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It is well-known that the Ginzburg-Landau equation on R has a global attractor [15] that attracts in Due to image rights restrictions, multiple line equation(s) cannot be graphically displayed. (ℝ) all the trajectories. This attractor contains bounded trajectories that are analytical functions in space. A famous theorem due to P. Collet and JP. Eckmann asserts that the ε-entropy per unit length in L∞ of this global attractor is finite and is smaller than the corresponding complexity for the space of functions which are analytical in a strip. This means that the global attractor is flatter than expected. We explain in this article how to establish the Collet-Eckmann Theorem in a Hilbert space framework. [ABSTRACT FROM AUTHOR]

The study investigated the differences in five different formulae for heart rate correction of the QT interval in serial electrocardiograms recorded in healthy subjects subjected to graded exercise. Twenty-one healthy subjects (aged 37+/-10 years, 15 male) were subjected to graded physical exercise on a braked bicycle ergometer until the heart rate reached 120 beats/min. Digital electrocardiograms (ECG) were recorded on baseline and every 30 seconds during the exercise. In each ECG, heart rate and QT interval were measured automatically (QT Guard package, Marquette Medical Systems, Milwaukee, WI, USA). Bazett, Fridericia, Hodges, Framingham, and nomogram formulae were used to obtain QTc interval values for each ECG. For each formula, the slope of the regression line between RR and QTc values was obtained in each subject. The mean values of the slopes were tested by a one-sample t-test and the comparison of the baseline and peak exercise QTc values was performed using paired t-test. Bazett, Hodges, and nomogram formulae led to significant prolongation of QTc intervals with exercise, while the Framingham formula led to significant shortening of QTc intervals with exercise. The differences obtained with the Fridericia formula were not statistically significant. The study shows that the practical meaning of QT, interval measurements depends on the correction formula used. In studies investigating repolarization changes (e.g., due to a new drug), the use of an ad-hoc selected heart rate correction formula is highly inappropriate because it may bias the results in either direction. [ABSTRACT FROM AUTHOR]

Background: Patients with Parkinson's disease (PD) experience changes in behavior, personality, and cognition that can manifest even in the initial stages of the disease. Previous studies have suggested that mild behavioral impairment (MBI) should be considered an early marker of cognitive decline. However, the precise neurostructural underpinnings of MBI in early- to mid-stage PD remain poorly understood., Objective: The aim was to explore the changes in white matter microstructure linked to MBI and mild cognitive impairment (MCI) in early- to mid-stage PD using diffusion magnetic resonance imaging (dMRI)., Methods: A total of 91 PD patients and 36 healthy participants were recruited and underwent anatomical MRI and dMRI, a comprehensive neuropsychological battery, and the completion of the Mild Behavioral Impairment-Checklist. Metrics of white matter integrity included tissue fractional anisotropy (FAt) and radial diffusivity (RDt), free water (FW), and fixel-based apparent fiber density (AFD)., Results: The connection between the left amygdala and the putamen was disrupted when comparing PD patients with MBI (PD-MBI) to PD-non-MBI, as evidenced by increased RDt (η 2  = 0.09, P = 0.004) and both decreased AFD (η 2  = 0.05, P = 0.048) and FAt (η 2  = 0.12, P = 0.014). Compared to controls, PD patients with both MBI and MCI demonstrated increased FW for the connection between the left orbitofrontal gyrus (OrG) and the hippocampus (η 2  = 0.22, P = 0.008), augmented RDt between the right OrG and the amygdala (η 2  = 0.14, P = 0.008), and increased RDt (η 2  = 0.25, P = 0.028) with decreased AFD (η 2  = 0.10, P = 0.046) between the right OrG and the caudate nucleus., Conclusion: MBI is associated with abnormal microstructure of connections involving the orbitofrontal cortex, putamen, and amygdala. To our knowledge, this is the first assessment of the white matter microstructure in PD-MBI using dMRI. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Interactions between tumor and microenvironment determine individual response to immunotherapy. Triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) have exhibited suboptimal responses to immune checkpoint inhibitors (ICIs). Aspartate β-hydroxylase (ASPH), an oncofetal protein and tumor associated antigen (TAA), is a potential target for immunotherapy., Methods: Subcutaneous HCC and orthotopic TNBC murine models were established in immunocompetent BALB/c mice with injection of BNL-T3 and 4 T1 cells, respectively. Immunohistochemistry, immunofluorescence, H&E, flow cytometry, ELISA and in vitro cytotoxicity assays were performed., Results: The ASPH-MYC signaling cascade upregulates PD-L1 expression on breast and liver tumor cells. A bio-nanoparticle based λ phage vaccine targeting ASPH was administrated to mice harboring syngeneic HCC or TNBC tumors, either alone or in combination with PD-1 blockade. In control, autocrine chemokine ligand 13 (CXCL13)-C-X-C chemokine receptor type 5 (CXCR5) axis promoted tumor development and progression in HCC and TNBC. Interactions between PD-L1 + cancer cells and PD-1 + T cells resulted in T cell exhaustion and apoptosis, causing immune evasion of cancer cells. In contrast, combination therapy (Vaccine+PD-1 inhibitor) significantly suppressed primary hepatic or mammary tumor growth (with distant pulmonary metastases in TNBC). Adaptive immune responses were attributed to expansion of activated CD4 + T helper type 1 (Th1)/CD8 + cytotoxic T cells (CTLs) that displayed enhanced effector functions, and maturation of plasma cells that secreted high titers of ASPH-specific antibody. Combination therapy significantly reduced tumor infiltration of immunosuppressive CD4 + /CD25 + /FOXP3 + Tregs. When the PD-1/PD-L1 signal was inhibited, CXCL13 produced by ASPH + cancer cells recruited CXCR5 + /CD8 + T lymphocytes to tertiary lymphoid structures (TLSs), comprising effector and memory CTLs, T follicular helper cells, B cell germinal center, and follicular dendritic cells. TLSs facilitate activation and maturation of DCs and actively recruit immune subsets to tumor microenvironment. These CTLs secreted CXCL13 to recruit more CXCR5 + immune cells and to lyse CXCR5 + cancer cells. Upon combination treatment, formation of TLSs predicts sensitivity to ICI blockade. Combination therapy substantially prolonged overall survival of mice with HCC or TNBC., Conclusions: Synergistic antitumor efficacy attributable to a λ phage vaccine specifically targeting ASPH, an ideal TAA, combined with ICIs, inhibits tumor growth and progression of TNBC and HCC., (© 2022. The Author(s).)

Objectives: Using a rabbit in vivo joint injury model, the primary objective of the study was to determine if a relationship exists between earlier time to initiation of ketotifen fumarate (KF) treatment and posttraumatic joint contracture (PTJC) reduction. The secondary objective was to determine if a coagulation response could be detected with serial thrombelastography (TEG) analysis following acute trauma in this model., Methods: PTJC of the knee were created in 25 skeletally mature, New Zealand White rabbits. Five groups of 5 animals were studied: a control group that received twice daily subcutaneous injections of normal saline and 4 treatment groups that received twice daily subcutaneous injections of KF (0.5 mg/kg) starting immediately, 1-, 2-, and 4-weeks post-injury. After 8 weeks of immobilization, flexion contractures were measured biomechanically. Serial TEG analysis was performed on the control group animals pre-injury and weekly post-injury., Results: The average joint contracture in the Control Group (43.1° ± 16.2°) was higher than all KF treatment groups; however, the differences were not statistically significant. The average joint contracture was lowest in the 2-week post-injury treatment group (29.4° ± 12.1°), although not statistically significant compared to the other treatment groups. Serial TEG analysis demonstrated significantly higher mean maximal amplitude (maximal amplitude = 68.9 ± 1.7 mm; P  < .001), alpha-angle (81.9° ± 0.9°; P  < .001), and coagulation index (4.5 ± 0.3; P  < .001) 1-week post-injury, which normalized to pre-injury values by 5-weeks post-injury., Conclusions: The use of the mast cell stabilizer KF within 2 weeks of injury demonstrated a nonsignificant trend towards reducing joint contracture in a rabbit in vivo model of PTJC. TEG and the in vivo rabbit joint injury model may be valuable in future preclinical studies of venous thromboembolism prevention and furthering our understanding of the pathophysiology of posttraumatic hypercoagulability., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

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Cognitive impairments are prevalent in Parkinson's disease (PD), but the underlying mechanisms of their development are unknown. In this study, we aimed to predict global cognition (GC) in PD with machine learning (ML) using structural neuroimaging, genetics and clinical and demographic characteristics. As a post-hoc analysis, we aimed to explore the connection between novel selected features and GC more precisely and to investigate whether this relationship is specific to GC or is driven by specific cognitive domains. 101 idiopathic PD patients had a cognitive assessment, structural MRI and blood draw. ML was performed on 102 input features including demographics, cortical thickness and subcortical measures, and several genetic variants (APOE, MAPT, SNCA, etc.). Using the combination of RRELIEFF and Support Vector Regression, 11 features were found to be predictive of GC including sex, rs894280, Edinburgh Handedness Inventory, UPDRS-III, education, five cortical thickness measures (R-parahippocampal, L-entorhinal, R-rostral anterior cingulate, L-middle temporal, and R-transverse temporal), and R-caudate volume. The rs894280 of SNCA gene was selected as the most novel finding of ML. Post-hoc analysis revealed a robust association between rs894280 and GC, attention, and visuospatial abilities. This variant indicates a potential role for the SNCA gene in cognitive impairments of idiopathic PD.

Aims: The estrogen-inducible protein Heat Shock Protein 27 (HSP27) as well as anti-HSP27 antibodies are elevated in healthy subjects compared to cardiovascular disease patients. Vaccination of ApoE -/- mice with recombinant HSP25 (rHSP25, the murine ortholog), boosts anti- HSP25 levels and attenuates atherogenesis. As estrogens promote HSP27 synthesis, cellular release and blood levels, we hypothesize that menopause will result in loss of HSP27 atheroprotection. Hence, the rationale for this study is to compare the efficacy of rHSP25 vaccination vs. estradiol (E2) therapy for the prevention of post-menopausal atherogenesis., Methods and Results: ApoE -/- mice subjected to ovariectomy (OVX) showed a 65 % increase atherosclerotic burden compared to sham mice after 5 weeks of a high fat diet. Relative to vaccination with rC1, a truncated HSP27 control peptide, atherogenesis was reduced by 5-weekly rHSP25 vaccinations (-43 %), a subcutaneous E2 slow release pellet (-52 %) or a combination thereof (-82 %). Plasma cholesterol levels declined in parallel with the reductions in atherogenesis, but relative to rC1/OVX mice plasma PCSK9 levels were 52 % higher in E2/OVX and 41 % lower in rHSP25/OVX mice (p < 0.0001 for both). Hepatic LDLR mRNA levels did not change with E2 treatment but increased markedly with rHSP25 vaccination. Conversely, hepatic PCSK9 mRNA increased 148 % with E2 treatment vs. rC1/OVX but did not change with rHSP25 vaccination. In human HepG2 hepatocytes E2 increased PCSK9 promoter activity 303 %, while the combination of [rHSP27 + PAb] decreased PCSK9 promoter activity by 64 %., Conclusion: The reduction in post-OVX atherogenesis and cholesterol levels with rHSP25 vaccination is associated with increased LDLR but not PCSK9 expression. Surprisingly, E2 therapy attenuates atherogenesis and cholesterol levels post-OVX without altering LDLR but increases PCSK9 expression and promoter activity. This is the first documentation of increased PCSK9 expression with E2 therapy and raises questions about balancing physiological estrogenic / PCSK9 homeostasis and targeting PCSK9 in women - are there effects beyond cholesterol?, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Acute megakaryoblastic leukemia is a rare subtype of pediatric acute myeloid leukemia (AML) with poor outcomes in patients with non-Down syndrome. The reported outcomes have been poor, and the prognostic factors have not been clearly determined., Patients and Methods: To evaluate the prognostic significance of various cytogenetic abnormalities and minimal residual disease status determined by flow cytometry after induction I, we retrospectively analyzed the data of 80 patients with non-Down syndrome with a diagnosis of M7 AML treated at Children's Cancer Hospital Egypt (CCHE-57357) from July 2007 through December 2016., Results: Of the 80 patients, 15 died during induction I and were excluded from the survival analysis. The overall survival, event-free survival, and cumulative incidence of relapse at 2 years was 52.6% ± 12.7%, 45.2% ± 12.3%, and 31.8% ± 11.5% respectively. Of the 90 patients, 61 had cytogenetic abnormalities, including trisomy 19,13q, trisomy 8, complex karyotype, t(1;22), KMT2A rearrangements, and trisomy 21. None of these had an effect on the outcomes. In addition, 34 patients had minimal residual disease < 0.1% after induction I, but the difference did not reach statistical significance. Patients with a delayed time to recovery (possibly due to myelofibrosis) had worse outcomes compared with those with early recovery (47% ± 19.2% vs. 63.2% ± 21.9%, respectively)., Conclusion: Acute megakaryoblastic leukemia in patients with non-Down syndrome has a poor outcome with no clearly defined prognostic factors. However, future directions to risk stratify and tailor therapy should include assessment of the tumor biology according to the molecular pathways and study of the pathogenesis of myelofibrosis in this disease, which could affect the prognosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The recognition of sex differences in cardiovascular disease, particularly the manifestations of coronary artery disease (CAD) in post-menopausal women, has introduced new challenges in not only understanding disease mechanisms but also identifying appropriate clinical means of assessing the efficacy of management strategies. For example, the majority of treatment algorithms for CAD are derived from the study of males, focus on epicardial stenoses, and inadequately account for the small intramyocardial vessel disease in women. However, newer investigational modalities, including stress perfusion cardiac magnetic resonance imaging and positron emission tomography are providing enhanced diagnostic accuracy and prognostication for women with microvascular disease. Moreover, these investigations may soon be complemented by simpler screening tools such as retinal vasculature imaging, as well as novel biomarkers (e.g. heat shock protein 27). Hence, it is vital that robust, sex-specific cardiovascular imaging modalities and biomarkers continue to be developed and are incorporated into practice guidelines that are used to manage women with CAD, as well as gauge the efficacy of any new treatment modalities. This review provides an overview of some of the sex differences in CAD and highlights emerging advances in the investigation of CAD in post-menopausal women., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Some women with genetic risk of breast and/or ovarian cancer (e.g., BRCA1/2) opt to undergo prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries & fallopian tubes) in order to reduce their risk of cancer. As a consequence, these women experience "surgical menopause" - accompanied by more severe climacteric symptoms that occur in a much shorter time frame. While the risk of coronary artery disease (CAD) rises with menopause, little is known about how the sudden loss of ovarian function from PSO alters the whole-body physiology, and whether it predisposes women to premature CAD., Methods/design: To manage CAD risk there is a prerequisite for reliable biomarkers that can help guide risk assessment and therapeutic interventions. To address these needs, this prospective, observational cohort study will evaluate surrogate markers reflective of CAD health in women experiencing surgical menopause after PSO. Twenty women representing each of the following groups will be enrolled over 3 years (total participants = 240): (i) pre-menopausal PSO, (ii) post-menopausal PSO, (iii) pre-menopausal women undergoing other pelvic surgery, and (iv) pre-menopausal controls (no surgery). All participants will provide blood plasma samples pre- and 1, 3, 6, & 12 months post-operatively, with serial samples collectively assessed for measurements of the study's primary endpoints of interest. These include a hormone profile (estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), and progesterone) and both conventional (lipid profile) and novel biomarkers (Heat Shock Protein 27 (HSP27), HSP27-antibodies (HSP27 Ab), proprotein convertase subtilisin/kexin 9 (PCSK9), inflammatory cytokines) of CAD. Another aspect of this study is the measurement and analysis of retinal vessel diameters - an emerging physiological parameter reflective of CAD risk. Finally, a patient engagement exercise will result in the drafting of patient-generated questionnaires that address the well-being and health concerns of these women as they transition through premature menopause and work with our research team to identify and discuss their health priorities., Discussion: The protocol of our planned study investigating the effects of PSO on CAD is described herein. Characterization of novel CAD markers in women experiencing surgical menopause will yield new insights into the role of the functional ovary in modulating lipid parameters and other CAD risk factors such as HSP27 and HSP27 Ab., Competing Interests: This research has obtained ethics approval at the University of Calgary (REB14–2335) and consent from participating PSO women and controls.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: Endothelial and smooth muscle cells must communicate with one another to regulate arterial diameter. A key structure driving heterocellular communication is the endothelial projection, a thin extension that crosses the internal elastic lamina (IEL) making contact with smooth muscle. This study sought to define the precise structural composition of endothelial projections in the mesenteric circulation., Methods: Third- and fourth-order mesenteric arteries from hamster were prepared for electron microscopy. Electron tomographic approaches were used to generate 3-D compositional models of endothelial projections., Results: Endothelial projections were categorized based upon their proximity to smooth muscle or how many projections projected through an IEL hole. Irrespective of the initial categorization, endothelial projections were largely devoid of organelles except for sparse membranous structures observed near the tip, close to potential smooth muscle contact sites. Unexpectedly, it was the base of projections which were rich with organelles including the endoplasmic reticulum, ribosomes, vesicles, caveolae, and mitochondria., Conclusions: Electron tomographic techniques suggest that the base of endothelial projections is likely a dynamic site for signal regulation and contractile control. As projections are largely devoid of membranous organelles, their principal function appears to ensure electrical contact between the two cell layers., (© 2016 John Wiley & Sons Ltd.)

Background: The role, interplay, and relative importance of the multifactorial hemodynamic and myocardial mechanisms causing dysfunction of the Fontan circulation remain incompletely understood., Methods and Results: Using an MRI catheterization technique, we performed a differential analysis of pulmonary vascular resistance and aortopulmonary collateral blood flow in conjunction with global ventricular pump function, myocontractility (end-systolic pressure-volume relation), and diastolic compliance (end-diastolic pressure-volume relation) in 10 patients with a Fontan circulation at rest and during dobutamine stress. Pulmonary and ventricular pressures were measured invasively and synchronized with velocity-encoded MRI-derived pulmonary and aortic blood flows and cine MRI-derived ventricular volumes. Pulmonary vascular resistance and end-systolic and end-diastolic pressure-volume relations were then determined. Aortopulmonary collateral flow was calculated as the difference between aortic and pulmonary flow. Compared to rest, dobutamine caused a small increase in mean pulmonary pressures (P<0.05). Collateral flow was significantly augmented (P<0.001) and contributed importantly to an increase in pulmonary flow (P<0.01). Pulmonary vascular resistance decreased significantly (P<0.01). Dobutamine did not increase stroke volumes significantly despite slightly enhanced contractility (end-systolic pressure-volume relation). Active early relaxation (τ) was inconspicuous, but the end-diastolic pressure-volume relation shifted upward, indicating reduced compliance., Conclusions: In patients with a Fontan circulation, aortopulmonary collateral flow contributes substantially to enhanced pulmonary flow during stress. Our data indicate that pulmonary vascular response to augmented cardiac output was adequate, but decreased diastolic compliance was identified as an important component of ventricular dysfunction.

Purpose: To describe the trends of potentially inappropriate medication (PIM) use in older adults from 1995 to 2004 in the East of France, by using the 1997 Beers criteria and its French update, and to assess risk factors for this PIM use., Methods: We carried out a repeated cross-sectional study using data collected among people aged >/=65 years, examined in the Center for Preventive Medicine. Studied variables were socio-demographic, clinical data, medication consumption and the self-health status. Joinpoint regression analysis was used to estimate the temporal changes in PIM rate., Results: 30 683 participants were included. 51.2% were women. The mean age was 70.1 +/- 4.3 years [65-99]. The annual overall rate of PIM use decreased significantly during the study period. These rates range from 14.9% in 1995 to 9.0% in 2004 according the Beers criteria (-3.4% per year) and from 33.5% in 1995 to 19.3% in 2004 according to the French update criteria (-3.6% per year). The annual rate of medication users increased during the same period (+0.75% per year). The risk of PIM consumption increased with age, number of drugs and frequency of the visits to the physician (OR = 1.26 [1.18-1.35]). This risk was also higher among women (OR = 1.29 [1.18-1.40]), elderly living alone (OR = 1.09 [1.02-1.17]) and with those with low education level (OR = 1.19 [1.02-1.38])., Conclusion: This study shows a decrease in PIM consumption. Despite an increase of drug use in the elderly, an improving of the quality of this consumption remains possible., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Objectives: This study sought to develop and validate a method for the integrated analysis of systolic and diastolic ventricular function., Background: An integrated approach to assess ventricular pump function, myocontractility (end-systolic pressure-volume relationship [ESPVR]), and diastolic compliance (end-diastolic pressure-volume relation [EDPVR]) is of high clinical value. Cardiac magnetic resonance (CMR) is well established for measuring global pump function, and catheterization-combined CMR was previously shown to accurately measure ESPVR, but not yet the EDPVR., Methods: In 8 pigs, the CMR technique was compared with conductance catheter methods (gold standard) for measuring the EDPVR in the left and right ventricle. Measurements were performed at rest and during dobutamine administration. For CMR, the ESPVR was estimated with a single-beat approach by synchronizing invasive ventricular pressures with cine CMR-derived ventricular volumes. The EDPVR was determined during pre-load reduction from additional volume data that were obtained from real-time velocity-encoded CMR pulmonary/aortic blood flow measurements. Pre-load reduction was achieved by transient balloon occlusion of the inferior vena cava. The stiffness coefficient beta was calculated by an exponential fit from the EDPVR. After validation in the animal experiments, the EDPVR was assessed in a pilot study of 3 patients with a single ventricle using identical CMR and conductance catheter techniques., Results: Bland-Altman tests showed good agreement between conductance catheter-derived and CMR-derived EDPVR. In both ventricles of the pigs, dobutamine enhanced myocontractility (p < 0.01), increased stroke volume (p < 0.01), and improved diastolic function. The latter was evidenced by shorter early relaxation (p < 0.05), a downward shift of the EDPVR, and a decreased stiffness coefficient beta (p < 0.05). In contrast, in the patients, early relaxation was inconspicuous but the EDPVR shifted left-upward and the stiffness constant remained unchanged. The observed changes in diastolic function were not significantly different when measured with conductance catheter and CMR., Conclusions: This novel CMR method provides differential information about diastolic function in conjunction with parameters of systolic contractility and global pump function.

The objective of this study was to analyse trends in the incidence of digestive cancers in France. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort models. An estimation of the incidence/mortality ratio was obtained from these models and was applied to the mortality rates predicted from an age-cohort model for the entire French population. Site-specific standardized-incidence rates by 1-year intervals and cumulative rate 0-74 years by birth cohort were estimated. On average, age-standardized incidence rates of large bowel cancers increased by 1.0% per year in men and 0.8% in women from 1980 to 2000. The estimated cumulative rate increased from 4.0% for men born in 1913 to 4.8% for those born in 1953. The corresponding values in women were 2.5 and 2.9%. The most striking increase in incidence was seen for primary liver cancer with an increase from 2000 incident cases in 1980 to nearly 6000 in 2000. The estimated cumulative rate was 0.5% for men born in 1913 and 2.9% for those born in 1953. The increase in incidence was lower for pancreas cancer. A decrease in the incidence of stomach cancer was observed for both sexes and of oesophageal cancer in men by slightly more than 2%. The study showed large changes in the cancer burden in France between 1980 and 2000.

Background: Dual-task-based assessment tests failed to establish a dependable relationship between dual-task-related gait changes and the risk of falls in the elderly., Objective: The aim of this study was to examine whether changes in gait while counting backward could be associated with the occurrence of a first fall among older adults., Methods: Walking while counting backward was investigated prospectively in a cohort of 187 older adults living independently in senior housing facilities. During enrollment, walking time, number of steps, and frequency of lateral line stepping-over and stops were measured while walking only and while walking with backward counting aloud. Information on the incident falls during the follow-up year was collected monthly., Results: Walking time and the number of steps increased significantly under the dual-task condition compared to the single-task condition among fallers and non-fallers (p < 0.001). Compared to non-fallers, fallers had significantly lower scores in the Mini-Mental State Examination (p = 0.029) and higher scores in the 15-item Geriatric Depression Scale (p = 0.003) and Timed Up & Go Test (p = 0.006) and increased walking time under both walking conditions (p = 0.030 for single-task condition and p = 0.007 for dual-task condition). After adjusting for these variables, depressive symptoms (adjusted OR = 2.6 with p = 0.041 and adjusted OR = 2.5 with p = 0.045 when walking time while walking only and walking with backward counting is considered, respectively) and walking time while walking only (OR = 2.3 with p = 0.032) were significantly associated with falls., Conclusion: Dual-task-related gait changes were poorly associated with the occurrence of a first fall and provided no additional predictive value compared to gait performance under a single task, suggesting that changes in basic clinical gait parameters while counting backward are unsuccessful to predict the first fall among older adults., (Copyright 2008 S. Karger AG, Basel.)

Malignancies are rare young French adults but represent the third significant cause of death in the cohort of 15-24 years of age. The aim of this study was to investigate incidence and survival rates of French adolescents and young adults with cancer. All cases of cancer occuring over a 20-year period (1978-1997) in the cohort of patients aged 15 to 24, were obtained from nine population-based registries (10 % of the French population). Basal cell carcinomas of the skin were excluded. 1161 and 1884 cases were recorded in adolescents and young adults, respectively. Overall incidence rates (IR) were 161.4/10(6) in adolescents aged 15-19 years (M/F ratio = 1.3), and 252.6/10(6) in young adults aged 20-24 years (M/F ratio : 1.2). During the 1978-97 period, the IRs appeared stable over the years, +0.4 % [CI95 % = -2.3 ; +3.1] (p = 0.79) for adolescents and +1.7 % [CI95 % = -4.0 ; +7.3] (p = 0.57) for young adults. Five-year overall survival rates were 69.1 % [CI95 % = 66.4-71.8] for adolescents and 74.5 % [CI95 % = 72.3-76.7] for young adults. The 5-year survival rate for patients 15-24 years improved from 62.0 % (CI95 % = 57.5-66.5) in 1978-82 to 80.2 % (IC95 % = 77.7-82.8) in 1993-97. Noteworthy, results in adolescents and young adults are poor compared to the ones from their younger counterparts, especially in patients with acute lymphoblastic leukemia, non-Hodgkin lymphoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and astrocytoma. Further studies are warranted to elucidate whether these differences are due to intrinsic biological properties of the tumor or to differences in clinical practices in the two populations.

Aim: The 1998 consensus conference dealing with colon cancer, and the 2003 Cancer Plan underlined the need for multidisciplinary meetings and for including patients in therapeutic trials. The aim of this study, which pooled data from the French Cancer Registries operating within the Francim network, was to report on diagnostic and therapeutic practices in the general French population before implementation of the Cancer Plan., Methods: The study population was composed of 2935 patients with colorectal cancer diagnosed in 2000 in twelve French administrative districts accounting for 15% of the geographical area of France. Data were collected using a standardized procedure. Three categories of place of diagnosis were defined: public university hospitals, public non-university hospitals, and private clinics., Results: Overall, multidisciplinary meeting was conducted for 32.2% of patients with colorectal cancer. This proportion varied from 6.4% to 76.9%, depending on the geographical area (P<0.001). The place of diagnosis affected this practice: 52% in public university hospitals, 31% in public non-university hospitals and 29% in private clinics (P<0.001). In multivariate analysis, age (OR(>75 years): 0.71, P<0.001), site (OR(rectum): 1.80, P<0.001) and health care facilities (OR(public non-university vs public university): 0.36, P<0.001, OR(private vs public university): 0.40, P<0.001) affected the use of multidisciplinary meeting. Overall, 4.3% of patients were included in a therapeutic trial. This concerned 6.2% of patients aged under 75 and 1.0% of those aged over 75 (P<0.001). The proportion of inclusions, taking into account the trials proposed in 2000 and 2001, varied from 0.7% to 16.4% according to geographical area (P<0.001). This proportion was 10.3% if there had been multidisciplinary meeting and 5.1% if not (P<0.001). Neither cancer site, gender, nor healthcare facility responsible for diagnosis influenced trial inclusion., Conclusion: This population-based study underlines geographical variations in the management of colorectal cancer in France. In 2000, multidisciplinary meeting was conducted for an insufficient proportion of patients, and an insufficient number of patients were included in therapeutic trials. Repeating the same survey in 2005 will provide information on the effects of the Cancer Plan and the diffusion of these recommendations.

We report an adolescent cancer pathway from referral, through diagnosis and treatment, to follow-up in France. All cases of cancer among 15-19 years, diagnosed from 1988 to 1997, recorded by nine French population-based cancer registries (10% of French population) were included. The management of adolescent cancer by paediatricians was rare. An adolescents' pathway through cancer care can be summarized as first visit to general practitioner, referral to adult oncologist for haematological malignancy and medical or surgical specialists for solid tumours, treatment in adult unit, and follow-up by adult oncologist, adult medical or surgical specialist, or general practitioner. Only 9% of the 15-19 years are entered into a clinical trial (respectively 6% and 3% into adult and paediatric clinical trial). The inclusion rate changes according to the diagnosis, higher for acute lymphoblastic leukaemia (39%), non-Hodgkin's lymphomas (NHL) (27%), and acute non-lymphoblastic leukaemia (20%). Only 4% of adolescent cancers were managed on shared adult/paediatric departments, especially for soft-tissue sarcomas (14.9%), malignant bone tumours (13.4), central nervous system tumours (6.2%), and NHL (4.4%). Whatever the reasons for lack of participation in clinical trials, an ideal model requiring communication and cooperation between all adult and paediatric specialists involved in adolescent cancer treatment should reduce the large gap in access to cooperative groups.