Decreased local control following radiation therapy alone in early-stage glottic carcinoma with anterior commissure extension.

PURPOSE: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. PATIENTS AND METHODS: Between 1983-2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106 : 16, and median age 62 years (35-92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60-74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21-79 days). Median follow-up period was 85 months. RESULTS: The 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5-58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (Cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. CONCLUSION: For early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted.

Local Tobacco Control Profiles for England

The Local Tobacco Control Profiles for England provides a snapshot of the extent of tobacco use, tobacco related harm, and measures being taken to reduce this harm at a local level. These profiles have been designed to help local government and health services to assess the effect of tobacco use on their local populations. They will inform commissioning and planning decisions to tackle tobacco use and improve the health of local communities. The tool allows you to compare your local authority against other local authorities in the region and benchmark your local authority against the England average.

PHE-CRCE-010: Estimating Local Mortality Burdens associated with Particulate Air Pollution

The increase in mortality risk associated with long-term exposure to particulate air pollution is one of the most important, and best-characterised, effects of air pollution on health. This report presents estimates of the size of this effect on mortality in local authority areas in the UK, building upon the attributable fractions reported as an indicator in the public health outcomes framework for England. It discusses the concepts and assumptions underlying these calculations and gives information on how such estimates can be made. The estimates are expected to be useful to health and wellbeing boards when assessing local public health priorities, as well as to others working in the field of air quality and public health. The estimates of mortality burden are based on modelled annual average concentrations of fine particulate matter (PM2.5) in each local authority area originating from human activities. Local data on the adult population and adult mortality rates is also used. Central estimates of the fraction of mortality attributable to long-term exposure to current levels of anthropogenic (human-made) particulate air pollution range from around 2.5% in some local authorities in rural areas of Scotland and Northern Ireland and between 3 and 5% in Wales, to over 8% in some London boroughs. Because of uncertainty in the increase in mortality risk associated with ambient PM2.5, the actual burdens associated with these modelled concentrations could range from approximately one-sixth to about double these figures. Thus, current levels of particulate air pollution have a considerable impact on public health. Measures to reduce levels of particulate air pollution, or to reduce exposure of the population to such pollution, are regarded as an important public health initiative.

Health inequalities: A toolkit to support local conversations

The National Conversation on Health Inequalities is a programme by Public Health England to start a conversation with the public about health inequalities and solutions to reduce these inequalities. This toolkit shows you how to start a conversation in your community.

How local excitation-inhibition ratio impacts the whole brain dynamics.

The spontaneous activity of the brain shows different features at different scales. On one hand, neuroimaging studies show that long-range correlations are highly structured in spatiotemporal patterns, known as resting-state networks, on the other hand, neurophysiological reports show that short-range correlations between neighboring neurons are low, despite a large amount of shared presynaptic inputs. Different dynamical mechanisms of local decorrelation have been proposed, among which is feedback inhibition. Here, we investigated the effect of locally regulating the feedback inhibition on the global dynamics of a large-scale brain model, in which the long-range connections are given by diffusion imaging data of human subjects. We used simulations and analytical methods to show that locally constraining the feedback inhibition to compensate for the excess of long-range excitatory connectivity, to preserve the asynchronous state, crucially changes the characteristics of the emergent resting and evoked activity. First, it significantly improves the model's prediction of the empirical human functional connectivity. Second, relaxing this constraint leads to an unrealistic network evoked activity, with systematic coactivation of cortical areas which are components of the default-mode network, whereas regulation of feedback inhibition prevents this. Finally, information theoretic analysis shows that regulation of the local feedback inhibition increases both the entropy and the Fisher information of the network evoked responses. Hence, it enhances the information capacity and the discrimination accuracy of the global network. In conclusion, the local excitation-inhibition ratio impacts the structure of the spontaneous activity and the information transmission at the large-scale brain level.

A Cannabis Reader: Global Issues and Local Experiences

The EMCDDA’s cannabis monograph addresses one basic question. How can I find quality information on cannabis, amid all the bias and opinion? The monograph is divided into two volumes. The first volume centres on political, legislative, commercial and social developments relating to cannabis. Its core audience thus comprises policymakers, sociologists, historians, journalists and those involved in enforcement. The second volume is targeted at drugs professionals working in the fields of treatment, prevention and healthcare.This resource was contributed by The National Documentation Centre on Drug Use.

A Report from a Local Initiative Concerning Alcohol / Drug Use Among Teenagers 1998-1999

This study was carried out by participants in a North Tipperary Community Services drug/alcohol awareness course. Its objectives were to: assess the level of drug and alcohol awareness among second-level students under the age of 18 years; to find out the extent of under-age drinking;to find out the extent of the use of illegal substances as well as stimulants such as glue and solvents in this age group; and to use this information to develop educational programmes for parents and students. Date was obtained through a survey of 1500 secondary school students in the North Tippeary area. The survey found that, although ilict drug use was very low, abuse of alcohol was quite common.This resource was contributed by The National Documentation Centre on Drug Use.

Reverse transcription quantitative real-time polymerase chain reaction reference genes in the spared nerve injury model of neuropathic pain : validation and literature search

La douleur neuropathique est définie comme une douleur causée par une lésion du système nerveux somato-sensoriel. Elle se caractérise par des douleurs exagérées, spontanées, ou déclenchées par des stimuli normalement non douloureux (allodynie) ou douloureux (hyperalgésie). Bien qu'elle concerne 7% de la population, ses mécanismes biologiques ne sont pas encore élucidés. L'étude des variations d'expressions géniques dans les tissus-clés des voies sensorielles (notamment le ganglion spinal et la corne dorsale de la moelle épinière) à différents moments après une lésion nerveuse périphérique permettrait de mettre en évidence de nouvelles cibles thérapeutiques. Elles se détectent de manière sensible par reverse transcription quantitative real-time polymerase chain reaction (RT- qPCR). Pour garantir des résultats fiables, des guidelines ont récemment recommandé la validation des gènes de référence utilisés pour la normalisation des données ("Minimum information for publication of quantitative real-time PCR experiments", Bustin et al 2009). Après recherche dans la littérature des gènes de référence fréquemment utilisés dans notre modèle de douleur neuropathique périphérique SNI (spared nerve injury) et dans le tissu nerveux en général, nous avons établi une liste de potentiels bons candidats: Actin beta (Actb), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal proteins 18S (18S), L13a (RPL13a) et L29 (RPL29), hypoxanthine phosphoribosyltransferase 1 (HPRT1) et hydroxymethyl-bilane synthase (HMBS). Nous avons évalué la stabilité d'expression de ces gènes dans le ganglion spinal et dans la corne dorsale à différents moments après la lésion nerveuse (SNI) en calculant des coefficients de variation et utilisant l'algorithme geNorm qui compare les niveaux d'expression entre les différents candidats et détermine la paire de gènes restante la plus stable. Il a aussi été possible de classer les gènes selon leur stabilité et d'identifier le nombre de gènes nécessaires pour une normalisation la plus précise. Les gènes les plus cités comme référence dans le modèle SNI ont été GAPDH, HMBS, Actb, HPRT1 et 18S. Seuls HPRT1 and 18S ont été précédemment validés dans des arrays de RT-qPCR. Dans notre étude, tous les gènes testés dans le ganglion spinal et dans la corne dorsale satisfont au critère de stabilité exprimé par une M-value inférieure à 1. Par contre avec un coefficient de variation (CV) supérieur à 50% dans le ganglion spinal, 18S ne peut être retenu. La paire de gènes la plus stable dans le ganglion spinal est HPRT1 et Actb et dans la corne dorsale il s'agit de RPL29 et RPL13a. L'utilisation de 2 gènes de référence stables suffit pour une normalisation fiable. Nous avons donc classé et validé Actb, RPL29, RPL13a, HMBS, GAPDH, HPRT1 et 18S comme gènes de référence utilisables dans la corne dorsale pour le modèle SNI chez le rat. Dans le ganglion spinal 18S n'a pas rempli nos critères. Nous avons aussi déterminé que la combinaison de deux gènes de référence stables suffit pour une normalisation précise. Les variations d'expression génique de potentiels gènes d'intérêts dans des conditions expérimentales identiques (SNI, tissu et timepoints post SNI) vont pouvoir se mesurer sur la base d'une normalisation fiable. Non seulement il sera possible d'identifier des régulations potentiellement importantes dans la genèse de la douleur neuropathique mais aussi d'observer les différents phénotypes évoluant au cours du temps après lésion nerveuse.

Local and regional drugs task forces: handbook.

This handbook has been developed within the context of the institutional structures recommended under the National Drugs Strategy 2009-2016 and within the overall framework of the National Social Inclusion Plan 2007-2016. It sets out the role of the Drugs Task Forces within the national and local framework required to address the existing and emerging problems associated with drug use for individuals, families and communities in the context of the long term development of the work of the Drugs Task Forces.This resource was contributed by The National Documentation Centre on Drug Use.

Development of allocentric spatial memory abilities in children from 18 months to 5 years of age.

Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a fundamental component of episodic memory, in two versions of a real-world memory task requiring 18 month- to 5-year-old children to search for rewards hidden beneath cups distributed in an open-field arena. Whereas children 25-42-months-old were not capable of discriminating three reward locations among 18 possible locations in absence of local cues marking these locations, children older than 43 months found the reward locations reliably. These results support previous findings suggesting that allocentric spatial memory, if present, is only rudimentary in children under 3.5 years of age. However, when tested with only one reward location among four possible locations, children 25-39-months-old found the reward reliably in absence of local cues, whereas 18-23-month-olds did not. Our findings thus show that the ability to form a basic allocentric representation of the environment is present by 2 years of age, and its emergence coincides temporally with the offset of infantile amnesia. However, the ability of children to distinguish and remember closely related spatial locations improves from 2 to 3.5 years of age, a developmental period marked by persistent deficits in long-term episodic memory known as childhood amnesia. These findings support the hypothesis that the differential maturation of distinct hippocampal circuits contributes to the emergence of specific memory processes during early childhood.

Estado del Arte de los procesos de la Administración Local para la adquisición de TIC. El caso de Guadalajara

L'objecte d'aquest treball és el d'analitzar les pràctiques i estratègies que es segueixen quant a l'adquisició de les Tecnologies de la Informació i la Comunicació (TIC) en l'àmbit de l'Administració Local de la província de Guadalajara i fer una valoració-punts forts i febles-de les mateixes.

Using Local Evidence to Motivate New Interventions to Reduce Childhood Obesity

Presentation by Margaret Eames at the Regional meeting on measuring body mass index (BMI) in the child population.

Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance.

Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression.

Health Equity Audit Made Simple: A briefing for Primary Care Trusts and Local Strategic Partnerships

A working/ consultation document outlining the key drivers and steps for undertaking health equity audit as required in the Performance and Planning Framework (PPF) 2003-2006