Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity.

BACKGROUND: Altered lipid metabolism in early life has been associated with subsequent weight gain and predicting this could aid in obesity prevention and risk management. Here, a lipidomic approach was used to identify circulating markers for future obesity risk in translational murine models and validate in a human infant cohort. METHODS: Lipidomics was performed on the plasma of APOE*3 Leiden, Ldlr-/-.Leiden, and the wild-type C57BL/6J mice to capture candidate biomarkers predicting subsequent obesity parameters after exposure to high-fat diet. The identified candidate biomarkers were mapped onto corresponding lipid metabolism pathways and were investigated in the Cambridge Baby Growth Study. Infants' growth and adiposity were measured at 0-24 months. Capillary dried blood spots were sampled at 3 months for lipid profiling analysis. FINDINGS: From the mouse models, cholesteryl esters were correlated with subsequent weight gain and other obesity parameters after HFD period (Spearman's r≥0.5, FDR p values <0.05) among APOE*3 Leiden and Ldlr-/-.Leiden mice, but not among the wild-type C57BL/6J. Pathway analysis showed that those identified cholesteryl esters were educts or products of desaturases activities: stearoyl-CoA desaturase-1 (SCD1) and fatty acid desaturase (FADS) 1 and 2. In the human cohort, lipid ratios affected by SCD1 at 3 months was inversely associated with 3-12 months weight gain (B±SE=-0.31±0.14, p=0.027), but positively with 12-24 months weight and adiposity gains (0.17±0.07, p=0.02 and 0.17±0.07, 0.53±0.26, p=0.04, respectively). Lipid ratios affected by SCD1 and FADS2 were inversely associated with adiposity gain but positively with height gain between 3-12 months. INTERPRETATION: From murine models to human setting, the ratios of circulating lipid species indicating key desaturase activities in lipid metabolism were associated with subsequent body size increase, providing a potential tool to predict early life weight gain.

On the distance to the North Polar Spur and the local CO-H2 factor.

AIMS: Most models identify the X-ray bright North Polar Spur (NPS) with a hot interstellar (IS) bubble in the Sco-Cen star-forming region at ≃130 pc. An opposite view considers the NPS as a distant structure associated with Galactic nuclear outflows. Constraints on the NPS distance can be obtained by comparing the foreground IS gas column inferred from X-ray absorption to the distribution of gas and dust along the line of sight. Absorbing columns towards shadowing molecular clouds simultaneously constrain the CO-H2 conversion factor. METHODS: We derived the columns of X-ray absorbing matter N Habs from spectral fitting of dedicated XMM-Newton observations towards the NPS southern terminus (l II ≃ 29°, b II ≃ +5 to +11°). The distribution of the IS matter was obtained from absorption lines in stellar spectra, 3D dust maps and emission data, including high spatial resolution CO measurements recorded for this purpose. RESULTS: N Habs varies from ≃ 4.3 to ≃ 1.3 × 1021 cm-2 along the 19 fields. Relationships between X-ray brightness, absorbing column and hardness ratio demonstrate a brightness decrease with latitude governed by increasing absorption. The comparison with absorption data, local and large-scale dust maps rules out a NPS near side closer than 300 pc. The correlation between N Habs and the reddening increases with the sightline length from 300 pc to 4 kpc and is the tightest with Planck τ 353GHz -based reddening, suggesting a much larger distance. N(H)/E(B-V) τ ≃ 4.1 × 1021 cm-2 mag-1, close to Fermi-Planck determinations. N Habs absolute values are compatible with HI-CO clouds at -5 ≤ V LSR ≤ +25 to +45 km s-1 and a NPS potentially far beyond the Local Arm. A shadow cast by a b=+9° molecular cloud constrains X CO in that direction to ≤ 1.0 × 1020 cm-2 K-1 km-1 s. The average X CO over the fields is ≤ 0.75 × 1020 cm-2 K-1 km-1 s.

The origin of the local 1/4-keV X-ray flux in both charge exchange and a hot bubble.

The solar neighbourhood is the closest and most easily studied sample of the Galactic interstellar medium, an understanding of which is essential for models of star formation and galaxy evolution. Observations of an unexpectedly intense diffuse flux of easily absorbed 1/4-kiloelectronvolt X-rays, coupled with the discovery that interstellar space within about a hundred parsecs of the Sun is almost completely devoid of cool absorbing gas, led to a picture of a 'local cavity' filled with X-ray-emitting hot gas, dubbed the local hot bubble. This model was recently challenged by suggestions that the emission could instead be readily produced within the Solar System by heavy solar-wind ions exchanging electrons with neutral H and He in interplanetary space, potentially removing the major piece of evidence for the local existence of million-degree gas within the Galactic disk. Here we report observations showing that the total solar-wind charge-exchange contribution is approximately 40 per cent of the 1/4-keV flux in the Galactic plane. The fact that the measured flux is not dominated by charge exchange supports the notion of a million-degree hot bubble extending about a hundred parsecs from the Sun.

A mathematical model of CO2 variation in the ventilated neonate.

A mathematical model of the variation of partial pressure of carbon dioxide in the arterial blood of a ventilated neonate is developed. The model comprises alveolar, arterial, pulmonary, venous and tissue compartments, with gas exchange in the lung determined by inspiration and expiration terms. Gas exchange is modelled through diffusion and convective transfer. Carbon dioxide is produced in the tissue by a metabolic term. Shunting is modelled by allowing blood flow to bypass the pulmonary compartment in which diffusion takes place. The model predicts changes in the carbon dioxide partial pressures that occur following abrupt changes in the ventilation settings, and show broad agreement with actual data obtained from novel sensing technology.

Friction burns within the tibia during reaming. Are they affected by the use of a tourniquet?

We have carried out a prospective, randomised trial to measure the rise of temperature during reaming of the tibia before intramedullary nailing. We studied 34 patients with a mean age of 35.1 years (18 to 63) and mean injury severity score of 10 (9 to 13). The patients were randomised into two groups: group 1 included 18 patients whose procedure was undertaken without a tourniquet and group 2, 16 patients in whom a tourniquet was used. The temperature in the bone was measured directly by two thermocouples inserted into the cortical bone near the isthmus of the tibial diaphysis. Reaming was carried out to at least 1.5 mm above the required diameter of the nail. Blood loss was assessed by recording the preoperative and postoperative haemoglobin (Hb) level. The minimum clinical follow-up was six months. In group 1 (no tourniquet), the mean Hb dropped 2.8 g/dl from 14.3 +/- 1.02 g/dl to 11.5 +/- 1.04 g/dl (p = 0.0001), whereas with the tourniquet, the mean decrease was 1.3 g/dl from 14 +/- 1 g/dl to 12.7 +/- 1.3 g/dl (p = 0.007). This difference was not statistically significant. The mean initial tibial temperature was 35.6 degrees C (SD 0.6) and rose with reaming to levels between 36.3 degrees C and 51.6 degrees C. The highest temperatures were obtained with the largest reamers (11 and 12 mm, p = 0.0001) and the most rapid rise with the smallest diameters of medullary canal (8 or 9 mm). The rise of temperature was transient (20 s). We were unable to identify any effect of the use of a tourniquet on the temperature achieved. Reamed intramedullary tibial nailing induces a transient elevation of temperature which is directly related to the amount of reaming.

Temperature rise during reamed tibial nailing.

The current study determined the temperature rise during reamed tibial intramedullary nailing in vivo. Eighteen adult patients were studied. The tibial medullary canal diameter ranged from 8 to 11 mm and was reamed to at least 1.5 mm above the required nail diameter with AO reamers. Reaming of the medullary cavity ranged from 9 to 12 mm before nail insertion. Intraoperative monitoring of the heat produced during reaming of the medullary cavity was done by inserting two platinum resistance thermometer probes into the cortical bone at the short isthmic segment of the tibial shaft. The probes were connected to a data logger, and temperature readings were taken every 5 seconds during each reaming procedure. The mean tibial temperature before initiation of reaming was 35.6 degrees C (standard deviation, +/- 0.5 degrees), and peak temperatures recorded were from 36.1 degrees C to 51.6 degrees C. A direct correlation was observed between temperature elevation and amount of reaming. With reaming above 10 mm, tibias with a canal diameter of 8 mm showed a statistically higher temperature rise compared with tibias with a canal diameter of 9, 10, or 11 mm. No patients had intraoperative or postoperative complications related to skin or bone thermal necrosis, and bony healing progressed uneventfully. The small amount of reaming required to insert a nail into a normal 9-, 10-, or 11- mm tibial canal does not seem to produce a clinical problem. Reaming smaller canals (8 mm) to a larger size may induce a significant heating effect.

General practitioner participants in a telemedicine trial: comparisons with their peers.

A study was conducted to determine whether general practitioners (GPs) participating in a telemedicine trial were self-selected enthusiasts for information technology compared with GPs in general. We compared two experimental groups of GPs in London and Wales (n = 126) who had volunteered to participate in a telemedicine trial and two randomly selected groups of GPs from the same areas (total n = 300) who acted as controls. A postal questionnaire was used and achieved a 79% response rate. There were no significant differences in the demographic characteristics of the experimental and control groups in London and Wales, except that the London telemedicine GPs (mean age 41.9 years) were significantly younger than the London controls (mean age 46.6 years). The control GPs were similar to the telemedicine GPs in terms of frequency of computer use and their responses to statements about their attitudes to computers. In the combined telemedicine and control groups, 85% and 77% respectively said that they enjoyed using computers. Telemedicine GPs used computers more frequently for administrative purposes but they shared the same attitudes towards information technology as GPs in general. In all situations where GPs could exercise personal choice, the control and experimental groups were similar.

A digital system for recording the electrical activity of the uterus.

The ability to identify true pre-term labour would be of considerable clinical benefit as electrical signals from the uterus, recorded using surface electrodes, may discriminate between labouring and non-labouring states in human pregnancy. A digital recording system for recording the electrical activity of the uterus has been developed and is described in this paper. A pilot study in which entire recordings in 21 women were subjected to power spectral analysis suggests that the relative power in two frequency bands (0.2-0.45 Hz and 0.8-3 Hz) changes as pregnancy progresses into early labour.

European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients.

Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 %-12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

Ruptured abdominal aortic aneurysm: a novel method of outcome prediction using neural network technology.

BACKGROUND: reported survival following emergency surgery for ruptured abdominal aortic aneurysm (RAAA) varies widely between institutions. This is largely attributable to differences in case mix. The aim of this study was to identify and evaluate a set of prognostic variables that would accurately predict outcome for individual patients from perioperative indices. METHODS: perioperative factors associated with subsequent mortality at our institution were identified by retrospective review of 102 consecutive operations for RAAA over a 7-year period (January 1990 to January 1997). Logistic regression analysis was used to select the most significant variables associated with subsequent mortality. These were used to construct, train, and validate a neural network designed to predict survival from surgery in individual cases on a prospective basis. RESULTS: the 30-day mortality rate was 53%. Multivariate analysis identified four highly significant independent predictors of mortality; preoperative hypotension, intraperitoneal rupture, preoperative coagulopathy, and preoperative cardiac arrest. Using these inputs, the neural network correctly predicted outcome in 82.5% of individual cases. CONCLUSION: a neural network based on just four perioperative variables can accurately predict outcome of RAAA. Prognostic variables should be reported in studies as a measure of the effect of case mix on survival data. Neural networks have potential to aid decision-making relating to outcome for individual cases.

Neural networks in the diagnosis of malignant ovarian tumours.

OBJECTIVE: To assess the role of neural networks in predicting the likelihood of malignancy in women presenting with ovarian tumours. DESIGN: Retrospective case study. SETTING: University Department of Obstetrics and Gynaecology, St James's Hospital, Leeds. METHODS: Information from 217 cases with histologically proven benign, borderline or malignant tumours was extracted for study. Four variables (age, ultrasound findings with and without colour Doppler imaging and CA125) were entered in the neural network classifier. The neural network results were compared with logistic regression analysis. RESULTS: When used in the neural network the variables of age, CA125 and ultrasound score produced the best result with a sensitivity of 95% and a corresponding specificity of 78% in predicting malignancy. Logistic regression gave a sensitivity or 82% for a specificity of 51%. CONCLUSION: The neural network is a good method of combining diagnostic variables and may be a useful predictor of malignancy in women presenting with ovarian tumours. A comparison of the performance of the neural network with conventional diagnostic methods would be warranted prior to use in clinical practice.

The application of neural networks in predicting the outcome of in-vitro fertilization.

Infertility affects one in six couples at some time in their lives, with 48% of these couples requiring assisted conception techniques in order to achieve a pregnancy. Whilst the overall clinical pregnancy rate per embryo transfer is 23%, this varies widely between clinics. The Human Fertilisation and Embryology Authority has attempted to analyse the results of all units, with weighting of different factors affecting assisted conception, and the published data have invariably led to comparisons between units. However, statistical models need to be developed to eliminate bias for valid comparisons. Neural networks offer a novel approach to pattern recognition. In some instances neural networks can identify a wider range of associations than other statistical techniques due in part to their ability to recognize highly non-linear associations. It was hoped that a neural network approach may be able to predict success for individual couples about to undergo in-vitro fertilization (IVF) treatment. A neural network was constructed using the variables of age, number of eggs recovered, number of embryos transferred and whether there was embryo freezing. Overall the network managed to achieve an accuracy of 59%.

An expert system to assist neonatal intensive care.

An expert system for neonatal intensive care (ESNIC) for the management of mechanically ventilated neonates on intermittent positive pressure ventilation (IPPV) has been developed. The system uses the rule based expert system shell XiPlus (Inference Inc.) and runs on an IBM-compatible PC. The rules have been derived from the knowledge of two consultant paediatricians. The inputs to the system are the current ventilator settings, blood gas tensions and pH. The output of the system is a set of suggested new ventilator settings. The aim of the system is to provide ventilator settings which will maintain the arterial blood gas tensions within an acceptable range, reducing pressures whenever feasible and increasing pressures only as a last resort. In addition, ESNIC provides data archiving, graphical displays of all parameters, ventilation and discharge summaries. With the 63 patients in the study ESNIC was consulted for 76% of all ventilator adjustments and the advice given was accepted on 83% of these occasions.

Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation.

BACKGROUND: Many patients with circulating antibodies to human leucocyte antigens (anti-HLA) are highly sensitised against renal transplantation and are liable to immediate graft loss through hyperacute rejection. Our aim was to find out whether removal of anti-HLA immediately before renal transplantation prevented hyperacute graft rejection. METHODS: 13 highly sensitised patients underwent cadaveric renal transplants immediately after immunoadsorption (IA) treatment to remove anti-HLA. Before IA, 12 patients had a positive crossmatch against donor cells either by cytotoxic or flow-cytometric assay; results for one patient were equivocal. FINDINGS: Renal biopsy samples were obtained 20 min after removal of the vascular clamps in nine patients. There was no evidence of hyperacute rejection in six of the nine patients; the other three patients showed glomerular thrombosis but no other evidence of hyperacute rejection. Two of these three grafts were functioning at 31 months of follow-up. Six episodes of acute rejection occurred in five patients during the first month after transplantation and overall there were 13 rejection episodes in nine patients. At latest follow-up (median 26 months, range 9-42), 12 of 13 patients were alive and seven of 13 grafts were surviving with a median plasma creatinine concentration of 185 mumol/L (range 106-296) in the functioning grafts. No graft was lost as a result of classic hyperacute rejection. INTERPRETATION: Immediate pretransplant IA can prevent hyperacute rejection and provide an opportunity for successful transplantation in highly sensitised patients.

Postoperative care of the lung transplant recipient.

This article reviews the nursing care of the patient who receives a lung transplant, starting with preparation for admission to the ICU. Issues of oxygenation, airway clearance, hemodynamic and fluid assessment, infection control, incisional assessment, and pain are addressed throughout the hospitalization. Emotional support, discharge and medication teaching, and changes in lifestyle are all important aspects of the rehabilitation phase before discharge.

Transplant renal artery stenosis in 77 patients--does it have an immunological cause?

Transplant renal artery stenosis (TRAS) is a common complication after transplantation and is an important cause of graft dysfunction. Damage from graft rejection, trauma, and atherosclerosis have been implicated as possible causes. We reviewed all 917 patients transplanted in our unit since 1978 to study the prevalence, clinical features, and possible causes of TRAS. Seventy-seven patients with TRAS were identified. The detected incidence was 2.4% before the introduction of color doppler ultrasonography (CDU) and rose to 12.4% after CDU was introduced in 1985, giving an overall incidence of 8.4% during a mean follow-up period of 6.9 years. The TRAS group was compared with a control group of 77 transplanted patients matched for age, year of transplant, sex, and number of previous grafts. Mean ages for the study and control groups were 43.6 +/- 15 and 44.8 +/- 13.7 yr. A total of 25% of cases of TRAS were diagnosed within the first 8 wk of transplantation and in 60% within the first 30 wk (median = 23 wk). All patients were treated with angioplasty, 28 patients had recurrence of TRAS requiring multiple angioplasties (maximum 5) and 1 went on to have surgery. Angioplasty resulted in a significant fall in plasma creatinine. Patient and graft survival were significantly worse in the TRAS group: 69% vs. 83% (P < 0.05) and 56% vs. 74% (P < 0.05) (TRAS vs. Control), respectively. There was a significantly higher incidence of rejection, especially cellular rejection in the TRAS group, 0.67 vs. 0.35 episodes per patient (P < 0.01) (TRAS vs. Control). Recurrence but not occurrence of TRAS was associated with the use of cyclosporine.