The effectiveness of personalised food choice advice tailored to an individual's socio-demographic, cognitive characteristics, and sensory preferences.

Personalised dietary advice has become increasingly popular, currently however most approaches are based on an individual's genetic and phenotypic profile whilst largely ignoring other determinants such as socio economic and cognitive variables. This paper provides novel insights by testing the effectiveness of personalised healthy eating advice concurrently tailored to an individual's socio-demographic group, cognitive characteristics, and sensory preferences. We first used existing data to build a synthetic dataset based on information from 3654 households (Study 1a), and then developed a cluster model to identify individuals characterised by similar socio-demographic, cognitive, and sensory aspects (Study 1b). Finally, in Study 2 we used the characteristics of 8 clusters to build 8 separate personalised food choice advice and assess their ability to motivate the increased consumption of fruit and vegetables and decreased intakes of saturated fat and sugar. We presented 218 participants with either generic UK Government "EatWell" advice, advice that was tailored to their allocated cluster (matched personalised), or advice tailored to a different cluster (unmatched personalised). Results showed that, when compared to generic advice, participants that received matched personalised advice were significantly more likely to indicate they would change their diet. Participants were similarly motivated to increase vegetable consumption and decrease saturated fat intake when they received unmatched personalised advice, potentially highlighting the power of providing alternative food choices. Overall, this study demonstrated that the power of personalizing food choice advice, based on a combination of individual characteristics, can be more effective than current approaches in motivating dietary change. Our study also emphasizes the viability of addressing population health through automatically delivered web-based personalised advice.

Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells.

BACKGROUND: Persin is a plant toxin that displays synergistic cytotoxicity with tamoxifen in human breast cancer cell lines. Here, we examined the ability of persin to circumvent tamoxifen resistance and delineated the intracellular signalling pathways involved. METHODS: The induction of apoptosis in tamoxifen-resistant and -sensitive breast cancer cells was measured by flow cytometry following treatment with persin±tamoxifen. Markers of endoplasmic reticulum stress (ERS) were analysed following treatment, and their causal role in mediating persin-induced apoptosis was determined using chemical inhibitors and RNA interference. RESULTS: Cells that were resistant to an apoptotic concentration of tamoxifen maintained an apoptotic response to persin. Persin-induced apoptosis was associated with an increase in markers of ERS, that is, CHOP expression and XBP-1 splicing and was decreased by CHOP siRNA. The CASP-4 inhibitor Z-YVAD-FMK markedly inhibited persin-induced apoptosis in both tamoxifen-sensitive and -resistant cells. CONCLUSION: The cytotoxic effects of persin are CASP-4 dependent and mediated by CHOP-dependent and -independent ERS signalling cascades. Increased ERS signalling contributes to persin-induced reversal of tamoxifen resistance.

The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer.

Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability.

A procedure-specific systematic review and consensus recommendations for postoperative analgesia following laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy has advantages over the open procedure for postoperative pain. However, a systematic review of postoperative pain management in this procedure has not been conducted. METHODS: A systematic review was conducted according to the guidelines of the Cochrane Collaboration. Randomized studies examining the effect of medical or surgical interventions on linear pain scores in patients undergoing laparoscopic cholecystectomy were included. Qualitative and quantitative analyses were performed. Recommendations for patient care were derived from review of these data, evidence from other relevant procedures, and clinical practice observations collated by the Delphi method among the authors. RESULTS: Sixty-nine randomized trials were included and 77 reports were excluded. Recommendations are provided for preoperative analgesia, anesthetic and operative techniques, and intraoperative and postoperative analgesia. CONCLUSIONS: A step-up approach to the management of postoperative pain following laparoscopic cholecystectomy is recommended. This approach has been designed to provide adequate analgesia while minimizing exposure to adverse events.

Effect of prostaglandins E1, E2 and F2alpha and pentagrastin on the gall bladder pressure in dogs.

The effect of prostaglandins E1, E2 and F2alpha on the gall bladder pressure was studied in anesthetized dogs with and without clamping of the cystic duct. Both PGE1 and PGE2 lowered the gall bladder pressure when the initial pressure was higher than 5 mm Hg, but caused no significant change when the initial pressure was lower than 3 mm Hg. On the other hand, PGF2alpha increased the gall bladder pressure regardless of its initial pressure. When the cystic duct was clamped, PGF2alpha markedly increased the gall bladder pressure while both PGE1 and PGE2 increased it slightly. This observation suggests that the smooth muscle in the gall bladder is markedly stimulated by PGF2alpha and stimulated to a lesser degree by PGE1 or PGE2. Furthermore, PGF2alpha appears to constrict, and PGE1 or PGE2 appears to relax the sphincter of Oddi. Pretreatment with indomethacin did not affect or slightly potentiated the cholecystokinetic effect of the three prostaglandins but abolished that of pentagastrin, suggesting that prostaglandins are possible mediators for the cholecystokinetic action of the gastrointestinal hormones.

Recalcitrant pancreatitis: eventual control by antioxidants.

A woman, 61 years of age at her first attack of pancreatitis, had further attacks every few months during the next two years despite cholecystectomy for gall stones, and pancreato-duodenectomy for pancreas divisum and duodenal diverticulum. Since starting treatment with antioxidants, she has been free of attacks for two years.

Critical issues in the management of gastroesophageal reflux disease.

AIM: To discuss some of the critical issues in the management of gastroesophageal reflux disease (GERD). OPINION: GERD is a chronic relapsing disease characterized by pathological exposure of the distal esophagus to gastric acid. Diagnosis of the condition can often be made on the basis of symptomatology alone. Endoscopy can help in assessing the degree of esophageal damage, influencing the choice of therapy, and should be performed at least once during a symptomatic patient's lifetime to exclude a diagnosis of Barrett's esophagus. However, endoscopy is mandatory at diagnosis if alarm symptoms are present. Treatment should aim to provide the lowest degree of acid suppression needed for the control of symptoms. Proton pump inhibitors (PPIs) represent the most cost-effective treatment option for the short- and long-term management of GERD. Compared with standard- and high-dose H2-receptor antagonists, PPIs result in superior and faster healing and symptom relief across all grades of esophagitis and are more effective at maintaining patients in symptomatic and endoscopic remission. Treatment with PPIs has also been shown to reduce the rate of recurrent stricture after initial dilatation. PPIs are generally well tolerated, and to date there have been no reports of gastric dysplasia resulting from their long-term use. Anti-reflux surgery should be reserved for patients who are unresponsive to continuous PPI therapy or perhaps for young patients. It will be several years before the impact of laparoscopic fundoplication as a cost-beneficial therapy for GERD can be assessed. CONCLUSION: The superior clinical efficacy of PPIs when compared with any other drug regimen for GERD make them the treatment of choice for the short- and long-term management of this troublesome condition.

A pilot study of antioxidant intake in patients with cholesterol gallstones.

Whereas macronutrient intake has been extensively investigated in an attempt to unravel the pathogenesis of human cholesterol gallstones, theoretical considerations and animal models suggest that deficits in micronutrient antioxidants may be more relevant. We report a pilot study of this aspect. The plan was to obtain 7-d weighed food inventories over a 6-mo period from equal numbers of patients who had not consciously changed their diets, patients who were on low-fat diets and age- and gender-matched controls. Food tables would be used to derive daily intakes of 16 known antioxidants, essential amino acids, and essential fatty acids. Under-reporting of food intake, a recognized drawback of this dietary method, would be sought retrospectively by reference to a key publication giving minimum cut-off limits for ratios of energy intakes to basal metabolic rates. There were 18 pairs for study. Analysis of data for the 9 pairs involving patients on their normal diets showed no differences in the intakes of energy macronutrients, and cholesterol, but the patients ingested lower amounts of 10 among 16 antioxidants (P < 0.05 for methionine, alpha-tocopherol, manganese, and vitamin D; 0.05 < P < 0.10 for cysteine, beta-carotene, vitamin C, selenium, zinc, and phosphorus). Both subsets of patients ingested lower amounts of linoleic acid (diet unchanged P = 0.009, changed P = 0.026) and several essential amino acids than did matched controls. Institution of a low-fat diet caused the expected fall in intakes of energy and saturated fatty acids such that the deficit in alpha-tocopherol was amplified, but substitution of fruit and vegetables by the patients resulted in a fortuitous increase in vitamin C, beta-carotene, and manganese intake. Retrospective analysis confirmed under-reporting of food intake by all four subsets of subjects but there was no significant difference in the mean ratio of energy intake to estimated basal metabolic rate in the subset of patients who had not consciously altered their diets and the subset of matched controls. Furthermore, the lower daily intake of alpha-tocopherol and linoleic acid by these patients persisted when results were expressed relative to total fat consumption. The results support the hypothesis that insufficiency of dietary antioxidants, particularly alpha-tocopherol, may be germane to human gallstone disease; they also suggest that low intakes of linoleic acid and essential amino acids may be relevant. Because of the small sample sizes, however, these deductions should be regarded as tentative, pending confirmation by biochemical analysis of blood and especially of hepatic bile.

Effects of a moderate dose of alcohol on simulated laparoscopic surgical performance.

BACKGROUND: In medicine, there is no professional regulation of the drinking of alcohol, nor a body of experimental evidence on which such regulation might be based. Here we report the acute and longer-term ("hangover") effects of a moderate dose of alcohol on performance, as assessed objectively on a laparoscopic surgical simulator. METHODS: In a single-blind, experimental study, medical student subjects were assigned randomly to an alcohol (1.05 mg/kg) or a placebo condition (n = 14 in each). The effects of alcohol on performance on the MIST Virtual Reality surgical simulator were examined 60-90 min and 600-630 min (after a night's sleep) following its ingestion. Measures of the number of errors, time taken, hand movement economy, and excessive use of diathermy were recorded. RESULTS: On each measure, performance was significantly impaired 60-90 min following alcohol ingestion, but there was no hangover effect 600-630 min later, following a night's sleep. This impairment could not be attributed to between-group differences in either predrink performance, expertise or estimated sleep duration during the night preceding the experimental session. CONCLUSIONS: Simulated surgical performance is impaired severely when estimated blood alcohol concentration (BAC) is just above the UK legal limit for driving. These results contribute new, objective and quantitative evidence to the current debate about the use and misuse of alcohol within the medical profession.

Navigating and visualizing three-dimensional data sets.

This paper provides an overview of the main techniques being used for three-dimensional (3D) visualization of medical data sets and highlights some of the clinical benefits that can be obtained. One of the major advantages of using a 3D representation is that all of the slice data produced by the latest multislice CT and high gradient MR scanners can be utilized, and then presented to the clinician in an intuitive format. Continued advances in technology mean that high resolution 3D representations of patient specific anatomy can now be routinely obtained and so provide valuable input to diagnosis, planning and navigation tasks. Examples from these areas are presented and illustrated below. Future developments and possibilities are also discussed.

Hypogastrinemia and esophageal atresia.

To investigate extraesophageal anomalies in infants with esophageal atresia, preoperative plasma gastrin was measured in 12 infants. The median plasma gastrin was 32 ng/L (interquartile range, 24 to 44). There was significant correlation with birth weight (rs = .73, P less than .05) and gestational age (rs = .74, P less than .05). Within this group 9 infants of greater than 36 weeks' gestation were matched to a group of 20 control infants without esophageal atresia. Infants with esophageal atresia had a significantly lower median plasma gastrin (38 ng/L v 55 ng/L, P less than .05). This may indicate preexisting vagal abnormalities in esophageal atresia unrelated to surgical intervention.

The classification of oesophageal 24 h pH measurements using a Kohonen self-organizing feature map.

Analysis of 24 h oesophageal pH studies can be problematic with many patients asymptomatic during the investigation, despite observations of reflux. The aim of this study was to carry out a cluster analysis of ambulatory pH studies to determine any underlying patterns and classes within the data. The results of 900 24 h pH studies were investigated using the Kohonen self-organizing feature map (SOFM), a neural network that can be used to identify clusters within multidimensional data. The clinical features were presented to the network and the main classes identified. The SOFM-based analysis showed that patients clinically assessed as having symptomatic reflux during the study could be described by four major classifications. The results also showed that the probability of identifying a correlation between symptoms and reflux during an investigation varies from 0.49 to 0.78 for the classes identified. The developed network may be a useful tool in the classification of pH data. The cluster-based technique may offer an alternative to standard statistical techniques for high-dimensional gastrointestinal data and form the basis of an expert system for the automated analysis of pH data.

An investigation into the spatial relationship between complexity and motility within the oesophagus.

Nonlinear analysis techniques have recently been used in the characterization of complex physiological signals seen in pathological disorders such as epilepsy and cardiac fibrillation. In this study a series of controlled swallows from an asymptomatic demonstration group was investigated using oesophageal manometry. The nonlinear measure of complexity, largest Lyapunov exponents and phase portraits were then used to explore the complexity of motility patterns at different points within the oesophagus. Results indicate greater complexity within the region of the striated muscle in the upper oesophagus than that observed within the region of smooth muscle in the lower oesophagus. Phase portraits showed that manometry patterns within the asymptomatic demonstration group could be quite different, highlighting the problems in clinical diagnosis. The characterization of motility disorders associated with complex manometry patterns such as diffuse oesophageal spasm (DOS) and nonspecific motility disorder (NOMD) still represents a diagnostic challenge. The use of nonlinear techniques enabling the quantitative and qualitative measurement of oesophageal complexity is considered in the classification of such disorders.

A pH-mucosa area unit of measure to consider morphology of the oesophagus when evaluating oesophagitis.

Gastro-oesophageal pH measurements are routinely carried out to quantify and determine if levels of acid reflux are responsible for symptoms. Although considered the 'gold standard', evidence suggests that pH measurements do not correlate well with the degree of oesophagitis seen during endoscopy. In this study the current measure of pH was critically examined taking into account both the effects of changes in luminal diameter and endoscopy observations. The oesophageal lumen diameter was investigated using a barium swallow for 25 patients presenting with oesophageal disorders. For each subject the widest luminal diameter was measured for a series of five controlled swallows. The results showed that the lumen diameter varied widely from 0.9 to 3.8 cm. An alternative approach to the current measurement of pH was explored. In this approach the exposure not only included the luminal pH and time exposed but also the area of mucosa exposed as a result of differing luminal diameters. Although it is currently not possible to assess the diameter or morphology of the oesophageal lumen during a pH study, the analysis highlighted that the current measure of pH exposure time does not include the area of mucosa exposed. These results may explain, to some extent, the poor correlation between pH measurements and degree of oesophagitis seen during endoscopy.

Synchronous recording and review of oesophageal manometry and video fluoroscopy using a portable manometry recorder and PC with integrated digital video acquisition.

We present the technical details of a new system for the synchronous recording and review of a combined oesophageal manometry and video fluoroscopic barium swallow examination. The system developed uses a portable manometry recorder and personal computer (PC) with an integrated digital video acquisition system. These are controlled using software to enable the real time capture of digital video and manometric data throughout the combined examination. The recorded pressure waveforms can then be synchronously displayed on a screen with the recorded digital video of the fluoroscopic barium swallow. This new tool enables both comparative measurement and detailed analysis of the relationship between visualized bolus transport and pressure measurements. It provides for a deeper understanding and improved clinical assessment of complex motility disorders over those obtained when these two modalities are applied separately. The system is easily incorporated into a clinical radiology suite and it is both user and patient friendly. It uses readily available computer hardware together with multimedia software and is a comparatively economical addition to the radiology suite with the manometry analysis available fulfilling the criteria laid down by the Clinical Associates Group of the British Society of Gastroenterology.

Laparoscopic cholecystectomy in England and Wales: results of an audit by the Royal College of Surgeons of England.

The results of an audit of open and laparoscopic cholecystectomy conducted by the Comparative Audit Service of The Royal College of Surgeons of England are presented. Data were submitted by 124 consultant surgeons on 3319 attempted laparoscopic and by 227 consultant surgeons on 8035 open cholecystectomies performed in England and Wales during the 2 years 1990 and 1991. These were contrasted with 9322 attempted laparoscopic cholecystectomies reported in 21 series reported in the world literature between 1991 and 1992, and with five other nations' audit studies. Among attempted laparoscopic cases, conversion to an open procedure was necessary in 175/3319 (5.2%) of cases and overall mortality was 0.15% (5/3319). Major complications were reported in 2.1% and minor complications in 5.9% of cases. Bile duct injury was reported to be significantly more common after attempted laparoscopic cholecystectomy (11/3319, 0.33%) than after open cholecystectomy (4/8035, 0.06%) (95% confidence intervals -0.48 to 0.08), but it was not significantly different from that reported for laparoscopic cholecystectomy in the combined world literature (28/9322, 0.3%) (95% confidence intervals -0.19 to 0.25). Most systemic complications were significantly more common after open cholecystectomy. For open cholecystectomy, the mortality was 55/8035 (0.76%), with major complications reported in 3.2% and minor complications in 9.8% of patients. Adoption of the laparoscopic approach was associated with a four-fifths reduction in the mortality of cholecystectomy, and a 40% reduction in the overall complication rate when compared with the open operation. While laparoscopic cholecystectomy has an impressively low mortality and morbidity profile during the first 2 years of its introduction into the UK, prevention of bile duct injury is the most important issue to be addressed in all laparoscopic cholecystectomy training programmes.

Learning rate for laparoscopic surgical skills on MIST VR, a virtual reality simulator: quality of human-computer interface.

Acquiring laparoscopic surgical skills involves initial learning of cognitive and motor skills followed by refinement of those skills. The successful use of a virtual reality simulator depends on the quality of the interface for the human-computer interaction and this can be determined by the initial learning rate. MIST VR, a part-task virtual reality laparoscopic simulator, provides objective assessment of psychomotor skills and can generate an overall score for performance, based upon errors made and time taken for six different tasks. This study analysed the rate of early task/instrument/computer familiarization on consecutive scores achieved by surgically experienced and naive individuals. Eleven surgeons, 18 medical students and seven non-medical personnel were tested on the simulator up to ten consecutive times, within a 2-week period. Performance data from every task and repetition were analysed to obtain individual scores of task performance. The calculation of overall score penalized errors far more heavily than total time taken, with high scores indicating poor performance. The surgeon-computer interface generated a rapid and significant early familiarization curve up to the third session on the simulator, with significant reductions in both time taken and total contact errors made. These results suggest that MIST VR represents a high quality interface. Surgeons scored consistently and significantly better than other subjects on all tasks. For surgically naive individuals, it was possible to predict the level of laparoscopic skills performance that would be attained after overcoming initial simulator learning curve, by studying their initial score. Overall scores reflected surgical experience and suggest that the simulator is measuring surgically relevant parameters. MIST VR provides a validated and much needed method for objective assessment of laparoscopic skills, for a variety of surgical disciplines.

Guidelines on appropriate indications for upper gastrointestinal endoscopy. Working Party of the Joint Committee of the Royal College of Physicians of London, Royal College of Surgeons of England, Royal College of Anaesthetists, Association of Surgeons, the British Society of Gastroenterology, and the Thoracic Society of Great Britain.

Upper gastrointestinal endoscopy is a valuable diagnostic tool, but for an endoscopy service to be effective it is essential that it is not overloaded with inappropriately referred patients. A joint working party in Britain has considered the available literature on indications for endoscopy, assessed standard practice through a questionnaire, and audited randomly selected cases using an independent panel of experts and an American database system. They used these data to produce guidelines on the appropriate and inappropriate indications for referral for endoscopy, although they emphasise that under certain circumstances there may be reasons to deviate from the advice given. The need for endoscopy is most difficult to judge in patients with dyspepsia, and this aspect is discussed in detail. Early endoscopy will often prove more cost effective than delaying until the indications are clearer.

Lessons learned during the INSURRECT project (INteractive SURgical Teaching at REmote CeNtres).

The INSURRECT project began in 1993 as a collaboration between six UK universities in distance teaching of undergraduate surgery. The first year was spent in testing the network and preparing the course material. This was followed by a two-year pilot teaching course. During this phase, 108 teaching sessions were conducted, involving more than 1300 students in all. It was found that successful teaching depended on increasing the amount of audience interaction was much as possible and transmitting high-quality video pictures. Although the time taken to deliver material by interactive video was greater than for conventional lectures, both students and teachers responded favourably to the project.

MIST VR. A laparoscopic surgery procedures trainer and evaluator.

The key bimanual instrument tasks involved in laparoscopic surgery have been abstracted for use in a virtual reality surgical skills evaluator and trainer. The trainer uses two laparoscopic instruments mounted on a frame with position sensors which provide instrument movement data that is translated into interactive real time graphics on a PC (P133, 16 Mb RAM, graphics acceleration card). An accurately scaled operating volume of 10 cm3 is represented by a 3D cube on the computer screen. "Camera" position and size of target objects can be varied for different skill levels. Targets appear randomly within the operating volume according to the skill task and can be grasped and manipulated with the instruments. Accuracy and errors during the tasks and time to completion are logged. Mist VR has tutorial, training, examination, analysis and configuration modes. Six tasks have been selected and include combinations of instrument approach, target acquisition, target manipulation and placement, transfer between instruments, target contact with optional diathermy, and controlled instrument withdrawal/replacement. Tasks can be configured for varying degrees of difficulty and the configurations saved to a library for reuse. Specific task configurations can be assigned to individual students. In the examination mode the supervisor can select the tasks, repetitions and order and save to a specific file for that trainee. Progress can be assessed and there is the option for playback of the training session or examination. Data analyses permit overall, including task, and right or left hand performances to be quantified. Mist VR represents a significant advance over the subjective assessment of training performances with existing "plastic box" basic trainers.