Variable selection and regression analysis for the prediction of mortality rates associated with foodborne diseases.

The purpose of this study was to apply a novel statistical method for variable selection and a model-based approach for filling data gaps in mortality rates associated with foodborne diseases using the WHO Vital Registration mortality dataset. Correlation analysis and elastic net regularization methods were applied to drop redundant variables and to select the most meaningful subset of predictors. Whenever predictor data were missing, multiple imputation was used to fill in plausible values. Cluster analysis was applied to identify similar groups of countries based on the values of the predictors. Finally, a Bayesian hierarchical regression model was fit to the final dataset for predicting mortality rates. From 113 potential predictors, 32 were retained after correlation analysis. Out of these 32 predictors, eight with non-zero coefficients were selected using the elastic net regularization method. Based on the values of these variables, four clusters of countries were identified. The uncertainty of predictions was large for countries within clusters lacking mortality rates, and it was low for a cluster that had mortality rate information. Our results demonstrated that, using Bayesian hierarchical regression models, a data-driven clustering of countries and a meaningful subset of predictors can be used to fill data gaps in foodborne disease mortality.

Radiological insertion of gastrostomy in patients in whom endoscopy was unsuccessful.

INTRODUCTION: Endoscopy is the standard technique of percutaneous gastrostomy placement, but failure of placement may occur due to difficulty with intubation or previous abdominal surgery. A review of personal experience is made. PATIENTS AND METHODS: Between January 1997 and May 1998, 90 gastrostomy devices were successfully placed endoscopically in our unit. Endoscopic placement was unsuccessful in 3 patients and not attempted in a further 7 because of oro-pharyngeal obstruction. These 10 patients (6 male, 4 female, aged 51-84 years) had advanced neuro-degenerative disease or malignancy of the head and neck or oesophagus. All patients underwent radiological insertion of a gastrostomy tube by the 'push' method after insufflation of air into the stomach via a naso-gastric tube. RESULTS: Radiological insertion of gastrostomy device was successful in 9 out of 10 patients. Failure occurred in 1 patient due to inability to pass a naso-gastric tube and surgical gastrostomy was required. Pain at the gastrostomy site was the most common problem post-procedure and 4 patients still required analgesia on discharge. One patient developed a wound infection. There were no procedure-related deaths. The 30-day mortality due to all causes was 20%. Only 1 patient remained alive at 6 months. DISCUSSION: Availability of a radiologist trained in the placement of percutaneous gastrostomy allowed 99% of such devices to be placed percutaneously, even in those patients in whom endoscopy was not possible. However advanced underlying disease in this patient group results in a high mortality.

Agents for the treatment of glycosphingolipid storage disorders.

We have developed a series of inhibitors of glucosylceramide synthase that are structurally based on the parent compound D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). These inhibitors provide useful tools for manipulating glycosphingolipid levels in cells and for elucidating questions associated with sphingolipid signaling. Recently, two highly active glucosylceramide synthase inhibitors, D-threo-3', 4'-ethylenedioxy-1-phenyl-2-palmitoylamino-3- pyrrolidino-1-propanol and D-threo-4'-hydroxy-1-phenyl-2-palmitoylamino-3- pyrrolidino-1-propanol, were designed, synthesized, and studied. These inhibitors markedly reduced glycosphingolipid levels in MDCK cells without any accumulation of intracellular ceramide and associated growth inhibition. Subsequently, each inhibitor was evaluated for its ability to lower glycolipid levels in virally transformed lymphoblasts from a patient with alpha-galactosidase A deficiency. Both compounds significantly reduced neutral glycosphingolipid levels in the lymphoblasts without any morphological changes and growth inhibition. Furthermore, the inhibitors were applied to a mouse knockout model of Fabry disease. Inhibitor treatment blocked accumulation of globotriaosylceramide (Gb3) in the kidney, liver and heart of mice. In contrast to another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, this treatment was not associated with any significant change in body weight or organ weight and without immunodepletion. These results suggest that these newest PDMP homologues are promising as therapeutic agents for the treatment of glycosphingolipid storage disorders.

Polynuclear aromatic hydrocarbons in the United Kingdom environment: a preliminary source inventory and budget.

This paper presents the first attempt to quantify the production, cycling, storage and loss of PAHs in the UK environment. Over 53 000 tonnes of sigmaPAHs (sum of 12 individual compounds) are estimated to reside in the contemporary UK environment, with soil being the major repository. If soils at contaminated sites are included, this estimate increases dramatically. Emission of PAHs to the UK atmosphere from primary combustion sources are estimated to be greater than 1000 tonnes sigmaPAHs per annum, with over 95% coming from domestic coal combustion, unregulated fires and vehicle emissions. It is estimated that approximately 210 tonnes of sigmaPAH are delivered to terrestrial surfaces each year via atmospheric deposition. Therefore, inputs of PAHs to the UK atmosphere outweigh the outputs by a factor of over 4. This may be explained by enhanced particulate deposition near point sources, PAH degradation in the atmosphere and transport away from the UK with prevailing winds. Disposal of waste residues is estimated to contribute a further 1000 tonnes of sigmaPAH per year to the terrestrial environment. It is illustrated that the use of creosote has the potential to release considerable quantities of PAHs to the UK environment. Temporal trends in PAH cycling are then considered. There is good evidence to suggest that air concentrations and fluxes to the UK surface are now lower than at any time throughout this century. Nonetheless, the UK sigmaPAH burden is still increasing at the present time, principally through retention by soils. However, there are marked differences in the behaviour of individual compounds: there is evidence, for example, that phenanthrene concentrations in soils have declined since the 1960s, although soil concentrations of benzo[a]pyrene and other heavier PAHs have continued to increase through this century. Volatilisation of low molecular weight PAHs accumulated in soils over previous decades may be making an important contribution to the current atmospheric burden. The major uncertainties identified by data on this budget are: (1) the lack of PAH concentrations in some environmental matrices; (2) the possible importance of contaminated soils as a major repository and source of PAHs; (3) the lack of emission data (especially vapour phase releases) for some PAH sources; (4) the importance of biodegradation and volatilisation as loss mechanisms for low molecular weight PAHs in soils; and (5) the importance of creosote use in the PAH cycle.

Significance of the thickness of the anal sphincters with age and its relevance in faecal incontinence.

BACKGROUND: Ultrasonographic studies in healthy volunteers showed that the external anal sphincter (EAS) and internal anal sphincter (IAS) thicknesses were inversely related at rest. The functional importance of the two sphincters in continence control was demonstrated in the relationship between the sum of the thicknesses of the two sphincters and the anal canal resting pressure. The aims of the present study were to assess the morphometric appearance of the anal sphincters by endosonography in faecally incontinent patients and to contrast this with that of older healthy subjects. METHODS: Twenty-eight female patients with neurogenic faecal incontinence (FI) were studied. An older group of 7 healthy women, aged 41-75 years, and a young group of 11 nulliparous healthy women, aged 20-23 years, served as control groups. Anal endosonography was performed with a radial rotating endoprobe, with the subject in the left lateral position. Conventional anal manometry was performed in all subjects. RESULTS: The EAS in the FI group was thicker than the EAS in the old (p < 0.04) but did not differ from the EAS in the young. The IAS thickness in the FI group did not differ from that in the older group. In both these groups the IAS was thicker than in the young women (p < 0.01). The anal pressures in the FI group were reduced compared with the normal groups (p < 0.04). There was a direct relationship between the two sphincters in FI (p < 0.001). CONCLUSIONS: The increased thickness of the IAS in the FI group does not seem to compensate for function and results in a failure of the sphincter mechanism to maintain continence, whereas in healthy elderly subjects the increased IAS thickness appears to be compensatory and important for continence control.

The diagnostic yield of intravenous urography: a demographic study.

OBJECTIVE: To examine the impact of intravenous urography (IVU) on patient management in unselected patients in an effort to identify groups in which the use of urography could be reduced. PATIENTS AND METHODS: The results of IVU in 235 consecutive unselected patients were assessed prospectively to establish the value of IVU in patient management. Patients were divided into subgroups on the basis of age, sex, presenting symptoms and source of referral. The percentage of examinations with findings affecting patient management was taken as the 'positive diagnostic yield.' Differences between the positive diagnostic yields of IVU in the various groups were examined using the chi 2 test. RESULTS: For all patients the diagnostic yield was 37.4%. In patients over 50 years of age the yield was 46% while below that age the yield fell to 20%. This difference was significant (chi 2 = 13.88, P < 0.001). There were no significant differences between the other defined groups. Specifically, patients referred by general practitioners were as likely to have an IVU abnormality as were patients referred by a hospital practitioner. Patients with painless microscopic haematuria had a lower diagnostic yield (20%) than the other groups examined but this was not significant. CONCLUSION: IVU has a high diagnostic yield in an unselected population. Although the yield is lower in younger patients IVU offers advantages over other techniques in the investigation of urolithiasis--the commonest positive diagnosis in this study. We argue that it should retain its position as the primary investigation for the majority of patients with urological disease, particularly those suffering loin pain or haematuria.

Polychlorinated biphenyls (PCBs) in the British environment: sinks, sources and temporal trends.

This paper estimates the present UK environmental loading of polychlorinated biphenyls (PCBs). Of the estimated approximately 40,000 t SigmaPCB sold in the UK since 1954, only an estimated 1% (400 t) are now present in the UK environment. Comparisons of estimated production and current environmental loadings of congeners 28, 52, 101, 138, 153 and 180 suggest that PCB persistence broadly increases with increasing chlorination. Those PCBs that are not now present in the UK environment are considered to have been destroyed--by natural or anthropogenic mechanisms, to be still in use, to reside in landfills or to have undergone atmospheric and/or pelagic transport from the UK. The dramatic fall in PCB levels in archived UK soils and vegetation between the mid-1960s and the present is evidence that the latter mechanism is the most important and that a significant proportion of PCBs released into the UK environment in the 1960s have subsequently undergone environmental transport away from the UK. The bulk (93.1%) of the estimated contemporary UK environmental burden of SigmaPCBs is associated with soils, with the rest found in seawater (3.5%) and marine sediments (2.1%). Freshwater sediments, vegetation, humans and sewage sludge combined account for 1.4% of the present burden, whilst PCB loadings in air and freshwater are insignificant. Although consideration of individual congeners does not reveal any major deviations from the relative partitioning of Sigma PCBs, the importance of sinks other than soils is enhanced for individual congeners, particularly 138 and 180. In particular, around 2% of the total UK burden of congener 180 is present in humans, implying that biodata as a whole may constitute an important sink for the higher chlorinated congeners. The contemporary flux of SigmaPCBs to the UK surface is estimated at 19 t yr(-1), compared with an estimated annual flux to the atmosphere of 44-46 t. This implies that the major sources of PCBs to the UK atmosphere have been identified and that there is currently a net loss of these compounds from the UK. These sources are: volatilisation from soils (88.1%), leaks from large capacitors (8.5%), the production of refuse-derived fuel (RDF) (2.2%), leaks from transformers (0.6%), the recovery of contaminated scrap metal (0.5%) and volatilisation from sewage sludge-amended land (0.2%). Interestingly, whilst large excesses of estimated annual fluxes to the atmosphere over deposition fluxes for individual congeners exist for congeners 28, 52 and 101, estimates of fluxes in both directions across the soil-atmosphere interface agree closely for congeners 138, 153 and 180. This suggests that lower chlorinated congeners are more susceptible to both long-range environmental transport beyond the UK and to atmospheric degradation. Retrospective analysis of dated sediment cores, vegetation and soils indicates that environmental transport from North America and continental Europe introduced PCBs into the British environment well before the onset of their commercial production in the UK in 1954. Since that time, the input of PCBs to the UK environment has essentially reflected temporal trends in UK use. After peaking in the 1960s they declined rapidly through the 1970s following restrictions on PCB use. Recent evidence, however, is that the rate of decrease has diminished and that further significant reductions in fresh environmental input will take some time to occur. Such reductions will be especially slow for humans and other biota with long life-spans. This stems partly from cross-generational transfer from parents to offspring and also because the persistence of PCBs in biota means that present body burdens will reflect past as well as current exposure.

The influence of sewage sludge applications to agricultural land on human exposure to polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs).

Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) are organic chemicals of suspected extreme toxicity. PCDD/Fs are ubiquitous in the environment and relatively enriched in sewage sludges. The deliberate application of sewage sludge to agricultural land can therefore potentially increase exposure of the human population to these compounds via transfers through the foodchain. This paper presents a protocol for assessing the background human exposure to all seventeen 2,3,7,8-substituted PCDD/Fs for which toxic equivalent factors (TEFs) are available. Background daily human exposure in the UK to 2,3,7,8-T(4)CDD and I-TEQ are calculated to be 0.0239 ng and 0.203 ng, respectively. The potential increases in crop plant and livestock tissue PCDD/F concentrations, and hence in human exposure, following applications of sewage sludge to agricultural land are quantified for different sludge application scenarios. The key role of PCDD/F transfer into livestock via ingestion of sludge adhered to vegetation in determining increases in human exposure is demonstrated.

Anal endosonography in asymptomatic subjects.

The anal sphincter thickness was measured ultrasonographically in 30 asymptomatic subjects (13 male and 17 female: 23 young and 7 old). The internal anal sphincter (IAS) was measured at its thickest portion in the anal canal, its borders lying between the submucosa and the external and sphincter (EAS). The EAS was measured at the lowermost point in the anal canal, its borders being the IAS and the coccyx. The EAS was thicker in men than in women (p < 0.02). The IAS showed no difference with regard to gender. The EAS became thinner with age (p < 0.005), whereas the IAS appeared thicker with age (p < 0.0002). The EAS thickness correlated inversely with the IAS thickness (p < 0.001). Anorectal manometry showed a correlation between the anal canal resting pressure and the sum of the thickness of the two sphincters (p < 0.001). Thus, although the visualized thickness of the two sphincters vary, they do so proportionally, and their sum reflects their tonic activity.

An integrated haematuria clinic.

The prognosis of bladder cancer is worsened by delay in its management. To reduce such delay we have organised a clinic where intravenous urography and cystoscopy, using a flexible cystoscope, are carried out at the patient's first visit. In a two-year period 321 patients attended this clinic. The results of investigation in 305 patients are reported. A total of 6% of patients with microscopic haematuria (n = 52) and 15% of patients with macroscopic haematuria (n = 253) had transitional cell carcinomata. This difference was not significant (P = 0.08, chi-squared). The delay between referral and trans-urethral resection of tumour for patients with bladder tumours was reduced from a mean of 60 days to a mean of 33 days by the institution of the clinic (P < 0.01, Mann-Whitney). We recommend that all patients referred to a urological service with haematuria, whether macroscopic or microscopic, should be investigated. The integration of that investigation in a single day decreases delays in diagnosis and management.

Prostate-specific antigen and prostate gland size in men receiving exogenous testosterone for male contraception.

Steroid regimens containing androgens are being evaluated currently as hormonal contraceptives for men. The possible non-reproductive effects of such treatment were assessed during an efficacy trial using a prototype regime of 200 mg testosterone enanthate i.m. weekly. Prostatic function and size were monitored by regular rectal examination, blood levels of prostate-specific androgen (PSA) were measured in 30 men and prostatic size was measured by trans-rectal ultrasound imaging in a representative subgroup of five subjects for 12 months and for a further 6 months after discontinuation. Despite the sustained rise in serum levels of testosterone, oestradiol and dihydrotestosterone during treatment, there was no detectable increase in prostatic size on rectal examination or any significant change in blood concentrations of PSA. A small but significant increase (14.3 +/- 2.0%) in maximal prostate transverse area was observed in four men while the remaining one showed no change. Our preliminary data demonstrate the feasibility and importance of monitoring prostatic function in the development of androgen-containing male hormonal contraceptives.

Duplicated müllerian duct remnants associated with unilateral renal agenesis.

A case of duplicated Müllerian duct remnants associated with unilateral renal agenesis in a male patient is described. This association is not uncommon in females, but is rarely recognized in male patients. The possibility of Müllerian duct cyst or enlarged prostatic utricle should be considered in the differential diagnosis of a pelvic cyst in a male patient with unilateral renal agenesis.

Survey of urological centres and review of current practice in the pre-operative assessment of prostatism.

A survey of 24 urological centres has shown a wide variation in the routine pre-operative assessment of patients being considered for prostatectomy. Imaging of the urinary tract by intravenous urography (IVU) or ultrasound (US) is performed in 21/24 centres (79%) and plain films in 16/24 (67%). Post-micturition residual volume (PMRV) is estimated quantitatively in 10/24 centers (42%). Although there is little agreement on what constitutes a significant PMRV, a large PMRV leads to increased likelihood of operation, and earlier operation. Peak urine flow rate (Q max) is measured in 19/24 centres (79%). The significance of these findings is discussed.

Is pre-operative imaging of the urinary tract worthwhile in the assessment of prostatism?

The reports of routine pre-operative imaging investigations performed on patients presenting with symptoms of uncomplicated benign prostatic hypertrophy were compared with management decisions and clinical outcome. In 175 patients with prostatism no urological abnormality which altered management was discovered on plain films of the abdomen and pelvis and ultrasound of the urinary tract which were performed routinely. Post-micturition residual volume (PMRV), estimated by ultrasound, was compared with the maximum urine flow rate (Q max) in 57 patients. PMRV showed negative correlation with Q max. Both high PMRV and low Q max were associated with the urologist's decision to operate, but multiple logistic regression revealed that ultrasound residual volume was not a significant predictor of operation when adjusted for Q max. Urologists in this hospital therefore use flow rates as the primary indication of the need to operate. We suggest that no routine pre-operative imaging need be performed in patients presenting with prostatism.

Organic chemicals entering agricultural soils in sewage sludges: screening for their potential to transfer to crop plants and livestock.

This paper presents a review and assessment of the pathways and transfers of organic contaminants applied to agricultural soils in sewage sludge. The purpose of the assessment has been to develop a simple screening approach to highlight different chemical fates of organic chemicals in soil and their potential transfers from soil to groundwaters, crop plants and grazing livestock using data on the physico-chemical properties of the compounds of interest. The fate of 46 compounds known to be present in sewage sludges are compared to illustrate the applicability of the procedure. Compounds are screened for their potential to adsorb, volatilise, degrade and leach in soils and to be transferred to plants via retention by root surfaces, root uptake and translocation and foliar uptake and to transfer to animal tissues via soil and herbage ingestion. Recommendations for experimental and field studies are made. It is envisaged that this screening approach can be applied to other chemicals and that it will focus research and aid risk assessments of organic compounds in sewage sludge following land application.

Adaptive time gain compensation for ultrasonic imaging.

The quality of ultrasonic images is often adversely affected by incorrect time gain compensation (TGC) settings. TGC set up by the operator is inadequate for two reasons: firstly, one gain function is unlikely to be appropriate for all the scan lines in an image and secondly, the operator may not have sufficient time or experience to optimise it. Adaptive processing offers a solution to this problem; it has the potential both to improve image quality and to let the operators make more effective use of their time. The literature concerned with adaptive TGC is briefly reviewed. A microcomputer-controlled system has been used to develop various algorithms for adaptive TGC. The algorithms operate in real-time and have been tested using a grey-scale test object, and clinically in routine abdominal and obstetric scanning. The imaging characteristics of each algorithm are determined largely by the value of a parameter beta, described in the text. It is concluded that adaptive TGC capable of applying a unique gain function to each part of the image can consistently produce better images than a single gain function set either automatically or manually.

Polynuclear aromatic hydrocarbons in crops from long-term field experiments amended with sewage sludge.

This study reports on the polynuclear aromatic hydrocarbon (PAH) content of crop plants grown at three different field experiments where controlled additions of sewage sludge were made a number of years ago. Archived samples of several crops have been analysed from sludge-amended and unsludged control plots for 15 PAH compounds. Root crops and above ground plant parts were available for several years following the last applications of sludge. Although the soil PAH burden increased substantially due to sewage sludge additions, and residues of these compounds have persisted in the soils for many years, increased PAH concentrations relative to the unsludged controls were not consistently detected in plant tissues. Plant samples were relatively enriched with low molecular weight compounds such as acenaphthene/fluorene nd phenanthrene. Various lines of evidence indicate that PAHs detected in above ground plant parts are chiefly derived from atmospheric inputs, while PAHs detected in root crops probably arise from adsorption to the root surface.

Arrested municipal solid waste incinerator fly ash as a source of heavy metals to the UK environment.

Arrested fly ash samples from most currently operating municipal solid waste (MSW) incinerators in the UK have been analysed for a range of elements. Some of the more important heavy metals ranged in concentration as follows: Cd, 21-4646 (median = 271) mg kg(-1); Cu, 296-1307 (642) mg kg(-1); Cr, 44-1328 (574) mg kg(-1); Ni, 45-2204 (74) mg kg(-1); Pb, 447-9704 (4337) mg kg(-1); and Zn, 2285-13,500 (9232) mg kg(-1). These concentrations represent considerable enrichments relative to median UK soil concentrations. Enrichment ratios (defined as median fly ash: median UK soil) were as follows: Mn 1.6; Co 2.6; Ni 3.3; Ba 11; Sr 11; Cr 15; Cu 35; Pb 108; Zn 113; Cd 387. It is estimated that MSW incinerator ash contributes c. 15 t Cd and 241 t Pb to UK landfill sites per annum. These figures compare with previous studies by Hutton & Symon (Hutton, M. & Symon, C. (1986). The quantities of cadmium, lead, mercury and arsenic entering the UK environment from human activities. Sci. Total Environ., 57, 129-50.) which estimated that annual inputs to UK landfills from coal fly ash are c. 60 t Cd and 1270 t Pb. However, it is argued that metals associated with MSW ashes are potentially of greater environmental significance than in coal ashes, because they are much more available and present at much higher concentrations.