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Summary The duration of eXDR carriage depends on several factors that might be difficult to recover. We aim to assess the duration of eXDR carriage by using a simple to recover parameter: the number of consecutive negative screening. 131 eXDR carriers (51 VRE and 80 CPE) were included. The number of consecutive negative screenings was strongly associated with eXDR clearance. All patients displaying at least three negative screenings over a seven-month period were never screened positive thereafter. Taking into account the number of negative screenings as a part of a case-by-case risk assessment would be helpful for the decision to maintain or lift eXDR-focused precautions.

BACKGROUND/AIMS: Herbal products are increasingly used in modern medicine for numerous indications. They are not considered as drugs and thus often not linked to side effects. MATERIAL: A 77-year-old patient presented with silent icterus and biochemical evidence of hepatocellular damage. Because of dyslipidaemia, he was recently prescribed Controchol(®), a food supplement containing red yeast and green tea extracts. RESULTS: Liver biopsy showed necro-inflammatory destruction of liver parenchym, collapse of reticulin matrix, cholestasis and gall duct damage, compatible with toxic hepatitis. After discontinuation of Controchol(®), there was a gradual normalisation of the liver function tests. Liver injury is a known side effect of both red yeast and green tea extracts. After exclusion of other causes, we therefore concluded our patient had suffered from Controchol(®)-induced toxic hepatitis. CONCLUSION: Products that are conceived as "natural" alternatives for pharmacological drugs, like food supplements, are not free of side effects per se, and should not be considered as "harmless".Copyright © 2016 Elsevier Masson SAS. All rights reserved. Language: en

The development of a new beam reference line to improve bend-twist response modelling is presented. The beam reference line is derived as the locus of the cross-section elastic energy centres under pure bending moment. The performance of the new reference line is assessed via experimental measurements performed on a Siemens Gamesa wind turbine blade. Bend-twist modelling capability is assessed by comparing the location of the zero-twist rotation line and zero-twist-rate lines.

Background: Hand hygiene is a fundamental component of infection prevention, but few studies have examined whether hand-drying method affects the risk of dissemination of potential pathogens. Aim: To perform a multi-centre, internal-crossover study comparing bacterial contamination levels in washrooms with hand-drying by either paper towels (PT) or jet air dryer (JAD; Dyson). Methods: A total of 120 sampling sessions occurred over 12 weeks in each of three hospitals (UK, France, Italy). Bacteria were cultured from air, multiple surfaces, and dust. Washroom footfall (patients/visitors/staff) was monitored externally. Findings: Footfall was nine times higher in UK washrooms. Bacterial contamination was lower in PT versus JAD washrooms; contamination was similar in France and the UK, but markedly lower in Italian washrooms. Total bacterial recovery was significantly greater from JAD versus PT dispenser surfaces at all sites (median: 100–300 vs 0–10 cfu; all P < 0.0001). In the UK and France, significantly more bacteria were recovered from JAD washroom floors (median: 24 vs 191 cfu, P < 0.00001). UK meticillin-susceptible Staphylococcus aureus recovery was three times more frequent and six-fold higher for JAD vs PT surfaces (both P < 0.0001). UK meticillin-resistant S. aureus recovery was three times more frequent (21 vs 7 cfu) from JAD versus PT surfaces or floors. Significantly more enterococci and extended-spectrum β-lactamase (ESBL)-producing bacteria were recovered from UK JAD versus PT washroom floors (P < 0.0001). In France, ESBL-producing bacteria were recovered from dust twice as often during JAD versus PT use. Conclusion: Multiple examples of significant differences in surface bacterial contamination, including by faecal and antibiotic-resistant bacteria, were observed, with higher levels in JAD versus PT washrooms. Hand-drying method affects the risk of (airborne) dissemination of bacteria in real-world settings.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown. This study investigates systemic hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model of severe steatosis. Wistar rats were fed a methionine-choline-deficient diet, inducing steatosis, or control diet for 4 weeks. In vivo hemodynamic measurements, aortic contractility studies, and in situ liver perfusion experiments were performed. The mean arterial blood pressure was lower and portal blood pressure was higher in steatosis compared to controls. The maximal contraction force in aortic rings from steatotic rats was markedly reduced compared to controls. While blockade of nitric oxide (NO) production did not reveal any differences, cyclooxygenase (COX) blockade reduced aortic reactivity in both controls and steatosis, whereas effects were more pronounced in controls. Effects could be attributed to COX-2 iso-enzyme activity. In in situ liver perfusion experiments, exogenous NO donation or endogenous NO stimulation reduced the transhepatic pressure gradient (THPG), whereas NO synthase blockade increased the THPG only in steatosis, but not in controls. Alpha-1-adrenergic stimulation and endothelin-1 induced a significantly more pronounced increase in THPG in steatosis compared to controls. Our results demonstrate that severe steatosis, without inflammation or fibrosis, induces portal hypertension and signs of a hyperdynamic circulation, accompanied by extrahepatic arterial hyporeactivity and intrahepatic vascular hyperreactivity. The arterial hyporeactivity seems to be NO-independent, but appears to be mediated by specific COX-2-related mechanisms. Besides, the increased intrahepatic vascular resistance in steatosis appears not to be NO-related but rather to vasoconstrictor hyperreactivity.

Two cats were presented with a recent history of difficulty in walking and jumping. Neurological examination was consistent with a lumbosacral or a sciatic nerve lesion in both cases with an additional C6-T2 spinal cord segment lesion in case 2. Differential diagnosis included neoplastic, inflammatory/infectious (neuritis, meningomyelitis, discospondylitis) and compressive disc disease. Computed tomography (CT) revealed an enlarged, contrast enhancing sciatic nerve from the L7-S1 intervertebral foramen, to the distal third portion of the femoral shaft. In case 2, CT also revealed an enlarged femoral nerve and an extradural mass causing mild compression of the spinal cord at T1-2 and T3-4. Ultrasonography allowed to perform fine needle aspiration of the affected sciatic nerve. Cytology was highly suggestive of indolent, small cell lymphoma in case 1, and confirmed a high-grade lymphoma in case 2, both belonging to the large granular lymphoma subtype.

When this paper was first published one conflict of interest statement was omitted from the section. The correct statement is printed below in full: Conflict of interest statement M.H.W. has received honoraria from the European Tissue Symposium (ETS) for microbiological advice and lectures, and travel expenses to attend meetings. F.B. has received honoraria from ETS for microbiological advice and travel expenses to attend meetings. S.B. has received honoraria from ETS for microbiological advice and travel expenses to attend meetings.

BACKGROUND: Low-dose Olanzapine has been used clinically for over a decade in anorexia nervosa (AN) patients failing standard treatment in order to decrease anxiety and facilitate weight gain. While Olanzapine has been generally well tolerated, large scale data regarding safety and side-effects in AN patients is lacking. OBJECTIVES: To examine possible association between severe bradycar-dia and Olanzapine use in AN patients. DESIGN/METHODS: Case study and literature review. RESULTS: We present a case of severe bradycardia (HR 18) following initiation of low-dose Olanzapine in a 16 year old female admitted to our inpatient ward with AN and bradycardia during sleep.To our best knowl-edgeno other case studies of severe bradycardia in AN patients treated with Olanzapine have been published to date.We relate our case to findings from available literature that examines potential association between bradycardia and Olanzapine. We point to challenges with obtaining larger scale data on Olanzapine safety and side-effects in AN patients. CONCLUSION: There areinherent cardiac risks associated with treatment of AN patients. Existing literature in patients with diagnosis other than AN suggests there may be inter-individual differences in pharmacoki-netics of Olanzapine and that bradycardia may be a possible adverse effect of Olanzapine even at a low dose. Caution should be used in initiating Olanzapine in AN patients with baseline bradycardia.

Background: Adult dogs with neosporosis can develop a variety of neurologic signs. No area of predilection within the nervous system so far has been identified in adult dogs. Objectives: To document neosporosis as a cause of progressive cerebellar ataxia and cerebellar atrophy in dogs. Animals: Seven client-owned dogs. Methods: Retrospective, descriptive study. Results: Age at diagnosis ranged from 1 year 6 months to 9 years 11 months. Neuroanatomic localization indicated cerebellar and brainstem disease in 6 dogs and a central vestibular lesion in 1 dog. In all 7 dogs, there was moderate to marked bilaterally symmetrical cerebellar atrophy, with the atrophied cerebellum being surrounded by a region of T2-weighted hyperintense and T1-weighted hypointense signal. Cerebrospinal fluid (CSF) analysis in all but 1 dog showed mononuclear pleocytosis and high protein concentration. Polymerase chain reaction testing for Neospora caninum performed on the CSF was positive in 4/5 dogs tested and there was a high titer of serum antibodies to N. caninum (≥ 1 : 800) in all 6 dogs tested. Postmortem examination in 1 dog confirmed cerebellar atrophy and multifocal nonsuppurative encephalitis with areas of malacia and leptomeningitis. All of the remaining 6 dogs were treated with some combination of clindamycin, trimethoprim, sulfadiazine, and pyrimethamine. Two dogs were euthanized because of deterioration or relapse of neurologic signs, but treatment of the remaining 4 dogs resulted in improvement (3 dogs) or resolution (1 dog) of neurologic signs. Conclusions and Clinical importance: Neosporosis is an important cause of progressive cerebellar ataxia and cerebellar atrophy in adult dogs.

Summary: Pachytene analysis was carried out on an infertile man heterozygous for a pericentric inversion of chromosome 6. The synaptic behavior of the bivalent 6 inversion was analyzed using electron microscopy in silver stained surface microspread of the inversion-bearing spermatocytes. Possible mechanisms of the sterilizing effect caused by the autosomal inversion are discussed. Zusammenfassung: Bei einem infertilen heterozygoten Mann mit perizentrischer Fehlstellung des Chromosoms Nr. 6 wurden Pachyten-Analysen durchgefuhrt. Das Synapseverhalten der bivalenten Sechserfehlstellung wurde bei den betroffenen Spermatozyten mit Hilfe silber-gefarbter Oberflachenausstriche im Elektronenmikroskop beurteilt. Mogliche Mechanismen eines durch die autosomale Fehlstellung verursachten Sterilitatseffekts werden diskutiert.

This paper, after stressing the current safety analysis practice for commercial reactors, investigates and discusses the new challenges facing the nuclear community in the field of advanced numerical simulation for the safety demonstration of the most attractive concepts among those selected by the Generation IV International Forum in 2002, i.e.: the High Temperature / Very High Temperature Reactors, HTR/VHTR, the Sodium Fast Reactors, SFR, and the Gas Fast Reactors, GFR. The paper widely emphasizes the new needs in terms of computation, validation and experimental qualification of computer codes and chains which show-up as a consequence of a new design and an advanced operation. All those needs engender new and quite challenging requests for well fitted experimental programs and connected R&D activities.

The optimization studies for the next generation of aircraft and engine families are typically associated with the insertion of technological advances to improve fuel efficiency, noise levels, and overall aircraft economics. In the conceptual study phase, the optimization process needs to address the uncertainties related to the anticipation of market requirements and potential technological advances at the time of entry into service, along with the fidelity of the modeling applied in the analysis. The current paper presents a framework using a robust design optimization methodology to mitigate these uncertainties when an airframe and its engines are designed jointly. The optimization of a seventy passenger aircraft illustrates the approach with a formulation seeking to optimize the design, while attenuating its sensitivity to the potentially adverse effects of uncertainties.

We report investigations of optical transmission bistability in an unprocessed InGaAs-InAlAs superlattice p-i-n structure acting as a wireless self-electro-optical effect device (SEED). We have observed and compared optical and electrical bistabilities, and examined the time dependence. The switching energy turns out to be as small as 2fJμm−2, which compares favourably with the performance of conventional silicon MOSFETs. Modeling shows that the observed hysteresis loop results from the combination of negative electro-absorption and built-in negative dynamic resistance (NDR). We finally report the computation of all-optical bistability for a p-i-n structure inserted in a Fabry-Perot interferometer.

We report the analysis of polyomavirus (Py) DNA integration into chromosomal DNA of two Py-induced mammary adenocarcinomas of athymic nude mice. Prior observations had established that these tumors had high levels of episomal Py DNA, making analysis of integration sites difficult. Propagation of tumor cells in culture allows the isolation of lines which have lost episomal Py DNA but are still tumorigenic and thus can be used for in situ and Southern analysis of Py sequences. The data reported here support the conclusion that Py DNA integrated into and next to the c-myc gene, adding further importance to this tumor system which, in its modifications of c-myc expression, appears to be similar to some human mammary cancers. In situ hybridization experiments on metaphase chromosomes of tumor cells showed that (i) in both cases, there was a single integration site at the same position on the same chromosome in all cells of a given tumor, and (ii) integration sites were different in the two tumors; in one, it was located on chromosome 15, near the c-myc proto-oncogene, and in the other, it was situated in the distal part of chromosome 1. We have demonstrated a probable rearrangement between chromosome 1 and chromosome 15, in the region of Py insertion, thus suggesting that a specific site on chromosome 15 is involved in tumorigenesis. The discovery that Py DNA was integrated at specific sites in host chromosomes raised the questions of whether such integrations were correlated with the activation of specific oncogenes. The rearrangements of the c-myc proto-oncogene observed on Southern blot analysis for both tumors, along with similar integration patterns of Py sequences, the overexpression of the c-myc gene, and the synthesis of abnormal oversized hybrid transcripts between c-myc and Py genes, favor this hypothesis. Finally, the analysis of episomal Py DNA in various tumors shows viral populations presenting a specific deletion in a part of the Py late region. This deleted region in the episomal virus genome was systematically found integrated in chromosomal DNA, thus arguing for the importance of Py integration in the induction of mammary tumor.

We report investigations of optical transmission bistability in an unprocessed InGaAs-InAlAs superlattice p-i-n structure acting as a wireless self-electrooptical effect device. We have observed and compared optical and electrical bistabilities, and examined the time and temperature dependences. The switching energy turns out to be as small as 2 fJ mu m-2, which compares favourably with the performance of conventional silicon MOSFETS. Modelling shows that the observed hysteresis loop results from the combination of negative electroabsorption and built-in negative dynamic resistance. We finally report the observation of a novel optical bistability effect which is entirely due to the negative dynamic resistance of the structure.

Feral swine are well known as environmentally destructive invasive animals in many areas around the world, where they degrade native habitats, harm rare plant and animal species, damage agricultural interests, and spread disease. We provide the first quantification of their potential as agents of disturbance at archaeological sites. Our study was conducted in south-central Florida at Avon Park Air Force Range, a base comprising over 40,000 ha and containing many archaeological sites. To determine the identifiable prevalence of feral swine disturbance, we examined 36 sites registered with the Florida State Historic Preservation Office and also eligible for inclusion in the National Register of Historic Places (NRHP). Moreover, we evaluated the extent of swine disturbance at a prehistoric site of extraordinary significance to Florida’s prehistory, “Dead Cow.” Fifteen of the 36 NRHP-eligible sites (42 %) had some level of swine disturbance, including 14 of 30 (47 %) sites known to have artifacts within 20 cm of the surface (well within swine rooting depths). At the Dead Cow site, we documented disturbance at 74 % of shovel test points. Sites with shallow artifact depositions appeared highly vulnerable to disturbance by feral swine, threatening destruction of artifact stratigraphy and provenience. Our observations likely are a minimal representation of accumulated damage. These irreplaceable sites tell the area’s land use story across the millennia. That they are under threat from feral swine should serve broad notice of potential threats that feral swine may pose to archaeological sites globally, making effective swine management imperative for site protection.

To describe the clinical phenotype of a new motor disorder in Labrador Retrievers.Case series study. Seven young male Labrador Retrievers presented for evaluation of stiff gait.All affected dogs had generalized muscular stiffness, persistent at rest and resulting in restricted joint movements. They showed a forward flexed posture, festinating gait, and bradykinesia. Signs developed between 2 and 16 months of age and tended to stabilize in adulthood. Needle electromyogram in the conscious state showed continuous motor unit activity in resting epaxial and proximal limb muscles. This activity was abolished by general anesthesia. Muscle and nerve histopathology was normal. In 2 dogs necropsied, astrocytosis was evident throughout the spinal cord gray matter, reticular formation and caudate nuclei. Decreased neuronal counts were selectively found in the spinal cord Rexed's lamina VII, but not in VIII and IX. Pedigree analysis showed that the affected dogs were from 5 related litters.This new hypertonicity syndrome in Labrador Retrievers is unique because of the selective distribution of the histological lesions, the lack of progression in adulthood, and its exclusive occurrence in male dogs. Pedigree analysis suggests an X-linked hereditary disease, although other modes of inheritance cannot be ruled out with certainty. We hypothesize that altered output from basal nuclei and reticular formation together with motor neuron disinhibition caused by a decreased number of spinal cord interneurons leads to the muscular stiffness.

Review on Kidney: Papillary renal cell carcinoma, with data on clinics, and the genes involved.

Review on Soft tissue tumors: Malignant melanoma of soft parts, with data on clinics, and the genes involved.

Review on Soft tissue tumors: Extraskeletal myxoid chondrosarcoma, with data on clinics, and the genes involved.

Review on Nervous system: Peripheral neuroblastic tumours (Neuroblastoma, Ganglioneuroblastoma, Ganglioneuroma), with data on clinics, and the genes involved.

Review on Soft tissue tumors: Rhabdomyosarcoma, with data on clinics, and the genes involved.

Growth and mental development: 30% of children have low birth weight and short stature, and 75% a head circumference at birth below the 3rd percentile; all patients develop a severe microcephaly during the first months of life; mental development is normal in 35% of the patients, moderately retarded in the others; cerebellar ataxia is absent; alphafoetoprotein levels are normal, in contrast to AT patients.

Existing commercial nuclear power plants (NPPs) have obtained excellent and outstanding performance records over the past decade. Nevertheless, even though the high safety level already achieved could be maintained without investing new exhaustive research efforts, anticipation of further tighter requirements for even higher standard levels should be made, which implies preparedness for new research. Accordingly, in the near and intermediate future, research will conceivably focus on new emerging trends as a result of further desire to reduce the current uncertainties for better economics and improved safety of the current reactors and requirements of the new reactor designs. As it has been usual in the past, the research will continue serving the short-term needs of the end-users (regulatory bodies, utilities and vendors) which mainly focus on both emerging and pending issues, but it will also contribute to addressing the long-term safety needs or the questions arising from the changes in plant designs and operating modes, and to preparing the emergence of new concepts. The sensibility of the stakeholders for a continuous enhancement of safety, mainly when dealing with the advanced and innovative concepts, will entail the development of reactor concepts able to intrinsically prevent severe accidents from occurring, and, should that not be possible, reduce either their probability or the level of expected consequences on the environment and the populations. That should be done in first priority by design, and not necessarily by improvements or the addition of safety systems. Such anticipatory research will involve new generation simulation tools and innovative experimental programs, to be carried out both in the research facilities currently in operation throughout the world and in new dedicated mock-ups supported by suitable laboratory infrastructures. Enhanced or complementary data banks to be generated and further investigations on human and organizational factors will be the primary research activities, from which the end users will definitely profit. In addition, significant efforts should be devoted to get the maximum benefit from the computation tools already available and start preparing their improvements as well by taking advantage from the development and availability of new computation techniques, such as advanced numerical simulation.

Genome study and expression profiling of the tumor seem to be the most significant biologic prognostic factor in uveal melanoma. Many cytogenetic and molecular tests are reported; our aim was to assess their ability to detect high metastatic risk patients through a literature review. Standard karyotyping, fluorescence in situ hybridization and microsatellite analysis are not adequate. DNA-based genome techniques must analyse the entire genome (comparative genomic hybridization [CGH]) and, optimally, detect chromosome 3 isodisomy ("single-nucleotid polymorphism" SNP-array). Multiplex ligation-dependent probe amplification (MLPA) is less expensive than array-CGH, but its interpretation may be delicate. Gene expression profiling is the most accurate molecular test for predicting metastatic death in patient with uveal melanoma even if it remains a costly technique. These prognostic tests could be useful to identify high-risk patients in future adjuvant therapy protocols.

Adult dogs with neosporosis can develop a variety of neurologic signs. No area of predilection within the nervous system so far has been identified in adult dogs.To document neosporosis as a cause of progressive cerebellar ataxia and cerebellar atrophy in dogs.Seven client-owned dogs.Retrospective, descriptive study.Age at diagnosis ranged from 1 year 6 months to 9 years 11 months. Neuroanatomic localization indicated cerebellar and brainstem disease in 6 dogs and a central vestibular lesion in 1 dog. In all 7 dogs, there was moderate to marked bilaterally symmetrical cerebellar atrophy, with the atrophied cerebellum being surrounded by a region of T2-weighted hyperintense and T1-weighted hypointense signal. Cerebrospinal fluid (CSF) analysis in all but 1 dog showed mononuclear pleocytosis and high protein concentration. Polymerase chain reaction testing for Neospora caninum performed on the CSF was positive in 4/5 dogs tested and there was a high titer of serum antibodies to N. caninum (or = 1 : 800) in all 6 dogs tested. Postmortem examination in 1 dog confirmed cerebellar atrophy and multifocal nonsuppurative encephalitis with areas of malacia and leptomeningitis. All of the remaining 6 dogs were treated with some combination of clindamycin, trimethoprim, sulfadiazine, and pyrimethamine. Two dogs were euthanized because of deterioration or relapse of neurologic signs, but treatment of the remaining 4 dogs resulted in improvement (3 dogs) or resolution (1 dog) of neurologic signs.Neosporosis is an important cause of progressive cerebellar ataxia and cerebellar atrophy in adult dogs.

We report here a karyotypic study of 6 individuals of Hylobates concolor leucogenys, 2 H. concolor siki, 3 H. concolor gabriellae, 1 hybrid H. concolor leucogenys Χ H. concolor siki, 3 hybrid H. concolor gabriellae Χ H. concolor siki and 2 hybrid H. concolor hainanus Χ H. concolor leucogenys. Difficulties raised by the mophological identification of subspecies are discussed, and a new morphological characteristic for recognising female H. concolor gabriellae is described. Each of the 4 subspecies appears to be distinguishable on the basis of its karyotype: H. concolor leucogenys differs from H. concolor siki by a reciprocal translocation, from H. concolor hainanus by a pericentric inversion and from H. concolor gabriellae by the presence of both of these two rearrangements. However, these data do not allow us to identify a phylogenetic relationship between the subspecies because, with respect to the karyotypes, none occupies an ancestral position in comparison with the others.

Objectives: The objectives of the study were (1) to report the incidence of Chiari-like malformation and syringomyelia in a normal French cavalier King Charles spaniel breeding population; (2) to precise the standard computed tomography dimensions of the caudal fossa and (3) to investigate the use of ultrasonography in diagnosis of this syndrome. Methods: Clinically normal adult cavalier King Charles spaniel underwent ultrasonographic examination of the spinal cord and caudal fossa. Computed tomography was used to measure the caudal fossa and magnetic resonance imaging allowed syringomyelia and cerebellar herniation identification. Results: Of the 16 dogs in the study, seven had syringomyelia (43·7 per cent). All dogs had cerebellar herniation, suggesting Chiari-like malformation and also a tendency to occipital dysplasia. Computed tomography measurements of the caudal fossa are reported. In one dog, a syrinx was identified by ultrasonography. The only difference between dogs with or without syringomyelia was that dogs with Chiari-like malformation/syringomyelia were statistically older. Clinical Significance: The incidence of Chiari-like malformation and syringomyelia may be high in an asymptomatic population of cavalier King Charles spaniel . Computed tomography measurements reported in this study should now be compared with those of a symptomatic population to evaluate the hypothesis that dogs with Chiari-like malformation/syringomyelia syndrome have a smaller caudal fossa. This study did not identify a smaller caudal fossa in an asymptomatic cavalier King Charles spaniel population with syringomyelia. Ultrasonography probably has a low sensitivity for diagnosis of Chiari-like malformation/syringomyelia.

Amplification of the HER2 gene, mapping to 17q21.1, is present in about 20 % of breast carcinomas. Amplification leads to an overexpression of the protein that made it possible to develop a targeted therapy by the monoclonal antibody trastuzumab (Herceptin). A good response to the treatment requires a stringent assessment of the gene status in tumours; only patients whose tumour shows a high expression of the protein or an amplification of the gene are eligible. Cases with intermediate level expression are checked by in situ hybridization, mainly by FISH, to identify amplifications in this subset of tumours. Results are sometimes difficult to interpret due to the frequent aneuploidy of the tumours. Moreover, copy number cut-offs of the gene for defining an amplification are variable according to the studies. A tumour is considered now as amplified when showing more than six HER2 copies per nucleus, or a ratio HER2 to centromere 17 greater than 2.2. The phenomenon of HER2 amplification in breast cancers is discussed in this paper, and distinguished from gene overrepresentation. It is recommended that tumours showing six to seven copies of HER2 are assessed with a kit including the centromere 17. Clusters of signals are characteristic of amplifications. The process designed for the assessment of HER2 is a model of strategies that will be used for the evaluation of markers involved in future targeted therapies.

In further developing the acoustic emission (AE) technology for bearing monitoring, it is essential that a relationship is determined between bearing operational parameters, such as speed and load, and the generation of AE activity. Hitherto, almost all published investigations on the application of AE technology to bearing monitoring have been based on systems that operate at fixed speed and/or load conditions. In reality, a significant proportion of bearings operate under variable speed and load conditions; therefore, the growth of AE technology in monitoring bearings under such conditions requires an understanding of the influence of bearing operational parameters on the generation of AE. This paper presents experimental tests undertaken at near isothermal conditions aimed at understanding the influence of speed and load on the generation of AE. The results of the program lead to the introduction of AE operational maps. It is concluded that under an elastohydrodynamic lubrication regime, AE activity can be directly related to the theoretically predicted specific film thickness within the bearing.

Two males with a 46, Y, der(X), t(X;Y)(p22.3;q11) complement were referred independently for evaluation of sterility with azoospermia. Both patients exhibited minimal symptomatology, characterized only by psychological disturbances. Study of X-chromosome breakpoints with pseudoautosomal probes 68B (DXYZ2 elements), 113D (locus DXYS15), and 19B (locus MIC2) indicated in both patients that at least 97% of the X pseudoautosomal sequences are lost. Hybridization with Xp22.3-specific probes DXS283, DXS284, and DXS31 shows that these loci are retained on the rearranged chromosome. Thus, the X-chromosome breakpoints are located close to the proximal boundary of the pseudoautosomal region, between MIC2 and DXS284.

Uveal melanoma is very rare in children, and in both adults and children it can in rare cases develop intralesional cavities resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in differentiating cavitary melanoma from a benign cyst. We report the case of a 5-year-old girl who presented with a large intraocular pigmented mass in the left eye, showing multiple hollow cavities on ocular ultrasonography, CT scan, and MRI. The patient was treated by enucleation and the pathology confirmed the diagnosis of choroidal melanoma. FISH revealed no aberration in chromosome 3.

HER2 protein is over-expressed in 15-30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in-situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2-IHC compared with HER2-FISH taken as the reference method.Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in-house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti-HER2 antibodies. Two cut-off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty-four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat-induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over-expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut-offs, respectively. The corresponding accuracy rates were 93% and 95%.This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in-house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti-HER2 antibody and the use of specific controls were crucial for HER2-IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2-IHC results as a continuous variable, and taking 60% invasive stained cells as the cut-off for HER2 over-expression.

We report the observation of optical transmission bistability at low temperature in unprocessed InGaAs‐AlInAs superlattice p‐i‐n structures. Bistability results, in analogy with the self‐electro‐optical effect device, from a positive feedback mechanism due to the interplay between Wannier–Stark effect, built‐in field, and screening by photocarriers.We report the observation of optical transmission bistability at low temperature in unprocessed InGaAs‐AlInAs superlattice p‐i‐n structures. Bistability results, in analogy with the self‐electro‐optical effect device, from a positive feedback mechanism due to the interplay between Wannier–Stark effect, built‐in field, and screening by photocarriers.

Few studies have clearly defined the risk factors and management of steroid-induced mania, particularly in children and adolescents. The case study of a 15-year-old woman with steroid-induced mania is examined to delineate risk factors and management. Genetic predisposition to mood disorders, previous exposure to steroids and the concomitant use of clarithromycin are potential risk factors. Mood stabilizers such as lithium and/or valproic acid may be useful in the acute and prophylactic treatment of steroid-induced mania.

The human COMA cell line has been established from a storiform pleomorphic malignant fibrous histiocytoma (MFH). As expected for this tumor type, a very complex karyotype was observed after R-banding analysis. An extensive analysis by 24-color painting, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) was performed. Twelve complex marker chromosomes recurrently observed were clearly identified; among them, three were systematically present in all analyzed metaphases. Amplifications detected by CGH were refined by FISH with probes specific for various candidate loci. A significant aneuploidy and numerous micronuclei were observed, which could be related to the anomalies of centriole numbers detected in a proportion of cells. Such an analysis, performed on a series of MFH cell lines, would allow the delineation of the genomic alterations specific for the oncogenesis or progression of this complex tumor type or both.

Fine-needle sampling, although a practical and noninvasive method of tissue acquisition, has rarely been used for HER-2/neu fluorescent in situ hybridization (FISH). To assess HER-2/neu gene amplification in mammary carcinoma, FISH signals on cytology and corresponding tissue biopsies were detected visually and measured by image analysis. The results were correlated with patient and tumor characteristics.In situ HER-2/neu DNA probe hybridization was performed on 61 cytology specimens and on 47 corresponding frozen sections of breast carcinomas. Tumors were classified by visual evaluation as unamplified, moderately amplified, or highly amplified. Multiparametric image analysis was performed using the Discovery automated image analyzer (Becton Dickinson, Leiden, Netherlands). The integrated fluorescence ratio (IFR) was calculated for each sample as the integrated FISH fluorescence of the tumor cells divided by the integrated FISH fluorescence of internal control cells containing two spots. The percentage positive nuclear area (PPN), calculated as the area of FISH fluorescence divided by the area of nuclear DNA fluorescence, and the PPR, ratio of the PPN of the tumor cells divided by the control cells, were also calculated for each sample.Visual analysis yielded 46 unamplified and 15 (24.6%) amplified (seven moderately amplified and eight highly-amplified) tumors. Strong (P0.001) correlation between results on cytological and histological materials was obtained. The FISH spots on the cytological preparations were more easily visualized and scored than those on the corresponding tissue sections. Visual HER-2/neu signal scoring was strongly correlated with IFR (P = 0.0001) and PPR (P = 0.0001). Within the tumors classified as highly amplified by visual examination, quantitation of the degree of amplification fluorescence signal was possible using image analysis.Cytologic specimens were a suitable and representative source of materials for detection and quantitation of HER-2/neu gene amplification by FISH and image analysis. Cancer (Cancer Cytopathol)

A 15-year-old adolescent male, with Asperger's disorder, Tourette's disorder and obsessive-compulsive disorder, on a tetracycline-risperidone-sertraline treatment regimen, had an acute exacerbation of motor and vocal tics. The increase in tics may have resulted from either a tetracycline-risperidone interaction leading to decreased levels of risperidone, or a tetracycline-sertraline interaction leading to increased levels of sertraline or the natural course of the Tourette's disorder. The sertraline dose was increased with no concomitant increase in tics, and subsequent discontinuation of tetracycline resulted in an improvement in tics, which indicates an interaction between tetracycline and risperidone. The addition of antibiotics to psychotropic medications requires close monitoring due to the potential interactions.

Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels. No direct effect of IL-17 on in vitro proliferation of cervical tumor cell lines could be demonstrated. However, two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This enhanced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supported by its expression on the cervical tumor in patients with CD4 infiltration. IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports concerning the deleterious effect of CD4 T cells in cancer.

HER2 is overexpressed in about 25% to 30% of breast cancers and associated with poor prognosis, resistance to hormonotherapy and lack of sensitivity to CMF-based adjuvant chemotherapy. Herceptin (trastuzumab), a humanized monoclonal antibody, administered as a single agent, produces objective responses in phase II trials in patients with metastatic breast cancers overexpressing HER2. It has shown a substantial benefit in a phase III trial which compares a standard first line chemotherapy (doxorubicin and cyclophosphamide or taxol alone) to the same chemotherapy with Herceptin in metastatic breast cancer. The Herceptin arm had significantly higher response rate (+ 53%), an improvement in the median duration of response (+ 57%) as well as in time to progression (+ 65%) compared to chemotherapy alone.

We describe a 32-year-old woman who presented with Hodgkin's disease, nodular sclerosis type II, subtype I, which necessitated several treatments over 11 years. The patient then developed pleomorphic, medium-sized T-cell lymphoma, which had a fatal outcome within 13 months. The role of radiotherapy, splenectomy, and chemotherapy in second tumor induction is compared with other sequential T-cell lymphomas. The significance of rare Epstein-Barr virus-infected cells during the T-cell lymphoma extension is discussed.