Assessment of distribution and evolution of mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance.

BACKGROUND: We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. METHODS: Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. RESULTS: Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). CONCLUSIONS: Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients

RESUME : Objectif: Le glioblastome multiforme (GBM) est la tumeur cérébrale maligne la plus agressive qui conduit au décès de la majorité des patients moins d'une année après le diagnostic. La plupart des agents chimiothérapeutiques actuellement disponibles ne traversent pas la barrière hémato¬encéphalique et ne peuvent par conséquent pas être utilisés pour ce type de tumeur. Le Temozolomide (TMZ) est un nouvel agent alkylant récemment développé pour le traitement des gliomes malins. A ce jour, très peu d'informations sont disponibles sur la pénétration intra-cérébrale de cet agent. Au cours d'une étude pilote de phase II menée auprès de 64 patients atteints de GBM, l'administration précoce de TMZ combinée à une radiothérapie standard (RT) afin d'intervenir au plus tôt dans l'évolution de la maladie, a permis de prolonger la survie de ces patients, résultat qui pu être confirmé par la suite lors de l'étude randomisée de phase III. L'objectif de cette étude a été de déterminer les paramètres pharmacocinétique du TMZ dans le plasma et le liquide céphalo-rachidien (LCR), d'évaluer l'influence de certains facteurs individuels (âge, sexe, surface corporelle, fonction rénale/hépatique, co-médications, RT concomitante) sur ces différents paramètres, et enfin d'explorer la relation existant entre l'exposition au TMZ et certains marqueurs cliniques d'efficacité et de toxicité. Matériel et Méthode: Les concentrations de TMZ ont été mesurées par chromatographie liquide à haute performance (HPLC) dans le plasma et le LCR de 35 patients atteints de GBM nouvellement diagnostiqués (étude pilote) ou de gliomes malins en récidive (étude récidive). L'analyse pharmacocinétique de population a été réalisée à l'aide du programme NONMEM. L'exposition systémique et cérébrale, définie par les AUC (Area Under the time-concentration Curve) dans le plasma et le LCR, a été estimée pour chaque patient et corrélée à la toxicité, la survie ainsi que la survie sans progression tumorale. Résultats: Un modèle à 1 compartiment avec une cinétique d'absorption et de transfert Kplasma -> LCR de ordre a été retenu afin de décrire le profil pharmacocinétique du TMZ. Les valeurs moyennes de population ont été de 10 L/h pour la clairance, de 30.3 L pour le volume de distribution, de 2.1 h pour la 1/2 vie d'élimination, de 5.78 hE-1 pour la constante d'absorption, de 7.2 10E4 hE-1 pour Kplasma->LCR et de 0.76 hE-1 pour KLCR plasma. La surface corporelle a montré une influence significative sur la clairance et le volume de distribution, alors que le sexe influence la clairance uniquement. L'AUC mesurée dans le LCR représente ~20% de celle du plasma et une augmentation de 15% de Kplasma->LCR a été observée lors du traitement concomitant de radiochimiothérapie. Conclusions: Cette étude est la première analyse pharmacocinétique effectuée chez l'homme permettant de quantifier la pénétration intra-cérébrale du TMZ. Le rapport AUC LCR/AUC Plasma a été de 20%. Le degré d'exposition systémique et cérébral au TMZ ne semble pas être un meilleur facteur prédictif de la survie ou de la tolérance au produit que ne l'est la dose cumulée seule. ABSTRACT Purpose: Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of ma¬lignant brain tumors. The purpose was to assess TNIZ phar¬macokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covari¬ates and to explore relationships between systemic or cere¬bral drug exposure and clinical outcomes. Experimental Design: TMZ levels were measured by high-performance liquid chromatography in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacoki¬netic analysis was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area un¬der the concentration-time curve (AUC) in plasma and CSF, was estimated for each patient and correlated with toxicity, survival, and progression-free survival. Results: A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 liter/h; volume of distribution (VD), 30.3 liters; absorption constant rate, 5.8 hE-1; elimination half-time, 2.1 h; transfer rate from plasma to CSF (Kplasma->CSF), 7.2 x 10E-4hE-1 and the backwards rate, 0.76hE-1. Body surface area signifi¬cantly influenced both clearance and VD, and clearance was sex dependent. The AU CSF corresponded to 20% of the AUCplasma. A trend toward an increased K plasma->CSF of 15% was observed in case of concomitant radiochemo-therapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect. Conclusions: This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUC CSF/ AUC plasma ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety.

Small bowel bacterial overgrowth is found in 71% of IBS patients and associated symptoms respond well to Rifaximin in a phase IV trial

Background a nd A ims: The prevalence of small intestinal bowel bacterial o vergrowth (SIBO) i n patients w ith irritable bowel syndrome (IBS) ranges from 43% to 78% as determined by t he lactulose hydrogen breath (LHBT) t est. Although rifaximine, a non-absorbable antibiotic, h as b een able to decrease I BS s ymptoms i n placebo-controlled r andomized trials, these results were not repeated in phase IV studies. We aimed to assess the prevalence of SIBO in an IBS cohort and to evaluate the response to rifaximin. Methods: I BS p atients f ulfilled Rome III criteria, had an absence of alarm symptoms, n ormal f ecal c alproectin, and normal e ndoscopic workup. They underwent lactulose hydrogen breath t esting (LHBT) for SIBO diagnosis. P atients with SIBO were t reated w ith rifaximine tablets f or 14 d ays. Symptoms were a ssessed by q uestionnaires before rifaximin treatment and at week 6. Results: Hundred-fifty IBS patients were enrolled (76% female, mean age 44 ± 16 years), of whom 106 (71%) were diagnosed with SIBO and consequently treated with rifaximine. Rifaximine treatment s ignificantly reduced the following symptoms as assessed by t he s ymptom q uestionnaire: bloating (5.5 ± 2.6 before vs. 3 .6 ± 2.7 after treatment, p <0.001), flatulence (5 ± 2.7 vs. 4 ± 2.7, p = 0.015), diarrhea (2.9 ± 2.4 vs. 2 ± 2.4, p = 0.005), abdominal pain (4.8 ± 2.7 vs. 3.3 ± 2.5, p <0.001) and resulted in improved overall well-being (3.9 ± 2.4 vs. 2.7 ± 2.3, p <0.001). The LHBT was repeated 2-4 weeks after rifaximine treatment in 6 5/93 (70%) patients. Eradication of SIBO was documented in 85% of all patients (55/65). Conclusions: The results o f our phase IV trial i ndicate that a high proportion of IBS p atients t ested positive f or SIBO. I BS symptoms w ere significantly diminished following a 2-week treatment with rifaximine.

Diffusion-weighted MRI in metastatic gastrointestinal tumors (GIST): A pilot study on the assessment of treatment response in comparison with 18F-FDG PET/CT

Purpose: To evaluate the clinical potential of diffusion-weighted MR imaging with apparent diffusion coefficient (ADC) mapping for the assessment of gastrointestinal stromal tumor (GIST) response to targeted therapy in comparison with 18F-FDG PET/CT. Methods and materials: Five patients (3W/2M, aged 56 ± 13 y) with metastatic GIST underwent both a 18F-FDG PET/CT (Discovery LS, GE Healthcare) and a MRI (VIBE T1 Gd, DWI [b = 50,300,600] and ADC mapping) before and after change in therapy. Exams were first analyzed blindly, then PET/CT images were coregistered to T1 Gd MR images for lesion detection. SUVmax and ADC were measured for the six largest lesions on MRI. The relationship between SUVmax and ADC was analyzed using Spearman's correlation. Results: Altogether, 24 lesions (15 hepatic and 9 non-hepatic) were analyzed on both modalities. Three PET/CT lesions (12.5%) were initially not considered on ADC and 4 lesions on the second PET/CT were excluded because of hepatic vascular activity spillover. SUVmax decreased from 7.2 ± 7.7 g/mL to 5.9 ± 5.9 g/mL (P = 0.53) and ADC increased from 1.2x10-3 mm2/s ± 0.4 to 1.4x10-3 mm2/s ± 0.4 (P = 0.07). There was a significant association between SUVmax decrease and ADC increase (rho= -0.64, P = 0.004). Conclusion: Changes in ADC from diffusion-weighted MRI reflect response of 18F-FDG-avid GIST to therapy. The exact diagnostic value of DWI needs to be investigated further, as well as the effect of lesion size and time under therapy before imaging. Furthermore, the proven association between SUVmax and ADC may be useful for the assessment of treatment response in 18F-FDG non-avid GIST.

Impact of Ownership Structure on the Performance of China’s Feed Mill Sector, April 2005

In the decade of the 1990s, China’s feed sector became increasingly privatized, more feed mills opened, and the scale of operation expanded. Capacity utilization remained low and multi-ministerial supervision was still prevalent, but the feed mill sector showed a positive performance overall, posting a growth rate of 11 percent per year. Profit margin over sales was within allowable rates set by the government of China at 3 to 5 percent. Financial efficiency improved, with a 20 percent quicker turnover of working capital. Average technical efficiency was 0.805, as more efficient feed mills increasingly gained production shares. This study finds evidence that the increasing privatization explains the improved performance of the commercial feed mill sector. The drivers that shaped the feed mill sector in the 1990s have changed with China’s accession to the World Trade Organization. With the new policy regime in place, the study foresees that, assuming an adequate supply of soy meal and an excess capacity in the feed mill sector, it is likely that China will allow corn imports up to the tariff rate quota (TRQ) of 7.2 mmt since the in-quota rate is very low at 1 percent. However, when the TRQ is exceeded, the import duty jumps to a prohibitive out-quota rate of 65 percent. With an import duty for meat of only 10 to 12 percent, China would have a strong incentive to import meat products directly rather than bringing in expensive corn to produce meat domestically. This would be further reinforced if structural transformation in the swine sector would narrow the cost differential between domestic and imported pork.

Carte du cours du Danube : depuis Passau jusqu'à Lintz : De l'Inn depuis Wœrgl jusqu'à son confluent : De la Salza depuis Hallein jusqu'à son confluent : et de la grande route de Kufften à Salzbourg / Atelier de gravure sur pierre de Hellrigel

Échelle(s) : [ca 1:205 000]

Dispensable role of myeloid differentiation primary response gene 88 (MyD88) and MyD88-dependent toll-like receptors (TLRs) in a murine model of osteoarthritis.

OBJECTIVES: The aim of our study was to evaluate the role of cell-membrane expressed TLRs and the signaling molecule MyD88 in a murine model of OA induced by knee menisectomy (surgical partial removal of the medial meniscus [MNX]). METHODS: OA was induced in 8-10weeks old C57Bl/6 wild-type (WT) female (n=7) mice and in knockout (KO) TLR-1 (n=7), -2 (n=8), -4 (n=9) -6 (n=5), MyD88 (n=8) mice by medial menisectomy, using the sham-operated contralateral knee as a control. Cartilage destruction and synovial inflammation were evaluated by knee joint histology using the OARSI scoring method. Apoptotic chondrocytes and cartilage metabolism (collagen II synthesis and MMP-mediated aggrecan degradation) were analyzed using immunohistochemistry. RESULTS: Operated knees exhibited OA features at 8weeks post-surgery compared to sham-operated ones. In menisectomized TLR-1, -2, -4, and -6 deficient mice, cartilage lesions, synovial inflammation and cartilage metabolism were similar to that in operated WT mice. Accordingly, using the same approach, we found no significant protection in MyD88-deficient mice in terms of OA progression as compared to WT littermates. CONCLUSIONS: Deficiency of TLRs or their signalling molecule MyD88 did not impact on the severity of experimental OA. Our results demonstrate that MyD88-dependent TLRs are not involved in this murine OA model. Moreover, the dispensable role of MyD88, which is also an adaptor for IL-1 receptor signaling, suggests that IL-1 is not a key mediator in the development of OA. This latter hypothesis is strengthened by the lack of efficiency of IL-1β antagonist in the treatment of OA.

Greece with part of Anatolia / Barnard Randolph Author

Échelle(s) : [1:2 581 000 environ] A Scale of English Miles 100 [= 7,2 cm]

Ultra-Thin Portland Cement Concrete Overlay Extended Evaluation, January 2005

In this day of the mature highway systems, a new set of problems is facing the highway engineer. The existing infrastructure has aged to or past the design life of the original pavement design. In many cases, increased commercial traffic is creating the need for additional load carrying capacity, causing state highway engineers to consider new alternatives for rehabilitation of existing surfaces. Alternative surface materials, thicknesses, and methods of installation must be identified to meet the needs of individual pavements and budgets. With overlays being one of the most frequently used rehabilitation alternatives, it is important to learn more about the limitations and potential performance of thin bonded portland cement overlays and subsequent rehabilitation. The Iowa ultra-thin project demonstrated the application of thin portland cement concrete overlays as a rehabilitation technique. It combined the variables of base preparation, overlay thickness, slab size, and fiber enhancement into a series of test sections over a 7.2-mile length. This report identifies the performance of the overlays in terms of deflection reduction, reduced cracking, and improved bonding between the portland cement concrete (PCC) and asphalt cement concrete (ACC) base layers. The original research project was designed to evaluate the variables over a 5-year period of time. A second project provided the opportunity to test overlay rehabilitation techniques and continue measurement of the original overlay performance for 5 additional years. All performance indicators identified exceptional performance over the 10-year evaluation period for each of the variable combinations considered. The report summarizes the research methods, results, and identifies future research ideas to aid the pavement overlay designer in the successful implementation of ultra-thin portland cement concrete overlays as an lternative pavement rehabilitation technique.

Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing - a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites.

BACKGROUND: Wound healing involves complex mechanisms, which, if properly chaperoned, can enhance patient recovery. The abilities of platelets and keratinocytes may be harnessed in order to stimulate wound healing through the formation of platelet clots, the release of several growth factors and cytokines, and cell proliferation. The aim of the study was to test whether autologous keratinocyte suspensions in platelet concentrate would improve wound healing. The study was conducted at the Lausanne University Hospital, Switzerland in 45 patients, randomized to three different topical treatment groups: standard treatment serving as control, autologous platelet concentrate (PC) and keratinocytes suspended in autologous platelet concentrate (PC + K). Split thickness skin graft donor sites were chosen on the anterolateral thighs of patients undergoing plastic surgery for a variety of defects. Wound healing was assessed by the duration and quality of the healing process. Pain intensity was evaluated at day five. RESULTS: Healing time was reduced from 13.9 ± 0.5 days (mean ± SEM) in the control group to 7.2 ± 0.2 days in the PC group (P < 0.01). An addition of keratinocytes in suspension further reduced the healing time to 5.7 ± 0.2 days. Pain was reduced in both the PC and PC + K groups. Data showed a statistically detectable advantage of using PC + K over PC alone (P < 0.01). CONCLUSION: The results demonstrate the positive contribution of autologous platelets combined with keratinocytes in stimulating wound healing and reducing pain. This strikingly simple approach could have a significant impact on patient care, especially critically burned victims for whom time is of the essence. CLINICAL TRIAL REGISTRY INFORMATION: Protocol Record Identification Number: 132/03Registry URL: http://www.clinicaltrials.gov.

Les guerres du règne de Louis XIII et de la minorité de Louis XIV : mémoires de Jacques de Chastenet, seigneur de Puységur. Tome 1 / publiés et annotés par Ph. Tamizey de Larroque

Collection : Petits mémoires sur l'histoire de France ; 7

Effect of obesity onset on pendular energy transduction at spontaneous walking speed: Prader-Willi versus nonsyndromal obese individuals.

OBJECTIVE: To compare the mechanical external work (Wext ) and pendular energy transduction (Rstep ) at spontaneous walking speed (Ss ) in individuals with Prader-Willi syndrome (PWS) versus subjects with nonsyndromal obesity (OB) to investigate whether the early onset of obesity allows PWS subjects to adopt energy conserving gait mechanics. DESIGN AND METHODS: Wext and Rstep were computed using kinematic data acquired by an optoelectronic system and compared in 15 PWS (BMI = 39.5 ± 1.8 kg m(-2) ; 26.7 ± 1.5 year) and 15 OB (BMI = 39.3 ± 1.0 kg m(-2) ; 28.7 ± 1.9 year) adults matched for gender, age and BMI and walking at Ss . RESULTS: Ss was significantly lower in PWS (0.98 ± 0.03 m s(-1) ) than in OB (1.20 ± 0.02 m s(-1) ; P < 0.001). There were no significant differences in Wext per kilogram between groups (PWS: 0.37 ± 0.04 J kg(-1) m(-1) ; OB: 0.40 ± 0.05 J kg(-1) m(-1) ; P = 0.66) and in Rstep (PWS: 69.9 ± 2.9%; OB: 67.7 ± 2.4%; P = 0.56). However, Rstep normalized to Froude number (Rstep /Fr) was significantly greater in PWS (6.0 ± 0.6) than in OB (3.8 ± 0.2; P = 0.001). Moreover, Rstep /Fr was inversely correlated with age of obesity onset (r = -0.49; P = 0.006) and positively correlated with obesity duration (r = 0.38; P = 0.036). CONCLUSION: Individuals with PWS seem to alter their gait to improve pendular energy transduction as a result of precocious and chronic adaptation to loading.

Interruptions de grossesse dans le canton de Vaud en 2006

En 2006, un total de 1306 interruptions de grossesse ont été pratiquées dans le canton de Vaud, soit 89 (7%) de plus que l'année précédente. La grande majorité (93%) de ces interruptions de grossesse concernent des femmes résidant dans le canton de Vaud. Si le nombre absolu d'interruptions de grossesse est en nette augmentation, le taux pour 1000 résidentes âgées de 15 à 49 ans ne marque qu'une légère progression, passant de 6,7 pour-mille en 2004 à 7,2 pour-mille en 2006. Un écart important se maintient entre les femmes de nationalité étrangère (2006 : 12,1 pour-mille) et les Suissesses (4,6 pour-mille). Dans les deux groupes, néanmoins, l'augmentation des interruptions de grossesse parmi les adolescentes (15-19 ans) semble se confirmer. Depuis 2003, les taux sont passés de 4,4 pour-mille à 6,2 pour-mille chez les Suissesses et de 9,1 pour-mille à 14,4 pour-mille chez les femmes de nationalité étrangère. [Extrait des conclusions, p. 26]

Integrated Materials and Construction Practice for Concrete Pavement: A State-of-the-Practice Manual, 2006

At the heart of all concrete pavement projects is the concrete itself. This manual is intended as both a training tool and a reference to help concrete paving engineers, quality control personnel, specifiers, contractors, suppliers, technicians, and tradespeople bridge the gap between recent research and practice regarding optimizing the performance of concrete for pavements. Specifically, it will help readers do the following:

Distribution of hospital admissions in a middle-income country of the African region

Introduction: Few studies have reported the distribution of all hospital admissions at the entire country level in low and middle-income countries (LMICs). We examined this question in Seychelles, a rapidly developing small island state in the Africa region, in which access to health care is provided free of charge to all inhabitants through a national health system and all hospital admissions are routinely registered. Methods: Based on all admissions to all hospitals in Seychelles in 2005-2008, we calculated the distribution of hospital admissions, age at admission, length of stay and bed occupancy (i.e. cumulated number of patients * number of days spent in all hospitals) according to both hospital departments and broad causes of diseases (using codes of the ICD-10 classification of diseases). Results: Bed occupancy was largest in the surgical wards (36.7% of all days spent in all hospitals), followed by the medical wards (24.3%), gynecology/obstetrics wards (18.4%), pediatric wards (11.2%), and psychiatric wards (7.2%). According to broad causes of diseases/conditions, bed occupancy was highest for obstetrics/gynecology conditions (19.9% of all days spent at hospital), mental diseases (8.6%), cardiovascular diseases (8.1%), upper aerodigestive/pulmonary diseases (8%), infectious/parasitic diseases (8%), gastrointestinal diseases (7.2%), and urogenital diseases (6.7%). Adjusted to 100'000 population, 153 hospital beds are needed every day, including 31 for obstetrics/gynecologic conditions, 13 for mental diseases, 12 for cardiovascular diseases, 12 for upper aerodigestive diseases, 12 for infectious/parasitic diseases, and 11 for gastrointestinal diseases. Conclusion: Our findings give a good indication of the overall distribution of admissions according to both hospital departments and broad causes of diseases in a middle-income country. These findings provide important information for health care planning at the national level