BACKGROUND AND OBJECTIVESIn multiple sclerosis (MS), peripheral immune cells use various cell trafficking molecules to infiltrate the CNS where they cause damage.The objective of this study was to ...investigate the involvement of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the CNS of patients with MS. METHODSExpression of CLMP was measured in primary cultures of human brain endothelial cells (HBECs) and human meningeal endothelial cells (HMECs), postmortem brain samples, and peripheral blood mononuclear cells (PBMCs) from patients with MS and controls by RNA sequencing, quantitative PCR, immunohistochemistry, and flow cytometry. In vitro migration assays using HBECs and HMECs were performed to evaluate the function of CLMP. RESULTSUsing bulk RNA sequencing of primary cultures of human brain and meningeal endothelial cells (ECs), we have identified CLMP as a new potential cell trafficking molecule upregulated in inflammatory conditions. We first confirmed the upregulation of CLMP at the protein level on TNFα-activated and IFNγ-activated primary cultures of human brain and meningeal ECs. In autopsy brain specimens from patients with MS, we demonstrated an overexpression of endothelial CLMP in active MS lesions when compared with normal control brain tissue. Flow cytometry of human PBMCs demonstrated an increased frequency of CLMP+ B lymphocytes and monocytes in patients with MS, when compared with that in healthy controls. The use of a blocking antibody against CLMP reduced the migration of immune cells across the human brain and meningeal ECs in vitro. Finally, we found CLMP+ immune cell infiltrates in the perivascular area of parenchymal lesions and in the meninges of patients with MS. DISCUSSIONCollectively, our data demonstrate that CLMP is an adhesion molecule used by immune cells to access the CNS during neuroinflammatory disorders such as MS. CLMP could represent a target for a new treatment of neuroinflammatory conditions.
Despite present optimal standard treatment of lower-extremity ulceration, a high incidence of recurrence and treatment failure is observed. The objective of this project was to evaluate the effect of ...a self-assembled skin substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in the treatment of hard-to-heal chronic ulcers.
The prospective uncontrolled case study includes patients suffering from venous or mixed ulcers lasting more than 6 months and unresponsive to compression therapy, with an Ankle Brachial Index greater than 0.5. Compression therapy was combined with the weekly application of SASS, produced from the patient's own skin cells, until healing. A weekly follow-up recorded wound size, skin aspect, pain, drainage, and percentage of wound healing. Photographs were also taken to assess ulcer evolution.
Fourteen ulcers present on 5 patients were treated. A mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers developed a minor wound infection, which was treated with oral antibiotics; another 2 ulcers recurred, and 1 healed with a second course of treatment, whereas 1 ulcer had a small recurrence treated with local wound care.
The authors' study suggests that the SASS used as a biological dressing is a promising treatment for hard-to-heal chronic venous and mixed ulcers that are unresponsive to compression therapy.
Summary Macroscopic sedimentary charcoal and plant macroremains from two lakes, 50 km apart, in north‐western O ntario, C anada, were analysed to investigate fire frequency and tree abundance in the ...central boreal forest. These records were used to examine the controls over the long‐term fire regime, and vegetative dynamics associated with fire return intervals ( FRI s). There were 52 fire events at L ake B en (surrounded by a xeric landscape) between 10 174 calibrated years before present (cal. year bp ) and the present with an average FRI of 186 years with values oscillating between 40 and 820 years. Forty‐three fire events were recorded at L ake S mall (surrounded by a mesic landscape) between 9972 cal. year bp and the present with an average FRI of 229 years and a range of 60–660 years. FRI s at L ake S mall decreased significantly after c . 4500 cal. year bp , whereas at L ake B en FRI s remained similar throughout the H olocene. Different FRI distributions and independence in the occurrence of fire events were detected between 10 000 and 4500 cal. year bp for the two sites. Between 4500 cal. year bp and the present, similar FRI s were observed, but fires continued to occur independently. Longer FRI s resulted in declining abundance of L arix laricina in both landscapes. Longer FRI s resulted in a decline in the abundance of P icea mariana in the xeric landscape, but a marginal increase in the mesic landscape. Abundances of P inus banksiana , P inus strobus and B etula papyrifera were unrelated to FRI , underlying that these species maintain their local abundance irrespective of fire frequency. Synthesis . Our results show contrasting fire regime dynamics between a xeric and mesic landscape in central boreal forests, C anada. These results highlight the influence of local factors as important drivers of fire frequency at centennial to millennial scales. Local site factors, especially soil moisture, need to be incorporated into predictive models of vegetation response to climate change.
Abstract 1641
Rituximab has proven efficacy and tolerability for treating B-cell malignancies. IV rituximab administration can take several hours, consuming considerable healthcare resources. A SC ...rituximab formulation has been developed which may shorten administration time, increase patient (pt) convenience, and potentially reduce IV administration-associated costs. Rituximab efficacy depends on CD20 binding, and Ctrough rituximab levels reflect rituximab exposure throughout the therapy cycle; therefore, achieving a non-inferior Ctrough level with SC dosing is expected to provide comparable efficacy to IV dosing. BP22333 (NCT00930514) is a two-stage phase Ib study assessing PK and tolerability of SC vs IV maintenance rituximab in pts with first-line or relapsed FL. Stage 1 dose-finding results (Salar et al, ASH 2010, abstract 2858; Salar et al, EHA 2012, abstract 0794) identified a fixed dose of 1400 mg for formal Ctrough non-inferiority testing in Stage 2. We report Stage 2 data.
The Stage 2 objective was to demonstrate non-inferiority of simulated Ctrough of rituximab SC and IV, using a non-inferiority test with a lower boundary of 0.8 for the 90% confidence interval (CI). Secondary endpoints include SC vs IV rituximab safety and area under the serum concentration-time curve. Eligible pts (N = 157) were aged ≥18 years with an ECOG performance status of ≤ 2, and histologically confirmed CD20-positive grade 1, 2, or 3a FL requiring treatment. Eligible pts must have achieved a complete or partial response following IV rituximab-based induction therapy for FL and have received ≥1 cycle of IV rituximab maintenance within 16 weeks of completing induction. Pts (N = 154) were randomized 1:1 to receive SC rituximab (1400 mg) or IV rituximab (375 mg/m2) for their remaining maintenance cycles, stratified by 2-monthly (q2m) vs 3-monthly (q3m) regimen. Study arms were balanced for age, sex, body surface area, FL grade at diagnosis, induction therapy and number of maintenance doses prior to study entry. As of May 11, 2012, 13 SC pts had withdrawn (7 for progressive disease PD, 4 for AEs, 1 at investigator’s decision, 1 for ineligibility) and 17 IV pts had withdrawn (10 for PD, 4 for AEs, 3 for ineligibility). Median treatment duration on-study was 14.8 months (range, 0–19) in the SC arm and 13.8 months (range, 0–19) in the IV arm.
The primary endpoint of the study was met. Geometric mean Ctrough,SC:Ctrough,IV ratios were 1.24 and 1.12, respectively, for q2m and q3m, and lower limits of the two-sided 90% CI (1.02 and 0.86, respectively) exceeded the protocol-specified non-inferiority limit (Ctrough,SC:Ctrough,IV ratio of 0.8). Therefore, 1400 mg SC rituximab was concluded to be non-inferior to 375 mg/m2 IV rituximab administration.
AE incidence and intensity were generally balanced; 79% of pts in each arm experienced AEs. Serious AEs were observed in 12% and 14% of pts in the SC and IV arms, respectively; none occurred in > 1 pt in either arm. Grade 3/4 AEs occurred in 18% and 17% of pts in the SC and IV arms, respectively; the only grade 3/4 AEs occurring in > 1 pt in either arm were neutropenia (2 pts in each arm) and arthralgia (2 pts in the IV arm). Administration-related reactions (ARRs) were the most frequent AE and had a higher incidence in the SC arm (reported in 31% of SC vs 4% of IV pts). ARRs were mostly local reactions; the most common in the SC arm were: erythema (13%), injection site erythema (5%), and myalgia (5%). Further safety data will be presented.
PK data for SC and IV rituximab administration demonstrate non-inferiority of 1400 mg rituximab SC administration to that of the approved IV rituximab maintenance regimen for both q2m and q3m schedules. The overall AE profiles were similar for SC and IV rituximab administration, with the exception of local ARRs, which had a higher incidence in the SC arm compared with the IV arm, reflecting the expected change in the ARR profile with SC administration. Induction and maintenance therapy using the 1400 mg SC rituximab dose is being assessed in the phase III BO22334 study.
Salar:Roche: Consultancy. Off Label Use: Subcutaneous (SC) administration of rituximab as maintenance therapy in patients with follicular lymphoma (FL). Larouche:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brewster:Roche: Employment, Equity Ownership. Catalani:Roche: Employment, Equity Ownership. McIntyre:Roche: Employment. Sayyed:Roche: Employment. Haynes:Roche: Consultancy, Honoraria.
In the past few years, considerable progress has been achieved in understanding the growth mechanism of single-walled carbon nanotubes (C-SWNTs). Nevertheless, the nucleation of C-SWNTs still remains ...partially unexplained by these models. A study of the critical synthesis parameters in the plasma torch process and a review of existing growth mechanisms lead us to propose a new growth mechanism for bundles of C-SWNTs, based on the Bénard–Marangoni instability. It is shown that the conditions occurring at the surface of the catalyst nanoparticle (NP) during the growth of the C-SWNTs give rise to the solutal BMI, which in turn results in a pattern of hexagonal convection cells in the liquid layer on the surface of the NP. The vortex ring flow pattern within these cells is then responsible for the structured growth of the C-SWNT bundles. This model highlights the important parameters required to optimize the synthesis of C-SWNTs.
In this study, we examine, in detail, the synthesis of single wall carbon nanotubes (C-SWNTs) with a plasma torch, using molecular sources for both carbon and catalyst (typically a carbon-containing ...gas such as ethylene and ferrocene for the metal catalyst). A comparison of the results obtained by Raman spectroscopy, using two different excitation wavelengths, permitted us to evaluate the importance of certain experimental parameters affecting the quality of the samples; these include the growth temperature of the nanotubes, and the temperature gradient between the flame and the oven. We have found that our method provides results that are qualitatively similar to those obtained using arc and laser techniques: C-SWNTs mixed with catalyst nanoparticles and amorphous carbon. Although the yields of C-SWNTs in the experiments reported here are somewhat lower than other approaches, our method avoids the inconveniences related to the solid phase of the initial material. Observations from scanning electron micrographs (SEM) and transmission electron micrographs (TEM) suggest that the mechanisms involved in the synthesis of the C-SWNTs by our plasma torch are similar to these latter techniques. An industrial-scale process based on a plasma torch could produce large amounts of C-SWNTs with good efficiency, since the present set-up produces continuously 1.5 g/h of deposit while using only 1 kW of power.
Le présent recueil est conçu à partir de trois grandes thématiques chères à Luc Van Campenhoudt : la question de l'articulation entre la théorie et l'empirie, abordée à travers le mode ...d'entrée de la « surprise » ; la question de l'évaluation des concepts de champ et de réseau ; et enfin la question de l'engagement du chercheur dans la cité, ou comment concilier l'autonomie du champ scientifique (la rigueur, la critique...) et le « service à la société ». À travers la diversité des contributions réunies ici se dessinent quelques-unes des lignes qui caractérisent la situation actuelle des sciences sociales, entre « convergences et divergences », fondements, innovations et points de débat. Se dégage également la figure du sociologue médiateur, soucieux de jeter des ponts, de dépasser les cloisonnements et les spécialisations, tout en maintenant la spécificité du « métier de sociologue » et en amenant les acteurs à « se mettre d'accord sur leurs désaccords » – condition d'un vivre-ensemble conçu démocratiquement à partir du modèle de la « coopération conflictuelle ». Les 18 et 19 octobre 2012 s'est déroulé aux Facultés universitaires Saint-Louis - entre-temps rebaptisées Université Saint-Louis- Bruxelles - un colloque international en hommage à Luc Van Campenhoudt, à l'occasion de son accession à l'éméritat. Cet ouvrage rassemble presque l'intégralité des communications présentées lors de ce colloque, l'ensemble étant en outre augmenté de quelques contributions proposées « en bonus ». Connu et reconnu pour ses livres, rédigés seul ou en collaboration, qui ont contribué à former plusieurs générations d'étudiants (cf. le Manuel de recherche en sciences sociales, l'Introduction à l'analyse des phénomènes sociaux, etc.), Luc Van Campenhoudt a par ailleurs déployé une intense et féconde activité de chercheur, en privilégiant le travail en équipe et en multipliant les champs d'études empiriques, notamment en tant que directeur du Centre d'études sociologiques (CES) ou comme promoteur de la méthode d'analyse en groupe (MAG).
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