Stereotactic body radiation therapy with helical tomotherapy for medical inoperable early-stage primary and second-primary non-small cell lung neoplasm : one-year outcome and toxicity analysis

Le cancer du poumon est la première cause de mortalité associée au cancer dans le monde. Le traitement curatif des tumeurs pulmonaires non-à-petites-cellules (NSCLC) diagnostiquées à un stade précoce se base sur une approche chirurgicale. Cependant, étant donné les comorbidités liées à la consommation de tabac, dont la bronchopneumopathie chronique occupe la première place, l'éligibilité chirurgicale pour ce type de cancer se trouve fréquemment limitée. Dans ce contexte, l'emploi de la radiothérapie stéréotaxique (SBRT) est une alternative valable chez les patients atteints d'un NSCLC primaire de stade précoce, et qui sont considérés inopérables à cause de leurs comorbidités. Depuis peu seulemement, le spectre de la SBRT a été élargi aux patients atteints d'un deuxième NSCLC primaire (SPLC), faisant suite à un premier NSCLC, traité avec un but curatif. Ils concernent donc des patients ayant déjà subits une intervention chirurgicale au préalable et qui présentent une réserve fonctionnelle pulmonaire extrêmement réduite. Le succès croissant de la SBRT résulte soit d'une efficacité thérapeutique comparables à la chirurgie, soit de sa toxicité qui semble limitée. À notre connaissance, seulement une étude a reporté des issues cliniques de patients affectés par des NSCLC primaires traités par SBRT. Cette dernière a utilisé la tomothérapie comme système d'irradiation (T-SBRT), sur un faible échantillon de patients (n = 27). Concernant l'irradiation des patients présentant des SPLC, la littérature disponible est pauvre et aucune publication a décrit l'utilisation de la T-SBRT. Ces éléments innovants ont donc motivé la rédaction d'un travail de thèse concernant les premières données cliniques de l'expérience faite au CHUV. Du point de vue des effets secondaires, si la pneumonie actinique précoce et tardive survenant au niveau du champ d'irradiation est désormais une complication iatrogène bien connue de la SBRT, une seule étude s'est intéressée à ce sujet dans le cadre de la T-SBRT. De plus, une entité bénigne et transitoire de pneumonie ( ?) a été reconnue depuis peu : la pneumonie organisée radio-induite (OP). Celle-ci semble se chevaucher comme un autre effet iatrogène à l'extérieur du champ d'irradiation. Originellement, cette dernière avait été rapportée dans les suites de la radiothérapie pour les cancer du sein. Elle a été décrite comme étant initialement limitée au champ d'irradiation et successivement pouvant s'étendre dynamiquement en dehors de celui-ci. Nous avons donc supposé que des infiltrats de OP peuvent être présents chez des patients asymptomatiques, et que ce dynamisme pourrait être identifié déjà au sein du champ d'irradiation. Notre étude a démontré que le traitement par T-SBRT garde des issues cliniques très encourageantes, aussi bien pour les tumeurs primaires que pour les SPLC. Entre autre, ce traitement semble avoir une toxicité limitée, et l'existence vraisemblable de la OP, déjà au sein du champ d'irradiation, peut aider les radiologues à différencier les infiltrats radio-induits d'une une récidive tumorale.

Impact of body tilt on the central aortic pressure pulse

Le but de cette thèse a été d'investiguer la relation entre, d'une part le temps de propagation de l'onde de pouls artérielle du coeur vers les membres inférieurs, et d'autre part le temps séparant, au niveau de l'aorte ascendante, la génération de l'onde antérograde du retour des ondes réfléchies. Le principe de la méthode employée a été de mesurer ces deux temps par deux méthodes indépendantes, ce en les faisant varier par changement rapide de la position du corps, chez sujets humains volontaires. Le facteur gravitationnel a en effet une influence majeure sur la pression transmurale des artères, dont dépend largement la vitesse de propagation des ondes de pouls, tant dans le sens antérograde que rétrograde. Vingt sujets jeunes, en bonne santé, dontIO hommes et 10 femmes, ont été examinés sur une table de tilt, dans deux positions différentes : tête vers le bas (angle de tilt : - 10°) et tête vers le haut (+45°).Dans chaque position, le temps de propagation carotido- femorale (Tcf, succédané du temps aorto-fémoral) et carotido-tibial (Tct, succédané du temps aorto-tibial) a été mesuré avec l'appareil Complior. De même, dans chaque position la pression aortique centrale a été enregistrée par tonométrie radiale en utilisant l'appareil SphygmoCor qui applique une fonction de transfert généralisé pour reconstruire la forme de l'onde de pouls aortique. L'analyse de celle-ci permet ensuite de calculer les temps d'aller-retour des ondes réfléchies atteignant l'aorte pendant la systole (début de l'onde réfléchie, sT1 r) et pendant la diastole (temps de transit moyen de l'onde diastolique réfléchie dMTT). Le changement de position de tête vers le haut à tête vers le bas, a provoqué une augmentation importante du temps de propagation Tct (chez le femmes de 130±10 à 185±18msec, P<0,001 et chez les hommes de 136±9 à 204±18msec P<0.001) ainsi que du temps moyen de transition de l'onde diastolique réfléchie dMTT (chez les femmes de 364±35 à 499±33msec P<0,001 et chez les hommes de 406±22 à 553±21msec, P<0,001). Un modèle de régression mixte montre qu'entre les deux positions, les variations de dMTT sont environ le double de celles de Tct (coefficient de régression 2.1; 95% intervalle de confiance 1.9-2,3, P<0,001). Ces résultats suggèrent que les ondes diastoliques observées dans l'onde de pouls aortique central reconstruites par tonométrie radiale, correspondent, du moins en partie, aux ondes réfléchies générées au niveau des membres inférieurs.

PPARα is Required for PPARδ action in regulation of body weight and hepatic steatosis in mice.

NlmCategory="UNASSIGNED">Peroxisome proliferator activated receptors alpha (PPARα) and delta (PPARδ) belong to the nuclear receptor superfamily. PPARα is a target of well established lipid-lowering drugs. PPARδ (also known as PPARβ/δ) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδ or deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARα also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARα endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδ in wild type mice. Our results show that both PPARδ and PPARα receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARα working downstream of PPARδ.

Entry Mode Choice in a Hard Service Company

Pro gradun tavoitteena oli löytää tärkeimmät seikat, jotka vaikuttavat kansainvälisen operaatiomuodon valintaan. Tutkimuskohteena olivat suomalaiset pienet tai keskisuuret tuotteistetut ohjelmistopalveluyritykset. Tutkimusmenetelmänä käytettiin kvalitatiivista tutkimusta sekä case-tutkimusta. Tutkimus koostui kahdesta osasta: teoreettinen osa sekä empiirinen kahden case yrityksen analyysi. Operaatiomuodon valintaan vaikuttavat tekijät jaettiin sisäisiin (yritys, tuote ja päätöksentekijä), ulkoisiin (ala ja maa) ja operaatiomuodon (kontrolli, riski, resurssit, joustavuus, tuotot ja kulut) tekijöihin. Teoreettisesti operaatiomuodon valinta on erittäin monimutkainen päätös ja sitä on tutkittu monelta kannalta. Tämä empiirinen tutkimus osoittaa, että yrityksen resurssit olivat tärkein vaikuttava tekijä molemmissa yrityksissä.

Validity of silhouette showcards as a measure of body size and obesity in a population in the African region : a practical research tool for general-purpose surveys.

BACKGROUND: The purpose of this study is to validate the Pulvers silhouette showcard as a measure of weight status in a population in the African region. This tool is particularly beneficial when scarce resources do not allow for direct anthropometric measurements due to limited survey time or lack of measurement technology in face-to-face general-purpose surveys or in mailed, online, or mobile device-based surveys. METHODS: A cross-sectional study was conducted in the Republic of Seychelles with a sample of 1240 adults. We compared self-reported body sizes measured by Pulvers' silhouette showcards to four measurements of body size and adiposity: body mass index (BMI), body fat percent measured, waist circumference, and waist to height ratio. The accuracy of silhouettes as an obesity indicator was examined using sex-specific receiver operator curve (ROC) analysis and the reliability of this tool to detect socioeconomic gradients in obesity was compared to BMI-based measurements. RESULTS: Our study supports silhouette body size showcards as a valid and reliable survey tool to measure self-reported body size and adiposity in an African population. The mean correlation coefficients of self-reported silhouettes with measured BMI were 0.80 in men and 0.81 in women (P < 0.001). The silhouette showcards also showed high accuracy for detecting obesity as per a BMI ≥ 30 (Area under curve, AUC: 0.91/0.89, SE: 0.01), which was comparable to other measured adiposity indicators: fat percent (AUC: 0.94/0.94, SE: 0.01), waist circumference (AUC: 0.95/0.94, SE: 0.01), and waist to height ratio (AUC: 0.95/0.94, SE: 0.01) amongst men and women, respectively. The use of silhouettes in detecting obesity differences among different socioeconomic groups resulted in similar magnitude, direction, and significance of association between obesity and socioeconomic status as when using measured BMI. CONCLUSIONS: This study highlights the validity and reliability of silhouettes as a survey tool for measuring obesity in a population in the African region. The ease of use and cost-effectiveness of this tool makes it an attractive alternative to measured BMI in the design of non-face-to-face online- or mobile device-based surveys as well as in-person general-purpose surveys of obesity in social sciences, where limited resources do not allow for direct anthropometric measurements.

Body Image in Eating Disorders: The Influence of Exposure to Virtual-Reality Environments.

The aim of this article was to study the effect of virtual-reality exposure to situations that are emotionally significant for patients with eating disorders (ED) on the stability of body-image distortion and body-image dissatisfaction. A total of 85 ED patients and 108 non-ED students were randomly exposed to four experimental virtual environments: a kitchen with low-calorie food, a kitchen with high-calorie food, a restaurant with low-calorie food, and a restaurant with high-calorie food. In the interval between the presentation of each situation, body-image distortion and body-image dissatisfaction were assessed. Several 2 x 2 x 2 repeated measures analyses of variance (high-calorie vs. low-calorie food x presence vs. absence of people x ED group vs. control group) showed that ED participants had significantly higher levels of body-image distortion and body dissatisfaction after eating high-calorie food than after eating low-calorie food, while control participants reported a similar body image in all situations. The results suggest that body-image distortion and body-image dissatisfaction show both trait and state features. On the one hand, ED patients show a general predisposition to overestimate their body size and to feel more dissatisfied with their body image than controls. On the other hand, these body-image disturbances fluctuate when participants are exposed to virtual situations that are emotionally relevant for them.

Marketing in support of sales in industrial high technology company

The aim of this study is to find out how Metso Paper’s marketing could better support sales and how sales people are executing marketing during the sales processes. This study is done from sales people’s point of view. The study is limited to cover only company’s internal environment. This research was executed through literature review and qualitative theme interviews, where 20 of Metso Paper’s sales people were interviewed. The interviewees were asked to tell their opinions about marketing’s support, marketing materials, information and the relationship between sales and marketing. The results of this study show that the relationship between marketing and sales is rather good, but there is still a great need for improvements. It is hoped that marketing would take more part in the selling processes. In addition, more information about the launches and schedules were also hoped for. Marketing is told to be quite Finland centric and sales people are wishing for more adopted marketing materials and occasions. It came up during the interviews, that sales people are not so willing to give regular feedback to marketing and quite often they think that marketing’s role in Metso Paper is not important at all.

Persistent spatial clusters of high body mass index in a Swiss urban population as revealed by the 5-year GeoCoLaus longitudinal study.

OBJECTIVE: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether and how BMI clusters evolve over time in a population is currently unknown. We aimed to determine the spatial dependence of BMI and its 5-year evolution in a Swiss general adult urban population, taking into account the neighbourhood-level and individual-level characteristics. DESIGN: Cohort study. SETTING: Swiss general urban population. PARTICIPANTS: 6481 georeferenced individuals from the CoLaus cohort at baseline (age range 35-74 years, period=2003-2006) and 4460 at follow-up (period=2009-2012). OUTCOME MEASURES: Body weight and height were measured by trained healthcare professionals with participants standing without shoes in light indoor clothing. BMI was calculated as weight (kg) divided by height squared (m(2)). Participants were geocoded using their postal address (geographic coordinates of the place of residence). Getis-Ord Gi statistic was used to measure the spatial dependence of BMI values at baseline and its evolution at follow-up. RESULTS: BMI was not randomly distributed across the city. At baseline and at follow-up, significant clusters of high versus low BMIs were identified and remained stable during the two periods. These clusters were meaningfully attenuated after adjustment for neighbourhood-level income but not individual-level characteristics. Similar results were observed among participants who showed a significant weight gain. CONCLUSIONS: To the best of our knowledge, this is the first study to report longitudinal changes in BMI clusters in adults from a general population. Spatial clusters of high BMI persisted over a 5-year period and were mainly influenced by neighbourhood-level income.

Risques et bénéfices d'une approche interventionnelle face aux corps étrangers digestifs [Digestive foreign body management].

Foreign body (FB) ingestion is a frequent reason for gastroenterology consulting. Eighty percent of these ingestions are accidental and observed among paediatric subjects. However, intentional repetitive ingestions are also observed, especially amongst prisoners or psychiatric patients. Most FBs pass throughout the digestive tract without any complication and without any need for surgical or endoscopic intervention. Nevertheless, around 10-20% of cases require an endoscopy examination and 1% will lead to a surgical intervention. Management approaches should favor inter-disciplinarity, balance benefits and risks of FB removal based on its location, and integrate psychiatric comorbidities into the decision process.

Distinct contributions of Brodmann areas 1 and 2 to body ownership.

Although body ownership-i.e. the feeling that our bodies belong to us-modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person's finger by asking participants to hold their palm against another person's palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person's finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousness.

Overspeed HIIT in Lower-Body Positive Pressure Treadmill Improves Running Performance.

PURPOSE: Optimal high-intensity interval training (HIIT) regimens for running performance are unknown, although most protocols result in some benefit to key performance factors (running economy (RE), anaerobic threshold (AT), or maximal oxygen uptake (V˙O2max)). Lower-body positive pressure (LBPP) treadmills offer the unique possibility to partially unload runners and reach supramaximal speeds. We studied the use of LBPP to test an overspeed HIIT protocol in trained runners. METHODS: Eleven trained runners (35 ± 8 yr, V˙O2max, 55.7 ± 6.4 mL·kg·min) were randomized to an LBPP (n = 6) or a regular treadmill (CON, n = 5), eight sessions over 4 wk of HIIT program. Four to five intervals were run at 100% of velocity at V˙O2max (vV˙O2max) during 60% of time to exhaustion at vV˙O2max (Tlim) with a 1:1 work:recovery ratio. Performance outcomes were 2-mile track time trial, V˙O2max, vV˙O2max, vAT, Tlim, and RE. LBPP sessions were carried out at 90% body weight. RESULTS: Group-time effects were present for vV˙O2max (CON, 17.5 vs. 18.3, P = 0.03; LBPP, 19.7 vs. 22.3 km·h; P < 0.001) and Tlim (CON, 307.0 vs. 404.4 s, P = 0.28; LBPP, 444.5 vs. 855.5, P < 0.001). Simple main effects for time were present for field performance (CON, -18; LBPP, -25 s; P = 0.002), V˙O2max (CON, 57.6 vs. 59.6; LBPP, 54.1 vs. 55.1 mL·kg·min; P = 0.04) and submaximal HR (157.7 vs. 154.3 and 151.4 vs. 148.5 bpm; P = 0.002). RE was unchanged. CONCLUSIONS: A 4-wk HIIT protocol at 100% vV˙O2max improves field performance, vV˙O2max, V˙O2max and submaximal HR in trained runners. Improvements are similar if intervals are run on a regular treadmill or at higher speeds on a LPBB treadmill with 10% body weight reduction. LBPP could provide an alternative for taxing HIIT sessions.

The Increasing Spectrum of Indications of Whole-Body MRI Beyond Oncology: Imaging Answers to Clinical Needs.

Whole-body coverage using MRI was developed almost 2 decades ago. The first applications focused on the investigation of the skeleton to detect neoplastic disease, mainly metastases from solid cancers, and involvement by multiple myeloma and lymphoma. But the extensive coverage of the whole musculoskeletal system, combined with the exquisite sensitivity of MRI to tissue alteration in relation to different pathologic conditions, mainly inflammation, has led to the identification of a growing number of indications outside oncology. Seronegative rheumatisms, systemic sclerosis, inflammatory diseases involving muscles or fascias, and multifocal osseous, vascular, or neurologic diseases represent currently validated or emerging indications of whole-body MRI (WB-MRI). We first illustrate the most valuable indications of WB-MRI in seronegative rheumatisms that include providing significant diagnostic information in patients with negative or ambiguous MRI of the sacroiliac joints and the lumbar spine, assessing disease activity in advanced (ankylosed) central disease, and evaluating the peripherally dominant forms of spondyloarthropathy. Then we review the increasing indications of WB-MRI in other rheumatologic and nonneoplastic disorders, underline the clinical needs, and illustrate the role of WB-MRI in the positive diagnosis and evaluation of disease burden, therapeutic decisions, and treatment monitoring.

Body donations today and tomorrow: What is best practice and why?

There is considerable agreement that the use of human bodies for teaching and research remains important, yet not all universities use dissection to teach human gross anatomy. The concept of body donation has evolved over centuries and there are still considerable discrepancies among countries regarding the means by which human bodies are acquired and used for education and research. Many countries have well-established donation programs and use body dissection to teach most if not all human gross anatomy. In contrast, there are countries without donation programs that use unclaimed bodies or perhaps a few donated bodies instead. In several countries, use of cadavers for dissection is unthinkable for cultural or religious reasons. Against this background, successful donation programs are highlighted in the present review, emphasizing those aspects of the programs that make them successful. Looking to the future, we consider what best practice could look like and how the use of unclaimed bodies for anatomy teaching could be replaced. From an ethical point of view, countries that depend upon unclaimed bodies of dubious provenance are encouraged to use these reports and adopt strategies for developing successful donation programs. In many countries, the act of body donation has been guided by laws and ethical frameworks and has evolved alongside the needs for medical knowledge and for improved teaching of human anatomy. There will also be a future need for human bodies to ensure optimal pre- and post-graduate training and for use in biomedical research. Good body donation practice should be adopted wherever possible, moving away from the use of unclaimed bodies of dubious provenance and adopting strategies to favor the establishment of successful donation programs. Clin. Anat. 29:11-18, 2016. © 2015 Wiley Periodicals, Inc.

Impact of body tilt on the central aortic pressure pulse.

The present work was undertaken to investigate, in young healthy volunteers, the relationships between the forward propagation times of arterial pressure waves and the timing of reflected waves observable on the aortic pulse, in the course of rapid changes in body position. 20 young healthy subjects, 10 men, and 10 women, were examined on a tilt table at two different tilt angles, -10° (Head-down) and + 45° (Head-up). In each position, carotid-femoral (Tcf) and carotid-tibial forward propagation times (Tct) were measured with the Complior device. In each position also, the central aortic pressure pulse was recorded with radial tonometry, using the SphygmoCor device and a generalized transfer function, so as to evaluate the timing of reflected waves reaching the aorta in systole (onset of systolic reflected wave, sT1r) and diastole (mean transit time of diastolic reflected wave, dMTT). The position shift from Head-up to Head-down caused a massive increase in both Tct (women from 130 ± 10 to 185 ± 18 msec P < 0.001, men from 136 ± 9 to 204 ± 18 msec P < 0.001) and dMTT (women from 364 ± 35 to 499 ± 33 msec P < 0.001, men from 406 ± 22 to 553 ± 21 msec P < 0.001). Mixed model regression showed that the changes in Tct and dMTT observed between Head-up and Head-down were tightly coupled (regression coefficient 2.1, 95% confidence interval 1.9-2.3, P < 0.001). These results strongly suggest that the diastolic waves observed on central aortic pulses reconstructed from radial tonometric correspond at least in part to reflections generated in the lower limbs.