Probability distributed time delays: integrating spatial effects into temporal models

Background: In order to provide insights into the complex biochemical processes inside a cell, modelling approaches must find a balance between achieving an adequate representation of the physical phenomena and keeping the associated computational cost within reasonable limits. This issue is particularly stressed when spatial inhomogeneities have a significant effect on system's behaviour. In such cases, a spatially-resolved stochastic method can better portray the biological reality, but the corresponding computer simulations can in turn be prohibitively expensive.Results: We present a method that incorporates spatial information by means of tailored, probability distributed time-delays. These distributions can be directly obtained by single in silico or a suitable set of in vitro experiments and are subsequently fed into a delay stochastic simulation algorithm (DSSA), achieving a good compromise between computational costs and a much more accurate representation of spatial processes such as molecular diffusion and translocation between cell compartments. Additionally, we present a novel alternative approach based on delay differential equations (DDE) that can be used in scenarios of high molecular concentrations and low noise propagation.Conclusions: Our proposed methodologies accurately capture and incorporate certain spatial processes into temporal stochastic and deterministic simulations, increasing their accuracy at low computational costs. This is of particular importance given that time spans of cellular processes are generally larger (possibly by several orders of magnitude) than those achievable by current spatially-resolved stochastic simulators. Hence, our methodology allows users to explore cellular scenarios under the effects of diffusion and stochasticity in time spans that were, until now, simply unfeasible. Our methodologies are supported by theoretical considerations on the different modelling regimes, i.e. spatial vs. delay-temporal, as indicated by the corresponding Master Equations and presented elsewhere

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

The effects of multivitamins on cognitive performance: a systematic review and meta-analysis

Complementary medicine use is becoming increasingly popular with multivitamins being the most commonly used vitamin supplement. Although adequate vitamin and nutrient concentrations are necessary for optimal health and cognitive functioning, there is no scientific consensus as to whether multivitamin use prevents cognitive decline or improves mental functioning. The aim of the present study was to determine if multivitamins can be used efficaciously to improve cognitive abilities. A systematic review of randomized controlled trials was performed. Meta-analysis was performed on those cognitive tests used across the largest number of studies. Multiple electronic databases were searched until July 2011 by two authors. Randomized, placebo-controlled trials were considered appropriate if they reported on the chronic effects (&ge;1 month) of oral multivitamin supplementation on any valid cognitive outcomes. Ten trials were included in review (n = 3,200). Meta-analysis indicated that multivitamins were effective in improving immediate free recall memory (SMD = 0.32; 95% CI: 0.09-0.56, p &lt; 0.01) but not delayed free recall memory (SMD = -0.14; 95% CI: -0.43-0.14, p = 0.33) or verbal fluency (SMD = 0.06; 95% CI: -0.05-0.18, p = 0.26). There was no evidence of publication bias or heterogeneity. Other cognitive abilities sensitive to AD pathology, such as executive and visuospatial functions, were found to be under researched. In conclusion, multivitamins were found to enhance immediate free recall memory but no other cognitive domains

Journal of advanced mechanical design, systems, and manufacturing

Background: Although arterial stiffness has recently been confirmed as a predictor of cardiovascular disease, the association between arterial stiffness and cognitive decline is less clear. Aim: We performed a systematic review and meta-analysis to examine the evidence for large artery stiffness as a cause of cognitive decline and dementia. Method: Electronic databases were systematically searched until September 2011 for studies reporting on the longitudinal relationship between any validated measure of large artery stiffness and cognitive decline or dementia. Meta-analysis was performed on four studies investigating the association between aortic pulse wave velocity and a decline in Mini-Mental State Examination scores. Results: Six relevant longitudinal studies were located, conducted over an average of 5 years follow up. Arterial stiffness was predictive of cognitive decline in five/six studies. In meta-analysis, higher aortic stiffness predicted lower Mini-Mental State Examination scores within the sample (&#0946;=&#8722;0.03, 95% confidence interval (CI): &#8722;0.06 to 0.01, n= 3947), although studies were not all homogeneous, and statistical heterogeneity was present (I2= 71.9%, P= 0.01). Removal of one study with a relatively younger cohort and lower median aortic stiffness found higher aortic stiffness to significantly predict cognitive decline (&#0946;=&#8722;0.04, 95% CI: &#8722;0.07 to &#8722;0.01, n= 3687) without evidence of heterogeneity (I2= 9.5%, P= 0.33). There was little research investigating the effects of aortic stiffness on the development of dementia. Conclusion: Aortic stiffness was found to predict cognitive decline in both qualitative review and quantitative analysis

Blood pressure and cognitive function: the role of central aortic and brachial pressures

Central (aortic) blood pressures differ from brachial pressures and may be more relevant to the study of cognitive function, given that blood is delivered to the brain through the central large arteries. Pulse-pressure amplification reflects the augmentation of blood pressure between the central and peripheral arteries, which diminishes with aging. We aimed to determine the association between central blood pressure and cognitive function in independently living adults aged 20 to 82 years (N = 493). In adjusted regression models, higher central systolic pressure and higher central pulse pressure were each associated with poorer processing speed, Stroop processing, and recognition memory. Lower amplification was associated with poorer Stroop processing, working memory, and recognition memory. Higher brachial systolic pressure and brachial pulse pressure were both associated with poorer Stroop processing. In summary, central pressures and amplification were sensitive indicators of cognitive aging, predicting aspects of cognitive performance not predicted by brachial blood pressure

Sleep After Traumatic Brain Injury

Traumatic brain injury (TBI) is an important cause of death and disability at all ages in the world. Complete functional recovery is not always complete, and, often, persistent symptoms may last for a long time. Sleep disorders and sleep-wake alterations are among the most common complications both in the acute and chronic phases after the trauma, and they may have a negative impact on daily activities and on quality of life of these patients. Sleep and sleep-wake cycle are not always carefully assessed in patients after TBI, they are overlooked, and often patients have a persistent excessive daytime sleepiness, even for years after the TBI, without receiving a proper diagnosis and treatment. Moreover, scientific evidence has been provided for the role of sleep in neuroprotection and recovery after brain injury; hence, promoting an optimal sleep function and early diagnosing and treating sleep disorders may be helpful for rehabilitation and functional recovery of patients after TBI