Fast track children's hearing pilot: final report of the evaluation of the pilot

This report presents key findings of the evaluation of the Fast Track children’s hearings pilot in Scotland1. The research was undertaken by staff at the Universities of Glasgow, Stirling and Strathclyde between February 2003 and January 2005

The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli

Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature. Mechanistically, cancer-induced bone pain (CIBP) is mediated by peripheral sensory neurons innervating the cancerous site, the cell bodies of which are housed in the dorsal root ganglia (DRG). How these somatosensory neurons encode sensory information in CIBP remains only partly explained. Using a validated rat model, we first confirmed cortical bone destruction in CIBP but not sham-operated rats (day 14 after surgery, designated “late”-stage bone cancer). This occurred with behavioural mechanical hypersensitivity (Kruskal–Wallis H for independent samples; CIBP vs sham-operated, day 14; P < 0.0001). Next, hypothesising that the proportion and phenotype of primary afferents would be altered in the disease state, dorsal root ganglia in vivo imaging of genetically encoded calcium indicators and Markov Cluster Analysis were used to analyse 1748 late-stage CIBP (n = 10) and 757 sham-operated (n = 9), neurons. Distinct clusters of responses to peripheral stimuli were revealed. In CIBP rats, upon knee compression of the leg ipsilateral to the tumour, (1) 3 times as many sensory afferents responded (repeated-measures analysis of variance: P < 0.0001 [vs sham]); (2) there were significantly more small neurons responding (Kruskal–Wallis for independent samples (vs sham): P < 0.0001); and (3) approximately 13% of traced tibial cavity afferents responded (no difference observed between CIBP and sham-operated animals). We conclude that an increased sensory afferent response is present in CIBP rats, and this is likely to reflect afferent recruitment from outside of the bone rather than increased intraosseous afferent activity

Interleukin-17 Expression in the Barrett’s Metaplasia-Dysplasia-Adenocarcinoma Sequence

Original Research ArticleIntroduction. This pilot study evaluated the expression of the proinflammatory cytokine IL-17 along the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence by establishing the expression levels of IL-17 in columnar epithelium, intestinal metaplastic cells, and dysplastic/glandular neoplastic cells. Immunohistochemical techniques were used to examine the accumulation of the proinflammatory cytokine IL-17 in forty () formalin-fixed, paraffin-embedded oesophageal archived specimens across a range of endoscopic diagnostic categories, and a highly significant difference was found, where , in IL-17 expression (Kruskall Wallis and Mann-Whitney ) between all the cell types examined. There was also a strong positive correlation (Spearman's rank correlation) between disease progression and IL-17 expression (, , ), IL-17 expression was absent or absent/weak in columnar epithelium, weak to moderate in columnar metaplastic cells, and moderate to strong in dysplastic/neoplastic cells, which demonstrated that the elevation of IL-17 expression occurs in the progression of the disease. Understanding the differential expression of IL-17 between benign and malignant tissue potentially has a significant diagnostic, prognostic, and therapeutic value. Ultimately, this selective biomarker may be employed in routine clinical practice for the screening of oesophageal adenocarcinoma.The authors thankfully acknowledge the University of Chester for their financial support

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients

The early and late-time spectral and temporal evolution of GRB 050716

We report on a comprehensive set of observations of Gamma Ray Burst 050716, detected by the Swift satellite and subsequently followed-up rapidly in X-ray, optical and near infra-red wavebands. The prompt emission is typical of long-duration bursts, with two peaks in a time interval of T90 = 68 seconds (15 - 350 keV). The prompt emission continues at lower flux levels in the X-ray band, where several smaller flares can be seen, on top of a decaying light curve that exhibits an apparent break around 220 seconds post trigger. This temporal break is roughly coincident with a spectral break. The latter can be related to the extrapolated evolution of the break energy in the prompt gamma-ray emission, and is possibly the manifestation of the peak flux break frequency of the internal shock passing through the observing band. A possible 3 sigma change in the X-ray absorption column is also seen during this time. The late-time afterglow behaviour is relatively standard, with an electron distribution power-law index of p = 2 there is no noticable temporal break out to at least 10 days. The broad-band optical/nIR to X-ray spectrum indicates a redshift of z ~> 2 for this burst, with a host-galaxy extinction value of E(B-V) ~ 0.7 that prefers an SMC-like extinction curve.Comment: Accepted to MNRAS. 8 pages, 5 figure

Ensemble prediction for nowcasting with a convection-permitting model—I: description of the system and the impact of radar-derived surface precipitation rates

A key strategy to improve the skill of quantitative predictions of precipitation, as well as hazardous weather such as severe thunderstorms and flash floods is to exploit the use of observations of convective activity (e.g. from radar). In this paper, a convection-permitting ensemble prediction system (EPS) aimed at addressing the problems of forecasting localized weather events with relatively short predictability time scale and based on a 1.5 km grid-length version of the Met Office Unified Model is presented. Particular attention is given to the impact of using predicted observations of radar-derived precipitation intensity in the ensemble transform Kalman filter (ETKF) used within the EPS. Our initial results based on the use of a 24-member ensemble of forecasts for two summer case studies show that the convective-scale EPS produces fairly reliable forecasts of temperature, horizontal winds and relative humidity at 1 h lead time, as evident from the inspection of rank histograms. On the other hand, the rank histograms seem also to show that the EPS generates too much spread for forecasts of (i) surface pressure and (ii) surface precipitation intensity. These may indicate that for (i) the value of surface pressure observation error standard deviation used to generate surface pressure rank histograms is too large and for (ii) may be the result of non-Gaussian precipitation observation errors. However, further investigations are needed to better understand these findings. Finally, the inclusion of predicted observations of precipitation from radar in the 24-member EPS considered in this paper does not seem to improve the 1-h lead time forecast skill

The effect of different types of hepatic injury on the estrogen and androgen receptor activity of liver

Mammalian liver contains receptors for both estrogens and androgens. Hepatic regeneration after partial hepatectomy in male rats is associated with a loss of certain male-specific hepatic characteristics. In this study we investigated the effects of lesser forms of hepatic injury on the levels of estrogen and androgen receptor activity in the liver. Adult male rats were subjected to portacaval shunt, partial portal vein ligation, hepatic artery ligation, or two-thirds partial hepatectomy. Another group of animals was treated with cyclosporine. At the time of sacrifice the livers were removed and used to determine the estrogen and androgen receptor activity in the hepatic cytosol. A significant reduction (p < 0.05) in the hepatic cytosolic androgen receptor activity and a slight increase in the estrogen receptor activity occurred following total portosystemic shunting. Partial ligation of the portal vein, which produces a lesser degree of portosystemic shunting, had no effect on the levels of the estrogen and androgen receptor activity present within hepatic cytosol. Cyclosporine-treated animals had significantly greater (p < 0.01) levels of estrogen receptor activity in the hepatic cytosol compared to vehicle-treated control animals. Levels of estrogen and androgen receptor activity within the hepatic cytosol remained unchanged after ligation of the hepatic artery. The reduction in the cytosolic estrogen and androgen receptor activity in the liver after partial hepatectomy was confirmed. In summary, certain types of hepatic injury are associated with profound changes in the estrogen and androgen receptor content within the liver. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted