Influence of tumour size on hypoxic fraction and therapeutic sensitivity of Lewis lung tumour.

Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co gamma-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours

In silico framework to inform the design of repair constructs for peripheral nerve injury repair

Peripheral nerve injuries affect millions of people per year and cause loss of sensation and muscle control alongside chronic pain. The most severe injuries are treated through a nerve autograft; however, donor site morbidity and poor outcomes mean alternatives are required. One option is to engineer nerve replacement tissues to provide a supportive microenvironment to encourage nerve regeneration as an alternative to nerve grafts. Currently, progress is hampered due to a lack of consensus on how to arrange materials and cells in space to maximize rate of regeneration. This is compounded by a reliance on experimental testing, which precludes extensive investigations of multiple parameters due to time and cost limitations. Here, a computational framework is proposed to simulate the growth of repairing neurites, captured using a random walk approach and parameterized against literature data. The framework is applied to a specific scenario where the engineered tissue comprises a collagen hydrogel with embedded biomaterial fibres. The size and number of fibres are optimized to maximize neurite regrowth, and the robustness of model predictions is tested through sensitivity analyses. The approach provides an in silico tool to inform the design of engineered replacement tissues, with the opportunity for further development to multi-cue environments

Gender-specific associations of short sleep duration with prevalent and incident hypertension : the Whitehall II Study

Sleep deprivation (5 hour per night) was associated with a higher risk of hypertension in middle-aged American adults but not among older individuals. However, the outcome was based on self-reported diagnosis of incident hypertension, and no gender-specific analyses were included. We examined cross-sectional and prospective associations of sleep duration with prevalent and incident hypertension in a cohort of 10 308 British civil servants aged 35 to 55 years at baseline (phase 1: 1985-1988). Data were gathered from phase 5 (1997-1999) and phase 7 (2003-2004). Sleep duration and other covariates were assessed at phase 5. At both examinations, hypertension was defined as blood pressure 140/90 mm Hg or regular use of antihypertensive medications. In cross-sectional analyses at phase 5 (n5766), short duration of sleep (5 hour per night) was associated with higher risk of hypertension compared with the group sleeping 7 hours, among women (odds ratio: 2.01; 95% CI: 1.13 to 3.58), independent of confounders, with an inverse linear trend across decreasing hours of sleep (P0.003). No association was detected in men. In prospective analyses (mean follow-up: 5 years), the cumulative incidence of hypertension was 20.0% (n740) among 3691 normotensive individuals at phase 5. In women, short duration of sleep was associated with a higher risk of hypertension in a reduced model (age and employment) (6 hours per night: odds ratio: 1.56 [95% CI: 1.07 to 2.27]; 5 hour per night: odds ratio: 1.94 [95% CI: 1.08 to 3.50] versus 7 hours). The associations were attenuated after accounting for cardiovascular risk factors and psychiatric comorbidities (odds ratio: 1.42 [95% CI: 0.94 to 2.16]; odds ratio: 1.31 [95% CI: 0.65 to 2.63], respectively). Sleep deprivation may produce detrimental cardiovascular effects among women. (Hypertension. 2007;50:694-701.) Key Words: sleep duration blood pressure hypertension gender differences confounders comorbiditie

Chemoanatomical organization of the noradrenergic input from locus coeruleus to the olfactory bulb of the adult rat.

The locus coeruleus contains noradrenergic neurons which project widely throughout the CNS. A major target of locus coeruleus projections in the rat is the olfactory bulb (Shipley et al.: Brain Res. 329:294–299, '85) but the organization of the projections within the bulb has not been systematically examined. In this study, the laminar distribution and densities of locus coeruleus-noradrenergic fibers in the main and accessory olfactory bulbs were determined with anterograde tracing and immunocytochemical techniques. Following iontophoretic injections of 1% wheat germ agglutinin-horseradish peroxidase into the locus coeruleus, the densest anterograde label in the accessory olfactory bulb was observed in the external plexiform layer, granule cell layer, and especially in the internal part of the mitral cell layer. Virtually no label was observed in the glomerular layer. In the main olfactory bulb, labelled axons were observed in the granule cell layer, in the internal and external plexiform layers, occasionally in the mitral cell layer, and least often in the glomerular layer. Noradrenergic fibers in the olfactory bulb were identified by using immunocytochemistry with an antibody to dopamine-β-hydroxylase. Laminar patterns and densities of noradrenergic innervation were determined with quantitative image analysis. In the accessory olfactory bulb, the densest innervation was in the innermost portion of the mitral cell layer followed by the granule cell layer, the superficial part of the mitral cell layer, and the external plexiform layer. The density of fibers in the glomerular layer was least. The laminar pattern of noradrenergic fiber distribution in the main olfactory bulb was similar to that in accessory olfactory bulb. The present studies demonstrate that locus coeruleus-noradrenergic fibers terminate preferentially in the internal plexiform, granule cell, and external plexiform layers. This suggests that the major influence of the locus coeruleus input to both the main and accessory the olfactory bulbs is on the predominant neuronal element in those layers, the granule cells. Additional studies are needed to resolve how this input influences specific olfactory bulb circuits

Reaction time and incident cancer: 25 years of follow-up of study members in the UK Health and Lifestyle Survey

<b>Objectives</b><p></p> To investigate the association of reaction time with cancer incidence.<p></p> <b>Methods</b><p></p> 6900 individuals aged 18 to 94 years who participated in the UK Health and Lifestyle Survey in 1984/1985 and were followed for a cancer registration for 25 years.<p></p> <b>Results</b><p></p> Disease surveillance gave rise to 1015 cancer events from all sites. In general, there was essentially no clear pattern of association for either simple or choice reaction time with cancer of all sites combined, nor specific malignancies. However, selected associations were found for lung cancer, colorectal cancer and skin cancer.<p></p> <b>Conclusions</b><p></p> In the present study, reaction time and its components were not generally related to cancer risk