Influence of Atmospheric Turbulence on Optical Communications using Orbital Angular Momentum for Encoding

We describe an experimental implementation of a free-space 11-dimensional communication system using orbital angular momentum (OAM) modes. This system has a maximum measured OAM channel capacity of 2.12 bits/photon. The effects of Kolmogorov thin-phase turbulence on the OAM channel capacity are quantified. We find that increasing the turbulence leads to a degradation of the channel capacity. We are able to mitigate the effects of turbulence by increasing the spacing between detected OAM modes. This study has implications for high-dimensional quantum key distribution (QKD) systems. We describe the sort of QKD system that could be built using our current technology.Comment: 6 pages, 5 figure

High-dimensional quantum cryptography with twisted light

Quantum key distributions (QKD) systems often rely on polarization of light for encoding, thus limiting the amount of information that can be sent per photon and placing tight bounds on the error that such a system can tolerate. Here we describe a proof-of-principle experiment that indicates the feasibility of high-dimensional QKD based on the transverse structure of the light field, allowing for the transfer of more than 1 bit per photon. Our implementation uses the orbital angular momentum (OAM) of photons and the corresponding mutually unbiased basis of angular position (ANG). Our experiment uses a digital micro-mirror device for the rapid generation of OAM and ANG modes at 4 kHz, and a mode sorter capable of sorting single photons based on their OAM and ANG content with a separation efficiency of 93\%. Through the use of a 7-dimensional alphabet encoded in the OAM and ANG bases, we achieve a channel capacity of 2.05 bits per sifted photon. Our experiment shows that, in addition to having an increased information capacity, QKD systems based on spatial-mode encoding will be more tolerant to errors and thus more robust against eavesdropping attacks

Global consultation on cancer staging: promoting consistent understanding and use

Disease burden is the most important determinant of survival in patients with cancer. This domain, reflected by the cancer stage and codified using the tumour-node-metastasis (TNM) classification, is a fundamental determinant of prognosis. Accurate and consistent tumour classification is required for the development and use of treatment guidelines and to enable clinical research (including clinical trials), cancer surveillance and control. Furthermore, knowledge of the extent and stage of disease is frequently important in the context of translational studies. Attempts to include additional prognostic factors in staging classifications, in order to facilitate a more accurate determination of prognosis, are often made with a lack of knowledge and understanding and are one of the main causes of the inconsistent use of terms and definitions. This effect has resulted in uncertainty and confusion, thus limiting the utility of the TNM classification. In this Position paper, we provide a consensus on the optimal use and terminology for cancer staging that emerged from a consultation process involving representatives of several major international organizations involved in cancer classification. The consultation involved several steps: a focused literature review; a stakeholder survey; and a consultation meeting. This aim of this Position paper is to provide a consensus that should guide the use of staging terminology and secure the classification of anatomical disease extent as a distinct aspect of cancer classification

Global consultation on cancer staging: promoting consistent understanding and use

Disease burden is the most important determinant of survival in patients with cancer. This domain, reflected by the cancer stage and codified using the tumour-node-metastasis (TNM) classification, is a fundamental determinant of prognosis. Accurate and consistent tumour classification is required for the development and use of treatment guidelines and to enable clinical research (including clinical trials), cancer surveillance and control. Furthermore, knowledge of the extent and stage of disease is frequently important in the context of translational studies. Attempts to include additional prognostic factors in staging classifications, in order to facilitate a more accurate determination of prognosis, are often made with a lack of knowledge and understanding and are one of the main causes of the inconsistent use of terms and definitions. This effect has resulted in uncertainty and confusion, thus limiting the utility of the TNM classification. In this Position paper, we provide a consensus on the optimal use and terminology for cancer staging that emerged from a consultation process involving representatives of several major international organizations involved in cancer classification. The consultation involved several steps: a focused literature review; a stakeholder survey; and a consultation meeting. This aim of this Position paper is to provide a consensus that should guide the use of staging terminology and secure the classification of anatomical disease extent as a distinct aspect of cancer classification

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Vulnerabilities and fisheries impacts:The uncertain future of manta and devil rays

Manta and devil rays of the subfamily Mobulinae (mobulids) are rarely studied, large, pelagic elasmobranchs, with all eight of well-evaluated species listed on the IUCN Red List as threatened or near threatened. Mobulids have life history characteristics (matrotrophic reproduction, extremely low fecundity, and delayed age of first reproduction) that make them exceptionally susceptible to overexploitation. Targeted and bycatch mortality from fisheries is a globally important and increasing threat, and targeted fisheries are incentivized by the high value of the global trade in mobulid gill plates. Fisheries bycatch of mobulids is substantial in tuna purse seine fisheries. Thirteen fisheries in 12 countries specifically targeting mobulids, and 30 fisheries in 23 countries with mobulid bycatch were identified. Aside from a few recently enacted national restrictions on capture, there is no comprehensive monitoring, assessment or control of mobulid fisheries or bycatch. Recent listing through the Convention on the International Trade in Endangered Species (CITES) may benefit mobulids of the genus Manta (manta rays), but none of the mobulids in the genus Mobula (devil rays) are protected. The relative economic costs of catch mitigation are minimal, particularly compared with a broad range of other, more complicated, marine conservation issues

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research