Significant Excess of Electronlike Events in the MiniBooNE Short-Baseline Neutrino Experiment.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions.

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (K^{+}→µ^{+}ν_{µ}) at the NuMI beamline absorber. These signal ν_{µ}-carbon events are distinguished from primarily pion decay in flight ν_{µ} and ν[over ¯]_{µ} backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9σ level. The muon kinetic energy, neutrino-nucleus energy transfer (ω=E_{ν}-E_{µ}), and total cross section for these events are extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of ω using neutrinos, a quantity thus far only accessible through electron scattering.

Dark Matter Search in a Proton Beam Dump with MiniBooNE.

The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil. Analysis methods developed for previous MiniBooNE scattering results were employed, and several constraining data sets were simultaneously analyzed to minimize systematic errors from neutrino flux and interaction rates. No excess of events over background was observed, leading to a 90% confidence limit on the dark matter cross section parameter, Y=ε^{2}α_{D}(m_{χ}/m_{V})^{4}≲10^{-8}, for α_{D}=0.5 and for dark matter masses of 0.01

Improved search for ν¯(µ)→ν¯(e) oscillations in the MiniBooNE experiment.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν[over ¯](e) appearance data from 11.27×10(20) protons on target in the antineutrino mode, an increase of approximately a factor of 2 over the previously reported results. An event excess of 78.4±28.5 events (2.8σ) is observed in the energy range 200

An intra-patient placebo-controlled phase I trial to evaluate the safety and tolerability of intradermal IMM-101 in melanoma.

BACKGROUND: IMM-101 is a heat-killed innate and adaptive immune-activating mycobacterial product; a phase I study aimed to determine its safety and tolerability in individuals with melanoma. PATIENTS AND METHODS: An intra-patient placebo-controlled study evaluated the safety and tolerability of three doses, namely, 0.1 (1 mg/ml), 0.5 (5 mg/ml) and 1.0 mg (10 mg/ml) of IMM-101 in stage III or IV melanoma. Each dose was administered in ascending order to one of the three cohorts. RESULTS: Based on observations from patients administered the 0.1-mg dose, it was considered appropriate to proceed with dosing the patients in the 0.5-mg dose cohort and then the 1.0-mg cohort (n = 6 per cohort). Treatment-emergent adverse events that would be considered typical of a post-vaccination state (including joint pains/aches, headaches and influenza-like symptoms) occurred at all dose levels, along with injection site reactions. These were mainly mild in intensity, resolved in a matter of days and responded well to supportive care. During post-study follow-up, two clinical responses (15%) were observed in patients with stage IV disease. CONCLUSION: IMM-101 is safe and well tolerated and there is a rationale for studying IMM-101 at a nominal 1.0-mg dose to complement conventional cytotoxic therapy for patients with advanced cancer.

Fallopian tube reanastomosis by laparotomy versus laparoscopy: a meta-analysis.

OBJECTIVE: To compare efficacy of sterilization reversals by laparotomy versus laparoscopy. DESIGN: Meta-analysis. SEARCH STRATEGY: Electronic searches were carried out for randomized controlled trials and retrospective and prospective clinical studies. Search engines such as PubMed, Science Direct, Medline and the Cochrane database were made use of. Our restrictions were English human studies published from 1989 to January 2010. INTERVENTIONS: Microsurgical tubal reanastomosis performed comparing laparoscopy with laparotomy using a microsurgical technique. OUTCOME MEASURES: Primary: overall pregnancy rates, including positive clinical pregnancy, intrauterine and ectopic pregnancy rates. Secondary: surgery time. RESULTS: Three retrospective comparative studies were retrieved from international data that investigated laparotomy versus laparoscopy. A total number of 184 patients were included, 88 and 96 respectively undergoing laparoscopy and laparotomy. Pregnancy rates achieved by laparoscopy ranged from 65 to 80.5% (mean 74.43%) and by laparotomy from 70 to 80% (mean 71.33%). A subanalysis of two of the three comparative studies show that laparoscopy reversal surgery requires a statistically significant longer operative time than does laparotomy (p < 0.00001). CONCLUSIONS: There is no difference between the laparoscopy and laparotomy approach to tubal reanastomosis when regarding overall pregnancy rates, intrauterine and ectopic pregnancy rates.

Event excess in the MiniBooNE search for ¯νµâ†’¯νe oscillations.

The MiniBooNE experiment at Fermilab reports results from a search for ¯ν_{µ}→¯ν_{e} oscillations, using a data sample corresponding to 5.66×10²° protons on target. An excess of 20.9±14.0 events is observed in the energy range 475

[Use of sorafenib in patients with hepatocellular or renal carcinoma]. / Bon usage du sorafénib chez les patients pris en charge pour un carcinome hépatocellulaire ou un cancer du rein.

Therapeutic approaches of cancers have been recently improved by the development of targeted therapies. Amongst these new drugs, some anti-angiogenic molecules have been approved by either the EMEA or the Food and Drug Administration. Sorafenib, one of these inhibitors of angiogenesis, has been established as the standard of care for advanced hepatocellular and renal carcinoma. This paper reviews the safety profile of sorafenib and presents guidelines for the prevention and the treatment of the main side effects associated with this molecule.

Chronic inflammation as a manifestation of defects in immunoregulatory networks: implications for novel therapies based on microbial products.

Based on a unifying theory presented here, it is predicted that the immune defects resulting in chronic inflammation rather than effective immune responses could be rectified by the therapeutic use of agents prepared from micro-organisms. With appropriate molecular patterns, these should be able to induce protective immunoregulatory networks or to reprogramme defective ones. In contrast to acute inflammation, chronic inflammation appears to have no beneficial role, but is a state of sustained immune reactivity in the presence or progression of a disease process. This results in an escalating cycle of tissue damage followed by unproductive tissue repair, breaks in self-tolerance, malignant transformation or deleterious changes in tissue morphology and function. Such inappropriate immune reactivity is an underlying characteristic, either in initiation or maintenance, of a diverse range of disease states including chronic infection, autoimmunity, allergy, cancer, vascular disease and metabolic alterations. Evidence is presented that the inappropriate immune reactivity is due, at least to some extent, to failures in the establishment of immunoregulatory networks as a result of hygiene-related factors. Such networks are the result of activation of antigen-presenting cells, principally dendritic cells, by molecular patterns of micro-organisms encountered sequentially during life and establishing the 'biography' of the immune system.

Successful immunotherapy with Mycobacterium vaccae in the treatment of adenocarcinoma of the lung.

Immunotherapy with a heat-killed suspension of Mycobacterium vaccae (SRL172), given with chemotherapy, in a phase III trial against non-small-cell-lung cancer showed no improvement in the primary endpoint of survival over chemotherapy alone in the initial published analysis. Compliance was poor, with on average only 53% of patients receiving more than 2 injections in the SRL172 arm of the study. Quality of life was, however, improved in those receiving SRL172. Secondary analyses based on compliance with therapy showed that immunotherapy led to significantly improved survival times of patients with adenocarcinoma but, by contrast, had no beneficial effect on survival times of patients with squamous cell carcinoma. Survival of adenocarcinoma patients receiving SRL172 was increased by a mean of 135 days (p=0.0009, Kaplan-Meier log rank test) and survival after 4 or 5 doses of SRL172 showed a difference of greater than 100 days (p<0.05, Mantel-Hänszel log rank test) in the group receiving SRL172 in addition to chemotherapy. Despite the problems inherent in a secondary analysis, these results encourage further research on the role of killed preparations of adjuvant-rich micro-organisms, including saprophytic mycobacteria such as M. vaccae, and members of related genera in the therapy of a range of cancers.

Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402).

The FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P=.68), respectively. Multivariate analysis identified four independent prognostic factors for survival: alpha-fetoprotein (AFP)>400ng/mL (P=.008), abdominal pain (P=.011), hepatomegaly (P=.023) and Child-Pugh score (P=.032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P=.70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P=.58). In this subgroup, two prognostic factors were statistically significant for survival: AFP>400ng/mL (P=.004) and Spitzer Index (P=.013) as shown by multivariable analysis. In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.

Phenotypic expression of ferroportin disease in a family with the N144H mutation.

Ferroportin is a putative transmembrane channel involved in the exit of iron out of the enterocytes, the macrophages and the hepatocytes. Mutations in the human gene coding ferroportin have been linked to an unusual form of iron overload, now referred to as "hemochromatosis type IV" or "ferroportin disease" characterized by a prevalent iron overload of macrophages and liver Küpffer cells. We report four patients from a same family with ferroportin disease associated with the N144H mutation. We show that in this family the mutation which is fully penetrant, may act through an increased iron export from macrophages as suggested by the unexpected absence of iron overload in the spleen and bone marrow detected by magnetic resonance imaging, that it co-segregates with a phenotype close to the classical form of HFE-associated hemochromatosis and was associated, in the oldest patient, with the development of hepatocellular carcinoma in a non cirrhotic liver. Our findings illustrate the existence of a genotype-phenotype relationship in "ferroportin disease", suggest that MRI may be useful in determining this phenotype and show that hepatocellular carcinoma may occur in these patients even without cirrhosis. This observation justifies careful follow-up of this subgroup of patients.

[Adjuvant contact radiotherapy for conjunctival malignancies: Preliminary results of a series of 14 patients treated with the Papillon 50 machine]. / Radiothérapie de contact adjuvante des tumeurs malignes de la conjonctive : résultats préliminaires d'une série de 14 patients traités avec l'appareil Papillon 50.

PURPOSE: To evaluate the results of an adjuvant contact irradiation using 50kV photons after resection of conjunctival malignancies. MATERIALS AND METHOD: From 2012 to 2014, 14 patients (male: nine; female: five) have been treated by contact irradiation after resection of a malignant tumor of the conjunctiva (melanoma: five patients; malignant fibrous histiocytoma: one patient; carcinoma: eight patients) The treatment was performed using the Papillon 50 machine (Ariane). Three to four sessions were delivered, each giving a dose of 10Gy. The median follow-up in survivors was 33 months. RESULTS: The tolerance was good. A cataract was seen in one patient, and a moderate eye dryness in one. There was no corneal ulcer. One patient died of intercurrent disease. One patient with carcinoma recurred locally. CONCLUSION: Adjuvant contact radiotherapy provides a good local control after resection of conjunctival malignancies (melanoma, malignant histiocytofibroma, carcinoma). Thanks to its precision, this technique is well tolerated with a low rate of complications. Furthermore, it is delivered on an ambulatory basis.

[Double-balloon catheter compared to vaginal dinoprostone for cervical ripening in obese women at term]. / Comparaison sonde à double ballonnet-dinoprostone pour la maturation cervicale chez les femmes obèses à terme.

OBJECTIVE: To compare the efficacy of a double-balloon catheter versus vaginal prostaglandin E2 (dinoprostone) for cervical ripening in obese patients with unfavorable cervix at term. METHODS: The study had an open-label, prospective combined with retrospective, observational design. From January 2013 until May 2016, a prospective cohort study of 46 women with pre-pregnancy BMI>30kg/m2, live singleton term fetuses (>37 weeks) in vertex presentation and unfavorable cervix (Bishop score<6), who underwent labor induction for conventional indications using a double-balloon catheter. In the same period, 46 obese women who had undergone cervical ripening using vaginal dinoprostone (3mg) were retrospectively included. Women in groups were paired according to Bishop score before the insertion, pre-pregnancy BMI and parity. The primary outcome was a favorable cervix (Bishop score ≥6) 24h after cervical ripening. RESULTS: After 24h, there was a significantly higher rate of women with favorable cervix (Bishop score ≥6) in the double-balloon group than in dinoprostone group (80.4% vs 47.8%; P=0.001). After adjustment, a double-balloon catheter was significantly associated with an efficient cervical ripening compared to vaginal dinoprostone (aOR 7.81, 95% CI 2.58-23.60). No difference was observed in cesarean section rate (39.1% in each group; P=0.96) and in mean induction time to vaginal delivery (34.5h in the balloon group vs 36.5h in the dinoprostone group; P=0.53). Maternal and neonatal outcomes were similar. CONCLUSION: For obese patients at term, cervical ripening using a double-balloon catheter is more efficient on Bishop score after 24h compared to vaginal dinoprostone.

Detection of c-Ki-ras mutation by PCR/RFLP analysis and diagnosis of pancreatic adenocarcinomas.

BACKGROUND: The c-Ki-ras oncogene (also known as KRAS2) is activated by point mutations involving codon 12 in 72%-100% of primary pancreatic adenocarcinomas, but the gene is not activated in nonneoplastic tissues. Therefore, the detection of c-Ki-ras mutations can facilitate the diagnosis of pancreatic adenocarcinomas, which are not always identified with current tests. Detection is usually performed by oligonucleotide hybridization combined with polymerase chain reaction (PCR), RNAse mismatch cleavage assay, or non-isotopic mismatched PCR, methods that are not feasible for routine screening of large numbers of samples because they are time consuming and/or expensive. PURPOSE: Our purpose was to evaluate a rapid, non-radioactive method of detection of a mutation in codon 12 of the c-Ki-ras gene in pancreatic tumor samples obtained by fine-needle aspiration for diagnostic screening. METHODS: Twenty consecutive patients (15 with pancreatic adenocarcinoma, one with pancreatic cystadenocarcinoma, one with endocrine islet cell tumor, and three with chronic pancreatitis) were selected for this study. A sample of pancreatic tissue from each patient with a tumor or pancreatitis was obtained and evaluated by fine-needle aspiration biopsy under computerized tomography scan or ultrasound guidance using a two-needle coaxial technique. Pancreatic DNA from each of these samples was evaluated by PCR amplification and restriction fragment length polymorphism (RFLP) analysis with nucleotide substitution in PCR primers, creating BstNI restriction patterns that distinguished mutated from normal alleles. The accuracy of the PCR/RFLP assay was validated with DNA from SW480 and HT29 colonic carcinoma cell lines with known mutated and wild-type c-Ki-ras gene sequences. Sensitivity was tested with a series of titration experiments. RESULTS: PCR/RFLP analysis can detect a mutation present in 1% of cells. No amplification could be performed in four (20%) samples because of the absence of cells in the aspirated sample. In the 16 samples adequate for PCR/RFLP analysis, a c-Ki-ras gene mutation was detected in 11 (92%) of 12 adenocarcinomas. Overall, diagnosis was obtained by pathologic (cytomorphologic) examination alone in 13 samples (81%). The presence of malignant cells and/or mutated c-Ki-ras gene was detected in 12 of 12 adenocarcinomas but not in chronic pancreatitis or islet cell tumor. CONCLUSION: Screening of pancreatic tissue samples obtained by fine-needle aspiration for c-Ki-ras mutation using PCR/RFLP analysis combined with pathologic examination could facilitate diagnosis of pancreatic tumors.

[Interest of an internist's consultation in uveitis. Comparative study in 66 cases]. / Apport de la consultation interniste dans le diagnostic étiologique des uvéites. Etude comparative portant sur 66 patients.

BACKGROUND: After exclusion of a masquerade syndrome, uveitis may be associated with infection, systemic diseases, specific ocular diseases, or may be drug-induced. In order to improve diagnostic strategy in uveitis, we performed a comparative study to assess the importance of internist and ophtalmologist's collaboration and we proposed a well-adapted diagnostic procedure. MATERIAL AND METHODS: A comparative study was performed in a tertiary centre. The population was divided in two groups. The first one was retrospective and consisted of patients treated at the Ophthalmology department of Croix Rousse Hospital from 1991 to 2002 without internist's collaboration. The second one was prospective and consisted of patients referred in the same centre in 2003 and 2004 with intervention of an internist. Patients of less than 18 years of age with pre-existent diagnosis, specific ocular diseases, toxoplasmosis infection, or with human immunodeficiency virus infection were excluded. RESULTS: Sixty-six patients were included. Anterior uveitis was the most frequent form (25 cases), followed by panuveitis (20 cases), posterior uveitis (14) and intermediate uveitis (7). The most frequent cause of uveitis was systemic disease (19 cases) followed by infection (7 cases) and neurological entities (4 cases). The rate of diagnosis was 30.3% without internist's intervention and 60.6% when patients were referred to an internist (P=0,01). The internist intervention was contributive in 75% of diagnoses. CONCLUSIONS: The internist intervention significantly enhances the rate of etiological diagnoses in uveitis. These results should further strengthen the internist/ophthalmologist collaboration for patients with uveitis.

[Expansion dilatation balloons for cervical ripening in obstetric practice]. / Utilisation des ballonnets de dilatation cervicale en obstétrique.

During recent decades, mechanical devices have been substituted by pharmacological methods. Their place in the therapeutic arsenal remains important with a renewed obstetrical interest for these devices. Due to a lack of data they are still not recommended as first-line. This review thus attempted to examine the use of expansion dilatation balloons (Foley catheter and double-balloons) to analyze their effectiveness in case of native uterus and previous cesarean section. Twenty-seven clinical trials had compared balloons catheter and prostaglandins in patients without a history of uterine scar. The risk of cesarean section did not differ. Mechanical methods seemed to be more effective in achieving delivery within 24hours, with fewer episodes of excessive uterine contractions, but they necessitated more oxytocin during labor. Ten clinical trials analyzed dilatation balloons in patients with previous cesarean section. More than 70% women had favorable cervical ripening (Bishop score>6), and vaginal delivery was reported between 35 and 70% of patients. The risk of uterine rupture was low between 0.64 and 0.72%, with neither increased risk of severe neonatal and maternal morbidity nor increased risk of infectious morbidity. Mechanical methods are effective and safe for third trimester cervical ripening, mainly in women with previous cesarean section. Potential advantages may include wide availability and reduction of some of the side effects.

[Intensity-modulated radiotherapy of head and neck cancers: Dose effects on the ocular, orbital and eyelid structures]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures : dose de tolérance de l'œil et des voies optiques.

Radiation-induced damage of ocular, orbital and eyelid structures are mainly reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume relationships are, however, inaccurate due to the small volume of most of the organs at risk involved and limited ability of irradiation techniques to spare these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The ability of newest radiation techniques including IMRT and proton therapy to generate steep dose gradients may yield more accurate models in the future. Some toxicities are severe and irreversible, leading to vision loss, as in the case of radiation-induced optic neuropathy for which curative treatments are suboptimal. Other toxicities can lead to reversible vision loss but can be surgically corrected, as is the case for radiation-induced cataract. In this paper, we will review the dose effects for the ocular; orbital and eyelid structures.

Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients.

There is increasing evidence that infections and vaccinations play an important role in the normal maturation of the immune system. It was therefore of interest to determine whether these immune events also affect the prognosis of melanoma patients. A cohort study of 542 melanoma patients in six European countries and Israel was conducted. Patients were followed up for a mean of 5 years and overall survival was recorded. Biometric evaluations included Kaplan-Meier estimates of survival over time and Hazard Ratios (HRs), taking into account all known prognostic factors. During the follow-up between 1993 and 2002, 182 of the 542 patients (34%) died. Survival curves, related to Breslow's thickness as the most important prognostic marker, were in accordance with those observed in previous studies where the cause of death was known to be due to disseminated melanoma. In a separate analysis of patients, vaccinated with vaccinia or Bacille Calmette-Guerin (BCG), HRs and the corresponding 95% Confidence Intervals (CIs) were 0.52 (0.34-0.79) and 0.69 (0.49-0.98), respectively. Joint analyses yielded HRs (and 95% CIs) of 0.55 (0.34-0.89) for patients vaccinated with vaccinia, 0.75 (0.30-1.86) with BCG, and 0.41 (0.25-0.69) with both vaccines. In contrast, infectious diseases occurring before the excision of the tumour had little, or, at the most, a minor influence on the outcome of the melanoma patients. These data reveal, for the first time, that vaccination with vaccinia in early life significantly prolongs the survival of patients with a malignant tumour after initial surgical management. BCG vaccination seems to have a similar, although weaker, effect. The underlying immune mechanisms involved remain to be determined.