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Competing Interests: Disclosure The authors have declared no conflicts of interest. List of associated partners ePAGs: Associazione Italiana Laringectizziati (AILAR), Digestive Cancer Europe (DiCE), European Association of NeuroOncology (EANO), European Cancer Organisation, European Cancer Patient Coalition (ECPC), European Head and Neck Society (EHNS), European Network of Gynaecological Cancer Advocacy Groups (ENGAGe), European Neuroendocrine Tumour Society (ENETS), European Organisation for Research and Treatment of Cancer (EORTC), European Rare Disease Patient Organisation (EURORDIS), European School of Oncology (ESO), European Society of Gynaecological Oncology (ESGO), European Society for Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO), Melanoma Patient Network Europe (MPNE); French National Network for the Treatment of Rare Peritoneal Surface Malignancies (RENAPE), Info Sarcomes, International Brain tumour Alliance (IBTA), International Neuroendocrine Cancer Alliance (INCA), Melanoma Info Deutschland (MID), Neuroendocrine Cancer, UK, Salivary Gland Cancer UK (SGC), Sarcoma Patients Euronet (SPAEN), Thyroid Cancer Alliance (TCA), Joint Action on Rare Cancers (JARC), Lyon Ingenierie Projets (LIP), Organisation of European Cancer Institute (OECI), Réseau Tumeurs Thymiques et Cancer (Rythmic), French Sarcoma Group, French Tumour Study Group (GSF-GETO), the NETSARC+ network, LYRICAN, Université Claude Bernard Lyon 1 (UCBL), Universita degli studi di Milano (UNIMI).

Alors que le médecin généraliste (MG) est en première ligne pour la prise en charge des troubles psychiatriques courants, seule la moitié de ces troubles est connue du MG. L’objectif était de comparer leur repérage par les MG avant et après l’introduction du dispositif du médecin traitant.

Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1highstates, characterized by highly active cell proliferation, and EWSR1-FLI1lowstates where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.

Giant cell reparative granuloma is a very rare benign osteolytic lesion. It typically arises in the mandible and rarely involves the skull.

•This paper introduces a new method for controlling the jet penetration depth in AWJ milling.•The developed ILC technique allows improvements in the output of the AWJ milling process.•A step-by-step methodology was introduced for implementing ILC in AWJ milling.•It was shown that the errors associated with the AWJ milling process can be reduced more than 50%.•Significant reduction of setup times compared with the manual, trial and error, approach was achieved.

Three type of uncertainties related to rainfall hazard study are presented. The first one concerns the measurement of extreme rainfall using a sparse rain gage network: it has been shown that before 1945, the probability that a rainfall event less than 200 km2 is not measured by the network, is up to three times more important comparing to the current period of observation. The second point is about the shape of the probability distribution of frequency (PDF) of the daily maxima annual rainfall: does the tail of the distribution correspond to a Gumbel PDF or does it show an ?hyper exponential? behaviour? According to the chronics duration, one can difficulty argue while analysing a single rainfall chronic because of sampling uncertainties. It has been shown that a regional PDF has an hyper exponential tail. The quantiles are less subject to sampling variability comparing to the one obtain with a local PDF fitting. In the last point the mean area rainfall PDF is studied according to the area. A scale relation between the PDF corresponding to different areas is presented. The sampling variability of the PDF shape parameter is presented. Conclusion concerning the asymptotic behaviour of the mean areal rainfall PDF needs further analysis.

Pathological examination of tumours of the central nervous system (CNS) is essential in terms of patient management. This examination is based on cytology, histology of fixed and paraffin-embedded specimens, and also on ancillary techniques such as immunohistochemistry and electron microscopy. Peroperative examination of biopsies is usually required to assess the representativeness of the fragments. If enough material is available, a specimen of the tumour is snap-frozen in liquid nitrogen. WHO classification of brain tumours distinguishes primitive and secondary tumours. Among primitive CNS tumours, the most frequent are neuroepithelial tumours, especially gliomas. Histopathological criteria for diagnosis and grading are well defined though sometimes controversial, such as for gliomas. Recently, molecular biology described specific genetic alteration patterns related to malignancy, for example for gliomas and meningiomas. Such data are added to pathological diagnosis.

The El Batan urban watershed covers about 50?km2in Quito, Ecuador. Rainfall and stream flow data were collected between 1982 and 1984 and then again in 1998. Although both geometric and hydraulic data were available, rainfall?–?runoff modelling was carried out using a conceptual rainfall?–?runoff model in order to avoid the very tedious work that defining the topology (pipes, channels, nodes, subcatchments) of such a large area implies. Considering both the physiographic heterogeneity and the high variability of the rainfall in this mountainous context, a distributed modelling approach was chosen that develops and generalizes the concept of the unit hydrogram to a grid-cell structure. For each cell, the contribution at a given time is computed by using an instant runoff coefficient. Then the elementary contributions are transferred through the drainage system by means of a translation and storage combination, which uses two parameters. The runoff coefficient primarily depends on the land-use characteristics, so this coefficient changes appreciably between 1982?–?1984 and 1998 due to urban growth and the development of drainage infrastructure. Discharge parameters are stable for the whole set of events and for both observation periods, and can be related to hydraulic characteristics of the drainage network. On the basis of simplified assumptions, it is shown that the distributed model is able to simulate the observed floods. Finally, the model was applied to the systematic detection of overloading in the Quito sewage network.

The determination of actinides concentration level in excreta, mainly urine is currently carried out to monitor people potentially exposed to α emitters. To measure actinides in such samples, specific analytical protocols have been set up. The chemical purification uses different chromatographic columns to selectively separate the actinides and each fraction, after electroplating, is measured by α spectrometry. To reach 1 mBq l−1of U, Pu or Am using these protocols, 6 days equally distributed between the chemical purification and the measurement are necessary. The protocol proposed here is based on a single extractant, the 1,3,5-trimethoxy-2,4,6-tricarboxy-p-tert-butyl-calix[6]arene, used to selectively separate U, Pu and Am from the urinary matrix prior to be measured. Using this analytical protocol, U and Pu are quantitatively and selectively recovered in two different acidic backextraction solutions whereas Am is quantitatively and selectively recovered in the organic phase. Furthermore, the purification stage is considerably shortened. The uranium and plutonium amounts are measured in aqueous phases using α spectrometry or inductively coupled plasma-mass spectrometry, whereas Am is measured in the organic phase using α liquid scintillation (photon/electron-rejecting alpha liquid scintillation).

ABSTRACTThe kinetics of copper(II) extraction from chloride solutions with ACORGA CLX-50 and three model dipentyl pyridine dicarboxylates having ester groups at various positions in the pyridine ring is investigated. It is shown that the extraction occurs in a diffusional regime and that both the ionic strength and temperature have a strong effect on the rate of copper extraction. Basically, the initial rate of copper extraction (denoted hereafter J0) increases as the ionic strength is increased, whereas J0increases or decreases versus temperature depending on the ionic strength. Such phenomena are explained in terms of salting-out effects and diffusion properties. Furthermore, ACORGA CLX-50 is shown to exhibit a good kinetic performance compared to the three model dipentyl pyridine dicarboxylates.

The dopaminergic system implicated in human disorders such as Parkinson's disease, schizophrenia and prolactinomas, exerts its effects through several dopamine receptors. The diversity of the dopaminergic system has been revealed by the application of molecular biology techniques to this system, which allowed the identification of five different types of dopamine receptors to date. Even though the structure of these receptors has now been identified, their physiological roles are still under investigation. The coupling of the D1 and D2 dopamine receptor to second messengers has been investigated using cell lines transfected with the cDNAs of these receptors. However, until recently, there was no technique allowing non-invasive real-time measurement of the metabolic activity of cells after agonist stimulation. We present here real-time measurement of events induced by dopaminergic agents on either the D1 or the D2 dopamine receptors using a novel technique employing a silicon-based microphysiometer.

Three genes closely related to the D1 dopamine receptor were identified in the human genome. One of the genes lacks introns and encodes a functional human dopamine receptor, D5, whose deduced amino acid sequence is 49% identical to that of the human D1 receptor. Compared with the human D1 dopamine receptor, the D5 receptor displayed a higher affinity for dopamine and was able to stimulate a biphasic rather than a monophasic intracellular accumulation of cAMP. Neither of the other two genes was able to direct the synthesis of a receptor. Nucleotide sequence analysis revealed that these two genes are 98% identical to each other and 95% identical to the D5 sequence. Relative to the D5 sequence, both contain insertions and deletions that result in several in-frame termination codons. Premature termination of translation is the most likely explanation for the failure of these genes to produce receptors in COS-7 and 293 cells even though their messages are transcribed. We conclude that the two are pseudogenes. Blot hybridization experiments performed on rat genomic DNA suggest that there is one D5 gene in this species and that the pseudogenes may be the result of a relatively recent evolutionary event.

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).

We report an anatomico-radiologic study of humerus, femur, and tibia from a case of total congenital afibrinogenemia. Juxtatrabecular hemorrhages occur mainly in metaphyses and seem to be related to normal lines of stress. They may lead to the formation of intraosseous cysts and to a remodelling of bone trabeculae.

Routine laboratory investigations carried out in 94 cases with acute spinal cord injury indicated moderate to severe deficiency within the extrinsic prothrombin activator system in 82.2 per cent of the patients. The clotting defect could be shown to be related to subnormal levels of vitamin K dependent plasma factors VII and X. There were 25 drop-outs in this study due to drug interference, irregular administration of vitamin K, intercurrent disease, etc. In the remaining group of 36 patients, none of the common etiological factors of acquired hypoprothrombinemia could be incriminated—such as poor intestinal resorption due to lack of bile salts, hepato-biliary disease, broad-spectrum oral antibiotherapy, drug interaction, hyperpyrexia, prolonged parenteral feeding, etc. In nine (25 per cent) of the cases total correction of factors VII and X was achieved after oral administration of vitamin K; in two (5.5 per cent) partial correction was similarly attained; in the remaining group of 25 (69.5 per cent) who proved to be resistant to oral vitamin K all but two normalised their factors after intravenous administration of the vitamin. These observations support the hypothesis that in acute spinal cord injury intestinal uptake of lipo-soluble substances may temporarily be impaired.

Abstract: Interfacial tension isotherms were determined and interpreted for ACORGA CLX-50. The hydration of extractant molecules in aqueous solution and at hydrocarbon/water interfaces was studied by molecular modelling. The usefulness of this technique to interpret the adsorption behavior was demonstrated. The interfacial kinetics was considered and relationships for various models of interfacial mechanism were derived and discussed. Despite its high hydrophobicity, ACORGA CLX 50 strongly adsorbs at the hydrocarbon/water interfaces and thus decreases effectively the interfacial tension. This high interfacial activity of ACORGA CLX 50 can be explained by the formation of hydrates. The interfacial tension isotherm can be well matched with the Szyszkowski equation. Molecular modelling suggests that ACORGA CLX 50 adsorbs at the hydrocarbon/water interface probably as a tetrahydrate containing two water molecules bonded to the same carbonyl oxygen atom (e.g., at position 3), one water molecule bonded to the oxygen atom of the second alkoxyl group (i.e., at position 5 when the hydration of carbonyl oxygen at position 3 is previously considered) and, finally, one water molecule bonded with the pyridine nitrogen atom. Positions 3 and 5 are equivalent. It is also shown that when the extraction of copper takes place in the kinetic regime, the reaction order with respect to ACORGA CLX 50 can change depending on the limiting step and the range of extractant concentration considered. Thus, a decrease of the extractant concentration from 10−5M to 3·10−3M causes a fall of the order with respect to ACORGA CLX 50 from 1 to 0 and 2 to 1 when the formation of the intermediate 1∶1 and final 2∶1 complexes are considered to be the limiting step, respectively.

The prognostic significance of c-erbB-2 oncoprotein overexpression detected in tumours by immunocytochemical assays (ICAs) was investigated in 148 breast carcinomas. ICAs were performed under optimal technical conditions with frozen tissue sections and included automated immunoperoxidase technique and computer-assisted analysis (densitometry) of digitized coloured microscopic images. Results of quantitative ICAs (expressed in percentages of c-erbB-2-positive surfaces and mean optical densities) were correlated with the patients' follow-up in axillary lymph node-positive (N+) and node-negative (N-) subgroups of patients. Patients' follow-up ranged from 9 months (for the first death) to 101 months (for the 121 alive patients) with a 62.5 months mean overall follow-up. It was shown that marked c-erbB-2 immunocytochemical expression in tumours (cut-off point 35%) significantly correlated with the patients' poor overall survival in N+ and in N- patients (Kaplan-Meier, log-rank test, P = 0.045 and P = 0.015). Also, marked c-erbB-2 immunohistochemical expression correlates with short disease-free (P = 0.005), recurrence-free (P = 0.048) and metastasis-free survival (P = 0.05) (Kaplan-Meier, log-rank test) in N+, but not in N- subgroups. It is concluded that in optimal conditions (automated and quantitative ICAs on frozen sections) c-erbB immunohistochemical expression is a significant prognostic indicator in terms of overall and disease-free survival. The c-erbB-2 protein prognostic significance is independent of node status in terms of overall survival, but not of disease-free survival.

A method has been developed for the isolation of rare cells in heterogeneous cell suspensions, for ultramicroscopic examination. Such cells cannot be located using conventional embedding screening techniques. The cells are embedded in Epon which is polymerized in the shape of an ordinary glass slide. Large numbers of suspended cells may be screened by light microscopy for the rare cells, which may then be sectioned for ultramicroscopy. The method has been used to locate and ultramicroscopically identify circulating endothelial cells in the blood of patients and experimental animals.Although artifacts were induced by the techniques used for collecting and concentrating circulating endothelial cells, the embedding method itself did not cause further morphological alterations.

Le granulome réparateur à cellules géantes est une lésion ostéolytique bénigne rare. Classiquement, elle atteint la mandibule, rarement la base du crâne.

Several letters to the editor are presented in response to articles published in the January 2008 issue including "A Mother's Heartbreak," by Lori Campbell, "Black Magic," by Valerie Steiker, and "Off the Deep End," by Hibi Pendleton.

Nurse developments in the management of neuroendocrine tumours have changed significantly over the past three years. At the Royal Free Hospital we set up the nurse specialist role due to the expansion of patients being referred to the specialist unit, and the obvious need for a nursing input into their care. The nurse specialist can make a significant contribution within the context of a multidisciplinary team especially in the production of guidelines and policies to ensure and maintain high standards of practice, education for the patient, and the provision of expertise and security that the patient requires when diagnosed with a rare disease.

We investigate the security of Diffie-Hellman key exchange as used in popular Internet protocols and find it to be less secure than widely believed. First, we present Logjam, a novel flaw in TLS that lets a man-in-the-middle downgrade connections to "export-grade" Diffie-Hellman. To carry out this attack, we implement the number field sieve discrete logarithm algorithm. After a week-long precomputation for a specified 512-bit group, we can compute arbitrary discrete logarithms in that group in about a minute. We find that 82% of vulnerable servers use a single 512-bit group, and that 8.4% of Alexa Top Million HTTPS sites are vulnerable to the attack. In response, major browsers have changed to reject short groups. We go on to consider Diffie-Hellman with 768- and 1024-bit groups. We estimate that even in the 1024-bit case, the computations are plausible given nation-state resources. A small number of fixed or standardized groups are used by millions of servers; performing precomputation for a single 1024-bit group would allow passive eavesdropping on 18% of popular HTTPS sites, and a second group would allow decryption of traffic to 66% of IPsec VPNs and 26% of SSH servers. A close reading of published NSA leaks shows that the agency's attacks on VPNs are consistent with having achieved such a break. We conclude that moving to stronger key exchange methods should be a priority for the Internet community. [ABSTRACT FROM AUTHOR]

A six-year study presented at the ESMO Gynaecological Cancers Congress 2024 highlights the benefits of cross-border tumour boards for women with complex rare gynaecological cancers. These tumour boards, consisting of cancer specialists from different European countries, meet virtually to review individual patient cases and provide new treatment recommendations. The study found that the boards resulted in increased access to clinical trials and recommended further diagnostic testing for over one-third of patients. Additionally, one in four patients gained access to off-label therapies or enrolled in clinical trials abroad based on the recommendations of the boards. The findings suggest that this approach could be beneficial for patients with other types of rare cancers as well. [Extracted from the article]