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International audience; Background The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn’s disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD. Methods Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms. Results In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model. Conclusions A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice.

The simulation of strongly correlated quantum impurity models is a significant challenge in modern condensed matter physics that has multiple important applications. Thus far, the most successful methods for approaching this challenge involve Monte Carlo techniques that accurately and reliably sample perturbative expansions to any order. However, the cost of obtaining high precision through these methods is high. Recently, tensor train decomposition techniques have been developed as an alternative to Monte Carlo integration. In this study, we apply these techniques to the single-impurity Anderson model at equilibrium by calculating the systematic expansion in power of the hybridization of the impurity with the bath. We demonstrate the performance of the method in a paradigmatic application, examining the first-order phase transition on the infinite dimensional Bethe lattice, which can be mapped to an impurity model through dynamical mean field theory. Our results indicate that using tensor train decomposition schemes allows the calculation of finite-temperature Green's functions and thermodynamic observables with unprecedented accuracy. The methodology holds promise for future applications to frustrated multi-orbital systems, using a combination of partially summed series with other techniques pioneered in diagrammatic and continuous-time quantum Monte Carlo.

Objective(s): Trainee assessments aim to identify areas for improvement and address problems within training programs. However, effectiveness is limited by an inability to assess programs anonymously. We hypothesized concern for undesired repercussions may discourage honest responses. To test this, we conducted a comprehensive survey of trainees to assess their educational and work-related experiences anonymously. Design: A 51-question survey was distributed electronically to the Thoracic Surgery Residents Association (TSRA) membership. Questions were multiple-choice. The Likert scale was utilized. Setting: The survey was accessed electronically and was completed by participants nationwide. Participants: Trainees were incentivized to complete the survey with the opportunity to receive a $50 gift card or TSRA textbook. 109 of 551 cardiothoracic surgery trainees completed the survey. Results: 109 trainees (109/551, 19.8%) completed the survey. 57.8% of respondents reported complying with work hour restrictions, but 32.2% (n=35) did not feel comfortable reporting violations honestly. The majority of respondents agreed or strongly agreed that their program was preparing them to independently perform low risk cardiac (4.19 [1.22]) and thoracic (4.08 [1.13]) cases independently, 30.3% of chief residents reported planning to pursue additional training. 66% of respondents stated they would select the same program again. 33% reported having high morale, 47.7% moderate and 19.3% poor or declining morale. 84.4% of respondents did not feel their race or gender significantly impacted their training, 26.6% reported systemic bias in recruitment of new trainees or faculty, and 38.5% believed there was inadequate diversity among faculty and trainees. 30.3% reported experiencing verbal or physical harassment by an attending or fellow (14.7%). Conclusions: Despite reporting an overall positive operative experience, a significant number of trainees plan to pursue additional training. The survey identifies important areas for attention including underreporting of issues related to diversity, as well as verbal and physical harassment by fellows and attendings.

Frame-based optical sensors have been used for many years to produce light curves of space objects,from which information about those objects may be inferred. A relatively new type of optical sensor, known as a neuromorphic, or event-based, sensor is gaining attention as a promising tool for space object detection and characterisation. Comprising an array of pixels that function entirely independently and asynchronously, event-based sensors operate with microsecond temporal resolution, high dynamic range, and often with far lower data rates than frame-based sensors. An event-based pixel only outputs data when there is a change of brightness incident on that pixel that exceeds adjustable thresholds. We used a Prophesee Gen 4 EM event-based sensor that outputs not only the time of each detected change in brightness, but also a time-encoded value proportional to the brightness at the pixel after the change, to produce light curves of five satellites.The temporal resolution of the light curves that we produced varied from object to object, but in all cases there were many data points per second. Furthermore, since the event-based sensor operates without a shutter or set exposure interval, sudden or short duration brightness changes that would otherwise be missed during frame readout or smoothed by the effect of an exposure interval are captured. The results demonstrate that event-based sensors have considerable potential as space situational awareness tools.

https://mspresearchcenter.com/MSP2020/

Background: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response. Methods: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031. Findings: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45–0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64–0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71–1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63–0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45–0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53–0·80], p

María Julieta Russo,1 Gabriela Cohen,1 Patricio Chrem Mendez,1 Jorge Campos,1 Federico E Nahas,1 Ezequiel I Surace,1 Silvia Vazquez,1 Deborah Gustafson,2,3 Salvador Guinjoan,1 Ricardo F Allegri,1 Gustavo Sevlever1 On behalf of the Argentina-Alzheimer’s Disease Neuroim­aging Initiative group 1Center of Aging and Memory of Neurological Research Institute (FLENI), Buenos Aires, Argentina; 2Department of Neurology, State University of NewYork-Downstate Medical Center, Brooklyn, NY, USA; 3Neuropsychiatric Epidemiology Unit, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenPurpose: Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance.Patients and methods: Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects.Results: A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P

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Background: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke (AIS) each differ between Europe (EU) and United States (US). Aims: To compare the effects of alteplase according to cohorts defined by current EU or US marketing approval labels, or by hypothetical revisions of the labels that would remove the EU upper age limit or extend the US treatment time window to 4.5 hours. Methods: Individual-patient-data meta-analysis of 8 randomized trials of intravenous alteplase (0.9 mg/kg) versus control for AIS. Outcomes included excellent outcome (modified Rankin score [mRS] 0-1) at 3-6 months, the distribution of mRS, symptomatic intracerebral hemorrhage, and 90 day mortality. Results: Among 2449/6136 (40%) patients who met the current EU label and 3491 (57%) patients who met the age-revised label, alteplase increased the odds of mRS 0-1 (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively) but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19 respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-hour revised approval, alteplase increased the odds of mRS 0-1 (OR 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively) but not for those outside the 4.5-hour revised approval (1.14, 0.97−1.34). By 90 days no increased mortality remained for the current and 4.5-hour revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20 respectively) but mortality remained higher outside the 4.5-hour revised approval (1.17, 0.98–1.41). Conclusions: An age-revised EU label or 4.5-hour-revised US label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

William Y Tong, Gilad Cohen, Yoshiya Yamada Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, USA Abstract: Whole-gland low-dose rate (LDR) brachytherapy has been a well-established modality of treating low-risk prostate cancer. Treatment in a focal manner has the advantages of reduced toxicity to surrounding organs. Focal treatment using LDR brachytherapy has been relatively unexplored, but it may offer advantages over other modalities that have established experiences with a focal approach. This is particularly true as prostate cancer is being detected at an earlier and more localized stage with the advent of better detection methods and newer imaging modalities. Keywords: prostate cancer, focal, low dose rate, brachytherapy

Narcissistic individuals are prone to become aggressive when their egos are threatened. We report a randomized field experiment that tested whether a social-psychological intervention designed to lessen the impact of ego threat reduces narcissistic aggression. A sample of 405 young adolescents (mean age = 13.9 years) were randomly assigned to complete either a short self-affirmation writing assignment (which allowed them to reflect on their personally important values) or a control writing assignment. We expected that the self-affirmation would temporarily attenuate the ego-protective motivations that normally drive narcissists' aggression. As expected, the self-affirmation writing assignment reduced narcissistic aggression for a period of a school week, that is, for a period up to 400 times the duration of the intervention itself. These results provide the first empirical demonstration that buttressing self-esteem (as opposed to boosting self-esteem) can be effective at reducing aggression in at-risk youth. © 2009 Association for Psychological Science.

La mise en oeuvre à la fois de cycles thermodynamiques et de fluides adaptés permet d'élargir considérablement les possibilités de récupération et de valorisation de la chaleur à bas niveau contenue dans les rejets thermiques industriels, l'eau géothermale, le rayonnement solaire ou le milieu environnant. Ceci permettra une meilleure préservation des ressources énergétiques dans les principaux secteurs consommateurs d'énergie : résidentiel, tertiaire et industriel. On décrit les possibilités que présentent : - Les cycles thermodynamiques directs (pompes de chaleur à compression ou à absorption) dans le domaine du chauffage résidentiel et tertiaire où elles sont déjà bien implantées et dont les applications commencent à pénétrer le secteur industriel. - Les cycles thermodynamiques inverses (thermotransformateurs et cycles moteurs à fluide organique) pour lesquels les progrès techniques accomplis et l'accroissement du prix de l'énergie devraient permettre d'en assurer la diffusion progressive dans le secteur industriel. The implementation of both thermodynamic cycles and suitable fluids makes for a considerable widening of the capacity to recover and upgrade the low-level heat contained in industrial heat wastes, geothermal water, solar radiation or the surrounding environment. This will make for better conservation of energy resources in the leading sectors of energy consumption, i. e. residential, tertiary and industrial. This article describes these possibilities in the form of: (a) Direct thermodynamic cycles (compression or absorption heat pumps) in the field of home and tertiary heating where they have already obtained a solid foothold and for which applications are beginning te penetrate into the industrial sector. (b) Reverse thermodynamic cycles (heat transformers and organic-fluid motor cycles) for which the technical advances made and the increase in energy prices should enable them to spread progressively throughout the industrial sector.

Contains fulltext : 82586.pdf (Publisher’s version ) (Open Access) the Ministry of Environmental Protection, the Central Bureau of Statistics and the Jerusalem Israel for Israel Studies

Contains fulltext : 82536.pdf (Publisher’s version ) (Open Access) the Ministry of Environmental Protection, the Central Bureau of Statistics and the Jerusalem Israel for Israel Studies

Objective: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. Methods: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aβ1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. Results: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non–Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. Conclusions: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice. Resumen Objetivo El objetivo de este estudio fue investigar el rol y pronóstico de los biomarcadores de enfermedad de Alzheimer en pacientes con diagnóstico clínico de deterioro cognitivo leve (DCL) en una clínica de memoria de Latinoamérica. Método Ochenta y nueve pacientes con DCL, 43 con demencia tipo Alzheimer y 18 controles normales apareados por edad, sexo y escolaridad fueron estudiados con un extenso protocolo demográfico, neurológico y neuropsicológico en la clínica de memoria del Instituto FLENI de Buenos Aires. Todos completaron una RM cerebral, una PET con FDG, una PET con estudios amiloideo (PIB), genotipificación de APOE y estudio de Aβ1-42, tau and f-tau de líquido cefalorraquídeo. Basado en la presencia/ausencia de patología amiloidea y neurodegeneración los pacientes fueron categorizados como A+/A− y N+/N− respectivamente. Resultados En el estudio de líquido cefalorraquídeo el 18% de los controles, el 64% de los DCL y el 92% de las demencia tipo Alzheimer tenían patología amiloidea; y un 11% de los controles, el 6% de los DCL y el 8% de las DTA eran sospechosos de fisiopatología no Alzheimer. En el seguimiento a los 30 meses el 45% de los DCL con amiloide positivo y el 20% de los que presentaron amiloide negativo progresaron a demencia. Conclusiones Este estudio muestra el pronóstico de los DCL basado en los biomarcadores, y respalda su importancia en la toma de decisiones en la práctica diaria. Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Universidad de la Costa; Colombia Fil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Russo, María Julieta. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Cohen, G.. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Calandri, I.. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Campos, J.. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Nahas, Federico Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Vazquez, S.. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina

AimTo compare blood pressure reactions (BPR) of infants to mild stress for evidence of adverse cardiovascular effects of passive exposure to tobacco smoke during pregnancy and early infancy. MethodsAn observational field study conducted in Crete. We compared 4- to 6-month olds of lifelong nonsmokers minimally (controls, n=9) or frequently exposed to tobacco smoke (passive smokers; n=10) with those born to habitual smokers (n=6). Smoke exposure was verified biochemically (urine cotinine each trimester and at study). We recorded beat-to-beat blood pressure (BP) during brief repositioning manoeuvres performed during a daytime nap and analysed BPR (% change in BP during head-up tilt) for associations with maternal and infant cotinine. ResultsWe observed a 20-fold difference between BPR of infants of controls versus passive smokers - exceptional given number of infants ( error/confidence level 90%). The BPR declined linearly as the infant’s (but not mother’s) cotinine level rose (p=0.04), indicating abnormal BPR was caused mainly by postnatal smoke exposure. Infants of active smokers differed from those of passive smokers. ConclusionCardiovascular effects of passive smoking by a newborn infant manifest early on and are exceptionally strong. They can be largely avoided by keeping the home smoke rigorously free.

Glycoprotein B (gB), the fusogen of herpes simplex virus (HSV), is a class III fusion protein with a trimeric ectodomain of known structure for the postfusion state. Seen by negative-staining electron microscopy, it presents as a rod with three lobes (base, middle, and crown). gB has four functional regions (FR), defined by the physical location of epitopes recognized by anti-gB neutralizing monoclonal antibodies (MAbs). Located in the base, FR1 contains two internal fusion loops (FLs) and is the site of gB-lipid interaction (the fusion domain). Many of the MAbs to FR1 are neutralizing, block cell-cell fusion, and prevent the association of gB with lipid, suggesting that these MAbs affect FL function. Here we characterize FR1 epitopes by using electron microscopy to visualize purified Fab-gB ectodomain complexes, thus confirming the locations of several epitopes and localizing those of MAbs DL16 and SS63. We also generated MAb-resistant viruses in order to localize the SS55 epitope precisely. Because none of the epitopes of our anti-FR1 MAbs mapped to the FLs, we hyperimmunized rabbits with FL1 or FL2 peptides to generate polyclonal antibodies (PAbs). While the anti-FL1 PAb failed to bind gB, the anti-FL2 PAb had neutralizing activity, implying that the FLs become exposed during virus entry. Unexpectedly, the anti-FL2 PAb (and the anti-FR1 MAbs) bound to liposome-associated gB, suggesting that their epitopes are accessible even when the FLs engage lipid. These studies provide possible mechanisms of action for HSV neutralization and insight into how gB FR1 contributes to viral fusion. IMPORTANCE For herpesviruses, such as HSV, entry into a target cell involves transfer of the capsid-encased genome of the virus to the target cell after fusion of the lipid envelope of the virus with a lipid membrane of the host. Virus-encoded glycoproteins in the envelope are responsible for fusion. Antibodies to these glycoproteins are important biological tools, providing a way of examining how fusion works. Here we used electron microscopy and other techniques to study a panel of anti-gB antibodies. Some, with virus-neutralizing activity, impair gB-lipid association. We also generated a peptide antibody against one of the gB fusion loops; its properties provide insight into the way the fusion loops function as gB transits from its prefusion form to an active fusogen.

Micromorphological and anatomical differences in leaf epidermis and stem xylem of Rosa hybrida `Lovely Red` (LR) and `Rouge Baiser` (RB), commercially grown in Buenos Aires, Argentina, were examined in the lower half of the terminal leaflet of 5-foliate leaves and in the basal part of stem, respectively. Digital images obtained from SEM and a phase contrast microscope were used with this purpose. Epicuticular wax, which was present on both sides of the leaves, was more abundant in LR than in RB. Stomata were only present on the abaxial side; they were 111 and 129 per mm2 in LR and RB, respectively; the number of epidermal cells was 1025 and 822 mm2 in LR and RB, respectively. No significant differences were observed between cultivars. Lovely Red and RB showed 267 and 308 vessels/mm2 stem, respectively, with a total area of 0.87 and 0.64 mm2/mm2 stem, respectively, and a vessel area of 0.33 and 0.21 mm2, respectively, with significant differences between cultivars for vessel and total area (p less or equal than 0.05). As a result, LR showed a smaller vessel number, but they were larger and with a greater total surface area. Therefore, this cultivar might be better than RB for water transport, although more prone to wilting under water stress. Our results complement other studies on cut rose cultivars in terms of the role of the leaf epidermis and xylem vessels in determining differences in water consumption and transport during the stem life in glasses. These results might also contribute to designing post-harvest techniques for optimizing flower quality.

BACKGROUND: Bortezomib and rituximab have shown additive activity in preclinical models of lymphoma, and have been shown to be active and generally well tolerated in a randomised phase 2 study in patients with follicular and marginal zone lymphoma. We compared the efficacy and safety of rituximab alone or combined with bortezomib in patients with relapsed or refractory follicular lymphoma in a phase 3 setting. METHODS: In this multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib 1·6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of all cycles. Randomisation was stratified by FLIPI score, previous use of rituximab, time since last therapy, and region. Treatment assignment was based on a computer-generated randomisation schedule prepared by the sponsor. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00312845. FINDINGS: Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median follow-up of 33·9 months (IQR 26·4-39·7), median progression-free survival was 11·0 months (95% CI 9·1-12·0) in the rituximab group and 12·8 months (11·5-15·0) in the bortezomib plus rituximab group (hazard ratio 0·82, 95% CI 0·68-0·99; p=0·039). The magnitude of clinical benefit was not as large as the anticipated prespecified improvement of 33% in progression-free survival. Patients in both groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%) and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab groups, respectively, completed five cycles. Of patients who did not complete five cycles, most discontinued early because of disease progression (77 [23%] patients in the rituximab group, and 56 [17%] patients in the bortezomib plus rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients) were lower in the rituximab group than in the combination group. The most common adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the rituximab group and 37 [11%] patients in the bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no patients and 25 [7%] patients, respectively), herpes zoster (one [

The concept of 'brand experience' has evolved as an imperative arena of study in the marketing discipline. Although the importance and the concept of experience have been adapted in marketing such as customer experience, consumption experience and so on, the explanations of brand experiences have remained vague and absent a thorough theoretical foundation. This research aims to understand the concept of 'brand experience' and its impact of consumer behaviour (loyalty) direct or indirect through brand personality, satisfaction or [and] brand trust in the luxury brand context (Thailand). This research is carried out in one stage 'quantitative'. Furthermore the research data will be collected based on distributing survey questionnaire. Among of 400 Thai citizen samples will be surveyed to measure a modify framework from (Brakus et al, 2009). The result will provide meaningful information in both academic research and marketing practice. Furthermore, it will be presented the prediction of consumer behaviour via brand experience. Moreover, it guides marketers to various marketing strategy option such as experiential marketing or traditional marketing.

AIMS/HYPOTHESIS: Membrane phospholipids are the major intracellular source for fatty acid-derived mediators, which regulate myriad cell functions. We showed previously that high glucose levels triggered the hydrolysis of polyunsaturated fatty acids from beta cell phospholipids. These fatty acids were subjected to free radical-catalysed peroxidation to generate the bioactive aldehyde 4-hydroxy-2E-nonenal (4-HNE). The latter activated the nuclear peroxisome proliferator-activated receptor-? (PPAR?), which in turn augmented glucose-stimulated insulin secretion. The present study aimed at investigating the combined effects of glucose and fatty acid overload on phospholipid turnover and the subsequent generation of lipid mediators, which affect insulin secretion and beta cell viability. METHODS: INS-1E cells were incubated with increasing glucose concentrations (5-25 mmol/l) without or with palmitic acid (PA; 50-500 ?mol/l) and taken for fatty acid-based lipidomic analysis and functional assays. Rat isolated islets of Langerhans were used similarly. RESULTS: PA was incorporated into membrane phospholipids in a concentration- and time-dependent manner; incorporation was highest at 25 mmol/l glucose. This was coupled to a rapid exchange with saturated, mono-unsaturated and polyunsaturated fatty acids. Importantly, released arachidonic acid and linoleic acid were subjected to peroxidation, resulting in the generation of 4-HNE, which further augmented insulin secretion by activating PPAR? in beta cells. However, this adaptive increase in insulin secretion was abolished at high glucose and PA levels, which induced endoplasmic reticulum stress, apoptosis and cell death. CONCLUSIONS/INTERPRETATION: These findings highlight a key role for phospholipid remodelling and fatty acid peroxidation in mediating adaptive and cytotoxic interactions induced by nutrient overload in beta cells.

Recent developments in marketing theory have resulted in the conceptualisation of the market orientation construct in different cultural and industrial settings. However, there is little research investigating the applicability of market orientation in the higher education context. Building on the existing literature on market orientation and higher education marketing, the authors propose a theoretical framework of market orientation from a higher education management perspective. The framework analysis leads to propositions relating to the antecedents and consequences of market oriented universities. On the basis of the formulated propositions, the authors conclude with a discussion of the implications both for academia and practice and further research.

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 microM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP+, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14CO2 from D-[14C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

In spite of the rising interest in marketing within professional service firms in the last twenty years, past research has identified a reluctant acceptance and application of marketing within these organisations. The present paper will debate whether this is due to lack of understanding of the role of marketing, lack of acceptance as a valid management discipline suitable for professional services or lack of legitimacy as a profession in its own right. A brief overview of the role of marketing will be followed by a discussion on the professions, professional legitimacy and the professional organisation. Qualitative research was done in the form of in-depth interviews with marketing executives and accountancy and law professionals in fourteen firms across the UK. The research has revealed generational differences, misconceptions and outright conflict leading to resistance in the introduction and application of marketing, although the professionals have individually practiced a wide variety of marketing activities in their pursuit of gaining and maintaining clients. There has been a conspicuous resistance to the acceptance of marketing as a management tool within certain firms. The findings have opened up the spectre of inter-professional competition on legitimacy grounds.

Information and Communication Technology (ICT) has become a major enabling technology that is nowadays very much 'en vogue'. It has also become an important tool to promote a variety of business goals and public policies. The growing importance of ICT in daily life, business activities and governance prompts the need to consider ICT more explicitly in local policies. The expected benefits from ICT encourage urban policy-makers to formulate proper strategies for public ICT policies. But, what are the urban policy-makers' expectations about ICT? And how do they assess the future implications of ICT for their city? This paper is focusing on the way urban decision-makers perceive the opportunities of modern ICT and its related ICT policy. By highlighting the importance of understanding the decision-maker's 'black box' on ICT, we will address three crucial issues in European cities, viz. perception of the city, attitude towards ICT, and assessment of the relevance of ICT policy. We will give an operational meaning to these three variables by using a survey comprising more than 200 European cities as the basis for a classification of these cities by means of their e-images.

“It seems probable that this study covers the period of practical extinction of empyema as an important disease.” Lionakis B et al , J Pediatr 1958. ### 1.1 Structure of the guideline The format follows that used for the BTS guidelines on the management of pleural disease in adults.1 At the start there is a summary table of the abstracted bullet points from each section. Following that is an algorithm summarising the management of pleural infection in children (fig 1). Each section starts with bulleted points of key recommendations using the revised SIGN grading system (table 1) available on http://www.sign.ac.uk/guidelines/fulltext/50/section6.html. Beneath each set of bullet points is a short paragraph detailing the referenced literature and the rationale behind the recommendations. The primary source literature has been individually graded for its methodology and the grading is given alongside each reference using the revised SIGN levels of evidence (table 2). View this table: Table 1 Revised SIGN grading system: grades of recommendation View this table: Table 2 Revised SIGN grading system: levels of evidence Figure 1 Algorithm for the management of pleural infection in children. ### 1.2 Methodology for generation of the guidelines The initial literature search was carried out by the Library of the National Heart Lung Institute, Imperial College London. Further searches were then carried out by members of the working group who concentrated on their own topics. Details of the search strategy are given in Appendix 1. Each section of the guideline was researched and drafted by a subgroup of the Paediatric Pleural Diseases Subcommittee (itself a subcommittee of the BTS Standards of Care Committee). Publications were rated according to the SIGN criteria for the calibre of the methodology of the research to give levels of evidence (table 2). Tables of evidence were then produced before writing the guideline sections using the SIGN grades of recommendations (table 1). Once all parts were merged into one document, the whole group then met to discuss …