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Positive blood cultures in very low birthweight or preterm infants usually reflect bacteraemia, septicaemia, or failure of asepsis during sampling and lead to increased costs and length of stay. Rates of nosocomial, or hospital acquired, bacteraemia may therefore be important indicators of neonatal unit performance, if comparisons are adjusted for differences in initial risk. In a preliminary study the risk of nosocomial bacteraemia was related to initial clinical risk and illness severity measured by the clinical risk index for babies (CRIB). Nosocomial bacteraemia was defined as clinically suspected infection with culture of bacteria in blood more than 48 hours after birth. One or more episodes of nosocomial bacteraemia were identified retrospectively in 36 of 143 (25%) infants in a regional neonatal unit between 1992 and 1994. Biologically plausible models were developed using regression analysis techniques. After correcting for period at risk, nosocomial bacteraemia was independently associated with gestation at birth and CRIB. Death was independently associated with CRIB, but not with nosocomial bacteraemia. CRIB may contribute, with other explanatory variables, to more comprehensive predictive models of death and nosocomial infection. These may facilitate future risk adjusted comparative studies between groups of neonatal units. [ABSTRACT FROM AUTHOR]

Aim: Phantom rectum is the sensation of an intact and/or functioning rectum, despite excision at surgery. Abdominoperineal excision of the rectum (APER) may be complemented by reconstructive operations and recently it was reported that patients undergoing APER and vertical rectus abdominis myocutaneous (VRAM) flap reconstruction are more prone to develop phantom sensations at an earlier timeframe and have more persistent symptoms than those who do not have perineal repairs. The aim of this study was to determine the prevalence of phantom rectal sensations in a cohort of these patients., Method: Patients who underwent APER and VRAM flap reconstruction for anorectal carcinomas were identified from May 2008 to July 2012. Patients completed a questionnaire evaluating their experience of rectal symptoms post-surgery., Results: Thirty-four of 47 eligible patients were enrolled in the study. PR sensations were experienced by 50 % of patients, the majority of which (65 %) were present for >1 year. The commonest sensation reported was the feeling of faeces in a normal rectum (24 %). Disturbances in quality of life were apparent in 44 %; notably, sleep was affected, patients expressed increased feelings of stress/sadness, heightened levels of anxiety and limitation of daily activities as consequences of PR symptoms. Few patients sought medical advice., Conclusion: Fifty percent of patients experience PR sensations post-surgery, comparable with reported data for patients who have undergone APER alone. The addition of VRAM reconstruction does not significantly alter the prevalence of PR symptoms. This paper provides further evidence that phantom rectum occurs frequently and thus all patients undergoing excision of the rectum should be counselled appropriately.

FGFs, in a complex with their receptors (FGFRs) and heparan sulfate (HS), are responsible for a range of cellular functions, from embryogenesis to metabolism. Both germ line and somatic FGFR mutations are known to play a role in a range of diseases, most notably craniosynestosis dysplasias, dwarfism and cancer. Because of the ability of FGFR signalling to induce cell proliferation, migration and survival, FGFRs are readily co-opted by cancer cells. Mutations in, and amplifications of, these receptors are found in a range of cancers with some of the most striking clinical findings relating to their contribution to pathogenesis and progression of female cancers. Here, we outline the molecular mechanisms of FGFR signalling and discuss the role of this pathway in women's cancers, focusing on breast, endometrial, ovarian and cervical carcinomas, and their associated preclinical and clinical data. We also address the rationale for therapeutic intervention and the need for FGFR-targeted therapy to selectively target cancer cells in view of the fundamental roles of FGF signalling in normal physiology., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We have analyzed constraints on parity-odd time-reversal noninvariant interactions derived from measurements of the energy dependence of parity-violating polarized neutron capture on unpolarized targets. As previous authors found, a perturbation in energy dependence due to a parity (P)-odd time (T)-odd interaction is present. However, the perturbation competes with T-even terms which can obscure the T-odd signature. We estimate the magnitudes of these competing terms and suggest strategies for a practicable experiment.

We present results of a study of neutrino oscillation based on a 766 ton/year exposure of KamLAND to reactor antineutrinos. We observe 258 nu (e) candidate events with energies above 3.4 MeV compared to 365.2+/-23.7 events expected in the absence of neutrino oscillation. Accounting for 17.8+/-7.3 expected background events, the statistical significance for reactor nu (e) disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from nu (e) oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2). A global analysis of data from KamLAND and solar-neutrino experiments yields Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2) and tan((2)theta=0.40(+0.10)(-0.07), the most precise determination to date.

Data corresponding to a KamLAND detector exposure of 0.28 kton yr has been used to search for nu;(e)'s in the energy range 8.3

KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.

Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by an apparently abnormal immune response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In order to examine the nature of the immune response at the molecular level, the expression of a range of immune regulatory genes, including cytokines and cyclooxygenase (COX)-2 was examined in naive unexposed fish and in naive fish exposed to parasite-infected water at three points during the course of a natural outbreak of PKD. Since fish with advanced PKD pathology generally exhibit increased susceptibility to secondary infections which is typical of stress/cortisol-mediated immune suppression, a further aim of this work was to examine in vitro the influence of the glucocorticoid cortisol on the bacterial lipopolysaccharide (LPS)-induced expression of the trout cytokine genes studied. Two weeks after the initial sampling, naive exposed fish showed a specific profile of up-regulated tumor necrosis factor (TNF)-alpha2, COX-2 and, to a lesser extent, transforming growth factor (TGF)-beta1 expression. As the disease pathology increased, TNF-alpha2 and COX-2 expression returned to normal levels. Stress levels of cortisol suppressed the LPS inducibility of pro-inflammatory cytokine genes, although TGF-beta1 and TNF-alpha2 appeared to be refractory. These data demonstrate that specific immune responses at the molecular level are affected during PKD infection, with the cortisol suppression of cytokine expression in vitro providing a possible link to PKD-mediated cytokine down-regulation and immune suppression.

Objective: To assess whether crude league tables of mortality and league tables of risk adjusted mortality accurately reflect the performance of hospitals., Design: Longitudinal study of mortality occurring in hospital., Setting: 9 neonatal intensive care units in the United Kingdom., Subjects: 2671 very low birth weight or preterm infants admitted to neonatal intensive care units between 1988 and 1994., Main Outcome Measures: Crude hospital mortality and hospital mortality adjusted using the clinical risk index for babies (CRIB) score., Results: Hospitals had wide and overlapping confidence intervals when ranked by mortality in annual league tables; this made it impossible to discriminate between hospitals reliably. In most years there was no significant difference between hospitals, only random variation. The apparent performance of individual hospitals fluctuated substantially from year to year., Conclusions: Annual league tables are not reliable indicators of performance or best practice; they do not reflect consistent differences between hospitals. Any action prompted by the annual league tables would have been equally likely to have been beneficial, detrimental, or irrelevant. Mortality should be compared between groups of hospitals using specific criteria-such as differences in the volume of patients, staffing policy, training of staff, or aspects of clinical practice-after adjusting for risk. This will produce more reliable estimates with narrower confidence intervals, and more reliable and rapid conclusions.

Aim: To investigate the feasibility of developing an objective tool for predicting death and severe disability using routinely available data, including an objective measure of illness severity, in very low birthweight babies., Method: A cohort study of 297 premature babies surviving the first three days of life was made. Predictive variables considered included birthweight, gestation, 3 day cranial ultrasound appearances and 3 day CRIB (clinical risk index for babies) score. Models were developed using regression techniques and positive predictive values (PPV) and likelihood ratios (LR) were calculated., Results: On univariate analysis, birthweight, gestation, 3 day CRIB score and 3 day cranial ultrasound appearances were each associated with death. On multivariate analysis, 3 day CRIB score and 3 day cranial ultrasound appearances remained independently associated. A 3 day CRIB score > 4 along with intraventricular haemorrhage (IVH) grade 3 or 4 was associated with a PPV of 64% and an LR of 9.8 (95% confidence limits 3.5, 27.9). Only 3 day CRIB score and 3 day cranial ultrasound appearances were associated with severe disability on univariate analysis. Both remained independently associated on multivariate analysis. A 3 day CRIB score > 4 along with an IVH grade of 3 or 4 was associated with a PPV of 60% and an LR of 24.2 (95% CI 4.4, 133.3)., Conclusion: Incorporating objective measures of illness severity may improve current prediction of death and disability in premature infants.

Objectives: Clinical Risk Index for Babies (CRIB) is a simple instrument used to measure clinical risk and illness severity in very low birth-weight infants. We assessed its reliability, validity beyond the first 12 hrs after birth, and responsiveness to individual change in condition after 7 days., Design: Cohort study., Setting: Three tertiary and three nontertiary UK hospitals., Patients: Three hundred ninety-eight infants whose birth weight was <1501 g or who were born before a 31-wk gestation period., Interventions: Inter- and intrarater reliability of data extraction were assessed by Pearson and intraclass correlation. To validate CRIB, we tested the correlation between clinical risk and illness severity with the risk of: a) death; b) prolonged treatment with supplemental oxygen; and c) disability at 2 yrs. Logistic regression models were fitted to assess validity and responsiveness., Measurements and Main Results: Reliability coefficients ranged from 0.76 (95% confidence interval, 0.71 to 0.81) to 0.97 (0.94 to 1.00). Throughout the first week, CRIB correlated with the risk of death (p < .001), prolonged treatment with oxygen (p < .001), and disability (p < .001 to p = .033). Improved condition, represented by a reduction in CRIB within the first week, was independently associated with lower risks of each adverse outcome, p < .05., Conclusions: During the first week, CRIB was reliable, valid, and responsive. These properties support the use of CRIB in the stratification of infants by risk and illness severity in cohort studies, and they also indicate that CRIB may have the potential to be used in other ways in the future.