prediction, than earlier classification systems. The strong independent predictive value of tSAH may reflect an underrated component of TBI pathophysiology. A change to these newer CT scoring systems may be warranted., Author(s): Eric Peter Thelin 1,2,*, David W. Nelson 3, Juho Vehviläinen 4, Harriet Nyström 1, Riku Kivisaari 4, Jari Siironen 4, Mikael Svensson 1,5, Markus B. Skrifvars 6,7, Bo-Michael Bellander [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.chb.2005.11.001 Byline: A. Aubteen Darabi (a), David W. Nelson (a), Srinivas Palanki (b) Keywords: Simulation-based training; Computer-based training; Worked examples; Troubleshooting; Problem solving; Practice Abstract: In a computer-based simulation of a chemical processing plant, the differential effects of three instructional strategies for learning how to troubleshoot the plant's malfunctions were investigated. In an experiment concerning learners' transfer performance and mental effort, the simulation presented the three strategies to three groups of learners and measured their performance on the transfer tasks. In this experiment, conventional problem solving was contrasted with two worked example strategies. The results indicated a significant difference between practicing problem solving and using worked examples. Learners who practiced problem solving in an interactive simulation outperformed the learners who studied computer-based worked examples. They also invested lower mental effort in transfer tasks. When accounting for the difference in the learners' domain knowledge, the strategies were not significantly different among the more experienced learners. For the less experienced learners, those who practiced problem solving significantly outperformed their worked example counterparts. Among all participants and also among less experienced learners the problem solving group invested significantly lower mental effort in the performance of transfer tasks. Based on the results of this study, the authors recommend the use of the conventional problem solving strategy with or without worked examples for learning complex skills. Author Affiliation: (a) The Learning Systems Institute, Florida State University, 4600-C University Center, Tallahassee, FL 32306-2540, United States (b) College of Engineering, Florida State University, United States

IGF binding protein-5 (IGFBP-5) modulates the availability of IGF-I to its receptor and potentiates the intestinotrophic action of IGF-I. Our aim was to test the hypothesis that stimulation of intestinal growth due to coinfusion of IGF-I with total parenteral nutrition (TPN) solution is dependent on increased expression of IGFBP-5 through conducting our studies in IGFBP-5 knockout (KO) mice. IGFBP-5 KO, heterozygote (HT) and wild type (WT) male and female mice were maintained with TPN or TPN plus coinfusion of IGF-I [recombinant human (rh)IGF-I; 2.5 mg x [kg.sup.-1] x [day.sup.-1]] for 5 days. The concentration of IGF-I in serum was 73% greater (P < 0.0001) in mice given TPN + IGF-I infusion compared with TPN alone. IGF-I attenuated the 2-3 g loss of body weight associated with TPN in WT mice, whereas KO and HT mice did not show improvement in body weight with IGF-I treatment. KO and HT mice had significantly greater levels of circulating IGF-I binding proteins (IGFBPs) compared with WT mice. Intestinal growth due to IGF-I was observed in all groups treated with IGF-I based on greater concentrations of protein and DNA in small intestine and colon and significantly greater crypt depth and muscularis thickness in jejunum. Jejunal expression of IGFBP-5 mRNA was greater in WT mice, whereas IGFBP-3 mRNA was greater in KO mice treated with IGF-I. In summary, the absence of the IGFBP-5 gene did not block the ability of IGF-I to stimulate intestinal growth, possibly because greater jejunal expression of IGFBP-3 compensates for the absence of IGFBP-5. total parenteral nutrition; jejunum; IGF-binding proteins-3 and 5 doi:10.1152/ajpregu.00903.2006

Luminal nutrients are essential for the growth and maintenance of digestive tissue including the pancreas and small intestinal mucosa. Long-term loss of luminal nutrients such as during animal hibernation has been shown to result in mucosal atrophy and a corresponding stress response characterized by the induction of heat shock protein (Hsp)70 expression. This study was conducted to determine if the loss of luminal nutrients during total parenteral nutrition (TPN) would result in atrophy of the exocrine pancreas and small intestinal mucosa as well as an induction of Hsp70 expression in rats. In experiment 1, the treatment groups included an orally fed control, a saline-infused surgical control, or TPN treatment for 7 days. In experiment 2, the treatment groups included an orally fed control and TPN alone or coinfused with varying doses of glucagon-like peptide (GLP)-2, a mucosal proliferation agent, for 7 days. In experiment 1, TPN resulted in a 40% reduction in pancreatic mass that was associated with a dramatic reduction in digestive enzyme expression, enhanced apoptosis, and a 200% increase in Hsp70 expression. Conversely, heat shock cognate 70, Hsp27, and Hsp60 expression was not changed in the pancreas. In experiment 2, TPN resulted in a 30% reduction in jejunal mucosa mass and a similar induction of Hsp70 expression. The inclusion of GLP-2 during TPN attenuated jejunal mucosal atrophy and inhibited Hsp70 expression, suggesting that Hsp70 induction is sensitive to cell growth. These data indicate that pancreatic and intestinal mucosal atrophy caused by a loss of luminal nutrient stimulation is accompanied by a compensatory response involving Hsp70. total parenteral nutrition; glucagon-like peptide 2; jejunal mucosa; atrophy of the pancreas; acinar cells; heat shock protein 70

Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal mucosa was not significantly different; ileal mucosal sucrase specific activity was significantly increased by resection in capsaicin-treated rats. Capsaicin did not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in plasma concentration of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not essential for GLP-2 secretion when the ileum has direct contact with luminal nutrients after resection. In summary, vagal afferent neurons are essential for maximal resection-induced intestinal adaptation through a mechanism that appears to involve stimulation by luminal nutrients. capsaicin; glucagon-like peptide-2; parenteral nutrition; proglucagon; sucrase

Total parenteral nutrition (TPN) induces dramatic mucosal hypoplasia in rat small intestine that is attenuated by insulin-like growth factor-I (IGF-I). Our aim was to determine the extent of TPN-induced intestinal atrophy and its response to infusion of IGF-I in mice. Male C57BL/6 mice (18-22 g) were maintained with TPN, TPN plus co-infusion of recombinant human IGF-I [2.5 mg/(kg * d)] or oral feeding for 5 d. Body weights did not differ among the groups although serum IGF-I was increased by 78% with IGF-I infusion. IGF-I prevented the significant 25% reduction in mass of the intact small intestine due to TPN compared with oral feeding. Greater TPN-induced atrophy was noted in duodenum and jejunum than ileum. Jejunal atrophy induced by TPN reflected significant decreases in muscularis mass and concentrations of protein and DNA; mucosal cellularity was not altered by TPN. TPN induced a significant decrease in jejunal muscularis width that was reversed by IGF-I with no differences in mucosal villus height and crypt depth. Local expression of IGF-I binding protein (IGFBP)-5 positively modulates the intestinotrophic effects of IGF-I. Jejunal atrophy due to TPN and growth due to IGF-I were directly associated with expression of IGFBP-5 mRNA. TPN decreased IGFBP-5 mRNA by 60% and IGF-I increased IGFBP-5 mRNA by 200% with no change in IGF-I mRNA compared with oral feeding. In summary, TPN induces significant 25% atrophy of the mouse small intestine that is attenuated by IGF-I in association with increased expression of IGFBP-5. Compared with rats, TPN-induced atrophy is less severe and occurs primarily in the jejunal muscularis layer in mice. KEY WORDS: * total parenteral nutrition * jejunal mucosa and muscularis * IGF-I

To elucidate the role of luminal nutrients and glucagon-like peptide-2 (GLP-2) in intestinal adaptation, rats were subjected to 70% midjejunoileal resection or ileal transection and were maintained with total parenteral nutrition (TPN) or oral feeding. TPN rats showed small bowel mucosal hyperplasia at 8 h through 7 days after resection, demonstrating that exogenous luminal nutrients are not essential for resection-induced adaptation when residual ileum and colon are present. Increased enterocyte proliferation was a stronger determinant of resection-induced mucosal growth in orally fed animals, whereas decreased apoptosis showed a greater effect in TPN animals. Resection induced significant transient increases in plasma bioactive GLP-2 during TPN, whereas resection induced sustained increases in plasma GLP-2 during oral feeding. Resection-induced adaptive growth in TPN and orally fed rats was associated with a significant positive correlation between increases in plasma bioactive GLP-2 and proglucagon mRNA expression in the colon of TPN rats and ileum of orally fed rats. These data support a significant role for endogenous GLP-2 in the adaptive response to mid-small bowel resection in both TPN and orally fed rats. parenteral nutrition; enterocyte proliferation and apoptosis; glucagon-like peptide-2; proglucagon; ileum

Key points: Several distinct strategies produce and conserve heat to maintain the body temperature of mammals, each associated with unique physiologies, with consequences for wellness and disease susceptibilityHighly regulated properties of skin offset the total requirement for heat production We hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservationWe found that insulating mouse dermal white adipose tissue accumulates in response to environmentally and genetically induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat productionIn contrast, the body‐wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue Mammalian skin impacts metabolic efficiency system‐wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding functions and regulation. For humans, we assay a skin‐associated fat (SAF) body‐wide depot to distinguish it from the subcutaneous fat pads characteristic of the abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6‐fold) in women than men, and highly subject‐specific. We used molecular and cellular assays of β‐adrenergic‐induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body‐wide human SAF depot becomes lipolytic, generating heat in response to β‐adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: a corresponding β‐adrenergic stimulation of human skin adipose (in vivo or in explant) depletes adipocyte lipid content. We summarize the regulation of skin‐associated adipocytes by age, sex and adiposity, for both species. We conclude that the body‐wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defence. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) has now emerged as a major global public health problem. Certain bacterial pathogens, particularly Gram negative organisms associated with patients with cystic fibrosis (CF), have become resistant to several classes of antibiotics resulting in pan-resistance, which creates a clinical treatment dilemma. This study wished to explore the production of antibacterial extracellular metabolites from plant pathogenic fungi. Fungal Culture Extracts (FCEs) were prepared from 10 fungi (Armillaria gallica, Clitocybe nebularis, Fusarium coeruleum, Fusarium oxysporum, Fusarium poae, Hymenoscyphus fraxineus, Nectria fuckeliana, Phytophthora infestans, Phytophthora ramorum, Postia placenta), which were tested for activity against the CF pathogens, Pseudomonas aeruginosa (PA) (n=8), Burkholderia cenocepacia (n=2) and Stenotrophomonas maltophilia (n=2). In addition, FCE were assessed for their ability to alter antibiotic susceptibility in PA (n=8), with six antipseudomonal antibiotics (ceftazidime, ciprofloxacin, colistin, meropenem, piperacillin/tazobactam, tobramycin). None of the FCEs showed inhibitory activity to the 12 bacterial isolates tested, with the exception of the FCE from Postia placenta, which showed inhibition against all 12 bacteria. An antagonistic interaction was observed, where a statistically significant decrease in mean zone sizes was noted with Armillaria gallica (p=0.03) and Phytophthora infestans (p=0.03) FCEs and their interaction with the fluoroquinolone antibiotic, ciprofloxacin. Given the increase in clinical morbidity and mortality associated with chronic lung infections with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia, coupled with the difficulty in treating such chronic infection due to overwhelming antimicrobial resistance, any novel substance showing inhibition of these organisms merits further investigation as a potential future antimicrobial agent, with potential clinical therapeutic application. [ABSTRACT FROM AUTHOR]

Statistical models for outcome prediction are central to traumatic brain injury research and critical to baseline risk adjustment. Glasgow coma score (GCS) and pupil reactivity are crucial covariates in all such models but may be measured at multiple time points between the time of injury and hospital and are subject to a variable degree of unreliability and/or missingness. Imputation of missing data may be undertaken using full multiple imputation or by simple substitution of measurements from other time points. However, it is unknown which strategy is best or which time points are more predictive. We evaluated the pseudo-R2 of logistic regression models (dichotomous survival) and proportional odds models (Glasgow Outcome Score—extended) using different imputation strategies on the The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset. Substitution strategies were easy to implement, achieved low levels of missingness (<< 10%) and could outperform multiple imputation without the need for computationally costly calculations and pooling multiple final models. While model performance was sensitive to imputation strategy, this effect was small in absolute terms and clinical relevance. A strategy of using the emergency department discharge assessments and working back in time when these were missing generally performed well. Full multiple imputation had the advantage of preserving time-dependence in the models: the pre-hospital assessments were found to be relatively unreliable predictors of survival or outcome. The predictive performance of later assessments was model-dependent. In conclusion, simple substitution strategies for imputing baseline GCS and pupil response can perform well and may be a simple alternative to full multiple imputation in many cases. [ABSTRACT FROM AUTHOR]

Background/Objective: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. Methods: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. Results: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4–8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0–3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1–4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient − 0.15 95% CI [− 0.18 to − 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01–1.61), p = 0.048). Conclusions: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients. [ABSTRACT FROM AUTHOR]