Generation of Squeezing in Higher Order Hermite-Gaussian Modes with an Optical Parametric Amplifier

We demonstrate quantum correlations in the transverse plane of continuous wave light beams by producing -4.0 dB, -2.6 dB and -1.5 dB of squeezing in the TEM00, TEM10 and TEM20 Hermite- Gauss modes with an optical parametric amplifier, respectively. This has potential applications in quantum information networking, enabling parallel quantum information processing. We describe the setup for the generation of squeezing and analyze the effects of various experimental issues such as mode overlap between pump and seed and nonlinear losses.Comment: 7 pages, 4 figure

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

Tetraploid Atropa belladonna

The use of smiley-face polling stations has had a rapid growth as a means of automatically and efficiently collecting user satisfaction verdicts in airports, restrooms, museums, and retail. Their advantages are that they are low cost, efficient for both respondents and analysts, in addition to having higher response rates than other survey types. Their main disadvantage is the lack of control with who is voting, meaning both repeat voters and non-voters may lead to biased results. The aim of this study is to assess the representativeness and functioning of such publicly located satisfaction polling stations (SPSs) in an indoor climate setting, and to evaluate their potential for real-time evaluation of occupant's satisfaction with the indoor climate. We carried out continuous field tests in two office buildings for more than two months where the results of SPSs were compared with 473 survey results collected in 10 rounds during the tests. To assess how sensitive the instrument was to changing conditions, we deliberately changed temperature setpoints on selected days in one of the buildings. We found that the SPSs had a high and variable non-response bias which could result in a low accuracy for benchmarking of building indoor climate satisfaction. Results also showed a high correlation between SPS complaints and complaints recorded in the surveys for the thermal comfort aspect of indoor climate, including thermal comfort induced by temperature interventions. SPSs can provide valuable continuous recordings of the occupant's satisfaction with the indoor climate

Early death during chemotherapy in patients with small-cell lung cancer: derivation of a prognostic index for toxic death and progression

Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were stored in a database and logistic regression analyses were performed to identify predictive factors for early death. During the first cycle, 118 out of 937 patients (12.6%) died. In 38 patients (4%), the cause of death was sepsis. Significant risk factors were age, performance status (PS), lactate dehydrogenase (LDH) and treatment with epipodophyllotoxins and platinum in the first cycle (EP). Risk factors for ENTD were age, PS and LDH. Extensive stage had a hazard ratio of 1.9 (P = 0.07). Risk factors for ETD were EP, PS and LDH, whereas age and stage were not. For EP, the hazard ratio was as high as 6.7 (P = 0.0001). We introduced a simple prognostic algorithm including performance status, LDH and age. Using a prognostic algorithm to exclude poor-risk patients from trials, we could minimize early death, improve long-term survival and increase the survival differences between different regimens. We suggest that other groups evaluate our algorithm and exclude poor prognosis patients from trials of dose intensification. © 1999 Cancer Research Campaig

Extra phase noise from thermal fluctuations in nonlinear optical crystals

We show theoretically and experimentally that scattered light by thermal phonons inside a second-order nonlinear crystal is the source of additional phase noise observed in Optical Parametric Oscillators. This additional phase noise reduces the quantum correlations and has hitherto hindered the direct production of multipartite entanglement in a single nonlinear optical system. We cooled the nonlinear crystal and observed a reduction of the extra noise. Our treatment of this noise can be successfully applied to different systems in the literature

Evaluation of a digital method to assess evening meal intake in a free-living adult population

Background: In recent years new applications of technologies, including digital images, to capture dietary behaviour in real time have been explored. Objectives: To validate a digital method for estimating evening meal intake in a free-living adult population, and to examine the feasibility of the method for recording evening meal intake over a prolonged period of time. Design: The digital method was compared against weighed records of 19 participants’ usual evening meals for five consecutive days. Two trained image analysts independently estimated the weight of individual foods within the meals into major food categories, and the nutrient content was calculated. A second study included interviews with 28 participants recording their evening meals on weekdays for three consecutive weeks to get their perspective on the feasibility of the method. Results: High correlation coefficients between the digital method and weighed records were found for all measured food categories and nutrients. Comparable means and acceptable limits of agreement (mean difference +/− 2 SD) were found with regard to macronutrient distribution (e.g. fat content −5 to 6 E%), energy density (−75 to 91 kJ/100 g), and energy-adjusted foods (e.g. fruit and vegetable content −241 to 236 g/10 MJ). The majority of the participants expressed satisfaction with the method and were willing to record their evening meals for 1 month or more using the digital method. Conclusion: The digital method is valid and feasible for evening meal estimation in real-time where a prolonged recording period of participants’ meals is needed