VISIR Upgrade Overview and Status

We present an overview of the VISIR upgrade project. VISIR is the mid-infrared imager and spectrograph at ESO’s VLT. The project team is comprised of ESO staff and members of the original VISIR consortium: CEA Saclay and ASTRON. The project plan is based on input from the ESO user community with the goal of enhancing the scientific performance and efficiency of VISIR by a combination of measures: installation of improved hardware, optimization of instrument operations and software support. The cornerstone of the upgrade is the 1k by 1k Si:As AQUARIUS detector array (Raytheon) which has been carefully characterized in ESO’s IR detector test facility (modified TIMMI 2 instrument). A prism spectroscopic mode will cover the N-band in a single observation. New scientific capabilities for high resolution and high-contrast imaging will be offered by sub-aperture mask (SAM) and phase-mask coronagraphic (4QPM/AGPM) modes. In order to make optimal use of favourable atmospheric conditions a water vapour monitor has been deployed on Paranal, allowing for real-time decisions and the introduction of a user-defined constraint on water vapour. During the commissioning in 2012 it was found that the on-sky sensitivity of the AQUARIUS detector was significantly below expectations and that VISIR was not ready to go back to science operations. Extensive testing of the detector arrays in the laboratory and on-sky enabled us to diagnose the cause for the shortcoming of the detector as excess low frequency noise (ELFN). It is inherent to the design chosen for this detector and can’t be remedied by changing the detector set-up. Since this is a form of correlated noise its impact can be limited by modulating the scene recorded by the detector. We have studied several mitigation options and found that faster chopping using the secondary mirror (M2) of the VLT offers the most promising way forward. Faster M2 chopping has been tested and is scheduled for implementation before the end of 2014 after which we plan to re-commission VISIR. In addition an upgrade of the IT infrastructure related to VISIR is planned in order to support burst-mode operations. The upgraded VISIR will be a powerful instrument providing close to background limited performance for diffraction-limited observations at an 8-m telescope. It will offer synergy with facilities such as ALMA, JWST, VLTI and SOFIA, while a wealth of targets is available from survey work (e.g. VISTA, WISE). In addition it will bring confirmation of the technical readiness and scientific value of several aspects of potential mid-IR instrumentation at Extremely Large Telescopes

A value-based comparison of the management of ambulatory respiratory diseases in walk-in clinics, primary care practices, and emergency departments : protocol for a multicenter prospective cohort study

Background: In Canada, 30%-60% of patients presenting to emergency departments are ambulatory. This category has been labeled as a source of emergency department overuse. Acting on the presumption that primary care practices and walk-in clinics offer equivalent care at a lower cost, governments have invested massively in improving access to these alternative settings in the hope that patients would present there instead when possible, thereby reducing the load on emergency departments. Data in support of this approach remain scarce and equivocal. Objective: The aim of this study is to compare the value of care received in emergency departments, walk-in clinics, and primary care practices by ambulatory patients with upper respiratory tract infection, sinusitis, otitis media, tonsillitis, pharyngitis, bronchitis, influenza-like illness, pneumonia, acute asthma, or acute exacerbation of chronic obstructive pulmonary disease. Methods: A multicenter prospective cohort study will be performed in Ontario and Québec. In phase 1, a time-driven activity-based costing method will be applied at each of the 15 study sites. This method uses time as a cost driver to allocate direct costs (eg, medication), consumable expenditures (eg, needles), overhead costs (eg, building maintenance), and physician charges to patient care. Thus, the cost of a care episode will be proportional to the time spent receiving the care. At the end of this phase, a list of care process costs will be generated and used to calculate the cost of each consultation during phase 2, in which a prospective cohort of patients will be monitored to compare the care received in each setting. Patients aged 18 years and older, ambulatory throughout the care episode, and discharged to home with one of the aforementioned targeted diagnoses will be considered. The estimated sample size is 1485 patients. The 3 types of care settings will be compared on the basis of primary outcomes in terms of the proportion of return visits to any site 3 and 7 days after the initial visit and the mean cost of care. The secondary outcomes measured will include scores on patient-reported outcome and experience measures and mean costs borne wholly by patients. We will use multilevel generalized linear models to compare the care settings and an overlap weights approach to adjust for confounding factors related to age, sex, gender, ethnicity, comorbidities, registration with a family physician, socioeconomic status, and severity of illness. Results: Phase 1 will begin in 2021 and phase 2, in 2023. The results will be available in 2025. Conclusions: The end point of our program will be for deciders, patients, and care providers to be able to determine the most appropriate care setting for the management of ambulatory emergency respiratory conditions, based on the quality and cost of care associated with each alternative

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.)

Design, pointing control, and on-sky performance of the mid-infrared vortex coronagraph for the VLT/NEAR experiment

Vortex coronagraphs have been shown to be a promising avenue for high- contrast imaging in the close-in environment of stars at thermal infrared (IR) wavelengths. They are included in the baseline design of the mid-infrared extremely large telescope imager and spectrograph. To ensure good performance of these coronagraphs, a precise control of the centering of the star image in real time is needed. We previously developed and validated the quadrant analysis of coronagraphic images for tip-tilt sensing estimator (QACITS) pointing estimator to address this issue. While this approach is not wavelength-dependent in theory, it was never implemented for mid-IR observations, which leads to specific challenges and limitations. Here, we present the design of the mid-IR vortex coronagraph for the "new Earths in the α Cen Region (NEAR) experiment with the Very Large Telescope (VLT)/Very Large Telescope imager and spectrometer for the mid-infrared (VISIR) instrument and assess the performance of the QACITS estimator for the centering control of the star image onto the vortex coronagraph. We use simulated data and on-sky data obtained with VLT/VISIR, which was recently upgraded for observations assisted by adaptive optics in the context of the NEAR experiment. We demonstrate that the QACITS-based correction loop is able to control the centering of the star image onto the NEAR vortex coronagraph with a stability down to 0.015 λ / D rms over 4 h in good conditions. These results show that QACITS is a robust approach for precisely controlling in real time the centering of vortex coronagraphs for mid-IR observations.Peer reviewe

A systematic encounter with a psycho-oncologist: Longitudinal study in women with breast cancer

Introduction: Cancer patients usually will not ask for psychological support. To increase the proportion of patients who may benefit from psychological support, an encounter was implemented in our hospital, within days following the announcement of a breast cancer diagnosis. In the current study the interest and the efficiency of such an intervention on the distress across the stages of the oncological treatment was assessed. Methods: A longitudinal design with an intervention group and a control group that did not receive the visit of the psychologist was performed. Sociodemographic and disease information, distress, coping, and patients’ needs were assessed on three occasions (diagnosis, treatment and end of treatment). Results: A significant decrease in depression (p < .05), in needs of medical information (p < .05) and a mobilization of distractive coping (p < .05) was found only in the encounter group. Conclusion: Current research indicates that an encounter with the psychologist can be helpful to cope with cancer. It also highlights the importance of coping from cancer patients. Hence, although the intervention of a psycho-oncologist is not always necessary, a systematic encounter is an adequate time where a possible psychological consultation is proposed

Tamoxifen and ovarian function.

BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I) and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II). All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol). Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year). All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year) b: Oligomenorrhea (5 to 9 cycles/year) c: Severe oligomenorrhea (1 to 4 cycles/year) d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status. These data are very important for the choice of endocrine therapy

Correction: Tamoxifen and Ovarian Function.

[This corrects the article on p. e66616 in vol. 8.]

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology