Joint Measurement of the

The PROSPECT and STEREO collaborations present a combined measurement of the pure ^{235}U antineutrino spectrum, without site specific corrections or detector-dependent effects. The spectral measurements of the two highest precision experiments at research reactors are found to be compatible with χ^{2}/ndf=24.1/21, allowing a joint unfolding of the prompt energy measurements into antineutrino energy. This ν[over ¯]_{e} energy spectrum is provided to the community, and an excess of events relative to the Huber model is found in the 5-6 MeV region. When a Gaussian bump is fitted to the excess, the data-model χ^{2} value is improved, corresponding to a 2.4σ significance.

Searching for Hidden Neutrons with a Reactor Neutrino Experiment: Constraints from the STEREO Experiment.

Different extensions of the standard model of particle physics, such as braneworld or mirror matter models, predict the existence of a neutron sterile state, possibly as a dark matter candidate. This Letter reports a new experimental constraint on the probability p for neutron conversion into a hidden neutron, set by the STEREO experiment at the high flux reactor of the Institut Laue-Langevin. The limit is p<3.1×10^{-11} at 95% C.L. improving the previous limit by a factor of 13. This result demonstrates that short-baseline neutrino experiments can be used as competitive passing-through-walls neutron experiments to search for hidden neutrons.

Constraints on Elastic Neutrino Nucleus Scattering in the Fully Coherent Regime from the CONUS Experiment.

We report the best limit on coherent elastic scattering of electron antineutrinos emitted from a nuclear reactor off germanium nuclei. The measurement was performed with the CONUS detectors positioned at 17.1 m from the 3.9 GW_{th} reactor core of the nuclear power plant in Brokdorf, Germany. The antineutrino energies of less than 10 MeV assure interactions in the fully coherent regime. The analyzed dataset includes 248.7 kg d with the reactor turned on and background data of 58.8 kg d with the reactor off. With a quenching parameter of k=0.18 for germanium, we determined an upper limit on the number of neutrino events of 85 in the region of interest at 90% confidence level. This new CONUS dataset disfavors quenching parameters above k=0.27, under the assumption of standard-model-like coherent scattering of the reactor antineutrinos.

Accurate Measurement of the Electron Antineutrino Yield of

We report a measurement of the antineutrino rate from the fission of ^{235}U with the STEREO detector using 119 days of reactor turned on. In our analysis, we perform several detailed corrections and achieve the most precise single measurement at reactors with highly enriched ^{235}U fuel. We measure an IBD cross section per fission of σ_{f}=(6.34±0.06[stat]±0.15[sys]±0.15[model])×10^{-43} cm^{2}/fission and observe a rate deficit of (5.2±0.8[stat]±2.3[sys]±2.3[model])% compared to the model, consistent with the deficit of the world average. Testing ^{235}U as the sole source of the deficit, we find a tension between the results of lowly and highly enriched ^{235}U fuel of 2.1 standard deviations.

[Epidermolysis bullosa acquisita with Brunsting-Perry type pemphigoid: Diagnostic and therapeutic difficulties]. / Épidermolyse bulleuse acquise à type de pemphigoïde de Brunsting-Perry : difficultés diagnostiques et thérapeutiques.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare auto-immune blistering disease. We report a case of Brunsting-Perry pemphigoid diagnosed by immunoelectron microscopy (IEM). PATIENTS AND METHODS: A 46-year-old man presented very pruriginous vesicles on the face and neck present for 6 years and which were difficult to diagnose and treat. The appearance of atrophic scars and milium cycts evoked EBA, which was confirmed at IEM. Due to limited involvement of the face and the neck, we conclude on EBA of the Brunsting-Perry pemphigoid variant. Treatment with dapsone produced a favorable outcome. DISCUSSION: Diagnosis of EBA is often difficult. In a case review, Asfour et al. collated 60 cases of Brunsting-Perry pemphigoid. These patients had either anti-collagen VII or anti-BP180 and anti-BP230 antibodies. IEM showed cleavage either under the lamina densa or within the lamina lucida, suggesting that Brunsting-Perry pemphigoid is a subtype of EBA or bullous pemphigoid (BP), depending on the paraclinical elements, and localized to the head and neck. The majority of EBA-like cases required systemic therapy, whereas in the presence of BP antibodies, topical corticosteroids were effective. CONCLUSION: We report a case of EBA of the Brunsting-Perry pemphigoid type, diagnosed by IEM after 6 years of progression. We highlight the diagnostic and nosological difficulties of Brunsting-Perry pemphigoid. Classification of this dermatosis as a subtype of EBA or BP may enable effective adaptation of therapeutic management, which has not as yet been coded.

[Cutaneous metastases on the extremities]. / Métastases cutanées des extrémités.

BACKGROUND: Cutaneous metastases (CM) on the extremities are rare complication of cancer with poor prognosis. In general, lesions simulate an infection. Herein, we report two new cases with atypical presentation. PATIENTS AND METHODS: Case no 1: a 71-year-old man consulted for suspicion of left hand pyogenic granuloma present for 3 months. His history revealed two treated squamous-cell carcinomas (tongue and lung). On physical examination, he presented three budding and foul-smelling lesions on his left hand. Histopathology showed metastasis of squamous-cell carcinoma. Radiographic examination revealed spread of pulmonary nodules with suspicion of metastasis. Case no 2: a 68-year-old man was hospitalized for indurated edema of the right leg present for several months. Six months earlier, he had undergone surgery for left pulmonary adenocarcinoma without metastasis. Physical examination revealed an indurated edema on the right foot. Histopathology showed metastasis from adenocarcinoma. A scan revealed several osteolytic lesions in the right foot as well as lymphadenopathy. DISCUSSION: Herein, we report two original cases of CM of the extremities diagnosed as tumor progression. This is a rare complication of variable clinical presentation and impacts both cancer management and prognosis. It is important to consider the diagnosis when distal cutaneous lesions persist, particularly where there is a history of cancer.

Sterile Neutrino Constraints from the STEREO Experiment with 66 Days of Reactor-On Data.

The reactor antineutrino anomaly might be explained by the oscillation of reactor antineutrinos toward a sterile neutrino of eV mass. In order to explore this hypothesis, the STEREO experiment measures the antineutrino energy spectrum in six different detector cells covering baselines between 9 and 11 m from the compact core of the ILL research reactor. In this Letter, results from 66 days of reactor turned on and 138 days of reactor turned off are reported. A novel method to extract the antineutrino rates has been developed based on the distribution of the pulse shape discrimination parameter. The test of a new oscillation toward a sterile neutrino is performed by comparing ratios of cells, independent of absolute normalization and of the prediction of the reactor spectrum. The results are found to be compatible with the null oscillation hypothesis and the best fit of the reactor antineutrino anomaly is excluded at 97.5% C.L.

[Vaccination status in psoriasis patients on immunosuppressant therapy (including biologics)]. / Couverture vaccinale avant et après instauration d'un traitement immunosuppresseur (y compris biothérapie) pour psoriasis.

OBJECTIVES: To evaluate the vaccine coverage of psoriasis patients prior to initiating or changing immunosuppressant therapy, and to verify that the prescribed vaccines have been administered. PATIENTS AND METHODS: We conducted a bi-centre, observational, cross-sectional study over 9 months. Psoriasis patients in whom immunosuppressant therapy (comprising cyclosporine, methotrexate, etanercept, infliximab, adalimumab or ustekinumab) was indicated were included. Medical history, previous treatments, vaccination status, viral serology results (for hepatitis B, measles, and chickenpox), and reasons for non-vaccination were assessed via questionnaire. RESULTS: Sixty-eight patients were included. One third brought their immunization records. Overall, 54.4% had already received immunosuppressant therapy; of these, 9 were up to date for influenza and 3 were up to date for pneumococcus. Only one patient was up to date for all of the recommended vaccinations. A total of 61% of patients were seronegative for hepatitis B. The following vaccines were updated: DTP (in 2 patients), DTP-pertussis (12), influenza (22), pneumococcus (45), and hepatitis B (6). None of the three patients with plans to travel to yellow fever-endemic countries had been vaccinated. In all, 53 (78%) stated that they had already had chickenpox and 43 (63.2%) stated that they had had one of the following three diseases: measles, rubella, or mumps. Fifty-two patients were serologically tested for chickenpox, and 98% were immunized. The most common reasons for not updating the immunization schedule were the absence of any notification or proposal by the patient's doctor and oversight. CONCLUSION: This study should help raise awareness among patients and health professionals concerning the new vaccination recommendations for a population particularly at risk of infection.

[Recognising and treating lipidema OMIM 614103]. / Le lipœdème. Le reconnaître et que faire OMIM 614103.

Lipedema is a poorly understood clinical entity that is frequently under-diagnosed and neglected or else confused with lymphoedema. However, in most cases, diagnosis is simple and does not usually necessitate laboratory examinations. There is an extremely high demand for therapy since the condition causes major morbidity and affects quality of life. The aim of treatment is to reduce patient weight; although weight loss does not affect the morphology of the lower limbs, it optimises patient mobility while reducing related complaints and improving quality of life. Conservative surgical measures, of which tumescent liposuction is the most frequent, provide improvement of certain symptoms. A better understanding of this entity will result in improved therapy.

[Aquagenic palmoplantar keratoderma during treatment of Langerhans cell histiocytosis]. / Kératodermie palmo-plantaire aquagénique au cours du traitement d'une histiocytose langerhansienne.

BACKGROUND: Aquagenic palmoplantar keratoderma (APPK) is characterised by whitish oedematous papules, sometimes itchy or painful of rapid onset following immersion of the palms and/or soles in water. We report a case that was atypical in terms of the secondary appearance of persistent fine desquamation. PATIENTS AND METHODS: A 6-year-old girl presented with typical APPK, present for three months and characterised by swelling, skin wrinkling, hyperhidrosis and secondary desquamation of the palms and soles, and which occurred after bathing. The patient had been treated with vinblastine, mercaptopurine and oral corticosteroids for Langerhans cell histiocytosis ongoing for six months. Physical examination revealed persistent fine desquamation of the palms and soles, occurring some time after immersion in water. There was no mutation of the CFTR gene. No similar cases could be found in the pharmacovigilance database. Topical therapy with an emollient provided some relief. Symptoms had partially resolved two months after discontinuation of chemotherapy and oral corticosteroids. DISCUSSION: Cases of unilateral palmar damage involving unusual sites have been reported. Neither secondary desquamation nor association with Langerhans cell histiocytosis have been described. Hyperhidrosis and association with 1 or 2 CFTR mutations appear to constitute predisposing factors. There are cases of APPK related to anti-inflammatory intake. In view of the clinical course, an iatrogenic origin cannot be excluded in this case. CONCLUSION: Persistent fine palmoplantar desquamation may be a manifestation of APPK.

EU demonstration project for separate discharge and treatment of urine, faeces and greywater--part I: results.

The main aim of this EU demonstration project was to test two new sanitation concepts to determine if these concepts are more sustainable, compared with the conventional sanitation system, particularly with regard to nutrient recycling. Two different sanitation concepts were tested. One concept comprised the use of gravity separation toilets, the other used vacuum separation toilets. Results from a life-cycle-assessment investigation show that the new sanitation concepts are more sustainable. A cost analysis for an existing residential area did not prove lower costs for the new sanitation concepts in this special case. The experience from this demonstration project shows that prior to a widespread use of the new sanitation concepts, several improvements have to be made. One important issue is the improvement of separation toilets. Since nutrient recycling, water saving and reuse as well energy reduction become more and more important, further research should be undertaken in this field.

EU demonstration project for separate discharge and treatment of urine, faeces and greywater--part II: cost comparison of different sanitation systems.

The experience from the EU demonstration project was used for a cost analysis of different sanitation systems with regard to nutrient recycling. The analysis was made for an existing residential area, for which the different sanitation systems have been applied. The cost calculations were made for a lifetime of 50 years. The multiple sewer systems cause higher investment costs, mainly for the installation of the additional facilities; the investment costs for the treatment are lower. The cost analysis did not prove lower costs for the new sanitation concepts in this special case in comparison with the conventional system. Economic benefits are demonstrated for the operation costs. The result will be reinforced by the consideration of an increase of the energy costs. The revenues for the nutrient related products have only a very small impact on the result.

Single nucleotide polymorphisms of protein tyrosine phosphatase 1B gene are associated with obesity in morbidly obese French subjects.

AIMS/HYPOTHESIS: The development of insulin resistance may contribute to the occurrence and progression of the metabolic syndrome associated with obesity. Components contributing to the insulin pathway and its regulation are good candidates for the molecular study of metabolic syndrome pathogenesis. Protein tyrosine phosphatase 1B (PTP 1B) is an important negative regulator of insulin. We investigated whether PTP 1B SNPs are associated with obesity and obesity-related traits as well as global metabolic syndrome in morbidly obese subjects. METHODS: Untranslated and coding regions of the PTP 1B gene were screened in groups of non-diabetic and diabetic obese subjects and in non-obese subjects. Unrelated morbidly obese ( n=711) and non-obese ( n=427) French Caucasian subjects were genotyped for a case-control study. RESULTS: Six SNPs were identified: two rare variants were located in 5'UTR (-109 C>T and -69 C>T), two in the intronic regions (IVS3+38 G>T and IVS5+3666delT) and two have been described previously (P303P in exon 8 and P387L in exon 9). A case-control study showed an association between the frequent IVS5+3666delT SNP and obesity ( p=0.02). In the obese group, associations between PTP 1B SNPs and features of dyslipidaemia were found. P303P was associated with lower apolipoprotein A1 levels ( p=0.05) whereas P387L was associated with higher triglyceride ( p=0.0003), apolipoprotein B ( p=0.09) and lipoprotein a concentrations ( p=0.006). CONCLUSIONS/INTERPRETATION: Our results support the hypothesis that the PTP 1B gene contributes to the polygenic basis of obesity. PTP 1B SNPs may interact with environmental factors to induce more severe phenotypes, e.g. atherogenic dyslipidaemia, in morbidly obese subjects.

Regulation of tumor necrosis factor alpha and its specific receptors during Toxoplasma gondii infection in human monocytic cells.

The coccidian Toxoplasma gondiiis an obligate intracellular parasite which can infect all cell types. Among the cytokines elicited by the immune response to Toxoplasma, tumor necrosis factor alpha (TNF-alpha) acts synergistically with gamma interferon (IFN-gamma) and plays a major role in host cell resistance. We have previously reported that TNF-alpha production induced by IFN-gamma/LPS decreases after T. gondii infection of human myelomonocytic THP-1 cells. Here, we investigated the regulation of TNF-alpha and its specific receptors during T. gondii infection of THP-1 cells. We found that TNF-alpha production was regulated at a post-transcriptional level and that TNF receptor expression was regulated at a pretranscriptional level. The TNF receptor I shedding and the fall in TNF-alpha levels observed after T. gondii infection would thus be induced by a parasite component with serine protease activity. These findings indicate that T. gondii participates not only in controlling the cytotoxic effects of TNF-alpha during the infection process, but also in signal transduction mediated mainly by TNF receptor I.

Membrane potential changes after infection of monocytes by Toxoplasma gondii.

Membrane potential changes in host cell plasma membrane were analyzed and the parasitophorous vacuole membrane (PVM) potential was characterized after infection by Toxoplasma gondii. Human monocytes infested by T. gondii were stained with two membrane potential sensitive dyes, DiOC(6)(3) carbocyanine and DiSBAC(2)(3) bis-oxonol, before fluorescence emission analysis by confocal laser scanning microscopy. After 24 and 48 h of infection, 34 and 39%, respectively, of monocytes showed several parasites (from two to six) per cell. At these infection times, significant decreases in cytoplasmic emissions were observed for both DiOC(6)(3) and DiSBAC(2)(3). Thus, hyperpolarisation of the host plasma membrane would occur consecutively to infection. Inside the parasitophorous vacuole, the fluorescence intensity of DiOC(6)(3) and DiSBAC(2)(3) increased significantly from 6 to 24 h after infection and the PVM became less polarised. Involvement of different ATPases in the membrane potential of infected monocytes was evaluated with ouabain, DCCD, omeprazole and sodium orthovanadate, ATPase inhibitors. All inhibitors induced a depolarisation of the plasma membrane. In the parasitophorous vacuole compartment, DCCD, omeprazole and sodium orthovanadate but not ouabain caused a significant depolarisation of the PVM, suggesting that H(+), H(+)/K(+) and P-type ATPases were at the origin of the PVM potential. This is the first report showing the presence of ion transporters in the T. gondii PVM and the existence of at least two members of the P-type family of ion pumps: an electrogenic H(+)ATPase and an electroneutral H(+)/K(+) ATPase.

Detection and localization of a Ca2+-ATPase activity in Toxoplasma gondii.

Toxoplasma gondii, the agent causing toxoplasmosis, is an obligate intracellular protozoan parasite. A calcium signal appears to be essential for intracellular transduction during the active process of host cell invasion. We have looked for a Ca2+-transport ATPase in tachyzoites and found Ca2+-ATPase activity (11-22 nmol Pi liberated/mg protein/min) in the tachyzoite membrane fraction. This ATP-dependent activity was stimulated by Ca2+ and Mg2+ ions and by calmodulin, and was inhibited by pump inhibitors (sodium orthovanadate or thapsigargin). We used cytochemistry and X-ray microanalysis of cerium phosphate precipitates and immunolabelling to find the Ca2+, Mg2+-ATPase. It was located mainly in the membrane complex, the conoid, nucleus, secretory organelles (rhoptries, dense granules) and in vesicles with a high calcium concentration. Thus, Toxoplasma gondii possesses Ca2+-pump ATPase (Ca2+, Mg2+-ATPase) as do eukaryotic cells.

Calmodulin distribution and the actomyosin cytoskeleton in Toxoplasma gondii.

The gliding motility of the protozoan parasite Toxoplasma gondii and its invasion of cells are powered by an actin-myosin motor. We have studied the spatial distribution and relationship between these two cytoskeleton proteins and calmodulin (CaM), the Ca(2+)-dependent protein involved in invasion by T. gondii. A 3D reconstruction using labeling and tomographic studies showed that actin was present as a V-like structure in the conoidal part of the parasite. The myosin distribution overlapped that of actin, and CaM was concentrated at the center of the apical pole. We demonstrated that the actomyosin network, CaM, and myosin light-chain kinases are confined to the apical pole of the T. gondii tachyzoite. MLCK could act as an intermediate molecule between CaM and the cytoskeleton proteins. We have developed a model of the organization of the actomyosin-CaM complex and the steps of a signaling pathway for parasite motility.