Ectopic calcification is an important contributor to chronic diseases, such as osteoarthritis. Currently, no effective therapies exist to counteract calcification. We developed peptides derived from ...the calcium binding domain of human Alpha-2-HS-Glycoprotein (AHSG/Fetuin A) to counteract calcification.
A library of seven 30 amino acid (AA) long peptides, spanning the 118 AA Cystatin 1 domain of AHSG, were synthesized and evaluated in an in vitro calcium phosphate precipitation assay. The best performing peptide was modified (cyclic, retro-inverso and combinations thereof) and evaluated in cellular calcification models and the rat Medial Collateral Ligament Transection + Medial Meniscal Tear (MCLT + MMT) osteoarthritis model.
A cyclic peptide spanning AA 1–30 of mature AHSG showed clear inhibition of calcium phosphate precipitation in the nM–pM range that far exceeded the biological activity of the linear peptide variant or bovine Fetuin. Biochemical and electron microscopy analyses of calcium phosphate particles revealed a similar, but distinct, mode of action in comparison with bFetuin. A cyclic-inverso variant of the AHSG 1–30 peptide inhibited calcification of human articular chondrocytes, vascular smooth muscle cells and during osteogenic differentiation of bone marrow derived stromal cells. Lastly, we evaluated the effect of intra-articular injection of the cyclic-inverso AHSG 1–30 peptide in a rat osteoarthritis model. A significant improvement was found in histopathological osteoarthritis score and animal mobility. Serum levels of IFNγ were found to be lower in AHSG 1–30 peptide treated animals.
The cyclic-inverso AHSG 1–30 peptide directly inhibits the calcification process and holds the potential for future application in osteoarthritis.
The paper describes the preparation of the short-pulse high-energy laser PETawatt Aquitaine Laser (PETAL), which will be coupled to the Laser Megajoule (LMJ) laser of CEA. The LMJ/PETAL facility will ...be opened for the academic access of European researchers. In parallel, diagnostics are being developed within the PETAL + project and many physical problems are being addressed ranging from the study of the problems of radiation generation and activation issues to the problem of generation of large electromagnetic pulses.
We report the dramatic effect of applied pressure and magnetic field on the layered intermetallic compound Pr(0.5)Y(0.5)Mn(2)Ge(2). In the absence of pressure or magnetic field this compound displays ...interplanar ferromagnetism at room temperature and undergoes an isostructural first order magnetic transition (FOMT) to an antiferromagnetic state below 158 K, followed by another FOMT at 50 K due to the reemergence of ferromagnetism as praseodymium orders (T(C)(Pr)). The application of a magnetic field drives these two transitions towards each other, whereas the application of pressure drives them apart. Pressure also produces a giant magnetocaloric effect such that a threefold increase of the entropy change associated with the lower FOMT (at T(C)(Pr)) is seen under a pressure of 7.5 kbar. First principles calculations, using density functional theory, show that this remarkable magnetic behavior derives from the strong magnetoelastic coupling of the manganese layers in this compound.
For several adult cancer types, there is evidence that treatment in high volume hospitals, high case volume providers, or in specialised hospitals leads to a better outcome. The aim of this study is ...to give an overview of the existing evidence regarding the volume effect in paediatric oncology related to the quality of care or survival.
An extensive search was carried out for studies on the effect of provider case volume on the quality of care or survival in childhood cancer. Information about study characteristics, comparisons, results, and quality assessment were abstracted.
In total, 14 studies were included in this systematic review. Studies with a low risk of bias provide evidence that treatment of children with brain tumours, acute lymphoblastic leukaemia, osteosarcoma, Ewing's sarcoma, or children receiving treatment with allogenic bone marrow transplantation in higher volume hospitals, specialised hospitals, or by high case volume providers, is related with a better outcome.
This systematic review provides support for the statement that higher volume hospitals, higher case volume providers, and specialised hospitals are related to the better outcome in paediatric oncology. No studies reported a negative effect of a higher volume.
High-quality care for all children with cancer Knops, R.R.G; Hulscher, M.E.J.L.; Hermens, R.P.M.G. ...
Annals of oncology,
07/2012, Letnik:
23, Številka:
7
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Providing high-quality care for children with cancer could improve treatment outcomes, survival and quality of life of the children and parents. The aim of this study is to select high-quality care ...recommendations for all children with cancer based on literature and consensus for future development of quality indicators.
We performed an extensive search in databases for scientific literature and in websites of international health care and guideline development organizations to create an inventory of recommendations for the care for all children with cancer. The RAND modified Delphi method was used to grade and select recommendations for high-quality care.
Our search resulted in a list of 131 recommendations on care for all children with cancer. The expert panel graded, discussed and prioritized these recommendations. Analysis of these ratings resulted ultimately in a list of 109 high-quality care recommendations for all children with cancer, including 31 prioritized recommendations.
This study defines a set of high-quality care recommendations based on literature and consensus. These recommendations provide a basis for the development of a comprehensive set of quality indicators to evaluate care in paediatric oncology.
Studying brain processes underlying tactile perception induced by natural-like stimulation is challenging yet crucial to closely match real-world situations.
We developed a computer-controlled ...pneumatic device that allows the delivery of complex airflow patterns on subject’s body, through a MR-compatible system fixed on an independent clippable mounting device. The intensity of stimulation as well as the timing of each of the four air channels are completely programmable and independent, allowing the precise control and modularity of the airflow delivery.
An analysis of signal-to-noise ratio (SNR) measurements did not show any impact of the PAF device on anatomical or functional scan acquisitions. A psychophysical experiment was also performed on 24 volunteers to evaluate the perception of different airflow patterns delivered over the lower part of their face. It revealed that all participants were able to finely discriminate the direction of these leftward to rightward flow motions. The fMRI experiment, which consisted in presenting to 20 participants four different airflow patterns, shed light on the brain network associated with tactile motion perception. A multivariate analysis further showed a specific coding of the different patterns inside this tactile brain network including the primary and secondary somatosensory cortex
The Patterned Air-Flow (PAF) is an easy-to-set-up, portable, adaptable device, which can be spatially and temporally modulated to provide complex tactile stimuli.
This device will be useful to further explore complex dynamic touch exerted over various body parts and can also be combined with visual or auditory stimulation to study multisensory mechanisms.
•The PAF can deliver stable and reliable complex airflow patterns.•The device is easy-to-set-up and fully fMRI compliant.•Psychophysical tests show that it can be used to discriminate airflow directions.•Different tactile patterns could be decoded by fMRI measurements.•It is useful for studying complex tactile motion coding/perception.
Objective
The KLIK method is an online tool that monitors and discusses electronic patient‐reported outcomes (ePROs), which has been shown to enhance outcomes. This study aimed (1) to determine the ...fidelity (ie, extent to which used as intended) of the KLIK method as implemented in outpatient pediatric cancer care and (2) to study health care professional (HCP)‐reported barriers and facilitators for implementation.
Methods
Two hundred five children with newly diagnosed cancer (enrollment rate 85%) participated. At 1 (T1), 3 (T2), and 6 (T3) months after diagnosis, patients (8‐18 years) or parents (of patients 0‐7 years) completed health‐related quality of life (HRQoL) questionnaires, which were transformed into an ePROfile and discussed by their HCP during consultations. Fidelity was determined by the following: percentage of website registrations, HRQoL questionnaires completed, and ePROfiles discussed. Implementation determinants were assessed with HCPs after the final T3 with the Measurement Instrument for Determinants of Innovations.
Results
Depending on the time point (T1‐T3), fidelity was 86% to 89% for website registration, 66‐85% for completed HRQoL questionnaires, and 56% to 62% for ePROfile discussion. Barriers were mainly related to organizational issues (eg, organizational change) and less frequently to users (eg, motivation to comply) or the intervention (compatibility). Facilitators were related to the user (eg, positive outcome expectations) and intervention (simplicity) but not to the organization.
Conclusions
When implementing ePROs in outpatient pediatric oncology practice, HCPs report determinants that influence ePRO integration. To improve implementation and outcomes, tailored organizational (eg, formal ratification by management and time) and specific local (eg, individualized assessments) strategies should be developed to achieve optimal ePRO discussion.
The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer ...survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline.
A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus.
There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations.
The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.
Résumé Le document ici proposé s’inscrit dans la lignée des recommandations pour la pratique que la Société française d’endocrinologie a constituées à l’usage de ses membres et mises à la disposition ...des communautés scientifiques et des médecins qui le souhaitent. Se fondant sur une analyse critique des données de la littérature, des consensus et recommandations déjà parues au plan international, il constitue une actualisation du rapport sur la prise en charge diagnostique du nodule thyroïdien, proposé en France, en 1995, sous l’égide de l’Agence nationale d’évaluation médicale. Les actuelles recommandations ont été préalablement réfléchies par un certain nombre de médecins reconnus pour leur expertise de la thématique, émanant de l’endocrinologie (groupe de recherche sur la thyroïde), de la chirurgie (Association française de chirurgie endocrinienne), de représentants de la biologie, de l’échographie, de la cytologie, de la médecine nucléaire. Elles ont été présentées et soumises à l’avis des membres de la société, présents au congrès annuel qui s’est tenu à Nice en octobre 2009. Le document amendé a été placé sur le site Internet de la société et a bénéficié de remarques complémentaires de membres de la société. La version finale ici proposée n’a pas fait l’objet d’une validation méthodologique. Elle n’a pas prétention à l’universalité et nécessitera d’évoluer parallèlement aux progrès des techniques et des conceptions. Elle constitue un document que la société juge utile de diffuser, pour une gestion actuelle, efficace et rentable de l’approche diagnostique et thérapeutique des nodules thyroïdiens.
Abstract Background Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic ...heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. Patients and methods All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. Results 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio HR = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal ULN; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). Conclusions We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.
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