The Metabolic Matrix: Re-engineering ultraprocessed foods to feed the gut, protect the liver, and support the brain.

Ultraprocessed food is established as a metabolic disruptor acting to increase adiposity, reduce mitochondrial efficiency, drive insulin resistance, alter growth, and contribute to human morbidity and mortality. Consumer packaged goods (CPG) companies are beginning to understand the detrimental impact of the food they market, and have employed substitution strategies to reduce salt, sugar, and fat. However, the harms of ultraprocessed foods are far more complex than any single component, and are not ameliorated by such simple substitutions. Over the past 2 years, the authors have worked with the Kuwaiti Danish Dairy Company (KDD) to conduct a comprehensive scientific evaluation of their entire commercial food and beverage portfolio. Assay of the macronutrients, micronutrients, additives, and toxins contained in each of their products was undertaken to determine the precise nature of each product's ingredients as well as the health impacts of processing. The authors formed a Scientific Advisory Team (SAT) and developed a tiered "Metabolic Matrix" founded in three science-based principles: (1) protect the liver, (2) feed the gut, and (3) support the brain. The Metabolic Matrix categorizes each product and provides the criteria, metrics, and recommendations for improvement or reformulation. Real-time consultation with the KDD Executive and Operations teams was vital to see these procedures through to fruition. This scientific exercise has enabled KDD to lay the groundwork for improving the health, well-being, and sustainability of their entire product line, while maintaining flavor, economic, and fiscal viability. This process is easily transferrable, and we are sharing this effort and its approaches as a proof-of-concept. The key aim of our work is to not only make ultraprocessed food healthier but to urge other food companies to implement similar analysis and reformulation of their product lines to improve the metabolic health and well-being of consumers worldwide.

A novel stacked generalization of models for improved TB detection in chest radiographs.

Chest x-ray (CXR) analysis is a common part of the protocol for confirming active pulmonary Tuberculosis (TB). However, many TB endemic regions are severely resource constrained in radiological services impairing timely detection and treatment. Computer-aided diagnosis (CADx) tools can supplement decision-making while simultaneously addressing the gap in expert radiological interpretation during mobile field screening. These tools use hand-engineered and/or convolutional neural networks (CNN) computed image features. CNN, a class of deep learning (DL) models, has gained research prominence in visual recognition. It has been shown that Ensemble learning has an inherent advantage of constructing non-linear decision making functions and improve visual recognition. We create a stacking of classifiers with hand-engineered and CNN features toward improving TB detection in CXRs. The results obtained are highly promising and superior to the state-of-the-art.

Systematic review and meta-analysis of enhanced recovery programmes in surgical patients.

BACKGROUND: Enhanced recovery programmes (ERPs) have been developed over the past 10 years to improve patient outcomes and to accelerate recovery after surgery. The existing literature focuses on specific specialties, mainly colorectal surgery. The aim of this review was to investigate whether the effect of ERPs on patient outcomes varies across surgical specialties or with the design of individual programmes. METHODS: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched from inception to January 2013 for randomized or quasi-randomized trials comparing ERPs with standard care in adult elective surgical patients. RESULTS: Thirty-eight trials were included in the review, with a total of 5099 participants. Study design and quality was poor. Meta-analyses showed that ERPs reduced the primary length of stay (standardized mean difference -1·14 (95 per cent confidence interval -1·45 to -0·85)) and reduced the risk of all complications within 30 days (risk ratio (RR) 0·71, 95 per cent c.i. 0·60 to 0·86). There was no evidence of a reduction in mortality (RR 0·69, 95 per cent c.i. 0·34 to 1·39), major complications (RR 0·95, 0·69 to 1·31) or readmission rates (RR 0·96, 0·59 to 1·58). The impact of ERPs was similar across specialties and there was no consistent evidence that elements included within ERPs affected patient outcomes. CONCLUSION: ERPs are effective in reducing length of hospital stay and overall complication rates across surgical specialties. It was not possible to identify individual components that improved outcome. Qualitative synthesis may be more appropriate to investigate the determinants of success.

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

BACKGROUND: National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. OBJECTIVES: In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). DATA SOURCES: A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. REVIEW METHODS: Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. RESULTS: The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from priorities expressed in the stakeholder survey. LIMITATIONS: We did not conduct systematic reviews to inform the model parameters, and so the results might not reflect all current evidence. Data limitations and time constraints restricted the number of analyses that we could conduct. We were also unable to obtain feedback from guideline stakeholders about the usefulness of the models within project time scales. CONCLUSIONS: Discrete event simulation can be used to model full guideline pathways for CEA, although this requires a substantial investment of clinical and analytic time and expertise. For some topics lack of data may limit the potential for modelling. There are also uncertainties over the accessibility and adaptability of full guideline models. However, full guideline modelling offers the potential to strengthen and extend the analytical basis of NICE's CGs. Further work is needed to extend the analysis of our case study models to estimate population-level budget and health impacts. The practical usefulness of our models to guideline developers and users should also be investigated, as should the feasibility and usefulness of whole guideline modelling alongside development of a new CG. FUNDING: This project was funded by the Medical Research Council and the National Institute for Health Research through the Methodology Research Programme [grant number G0901504] and will be published in full in Health Technology Assessment; Vol. 17, No. 58. See the NIHR Journals Library website for further project information.

The potential for underutilized crops to improve security of food production.

Staple crops face major challenges in the near future and a diversification away from over-reliance on staples will be important as part of the progress towards the goal of achieving security of food production. Underutilized or neglected crops species are often indigenous ancient crop species which are still used at some level within the local, national or even international communities, but have the potential to contribute further to the mix of food sources than they currently do. The most cost-effective and easily disseminated changes that can be made to a crop are changes to the genetics, as these are contained within the seed itself and, for many species, the seed is a pure breeding, self-replicating, resource. This article focuses on the potential of underutilized crops to contribute to food security and, in particular, whether genetics and breeding can overcome some of the constraints to the enhanced uptake of these species in the future. The focus here is on overview rather than detail and subsequent articles will examine the current evidence base.

Intraguild interactions between the entomopathogenic fungus Pandora neoaphidis and an aphid predator and parasitoid at the population scale.

The interactions that occur between the entomopathogenic fungus Pandora neoaphidis and a predator (Coccinella septempunctata) and a parasitoid (Aphidius ervi) were assessed in microcosm and polytunnel experiments. Transmission of P. neoaphidis to the pea aphid, Acyrthosiphon pisum, was enhanced in the presence of both C. septempunctata and A. ervi in microcosm experiments done under fixed abiotic conditions. In contrast, the reproductive success of A. ervi was reduced in the presence of P. neoaphidis. Despite the increased fungal transmission in the presence of C. septempunctata, there was no additional decrease in the aphid population indicating that P. neoaphidis is functionally redundant in the presence of the coccinellid. In polytunnel experiments the reproductive success of A. ervi was not affected by P. neoaphidis. These results do not support those of the microcosm and may be due to the more natural abiotic conditions in the polytunnel reducing the competitive advantage of the fungus. Microcosms therefore provide an arena in which the interactions between fungal pathogens and other aphid-natural enemies can be assessed however, further assessments at increased spatial scales under more natural abiotic conditions are also required to accurately determine the outcome of these interactions.

Phenolic content and antioxidant capacity of hybrid variety cocoa beans.

Cocoa (Theobroma cacao L.) is a major, economically important, international crop and has been associated with several nutritional benefits including high antioxidant capacity. New cocoa hybrids have been developed in Ghana that exhibit resistance to pest damage during storage. The aim of this work was to assess the phenolic content and antioxidant capacity of these new hybrids in comparison to more traditional cocoa varieties. Total extractable phenolics were similar in all the four hybrids tested ranging from 69.9 to 81.6FAEg(-1). These levels were very similar to that extracted from traditional beans (73.8±2.5FAEg(-1)). The "phenolic profile" was determined by HPLC. A total of 25 peaks was observed but there were only minor differences in this profile between traditional and hybrid bean extracts. Antioxidant capacity was determined using the FRAP assay and traditional beans were found to possess 12.4µmolTEg(-1). In comparison the hybrid beans had antioxidant capacities ranging from 21.6 to 45.5µmolTEg(-1), and these were significantly higher than in the traditional beans for three out of the four hybrids. Since the phenolic and antioxidant levels and in these hybrid varieties were either similar to, or higher than, that obtained from traditional beans, the introduction of these new varieties would be unlikely to impact detrimentally on these nutritional components of the beans.

A comparative study of thoracic radiation doses from 64-slice cardiac CT.

The goal of this study was to measure radiation doses for 64-slice cardiac CT angiography studies and to study the dose-savings features of these CT scanners. This was done using various phantoms. These radiation doses were compared with those from typical helical body CT scans, fluoroscopy cardiac catheterization studies and mammography examinations. Radiation measurements were made with a CT ionization detector and a solid state dosimeter. A GE 64-slice Lightspeed VCT and a Siemens Somatom Sensation 64 CT were used to scan a standard 32 cm acrylic phantom and an anthropomorphic phantom. Data were collected in axial and various gated cardiac helical modes. Organ doses and the effective doses were calculated from the measurements. In gated CT cardiac mode with the 32 cm acrylic phantom, the measured radiation doses per study were generally three to seven times greater than those from typical body helical CT examinations; the range depended upon selectable scan parameters. With the anatomical phantom, the surface doses in the anteroposterior (AP) plane were typically 20-60% higher than those measured using the 32 cm phantom. The lateral surface doses were -4% to +15%. These results can be attributed to the shorter AP dimension and the air in the lungs. The CT skin entrance radiation doses were 80-90% less than diagnostic cardiac catheterization studies, and organ doses were similar. Because 64-slice cardiac gated CT uses pitches equal to 0.20-0.27 and high mAs values, the patient radiation doses are appreciably higher than in routine body CT examinations. The female breast, which could receive a radiation dose 10-30 times that received from mammography screening, is an organ of particular concern.

Behavioural responses of Tribolium castaneum (Herbst) to volatiles identified from dry cocoa beans.

New hybrid types of cocoa beans are attractive to insects in storage, however some of the insects feed little, if at all, on these beans compared to those of the traditional type (mixed genotypes). Based on a sniffing test using GCMS, differences in flavour volatiles in these types of beans have been determined and from these, six major volatiles of cocoa beans were selected for olfactometric analysis using a Pettersson olfactometer to determine which of them contributed to the attraction of Tribolium castaneum (Herbst) to the cocoa beans. The behaviour of Tribolium was affected by dose of 2-phenyl ethanol, acetophenone, 3-methyl butyraldehyde, ethyl butyrate, ethyl 3-hydroxybutyrate and butyl 2-methacrylate. Compared to beans of the new hybrid varieties, beans of the traditional type cocoa contained less 3-methylbutyraldehyde but more ethyl butyrate and acetophenone. In future breeding programmes, reducing the amount of acetophenone and ethyl butyrate but increasing the amount of 3-methylbutyraldehyde in cocoa beans may deter Tribolium from feeding on beans in storage.

The growth of Tribolium castaneum (Herbst) and Lasioderma serricorne (Fabricius) on feed media dosed with flavour volatiles found in dry cocoa beans.

Acetophenone, ethyl butyrate and 2-phenyl ethanol were used as additives to media on which Tribolium castaneum (Herbst) and Lasioderma serricorne (Fabricius) were cultured for 65 days. Acetophenone and ethyl butyrate had a positive impact on the weight and multiplication of the insects. The weight and rate of multiplication was higher in feed media containing acetophenone alone. The amount of the flavour volatiles added was high enough to deter the Lasioderma from feeding well, which affected their growth. This attraction to specific flavour volatiles in some stored products could be used in the formulation of effective control measures for insect pests.

Effect of fungal infection on the reproductive potential of aphids and their progeny.

The effect of infection by Pandora neoaphidis and Beauveria bassiana on the reproductive potential of the pea aphid, Acyrthosiphon pisum, and their progeny was assessed. Infection by either P. neoaphidis or B. bassiana reduced the number of nymphs produced within 24 h of inoculation and over the entire infection period compared to uninfected aphids. However, infection by either P. neoaphidis or B. bassiana for 24 or 72 h did not alter the intrinsic rate of increase of the host aphid's progeny. Therefore, fungal infection appears to have no indirect effects on the fitness of the host's progeny.

Children as partners with adults in their medical care.

AIMS: To investigate the seldom published views of children with type 1 diabetes about their condition and ways in which they share in managing their medical and health care with adults. METHODS: Semi-structured, tape recorded interviews, during 2003, with a purposive sample of 24 children aged 3-12 years who have type I diabetes and who attend two inner London hospitals and one hospital in a commuter town. RESULTS: The children reported high levels of understanding, knowledge, and skill gained from their experience of living with diabetes and constantly having to take account of the condition and their paediatrician's guidance. Their key goals were to be "normal" and "just get on with their lives". DISCUSSION: The interviews showed that children's experiences of diabetes tended to enable them to make informed, "wise" decisions in their own best interests, even at a young age. They achieved a complicated balance between the sometimes competing goals of social health "being normal" and physiological health in controlling glycaemia. Their competence supports approaches in children's rights and in policy makers' aims that people with diabetes--including children--gain more knowledge, skills, and responsibility for their own care in partnership with healthcare professionals. Consent is usually considered in relation to surgery; however the children showed how they constantly dealt with decisions about consent or refusal, compliance with, or resistance to their prescribed treatment. Their health depends on their informed commitment to medical guidance; more research is needed about the daily realities of children's committed and responsible co-management of their chronic illness.

Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia.

BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy. OBJECTIVES: To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia. SEARCH STRATEGY: We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004. SELECTION CRITERIA: Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators. MAIN RESULTS: Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials. AUTHORS' CONCLUSIONS: We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Pandora neoaphidis transmission and aphid foraging behaviour.

Pandora neoaphidis is an aphid-specific entomopathogen that produces infective conidia. As aphid movement increases, so does the likelihood of contact with conidia. Volatile distress signals released in response to aphid infestation as an indirect defence against herbivory may affect aphid foraging and, therefore, the fungus-aphid interaction. In this study, two different methods were used to investigate the effect of plant volatiles and P. neoaphidis-sporulating cadavers on (1) the colonisation of Vicia faba plants by Acyrthosiphon pisum and (2) P. neoaphidis transmission. This study indicates that A. pisum does not avoid bean plants containing P. neoaphidis and that transmission of conidia occurs during plant colonisation and, to a lesser extent, during in situ feeding. Although significantly more aphids were recovered from damaged plants compared to undamaged plants, the likelihood of infection was not affected by previous infestation by aphids.

Response of the entomopathogenic fungus Pandora neoaphidis to aphid-induced plant volatiles.

We used a model plant-aphid system to investigate whether the aphid-specific entomopathogenic fungus Pandora neoaphidis responds to aphid-induced defence by the broad-bean plant, Vicia faba. Laboratory experiments indicated that neither in vivo sporulation, conidia size nor the in vitro growth of P. neoaphidis was affected by Acyrthosiphon pisum-induced V. faba volatiles. The proportion of conidia germinating on A. pisum feeding on previously damaged plants was significantly greater than on aphids feeding on undamaged plants, suggesting a direct functional effect of the plant volatiles on the fungus. However, there were no significant differences in the infectivity of P. neoaphidis towards A. pisum feeding on either undamaged V. faba plants or plants previously infested with A. pisum. Therefore, these results provide no evidence to suggest that P. neoaphidis contributes to plant indirect defence strategies.

Corticosteroids for acute traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability. Corticosteroids have been widely used in treating people with traumatic brain injury. OBJECTIVES: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. SEARCH STRATEGY: Electronic sources: MEDLINE, EMBASE, Cochrane Library and specialised database searches. Additional hand searching and contact with trialists. Date of the most recent search October 2004. SELECTION CRITERIA: All randomised controlled trials of corticosteroid use in acute traumatic brain injury with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Quality of allocation concealment was scored. Data on numbers of participants randomised, numbers lost to follow up, length of follow up, case fatality rates, disablement, infections and gastrointestinal bleeds were extracted independently and checked. MAIN RESULTS: We identified 20 trials with 12303 randomised participants. The effect of corticosteroids on the risk of death was reported in 17 included trials. Due to significant heterogeneity we did not calculate a pooled estimate of the risk of death. The largest trial, with about 80% of all randomised participants, found a significant increase in the risk ratio of death with steroids 1.18 (1.09 to 1.27). For the nine trials that reported death or severe disability, the pooled relative risk was 1.01 (0.91 to 1.11), although this does not yet contain data from the largest trial. For infections the pooled risk ratio from five trials was 1.03 (0.99 to 1.07) and for the ten trials reporting gastrointestinal bleeding 1.23 (0.91 to 1.67). AUTHORS' CONCLUSIONS: In the absence of a meta-analysis, we feel most weight should be placed on the result of the largest trial. The increase in mortality with steroids in this trial suggest that steroids should no longer be routinely used in people with traumatic head injury.

Colloids versus crystalloids for fluid resuscitation in critically ill patients.

BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects on mortality of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Injuries Group specialised register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings, and checked reference lists of trials and review articles. SELECTION CRITERIA: All randomised and quasi-randomised trials of colloids compared to crystalloids, in patients requiring volume replacement. Cross-over trials and trials in pregnant women and neonates were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and rated quality of allocation concealment. Trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, were analysed separately. The analysis was stratified according to colloid type and quality of allocation concealment. MAIN RESULTS: Colloids compared to crystalloidsAlbumin or plasma protein fraction. Nineteen trials reported data on mortality, including a total of 7576 patients. The pooled relative risk (RR) from these trials was 1.02 (95% confidence interval [95% CI] 0.93 to 1.11). When the trial with poor quality allocation concealment was excluded, pooled RR was 1.01 (95% CI 0.92 to 1.10). Hydroxyethyl starch. Ten trials compared hydroxyethyl starch with crystalloids, including a total of 374 randomised participants. The pooled RR was 1.16 (95% CI 0.68 to 1.96). Modified gelatin. Seven trials compared modified gelatin with crystalloid, including a total of 346 randomised participants. The pooled RR was 0.54 (95% CI 0.16 to 1.85). Dextran. Nine trials compared dextran with a crystalloid, including a total of 834 randomised participants. The pooled relative risk was RR 1.24 (95% CI 0.94 to 1.65). Colloids in hypertonic crystalloid compared to isotonic crystalloidEight trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1283 randomised participants. Pooled RR was 0.88 (95% CI 0.74 to 1.05). REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patients can be justified outside the context of randomised controlled trials.