Experimental setup for thermal measurements at the nanoscale using a SThM probe with niobium nitride thermometer.

Scanning Thermal Microscopy (SThM) has become an important measurement technique for characterizing the thermal properties of materials at the nanometer scale. This technique requires a SThM probe that combines an Atomic Force Microscopy (AFM) probe and a very sensitive resistive thermometer; the thermometer being located at the apex of the probe tip allows for the mapping of temperature or thermal properties of nanostructured materials with very high spatial resolution. The high interest of the SThM technique in the field of thermal nanoscience currently suffers from a low temperature sensitivity despite its high spatial resolution. To address this challenge, we developed a high vacuum-based AFM system hosting a highly sensitive niobium nitride (NbN) SThM probe to demonstrate its unique performance. As a proof of concept, we utilized this custom-built system to carry out thermal measurements using the 3ω method. By measuring the V3ω voltage on the NbN resistive thermometer under vacuum conditions, we were able to determine the SThM probe's thermal conductance and thermal time constant. The performance of the probe is demonstrated by performing thermal measurements in-contact with a sapphire sample.

Infrared thermotransmittance-based temperature field measurements in semitransparent media.

Contactless temperature field measurements in or at the surfaces of semitransparent media are a scientific challenge as classical thermography techniques based on proper material emission cannot be used. In this work, an alternative method using infrared thermotransmittance for contactless temperature imaging is proposed. To overcome the weakness of the measured signal, a lock-in acquisition chain is developed and an imaging demodulation technique is used to retrieve the phase and amplitude of the thermotransmitted signal. These measurements, combined with an analytical model, enable the estimation of the thermal diffusivity and conductivity of an infrared semitransparent insulator (wafer of Borofloat 33 glass) and the monochromatic thermotransmittance coefficient at 3.3 µm. The obtained temperature fields are in good agreement with the model, and a detection limit of ±2 °C is estimated with this method. The results of this work open new opportunities in the development of advanced thermal metrology for semitransparent media.

Prevalence of Pathologic N2/N3 Disease in Postmenopausal Women with Clinical N0 ER+/HER2- Breast Cancer.

BACKGROUND: The RxPONDER trial demonstrated that the 21-gene recurrence score can be used to guide adjuvant systemic therapy decisions in postmenopausal women with pN1 ER+/HER2- breast cancer. As such, a sentinel lymph node biopsy (SLNB) may not provide systemic treatment-altering information for many patients, and omission of SLNB in patients with low probability of pN2/N3 disease could be considered. METHODS: Postmenopausal women (aged ≥ 50 years) diagnosed with cN0cM0, ER+/HER- breast cancer from 2013 to 2017 were identified in the National Cancer Database. The primary outcome was the prevalence of pN2/N3 disease. RESULTS: Of 325,692 postmenopausal women with cN0 ER+/HER2- breast cancer, 7106 (2.2%) were pN2/N3. In total, 81.7% had cT1 tumors, 16.8% T2, 1.3% T3, and 0.2% T4. In patients with T1 tumors, the prevalence of pN2/N3 disease was 1.2% compared with 17.2% in patients with T3/T4 tumors. In multivariable models, cT stage was the strongest predictor of pN2/N3 disease (adjusted odds ratio [aOR] 14.9 [12.1-18.4]). Lobular histology (aOR 2.4 [2.3-2.6]), higher grade (aOR 2.9 [2.6-3.1]), and young age (aOR 1.5 [1.3-1.7]) were also associated with increased prevalence of pN2/N3. We created a model using histology, grade, and T stage that stratifies patients with low prevalence of pN2/3 disease (< 1%) and those at high risk (> 20%). CONCLUSIONS: In postmenopausal women with cN0 ER+/HER2- breast cancer, the prevalence of pN2/N3 disease is low, indicating a potential opportunity to use the results of RxPONDER to extend criteria to omit SLNB. Prospective study is needed to determine safety, including risk of nodal recurrence, of omission of SLNB in carefully selected patients.

Synchronization of Optomechanical Nanobeams by Mechanical Interaction.

The synchronization of coupled oscillators is a phenomenon found throughout nature. Mechanical oscillators are paradigmatic examples, but synchronizing their nanoscaled versions is challenging. We report synchronization of the mechanical dynamics of a pair of optomechanical crystal cavities that, in contrast to previous works performed in similar objects, are intercoupled with a mechanical link and support independent optical modes. In this regime they oscillate in antiphase, which is in agreement with the predictions of our numerical model that considers reactive coupling. We also show how to temporarily disable synchronization of the coupled system by actuating one of the cavities with a heating laser, so that both cavities oscillate independently. Our results can be upscaled to more than two cavities and pave the way towards realizing integrated networks of synchronized mechanical oscillators.

Facial emotion recognition in children with or without Attention Deficit/Hyperactivity Disorder: Impact of comorbidity.

OBJECTIVES: This study sought to assess facial emotion recognition deficit in children with Attention Deficit/Hyperactivity Disorder (ADHD) and to test the hypothesis that it is increased by comorbid features. METHOD: Forty children diagnosed with ADHD were compared with 40 typically developing children, all aged from 7 to 11years old, on a computerized facial emotion recognition task (based on the Pictures of Facial Affect). Data from parents' ratings of ADHD and comorbid symptoms (on the Conners' Revised Parent Rating Scale) were also collected. RESULTS: Children with ADHD had significantly fewer correct answer scores than typically developing controls on the emotional task while they performed similarly on the control task. Recognition of sadness was especially impaired in children with ADHD. While ADHD symptoms were slightly related to facial emotion recognition deficit, oppositional symptoms were related to a decrease in the number of correct answers on sadness and surprise recognition. CONCLUSION: Facial emotion recognition deficit in children with ADHD might be related to an impaired emotional process during childhood. Moreover, Oppositional Defiant Disorder seems to be a risk factor for difficulties in emotion recognition especially in children with ADHD.

Mechanisms behind the enhancement of thermal properties of graphene nanofluids.

While the dispersion of nanomaterials is known to be effective in enhancing the thermal conductivity and specific heat capacity of fluids, the mechanisms behind this enhancement remain to be elucidated. Herein, we report on highly stable, surfactant-free graphene nanofluids, based on N,N-dimethylacetamide (DMAc) and N,N-dimethylformamide (DMF), with enhanced thermal properties. An increase of up to 48% in thermal conductivity and 18% in specific heat capacity was measured. The blue shift of several Raman bands with increasing graphene concentration in DMF indicates that there is a modification in the vibrational energy of the bonds associated with these modes, affecting all the molecules in the liquid. This result indicates that graphene has the ability to affect solvent molecules at long-range, in terms of vibrational energy. Density functional theory and molecular dynamics simulations were used to gather data on the interaction between graphene and solvent, and to investigate a possible order induced by graphene on the solvent. The simulations showed a parallel orientation of DMF towards graphene, favoring π-π stacking. Furthermore, a local order of DMF molecules around graphene was observed suggesting that both this special kind of interaction and the induced local order may contribute to the enhancement of the fluid's thermal properties.

Nanocrystalline silicon optomechanical cavities.

Silicon on insulator photonics has offered a versatile platform for the recent development of integrated optomechanical circuits. However, there are some constraints such as the high cost of the wafers and limitation to a single physical device level. In the present work we investigate nanocrystalline silicon as an alternative material for optomechanical devices. In particular, we demonstrate that optomechanical crystal cavities fabricated of nanocrystalline silicon have optical and mechanical properties enabling non-linear dynamical behaviour and effects such as thermo-optic/free-carrier-dispersion self-pulsing, phonon lasing and chaos, all at low input laser power and with typical frequencies as high as 0.3 GHz.

Distinct pathways for norepinephrine- and opioid-triggered antinociception from the amygdala.

BACKGROUND: The amygdala has an important role in pain and pain modulation. We showed previously in animal studies that α2 -adrenoreceptor activation in the central nucleus of the amygdala (CeA) mediates hypoalgesia produced by restraint stress, and that direct application of an α2 -agonist in this region produces analgesia. AIMS: In the present animal experiments, we investigated the pathways through which α2 -sensitive systems in the CeA produce behavioural analgesia. The CeA has dense connections to a descending pain modulatory network, centred in the midbrain periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM), which is implicated in various forms of stress-related hypoalgesia and which mediates the antinociceptive effect of morphine applied in the basolateral amygdala. We investigated whether this circuit mediates the hypoalgesic effects of α2 -adrenergic agonist administration into the CeA as well as the contribution of endogenous opioids and cannabinoids. We also tested the possibility that activation of α2 -receptors in the CeA produces antinociception by recruitment of noradrenergic pathways projecting to the spinal cord. RESULTS: Hypoalgesia resulting from bilateral application of the α2 -adrenergic agonist clonidine in the CeA was not reversed by chemical inactivation of the RVM or by systemic injections of naloxone (µ-opioid antagonist) or rimonabant (CB1 antagonist). By contrast, spinal α2 -receptor blockade (intrathecal idazoxan) completely prevented the hypoalgesic effect of clonidine in the CeA, and unmasked a small but significant hyperalgesia. CONCLUSION: In rats, adrenergic actions in the CeA mediating hypoalgesia require spinal adrenergic neurotransmission but not the PAG-RVM pain modulatory network, or opiate or cannabinoid systems.

French multicentre clinical evaluation of helical TomoTherapy for anal cancer in a cohort of 64 consecutive patients.

PURPOSE/OBJECTIVES: To assess feasibility and toxicity of Helical TomoTherapy for treating anal cancer patients. METHODS: From 2007 to 2011, 64 patients were consecutively treated with TomoTherapy in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Median follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7%) had T2, 16 patients (25.0%) T3, and 27 patients (42.2%) T4 tumours. Thirty-nine patients (60.9%) had nodal involvement. Median tumour size was 45 mm (range, 10-110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6% (95 %CI [71.1%-93.0%]), and the one-year disease-free survival, and colostomy-free survival were 68.7% (95 %CI [54.4%-79.4]), and 75.5% (95 %CI [60.7%-85.3%]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade ≥3 toxicity included dermatologic (46.9% of patients), gastrointestinal (20.3%), and hematologic (17.2%) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed. CONCLUSIONS: TomoTherapy for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement.

[Guidelines for delineation of pelvic lymph nodes in anal cancer treatment]. / Recommandations pour la délinéation des aires ganglionnaires pelviennes dans le cancer du canal anal.

Squamous cell anal cancer is a rare malignancy, its incidence increases due to higher exposure of the young adults to risk factors. The current management is based on chemoradiotherapy, which is highly effective and achieves locoregional control but causes important morbidity. Improvement of radiation technique such as intensity modulated radiation therapy has led to reduce acute toxicities, but also requires an accurate delineation of the target volumes in order not to underestimate potential and pathological sites resulting in an increase of the locoregional failures. PET scanner has an important place in the pretreatment work-up for staging and targeting the delineation of the volumes, allowing to select patients with localized disease, avoid geographic miss and appropriately boost nodal disease. The study of recurrences sites has not yet provided a real mapping of the recurrences depending on the treatment volumes. Different radiation oncologist cooperative groups have published guidelines and tools for delineation, in order to provide homogeneity but also customize the management of anal carcinoma.

[Stereotactic radiotherapy for intracranial meningioma]. / Radiothérapie stéréotaxique des méningiomes intracrâniens.

Meningiomas are the most common non-malignant tumours of the brain. Gross-total resection remains the preferred treatment, if achievable without morbidity. Radiation therapy is advocated for inoperable, incompletely resected, or recurrent grade 1 tumours, if there is a progressive, symptomatic lesion, or in case of functional impairment. Postoperative radiation therapy is recommended for grade 2 or 3 lesions. Fractionated stereotactic radiotherapy and stereotactic radiosurgery are high precision techniques, allowing good sparing of surrounding tissues. Fractionated stereotactic radiotherapy and stereotactic radiosurgery give comparable results, with excellent 5-year tumour control rates of more than 90% for benign meningiomas. Toxicity is low and seems equivalent, despite a biased use of fractionated stereotactic radiotherapy for larger meningiomas, close to critical structures. Fractionated stereotactic radiotherapy seems to be of special interest in the treatment of cavernous sinus or optic pathways meningiomas. The different therapeutic modalities should be discussed by a multidisciplinary team.

Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000-2007.

An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000-2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors.

Evaluation of cardiorespiratory functional reserve from arm exercise in the elderly.

BACKGROUND: When the subject is not able to satisfy traditional testing procedures, alternative exercises or indices such as arm cranking or the oxygen uptake efficiency slope (OUES) have been proposed. However, the OUES has not yet been used on elderly subjects from an exercise performed with the arms. OBJECTIVE: The aim of our study was to evaluate the possibility of using the OUES as an index of the cardiorespiratory functional reserve in the elderly when the exercise evaluation test is performed with the arms and when this parameter is estimated from submaximal responses. METHODS: Seventeen adults (62-82 years) undergoing total joint arthroplasty of the hip took part in this study. Maximal incremental exercise tests were performed on an arm crank ergometer 1 month before (T1) and 2 months after (T2) surgery. Gas exchanges were measured continuously to determine oxygen consumption at peak exercise (V˙O2 peak) and were used to calculate the OUES. The correlation coefficient was calculated between V˙O2 peak and OUES, and their relative changes between T1 and T2. RESULTS: V˙O2 peak was not significantly different between T1 and T2: 10.3 ± 0.7 and 9.8 ± 0.5 mL/min per kilogramme respectively. The OUES estimated from submaximal responses did not show a significant difference between T1 and T2. Significant correlations were observed between individual V˙O2 peak and OUES, as well as at T1 and T2. CONCLUSION: The use of arm cranking exercises and the calculation of the OUES from the submaximal respiratory response can be used for the objective quantification of cardiorespiratory functional reserve in the elderly.

[Physical activity and exercise training for patients with cystic fibrosis]. / Activité physique et réentraînement à l'effort du patient atteint de mucoviscidose.

In France patients with cystic fibrosis benefit from a multidisciplinary follow-up in Cystic Fibrosis Centres. In this follow-up, despite the numerous therapeutic benefits of exercise in this disease, little emphasis is placed on the promotion of physical activity. The aim of this article is to improve this aspect of management, giving advice from a working group of experts, based on the medical literature and clinical experience. These proposals include quantification of physical activity, evaluation of exercise, training and rehabilitation programs and finally, modification of behaviour to include physical activity in the overall cystic fibrosis treatment strategy. It is intended to set up multicentre studies to evaluate the impact of these proposals.

[Molecular imaging of tumor hypoxia]. / Imagerie moléculaire de l'hypoxie tumorale.

By allowing an earlier diagnosis and a more exhaustive assessment of extension of the disease, the tomography by emission of positrons (TEP) transforms the care of numerous cancers. At present, (18)F-fluorodesoxyglucose ([(18)F]-FDG) imaging appears as the only one available but new molecular markers are being developed. In the next future they would modify the approach of cancers. In this context, the molecular imaging of the hypoxia and especially the (18)Ffluoromisonidazole TEP ([(18)F]-MISO TEP) can give supplementary information allowing the mapping of hypoxic regions within the tumour. Because of the links, which exist between tumour hypoxia and treatment resistance of very numerous cancers, this information can have an interest, for determination of prognosis as well as for the delineation, volumes to be irradiated. Head and neck tumours are doubtless those for which the literature gives the most elements on the therapeutic impact of tumour hypoxia. Targeted therapies, based on hypoxia, already exist and the contribution of the molecular imaging could be decisive in the evaluation of the impact of such treatment. Molecular imaging of brain tumours remains to be developed. The potential contributions of the [(18)F]-MISO TEP for the care of these patients need to be confirmed. In this context, we propose a review of hypoxia molecular imaging taking as examples head and neck tumours and glioblastomas (GB), two tumours for which hypoxia is one of the key factors to overcome in order to increase therapeutics results.

[Radiotherapy of adult glial tumors: new developments and perspectives]. / Radiothérapie des tumeurs gliales de l'adulte : actualités et perspectives.

Adult gliomas (WHO grade II, III and IV) are heterogeneous primitive brain tumors. The prognosis of these tumors depends on multiple factors such as age at diagnosis, Karnofsky score, histopathology, biology and treatments. Radiotherapy (RT) plays an important role in the treatment strategy, after surgery. RT has been evaluated in terms of survival, median time to progression and toxicity. Techniques of RT have improved, during the last two decades: neuro-imaging (CT-scan, MRI and PET) and dedicated computers for dosimetry make it possible to deliver an homogeneous dose in the target volume while sparing normal tissues. Photons X are usually delivered with stereotactic or conformational noncoplanar techniques. Total doses delivered range from 50.4 to 60 Gy (1.8-2 Gy/fraction). Median survivals are different with regard to the tumor grade. However, genetic and biological factors also are important prognostic factors such as inactivation of the MGMT gene for glioblastomas and loss of heterozygosity (LOH) 1p/19q, usually associated with pure oligodendroglioma. During the 1990s, temozolomide (TMZ) was specifically developed as a chemotherapy agent against primary brain tumors. The current TMZ/RT regimen in newly diagnosed GBM has been proposed as a standard treatment. The optimal treatment strategy is not known. New clinical trials are needed to assess new techniques of RT; a further improvement in medical treatment requires novel agents.

[Bevacizumab/irinotecan. An active treatment for recurrent high grade gliomas: preliminary results of an ANOCEF Multicenter Study]. / Bevacizumab/irinotecan. Un nouveau traitement actif dans les gliomes de haut grade récidivants: résultats préliminaires d'une étude multicentrique de l'Anocef.

RATIONALE: Second-line chemotherapy is disappointing in recurrent high-grade gliomas. Dramatic responses in recurrent high-grade gliomas have been reported in a recent monocentric trial with a novel association combining bevacizumab (anti-VEGF monoclonal antibody agent) and irinitecan. OBJECTIVE: To report the experience of the ANOCEF group (French speaking neuro-oncology association) using the bevacizumab-irinotecan combination in recurrent high-grade gliomas. METHODS: Eight centers were involved in this retrospective multicenter study. Bevacizumab-irinotecan was delivered as previously described in a compassional setting to non-selected patients suffering from a high-grade glioma (WHO grade III and IV). Response rate at two months of the onset of the treatment was analyzed using the Macdonald criteria. The toxicity profile of the treatment was also investigated. RESULTS: From 2006 to 2007, 77 patients were treated (median age: 52 years; median Karnofsky score: 70) for a recurrent high-grade glioma (49 grade IV, 28 grade III). At two months, the response rates were objective response=36% (54% in grade III and 27% in grade IV); stable disease=39%; progressive disease=13%; patients not evaluable because of a rapid fatal clinical deterioration=12%. Improvement was noted in 49% of patients. Among the main toxicities, we noted; intratumoral hemorrage (n=5 with spontaneous regression in three) and thromboembolic complications including venous thrombophlebitis (n=4), pulmonary embolism (n=2), myocardial infarction (n=1), grade III-IV hematotoxicity (n=2), reversible leukoencephalopathy (n=1). CONCLUSION: This retrospective multicenter study adds further arguments in favor of the promising results of this new combination and its potential rapidity of action in recurrent high-grade gliomas. Antiangiogenic agents expose the patients to a well-known risk of thromboembolic and hemorragic complications, necessitating careful follow-up and patient selection in light of the cardiovascular contraindications.

[Interest of radiotherapy of rectal cancer with synchronous metastases]. / Intérêt de la radiothérapie dans le traitement de la tumeur primitive rectale lorsque sont associées des métastases synchrones.

PURPOSE: There is no consensus about the treatment of rectal tumour when there are synchronous metastases. The interest of radiotherapy is debated. PATIENTS AND METHODS: Thirty-seven patients with rectal tumour and synchronous metastases were treated with radiotherapy first between September 1994 and December 2004. We analysed the tolerance, local control, resecability, overall survival of such a therapeutic strategy. RESULTS: The mean follow-up was 30 months. Twenty-four tumors were resecable for both the primary site and the metastases. Thirteen were unresecable at the time of diagnosis. Thirty-three patients were treated with radiochemotherapy, ten with radiotherapy alone. Eighty-six decimal five percent of them had no pelvic symptom six weeks after the treatment. Twenty-one rectal tumours were finally resected. The disease progressed in six cases during the radiotherapy. Surgery of the metastases was possible for 12 patients with tumour initially resecable. CONCLUSION: Radiochemotherapy is a "tolerable" treatment, in spite of more frequent urinary or digestive side-effects. But, if there is no surgery, palliative effect of radiotherapy is limited.