Measurements of Phase Dynamics in Planar Josephson Junctions and SQUIDs.

We experimentally investigate the stochastic phase dynamics of planar Josephson junctions (JJs) and superconducting quantum interference devices (SQUIDs) defined in epitaxial InAs/Al heterostructures, and characterized by a large ratio of Josephson energy to charging energy. We observe a crossover from a regime of macroscopic quantum tunneling to one of phase diffusion as a function of temperature, where the transition temperature T^{*} is gate-tunable. The switching probability distributions are shown to be consistent with a small shunt capacitance and moderate damping, resulting in a switching current which is a small fraction of the critical current. Phase locking between two JJs leads to a difference in switching current between that of a JJ measured in isolation and that of the same JJ measured in an asymmetric SQUID loop. In the case of the loop, T^{*} is also tuned by a magnetic flux.

[Impact of NGS results on patient outcome with a multiform glioblastoma]. / Analyse de l'impact des résultats du séquençage de nouvelle génération chez les patients atteints de glioblastome.

PURPOSE: Although some genetic alterations in glioblastoma (GBM) have been characterized, the prognostic value of these gene mutations is not yet established in patients treated with standard therapy. PATIENTS AND METHOD: 40 patients with newly diagnosed GBM, treated between July 2017 and December 2019, and who had genomic analysis were analyzed. Next-generation sequencing techniques (NGS) were used with a panel of 26 genes. Patients were grouped according to MGMT status, the presence or absence of at least one mutated gene on the panel, and p53 expression by immunohistochemistry. RESULTS: the median follow-up was 11.5 months (1.0-37). For all patients, the median duration of progression-free survival was 8 months (95% CI, 5.3-10.7) and the median overall survival (OS) was 17 months (95% CI, 7.5-26.5). Progression-free and overall survival were significantly different according to MGMT status but not according to NGS and p53 status. Three groups of patients according to different combined status could be distinguished due to significant differences in overall survival. CONCLUSION: we have shown that the presence of MGMT promoter methylation is a good prognostic factor. By grouping the patients according to their MGMT, NGS and p53 status, three groups of patients could be separated according to their overall survival. However, these results must be confirmed on a larger number of patients.

Wafer-scale epitaxial modulation of quantum dot density.

Precise control of the properties of semiconductor quantum dots (QDs) is vital for creating novel devices for quantum photonics and advanced opto-electronics. Suitable low QD-densities for single QD devices and experiments are challenging to control during epitaxy and are typically found only in limited regions of the wafer. Here, we demonstrate how conventional molecular beam epitaxy (MBE) can be used to modulate the density of optically active QDs in one- and two- dimensional patterns, while still retaining excellent quality. We find that material thickness gradients during layer-by-layer growth result in surface roughness modulations across the whole wafer. Growth on such templates strongly influences the QD nucleation probability. We obtain density modulations between 1 and 10 QDs/µm2 and periods ranging from several millimeters down to at least a few hundred microns. This method is universal and expected to be applicable to a wide variety of different semiconductor material systems. We apply the method to enable growth of ultra-low noise QDs across an entire 3-inch semiconductor wafer.

Interventional magnetic-resonance-guided cryotherapy combined with microsurgery for recurrent glioblastoma: An innovative treatment?

BACKGROUND: Glioblastoma invariably recurs after primary Stupp tumor therapy and portends a poor prognosis. Cryoablation is a well-established treatment strategy for extra-cranial tumors. The safety and efficacy of interventional MR-guided cryoablation (iMRgC) has not been explored in recurrent glioblastoma. METHODS: A retrospective analysis of data collected over a period of 24 months was performed. The inclusion criteria were: (I) recurrent glioblastoma despite Stupp protocol; (II) MRI followed by histological confirmation of recurrent glioblastoma; (III) location allowing iMRgC followed by microsurgical resection; and (IV) patient's consent. The primary objective was to assess feasibility in terms of complications. The secondary objective was to analyze progression-free survival (PFS), post-iMRgC survival and overall survival (OS). RESULTS: The study included 6 patients, with a mean age of 67±7.6 years [range, 54-70 years]. No major complications were observed. Median PFS was 7.5 months [IQR 3.75-9.75] and 6-month PFS was 50%. Median post-iMRgC survival was 9 months [IQR 7.5-15.25] and 6-month post-iMRgC survival was 80%. Median OS was 22.5 months [IQR 21.75-30]. CONCLUSION: iMRgC for recurrent glioblastoma demonstrated a good safety profile, with no major complications. Our data suggest improved PFS and OS. TRIAL REGISTRATION NUMBER: No. IRB00011687 retrospectively registred on July 7th 2021.

Optical Detection of Single-Electron Tunneling into a Semiconductor Quantum Dot.

The maximum information of a dynamic quantum system is given by real-time detection of every quantum event, where the ultimate challenge is a stable, sensitive detector with high bandwidth. All physical information can then be drawn from a statistical analysis of the time traces. We demonstrate here an optical detection scheme based on the time-resolved resonance fluorescence on a single quantum dot. Single-electron resolution with high signal-to-noise ratio (4σ confidence) and high bandwidth of 10 kHz make it possible to record the individual quantum events of the transport dynamics. Full counting statistics with factorial cumulants gives access to the nonequilibrium dynamics of spin relaxation of a singly charged dot (γ_{↑↓}=3 ms^{-1}), even in an equilibrium transport measurement.

Pulmonary anatomy and a case of unilateral aplasia in a common snapping turtle (Chelydra serpentina): developmental perspectives on cryptodiran lungs.

The common snapping turtle (Chelydra serpentina) is a well studied and broadly distributed member of Testudines; however, very little is known concerning developmental anomalies and soft tissue pathologies of turtles and other reptiles. Here, we present an unusual case of unilateral pulmonary aplasia, asymmetrical carapacial kyphosis, and mild scoliosis in a live adult C. serpentina. The detailed three-dimensional (3D) anatomy of the respiratory system in both the pathological and normal adult C. serpentina, and a hatchling are visualized using computed tomography (CT), microCT, and 3D digital anatomical models. In the pathological turtle, the right lung consists of an extrapulmonary bronchus that terminates in a blind stump with no lung present. The left lung is hyperinflated relative to the normal adult, occupying the extra coelomic space facilitated by the unusual mid-carapacial kyphotic bulge. The bronchial tree of the left lung retains the overall bauplan of the normal specimens, with some minor downstream variation in the number of secondary airways. The primary difference between the internal pulmonary structure of the pathological individual and that of a normal adult is a marked increase in the surface area and density of the parenchymal tissue originating from the secondary airways, a 14.3% increase in the surface area to volume ratio. Despite this, the aplasia has not had an impact upon the ability of the turtle to survive; however, it did interfere with aquatic locomotion and buoyancy control under water. This turtle represents a striking example of a non-fatal congenital defect and compensatory visceral hypertrophy.

Outbreak of Campylobacteriosis Associated with Raccoon Contact at a Wildlife Rehabilitation Centre, Minnesota, 2013.

Campylobacteriosis is an enteric illness caused by bacteria of the genus Campylobacter. There are approximately 900 culture-confirmed cases of campylobacteriosis reported annually to the Minnesota Department of Health (MDH). Case patients are interviewed about risk factors, including foods eaten, recreational and drinking water exposures and animal contact. In September 2013, MDH identified two Campylobacter jejuni cases who reported working at the same wildlife rehabilitation centre before illness onset. This report describes the investigation, which used a case-control study design, and identified 16 additional ill persons, for a total of 18 ill persons. Both cases and controls reported working with a variety of animals, including squirrels, chipmunks, mice, raccoons, opossums, rabbits, songbirds, waterfowl and reptiles. In univariate analyses, contact with a number of different animal species was significantly associated with illness, including raccoons (odds ratio [OR], 11.1; P < 0.001), chipmunks (OR, 3.65; P = 0.01), opossums (OR, 4.38; P = 0.005), mice (OR, 4.18; P = 0.01) and rabbits (OR, 4.36; P = 0.003). In a multivariate model, contact with raccoons was the only exposure independently associated with illness (adjusted OR, 12.2; P = 0.01). Bacterial culture and subtyping of the outbreak strain of C. jejuni from raccoon faecal samples further implicated raccoons as the source of the outbreak. Not all of the cases reported handling raccoons, suggesting that environmental contamination contributed to transmission. MDH worked with the wildlife rehabilitation centre's management to strengthen biosecurity and infection control protocols.

[Bevacizumab in combination with first-line treatment for metastatic non-small cell lung cancer in clinical practice. Results of the EOLE study]. / Bevacizumab en association à une première ligne de chimiothérapie chez des patients atteints d'un cancer bronchique non à petites cellules, non épidermoïde, à un stade avancé ou en rechute : résultats de l'étude non interventionnelle EOLE.

INTRODUCTION: The EOLE cohort aimed to describe, in routine clinical practice, the characteristics and management of patients receiving bevacizumab in combination with first-line metastatic chemotherapy for advanced metastatic or recurrent non squamous non-small cell lung cancer (nsNSCLC), as well as its efficacy and safety. METHODS: A total of 423 patients were enrolled in this prospective, national, multicenter study. Data were collected every 3 months over an 18-month period. RESULTS: Amongst the 407 patients analyzed (mean age 60±10 years, male 68%, ECOG-PS≤1 88%, smokers or former smokers 87%, cardiovascular comorbidities 40%), all except for 2 patients received bevacizumab (7.5 or 15mg/kg/3 weeks in 99% of patients) in combination with doublet chemotherapy. A total of 160 (60%) patients who completed induction received bevacizumab maintenance therapy. Median progression-free survival was 6.9 months (95% CI=[6.0-7.5]). Median overall survival (12.8 months [10.4-14.7]) was longer in patients with ECOG-PS≤1 (14.4 months [12.3-15.9] versus 4.9 months [3.4-8.3] if ECOG-PS=2). A total of 131 (32%) patients experienced at least one serious adverse event (SAE), and 51 (12%) at least one bevacizumab-related SAE. CONCLUSION: EOLE confirms the efficacy and safety of bevacizumab in aNSCLC patients, in current medical practice.

Patterns of relapse in patients with high grade glioma receiving combined treatments including stereotactic re-irradiation for a first relapse.

PURPOSE: Bevacizumab and stereotactic treatment are efficient combined or alone in relapse glioma. However, patterns of relapse after this kind of salvage treatment have never been studied. The purpose of this unicentric retrospective analysis was to assess and understand the patterns of relapse of high grade glioma treated with stereotactic radiation, with or without bevacizumab. PATIENTS AND METHODS: Twenty patients with high grade glioma relapse received a stereotactic radiation; among them two patients received temozolomide and eight patients received bevacizumab; among the latter, four received also irinotecan. We matched the stereotactic radiation treatment planning scan with the images of the first treatment and of the second relapse in order to determine the patterns of failure and associate dosimetric profile. RESULTS: For the total population, median follow-up from the first diagnosis and relapse were 46.1 and 17.6 months, respectively. Among the 13 patients who relapsed, ten did not receive chemotherapy and three received it (P<0.05), two received temozolomide and one bevacizumab. Patients who received bevacizumab had no "out-of-field" recurrences. Among the 32 irradiated relapses, 15 were "in-field" recurrences; among them two were treated with bevacizumab and 13 were not (P<0.05). For the 32 lesions, a favourable prognostic factor of control was the association of a high-dose of irradiation and the use of bevacizumab. CONCLUSION: For patients with relapsed high grade glioma, local control was higher with combined bevacizumab and high-dose stereotactic radiation.

Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study.

BACKGROUND: Concomitant administration of erlotinib with standard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer (NSCLC), but preliminary studies suggest that sequential administration might be effective. OBJECTIVE: To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC. METHODS: In an open-label phase II trial, patients with advanced NSCLC, EGFR wild-type or unknown, PS 0-2, in whom initial cisplatin-based chemotherapy had failed were randomized to sequential erlotinib 150 mg/d (day 2-16)+docetaxel (75 mg/m(2) d1) (arm ED) or docetaxel (75 mg/m(2) d1) alone (arm D) (21-day cycle). The primary endpoint was the progression-free survival rate at 15 weeks (PFS 15). Secondary endpoints included PFS, overall survival (OS), the overall response rate (ORR) and tolerability. Based on a Simon optimal two-stage design, the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages. RESULTS: 147 patients were randomized (median age: 60±8 years, PS 0/1/2: 44/83/20 patients; males: 78%). The ED strategy was rejected, with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D, respectively, median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months. CONCLUSION: Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status.

Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared with temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEF†.

BACKGROUND: Prognosis of unresectable glioblastoma (GB) remains poor, despite temozolomide (TMZ)-based chemoradiation. Activity of bevacizumab (BEV) and irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB. PATIENTS AND METHODS: Patients with unresectable GB, age 18-70, IK ≥50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant intravenous BEV, 10 mg/kg, and IRI, 125 mg/m(2), every 2 weeks for four cycles before radiotherapy (RT) (60 Gy), concomitant oral TMZ, 75 mg/m(2)/day, and BEV, 10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6 months. The control arm consisted of concomitant oral TMZ, 75 mg/m(2)/day during RT, and 150-200 mg/m(2) for 5 days every 28 days for 6 months. The use of BEV was allowed at progression in the control arm. RESULTS: Patients (120) were included from April 2009 to January 2011. The working hypothesis was that treatment would increase the progression-free survival at 6 month (PFS-6) from 50% to 66%. The primary objective was not achieved, and only 30 out of 60 patients were alive without progression at 6 months (50.0% [IC95% (36.8; 63.1)] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules. PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. The median overall survival was not different between the two arms (11.1 months). Main toxicities were three fatal intracranial bleedings, three bile duct or digestive perforations/infections (1 fatal), and six thrombotic episodes in the BEV/IRI arm, whereas there was one intracranial bleeding, two bile duct or digestive perforations/infections (1 fatal), and one thrombotic episode in the control arm. CONCLUSIONS: Neo-adjuvant and adjuvant BEV/IRI, combined with TMZ-radiation, is not recommended for further evaluation in the first-line treatment of unresectable GB. CLINICAL TRIAL REGISTRATION: Clinical trial registered under EUDRACT number 2008-002775-28 (NCT01022918).

[An analysis of 20 consecutive patients treated with stereotactic body radiotherapy on Novalis Tx(®) for stage I non-small-cell lung cancer]. / Analyse des résultats d'une série de 20 patients traités par irradiation hypofractionnée en conditions stéréotaxiques par Novalis Tx(®) pour un cancer bronchopulmonaire non à petites cellules de stade I.

PURPOSE: Recent clinical results of dose escalation with stereotactic body radiation therapy to increase local tumour control for patients with stage I non-small-cell lung cancer who either refuse surgery or are medically inoperable resulted in making it a standard treatment in this setting. This treatment technique was implemented at the Paul-Strauss Centre, Strasbourg, in 2010. The objective of this study is to describe and analyze the data of the first 20 treated patients. PATIENTS AND METHODS: From October 2010 to May 2012, 20 patients were treated with this technique for T1N0M0 or T2N0M0 lung tumour. The indication was proposed by the multidisciplinary thoracic oncology team meeting, and approved by the technical committee of the Department of Radiotherapy. After the realization of a dosimetric CT Scan (4DCT or three phases-free breathing and deep breath-hold inspiration and expiration) and after performing a ((18)F)-FDG PET scan in the treatment position, all patients were treated on Novalis Tx(®) linear accelerator, with arctherapy or modulated intensity radiotherapy (IMRT). A protocol has been defined for the prescribed dose, depending on the size and location of the tumor, central or peripheral. The patients underwent follow-up during treatment and at 1 month, 3-4 months, 6 and 9 months to assess outcomes and toxicities. RESULTS: The mean age was 72.6 years (52-89). Seventeen patients had one or more pulmonary comorbidities. The mean delivered dose was 59.9 Gy (40-70) in 4 Gy to 17.5 Gy fractions. The mean gross tumour volume was 14.9 mL (median 7.2, 0.9 to 73.5) and the mean planning target volume was 77.8 mL (median 49.5; 17-300). The mean initial SUV max was 7.7 (1.8 to 16.7). Dose constraints and planning target volume coverage recommended by the protocol were achieved in the majority of cases. The mean lung V20 was 7.63% (1.2 to 17.7) and the mean dose delivered to the planning target volume was 94.6% (88-99). The duration of treatment was 21 days (median: 23; 8-27), and no change or interruption of prescribed treatment has occurred. Median follow-up was 6.6 months, and crude rates of objective response for patients evaluated were 85% (11/13 patients) at 3 months and 100% at 6 and 9 months. The complete response rate at 3 and 6 months were 0 (0/13 patients) and 50% (5/10 patients). Two patients had metastatic disease in the 6 months following treatment. Concerning pulmonary toxicity at 3 months, 6 patients developed G2 radiation pneumonitis and three patients G3, with positive evolution. CONCLUSION: The analysis of the results of this series, comparable with those described in literature, shows that lung stereotactic radiotherapy is an effective and well-tolerated treatment for inoperable patients. The extension of the indications could be envisaged based on the results of ongoing trials.

Relationships between platelet MAO-B activity and personality styles in acute and weight-recovered young patients with anorexia nervosa.

OBJECTIVE: Previous studies have shown relationships between personality styles and markers of serotonergic functioning, but data on patients with anorexia nervosa (AN) are scarce. METHODS: The personality styles and disorder inventory was administered to 47 acute patients with anorexia nervosa (acAN), 27 weight-recovered patients (recAN) and 72 healthy controls (HC) aged between 14 and 21 years. Platelet monoamine oxidase (MAO-B) activity was assayed with [14C]-ß-phenylethylamine as substrate. RESULTS: AcAN had significant elevated scores on 9 of the 14 personality style subscales when compared to HC, whereas recAN were largely normal. Platelet MAO-B activity and "ambitious/narcissistic" scores correlated negatively in acAN. In recAN we found positive correlations between MAO-B and personality subscores. CONCLUSIONS: The inverse relationship between a cluster B personality style and MAO-B activity in acAN is in accordance with studies in other patient populations. In contrast, positive associations between problematic personality styles and MAO-B activity in recAN combined with the overall decreased MAO-B activity in this group adds to the existing evidence suggesting a general dysfunction of the serotonergic system as a trait marker for AN.

Glioblastoma multiforme presenting with ischemic stroke: case report and review of the literature.

A 58-year-old woman presented with acute onset of global aphasia. Imaging studies revealed a left frontotemporal enhancing tumor and ischemic stroke in the territory of the middle cerebral artery. The patient was operated on, and the diagnosis of glioblastoma multiforme was confirmed. At the time of surgery, several branches of the left middle cerebral artery were found embedded in the tumor. One branch, which was infiltrated by tumor and completely occluded, was resected to achieve complete resection. Postoperatively, the stroke area within the middle cerebral artery territory increased, together with worsening of the patient's clinical status, thus requiring urgent decompressive craniectomy. Thereafter, the patient gradually improved, and received radiation therapy and chemotherapy with no recurrence after 24 months of follow-up. To our knowledge, glioblastomas presenting with ischemic stroke are rare, and such patients should be considered to be at high surgical risk.

[Diagnostic and treatment delays do not modify the treatment outcome of patients with multiform glioblastoma]. / Les délais au diagnostic et à la mise en traitement n'altèrent pas les résultats des traitements délivrés aux patients atteints de glioblastome.

PURPOSE: To assess waiting time effect in patient with multiform glioblastoma (GBM) treated with 3D conformal planned postoperative radiotherapy and to investigate the impact of chemotherapy as first adjuvant treatment. PATIENTS AND METHODS: We retrospectively analyzed 94 consecutive patients with histologically proven GBM. Surgery was considered as macroscopically complete in 33 cases (35%). Median irradiation dose was 60 Gy (8-63, mean 56 Gy). Dose per fractions was 1.8 Gy (five patients), 2 Gy (76 patients) and 2.7 Gy (13 patients). Forty patients received adjuvant pre-radiotherapy chemotherapy as intra-operative carmustine (nine patients) and adjuvant five-day protocol temozolomide alone (31 patients) or with cisplatinum (two patients). All patients received only one chemotherapy cycle. RESULTS: There were 56 males and 38 females. Median age was 62.1 years old (7-82, mean: 59.2 year). Median follow-up was nine months (1-49). For overall patients, median waiting time between fist clinical sign and start of the non surgical treatment was 68 days ((3-274, mean: 81.9 days). For those who received chemotherapy as first treatment, this waiting time was 54 days (3-221, mean 68.3 days). For overall patients, median waiting time between surgery and beginning of radiotherapy was 46 days (8-401, mean 59.3 days). For patients who did not receive chemotherapy as first adjuvant treatment this waiting time was 46 days (-278, mean 55.4 days). Median local control was 14.5 months. Six, 12-, 18-, and 24-month local control rates were 75.6+/-4.6%, 57.6+/-6.2%, and 36.7+/-8% and 27.6+/-8.2%, respectively. According to multivariate analysis, we retrieved two independent prognostic factors of local control, macroscopically total removal of the tumor [RR=2.85, IC 95% (1.3-6.5), p=0.012] and irradiation dose above 60 Gy, [RR=3.14, IC 95% (1.5-6.6), p=0.002]. Median overall survival was 14.3 months. Six-, 12-, 18, and 24-month overall survival rates were 84+/-3.9%, 55.1+/-5.9%, 34.2+/-6.3% and 30.4+/-6.7%, respectively. There was no independent prognostic factor. CONCLUSION: In our series neither waiting times nor adjuvant immediate chemotherapy were prognosticator of local control and overall survival outcome of patients with glioblastoma.

Platelet monoamine oxidase activity in underweight and weight-recovered females with anorexia nervosa.

INTRODUCTION: Central serotonergic pathways may play an important role in the etiology of anorexia nervosa (AN). Although platelet monoamine oxidase activity (MAO-B) has been proposed as an index of cerebral serotonin activity, studies in patients with AN are scarce. METHODS: Platelet MAO-B activity was determined in 59 acutely underweight AN patients (acAN, aged 14-29 years, BMI=15.2+/-1.4), 35 weight-recovered AN patients (recAN, aged 15-29, BMI=20.8+/-2.2) and 59 healthy control women (HCW, aged 14-26, BMI=21.6+/-2.1). Plasma leptin served as an indicator of malnutrition. Results were compared by ANCOVA controlling for confounding variables. RESULTS: Platelet MAO-B activity in acAN patients (5.2+/-1.4 nmol/10 (9)pltx15 min) was similar to HCW (5.5+/-1.9) but significantly lower in recAN patients (4.4+/-1.5). BMI and leptin showed a significant negative correlation with MAO-B activity in AN patients, but not in HCW. DISCUSSION: Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Whether low MAO-B activity in weight-recovered AN patients indicates a premorbid trait or a secondary change due to recovery remains to be elucidated.

[Pituitary metastases from lung cancer. Five cases]. / Métastases hypophysaires de cancers bronchiques. A propos de 5 cas.

Pituitary metastases are rare and generally asymptomatic. We studied 5 patients with pituitary metastases from lung cancer, illustrating the different clinical features. These metastases were in these cases symptomatic with the manifestation being diabetes insipidus or visual field defect. Histological subtypes from our five patients were as well small cell or non small cell lung cancer. After diagnosis of pituitary metastasis, prognosis seems to be linked to the histological subtype and the stage of lung cancer, rather than to the presence of such metastases.