The real-world impact of the COVID-19 pandemic on patients with cancer: a multidisciplinary cross-sectional survey.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruptions to cancer care worldwide. We conducted a multidisciplinary survey of the real-world impact of the pandemic, as perceived by patients with cancer. METHODS: A total of 424 patients with cancer were surveyed using a 64-item questionnaire constructed by a multidisciplinary panel. The questionnaire examined patient perspectives regarding COVID-19-related effects (eg, social distancing measures) on cancer care delivery, resources, and healthcare-seeking behaviour, along with the physical and psychosocial aspects of patient well-being and pandemic-related psychological repercussions. RESULTS: Overall, 82.8% of respondents believed that patients with cancer are more susceptible to COVID-19; 65.6% expected that COVID-19 would delay anti-cancer drug development. Although only 30.9% of respondents felt that hospital attendance was safe, 73.1% expressed unaltered willingness to attend scheduled appointments; 70.3% of respondents preferred to receive chemotherapy as planned, and 46.5% were willing to accept changes in efficacy or side-effect profile to allow an outpatient regimen. A survey of oncologists revealed significant underestimation of patient motivation to avoid treatment interruptions. Most surveyed patients felt that there was an insufficient amount of information available concerning the impact of COVID-19 on cancer care, and most patients reported social distancing-related declines in physical, psychological, and dietary wellness. Sex, age, education level, socio-economic status, and psychological risk were significantly associated with patient perceptions and preferences. CONCLUSION: This multidisciplinary survey concerning the effects of the COVID-19 pandemic revealed key patient care priorities and unmet needs. These findings should be considered when delivering cancer care during and after the pandemic.

The role of adjuvant radiation therapy in older patients with node-positive vulvar cancer: A national cancer database analysis.

OBJECTIVE: We sought to evaluate whether the survival benefit of adjuvant radiotherapy in patients with node-positive vulvar cancer is maintained in older patients, who comprise a large subgroup of patients with vulvar cancer. METHODS: The National Cancer Database (NCDB) was queried for patients aged 65 years or older, who were diagnosed with vulvar squamous cell carcinoma from 2004 to 2017 and underwent surgery with confirmed node-positive disease. Statistical analysis was performed with propensity-score matching, chi-square test, log-rank test, Kaplan-Meier, and multivariable Cox proportional regression. RESULTS: A total of 2396 patients were analyzed, and 1517 (63.3%) received adjuvant radiotherapy. Median follow-up was 73 months. Median age at diagnosis was 77 years (range 65-90). In the propensity score-matched cohort, five-year overall survival (OS) was 29%. Five-year OS was 33% in patients who received surgery followed by adjuvant radiotherapy and 26% in patients who received surgery alone (p < 0.0001). Multivariable analysis continued to demonstrate a survival benefit associated with the addition of adjuvant radiotherapy (OR 0.77 [95% CI 0.69-00.87], p < 0.001). Adjuvant radiotherapy was associated with improved OS among patients aged 65-84 (5-year OS 35% vs 29%, p = 0.0004), but not in patients aged 85 years and older (5-year OS 20% vs 19%, p = 0.32). CONCLUSION: This NCDB study suggests that in older patients with node-positive vulvar cancer, radiotherapy continues to be a vital component of multimodality therapy. However, a comprehensive and geriatrics-specific approach is crucial for treating older adults with node-positive vulvar cancer, as the benefit of adjuvant radiotherapy may be compromised by treatment-related morbidity/toxicity.

Very low risk of monkeypox among staff and students after exposure to a confirmed case in educational settings, England, May to July 2022.

We investigated a secondary school (11-16 year-olds), a primary school (5-11 year-olds), reception year (4-5 year-olds) and a nursery (2-5 year-olds) following confirmed monkeypox in an adult in each educational setting during June and July 2022. MVA-BN vaccine was offered up to 14 days post exposure to 186 children < 12 years and 21 were vaccinated. No secondary cases occurred among at least 340 exposed students and more than 100 exposed staff during the 28-day follow-up period.

Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020.

Two London care homes experienced a second COVID-19 outbreak, with 29/209 (13.9%) SARS-CoV-2 RT-PCR-positive cases (16/103 residents, 13/106 staff). In those with prior SARS-CoV-2 exposure, 1/88 (1.1%) individuals (antibody positive: 87; RT-PCR-positive: 1) became PCR-positive compared with 22/73 (30.1%) with confirmed seronegative status. After four months protection offered by prior infection against re-infection was 96.2% (95% confidence interval (CI): 72.7-99.5%) using risk ratios from comparison of proportions and 96.1% (95% CI: 78.8-99.3%) using a penalised logistic regression model.

Outcomes of Subliminal Transscleral Cyclophotocoagulation treatment in glaucoma.

BACKGROUND: Subliminal transscleral cyclophotocoagulation (SL-TSCPC) is a new alternative therapy to reduce intraocular pressure (IOP) safely and effectively. However, there are few studies regarding SL-TSCPC by Supra 810 laser machine and limited data regarding its effectiveness in moderate severity glaucoma that still has good preservation of vision. This study was conducted to evaluate the outcome of SL-TSPCPC in various types of glaucoma including patients with good vision. METHODS: A retrospective, non-comparative, analytical case series of all patients who received SL-TSCPC treatment from October 2018 to April 2019 at Hospital Tengku Ampuan Afzan, Pahang, Malaysia. Data was collected during the second week, sixth week, third month and sixth month follow-up. The primary outcome measure gave success rate at six months post-treatment. Secondary measures were changes in visual acuity, mean IOP reduction, mean number of IOP lowering medications reduced and ocular side effects noted during follow-up. RESULTS: The success rate was 43.8% (seven eyes out of sixteen eyes) at six months post-treatment. The mean IOP reduced from 43.0mmHg±14.8mmHg pre-treatment to 24.7mmHg±12.0mmHg at two weeks post treatment with 42.6% reduction. Subsequently, mean IOP at sixth week, third month and sixth month were 33.8mmHg±16.9mmHg, 35.2mmHg±14.9mmHg, and 29.0mmHg±16.2mmHg respectively. Vision maintained in 13 patients, two patients had improvement in vision however, five patients had deterioration in vision. No serious ocular side effects were noted. CONCLUSION: Subliminal TSCPC is a safe and alternative method of lowering IOP in moderate to advanced glaucoma over 6 months duration of follow-up. As it has good safety profile and repeatability, it is a good treatment option for patients with uncontrolled glaucoma.

Adjuvant radiation followed by chemotherapy is associated with improved overall survival in endometrial cancer.

OBJECTIVE: Although multimodality therapy has been shown to improve outcomes for patients with high-risk endometrial carcinoma, optimal type and timing of adjuvant therapies is unknown. METHODS: Patients with stage I-IVA endometrial carcinoma diagnosed from 2004 to 2015, and treated with surgery, chemotherapy, and radiation were identified in the National Cancer Database. Adjuvant treatment was categorized as sequential radiation followed by chemotherapy (RT-CT), concurrent chemoradiation (CCRT, RT and CT started within 7 days), or sequential chemotherapy followed by radiation (CT-RT). Analysis for propensity score matched (PSM) cohorts comparing RT-CT to CCRT and CT-RT groups was additionally performed. RESULTS: A total of 17,070 patients were identified, including 12,402 (72.7%) treated with RT-CT, 2,153 (12.6%) with CCRT, and 2,515 (14.7%) with CT-RT. Median follow-up was 44.3 months. Five-year overall-survival (OS) by adjuvant treatment regimen was 77.3% (95% CI 76.4%-78.2%), 74.3% (95% CI 72.0%-76.3%), and 74.4% (95% CI 72.5%-76.3%), respectively (p < .001). When unmatched cohorts were stratified by stage, adjuvant RT-CT was associated with improved OS in stage I and III patients. A similar survival advantage associated with RT-CT was observed in PSM cohorts comparing RT-CT group to CCRT/CT-RT group (5-year OS 77.4% vs 74.2%, p = .001). However, the difference in OS was significant only among stage III patients (RT-CT 73.9% compared to CCRT/CT-RT 69.7%, p =.002). CONCLUSION: Our findings suggest survival benefit with adjuvant RT-CT compared to CT-RT or CCRT in patients undergoing trimodality therapy for endometrial cancer. This survival benefit may be limited to stage III patients.

Elevated fibrinogen, von Willebrand factor, and Factor VIII confer resistance to dilutional coagulopathy and activated protein C in normal pregnant women.

BACKGROUND: Gestational changes in coagulation factor concentrations include elevations in fibrinogen, Factor VIII, and von Willebrand factor (vWF). We hypothesised that blood samples from term pregnant (TP) subjects are less prone to coagulation disturbances from haemodilution compared with those from non-pregnant (NP) females. METHODS: Blood samples were collected from 15 NP and 15 TP subjects. In vitro haemodilution with normal saline was assessed by modified Clauss fibrinogen assay, factor activity, flow-chamber assay, and thromboelastometry. The impact of human fibrinogen concentrate (hFC), cryoprecipitate, and vWF/Factor VIII (FVIII) concentrate replacement in diluted TP and NP blood was compared. Thrombin generation and activated protein C sensitivity were assessed. RESULTS: TP blood contained twice the concentrations of fibrinogen, FVIII, and vWF relative to NP blood (P<0.0001). Platelet thrombus formation (PTF) under flow was reduced by 99.2% and 69.2% in diluted NP and TP blood, respectively. Platelet thrombus formation was partially restored by adding vWF/FVIII, but not hFC or cryoprecipitate. Fibrin clot firmness approached the threshold of 10 mm in diluted NP blood, and clot firmness was effectively restored by hFC, but not by vWF/FVIII. In the presence of thrombomodulin, peak thrombin generation was decreased by 86.7% in NP plasma, but by 31.8% in TP plasma (P<0.0001 vs NP plasma), indicating reduced activated protein C sensitivity in TP plasma. Both elevated FVIII and haemodilution contributed to activated protein C insensitivity. CONCLUSIONS: Our in vitro model showed relative resistance of TP blood to dilutional coagulation changes with respect to platelet adhesion, fibrin polymerisation, and thrombin generation. Careful therapeutic monitoring for different pro-haemostatic agents in pregnant women is warranted.

The clinical utility of PGD with HLA matching: a collaborative multi-centre ESHRE study.

STUDY QUESTION: Has PGD-HLA been successful relative to diagnostic and clinical efficacy? SUMMARY ANSWER: The diagnostic efficacy of PGD-HLA protocols was found lower in this study in comparison to published PGD-HLA protocols and to that reported for general PGD by ESHRE (78.5 vs 94.1% and vs 92.6%, respectively), while the clinical efficacy has proven very difficult to assess due to inadequate follow-up of both the ART/PGD and HSCT procedure outcomes. WHAT IS KNOWN ALREADY: The first clinical cases for PGD-HLA were reported in 2001. It is now a well-established procedure, with an increasing number of cycles performed every year. However, PGD-HLA is still offered by relatively few PGD centres, the currently available data is fragmented and most reports on PGD-HLA applications are limited in number and scope. Published systematic details on methodology, diagnostic results, overall ART success and haematopoietic stem cell transplantation (HSCT) outcomes are limited, precluding an evaluation of the true clinical utility of PGD-HLA cycles. STUDY DESIGN, SIZE, DURATION: This retrospective multi-centre cohort study aimed to investigate the diagnostic and clinical efficacy of the PGD-HLA procedure and the aspects of PGD-HLA cycles influencing positive outcomes: birth of genetically suitable donor-baby (or babies) and HSCT. In April 2014, 32 PGD centres (Consortium members and non-members) with published/known PGD-HLA activity were invited to participate. Between February and September 2015, 14 centres submitted their data, through a custom-designed secure database, with unique login access for each centre. Data parameters covered all aspects of PGD-HLA cycles (ART, embryology and genetic diagnosis), donor-babies born and HSCT. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 716 cycles submitted by 14 centres (performed between August 2001 and September 2015), the quality evaluation excluded 12 cycles, leaving 704, from 364 couples. The online database, based on REDCap, a free, secure, web-based data-capture application, was customized by Centre for Clinical Epidemiology and Outcomes Research (CLEO), Athens. Continuous variables are presented using mean, standard deviation, median and interquartile range, and categorical variables are presented as absolute and relative frequencies. MAIN RESULTS AND THE ROLE OF CHANCE: The data included 704 HLA-PGD cycles. Mean maternal age was 33.5 years. Most couples (81.3%) requested HLA-typing with concurrent exclusion of a single monogenic disease (58.6% for beta-thalassaemia). In 92.5% couples, both partners were fertile, with an average 1.93 HLA-PGD cycles/couple. Overall, 9751 oocytes were retrieved (13.9/cycle) and 5532 embryos were analysed (7.9/cycle). Most cycles involved fresh oocytes (94.9%) and Day 3 embryo biopsy (85.3%). In 97.5% of cycles, the genotyping method involved PCR only. Of 4343 embryos diagnosed (78.5% of analysed embryos), 677 were genetically suitable (15.4% of those analysed for HLA alone, 11.6% of those analysed for HLA with exclusion of monogenic disease). Of the 364 couples, 56.6% achieved an embryo transfer (ET) and 598 embryos were transferred in 382 cycles, leading to 164 HCG-positive pregnancies (pregnancy rate/ET 41.3%, pregnancy rate/initiated cycle 23.3%) and 136 babies born (live birth rate/ET 34.3%, live birth rate/initiated cycle 19.3%) to 113 couples. Data analysis identified the following limitations to the overall success of the HLA-PGD procedure: the age of the mother undergoing the treatment cycle, the number of oocytes collected per cycle and genetic chance. HSCT was reported for 57 cases, of which 64.9% involved combined umbilical cord-blood and bone marrow transplantation from the HLA-identical sibling donor; 77.3% of transplants reported no complications. LIMITATIONS REASONS FOR CAUTION: The findings of the study may be limited as not all PGD centres with PGD-HLA experience participated. Reporting bias on completion of the online database may be another potential limitation. Furthermore, the study is based on retrospective data collection from centres with variable practices and strategies for ART, embryology and genetic diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: This is the first multi-centre study evaluating the clinical utility of PGD-HLA, indicating variations in practice and outcomes throughout 15 years and between centres. The study highlights parameters important for positive outcomes and provides important information for both scientists and couples interested in initiating a cycle. Above all, the study underlines the need for better collaboration between all specialists involved in the ART-PGD/HLA procedure, as well as the need for comprehensive and prospective long-term data collection, and encourages all specialists to aim to properly evaluate and follow-up all procedures, with the ultimate aim to promote best practice and encourage patient informed decision making. STUDY FUNDING/COMPETING INTEREST(S): The study wishes to acknowledge ESHRE for funding the customization of the REDCap database. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

An automated quantitative DNA image cytometry system detects abnormal cells in cervical cytology with high sensitivity.

OBJECTIVE: To evaluate the performance of an automated DNA-image-cytometry system as a tool to detect cervical carcinoma. METHODS: Of 384 liquid-based cervical cytology samples with available biopsy follow-up were analyzed by both the Imager System and a high-risk HPV test (Cobas). RESULTS: The sensitivity and specificity of Imager System for detecting biopsy proven high-grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low-grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high-risk HPV test agreed in 69.43% (268) of all samples. CONCLUSIONS: The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2-3+) lesions.

Mortality and morbidity of extremely low birth weight infants in Hong Kong, 2010-2017: a single-centre review.

BACKGROUND: Extremely low birth weight (ELBW) infants exhibit high rates of mortality and morbidity. We retrospectively assessed factors associated with mortality and morbidity among ELBW infants. METHODS: Perinatal demographic data were reviewed for all ELBW infants born between 2010 and 2017 at a tertiary neonatal unit. RESULTS: For non-survivors (21% of ELBW infants) and survivors, the median gestational ages were 24.1 and 26.2 weeks, respectively, and median birth weights were 650 g and 780 g, respectively (all P<0.001). Regression analyses showed that non-survival was positively associated with lower gestational age (adjusted odds ratio [aOR]=6.71 for every 1-week decrease; 95% confidence interval [CI]=1.73-26.00; P=0.006) and grade 3 or 4 intraventricular haemorrhage (aOR=29.23; 95% CI=1.39-613.84; P=0.030); non-survival was negatively associated with the presence of bronchopulmonary dysplasia (aOR=0.01; 95% CI= <0.001-0.23; P=0.005); length of neonatal intensive care unit stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=89.60; 95% CI=43.86-135.34; P<0.001); and length of hospital stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=2.08; 95% CI=0.43-3.73; P=0.015) and a low Apgar score at 1 minute (B-coefficient=-0.63; 95% CI=-1.04 to -0.22; P=0.003). CONCLUSION: Extremely low birth weight infants exhibited significant mortality and morbidity; there was no survival prior to 23.6 weeks' gestation or below 550 g birth weight. The presence of grade 3 or 4 intraventricular haemorrhage was independently associated with non-survival. Survivors were significantly more likely to exhibit bronchopulmonary dysplasia; survivors with necrotising enterocolitis were more likely to require longer stays in the neonatal intensive care unit and in hospital.

Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre.

INTRODUCTION: Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. METHODS: This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. RESULTS: During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. CONCLUSIONS: The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate and implantation rate when compared with transfer in a stimulated cycle.

Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014.

Scarlet fever notifications surged across the United Kingdom in spring 2014. Molecular epidemiologic investigation of Streptococcus pyogenes infections in North-West London highlighted increased emm4 and emm3 infections coincident with the upsurge. Unlike outbreaks in other countries, antimicrobial resistance was uncommon, highlighting an urgent need to better understand the drivers of scarlet fever activity.

Investigation of an outbreak of vomiting in nurseries in South East England, May 2012.

On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2-73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.

Preparation and measurement of three-qubit entanglement in a superconducting circuit.

Traditionally, quantum entanglement has been central to foundational discussions of quantum mechanics. The measurement of correlations between entangled particles can have results at odds with classical behaviour. These discrepancies grow exponentially with the number of entangled particles. With the ample experimental confirmation of quantum mechanical predictions, entanglement has evolved from a philosophical conundrum into a key resource for technologies such as quantum communication and computation. Although entanglement in superconducting circuits has been limited so far to two qubits, the extension of entanglement to three, eight and ten qubits has been achieved among spins, ions and photons, respectively. A key question for solid-state quantum information processing is whether an engineered system could display the multi-qubit entanglement necessary for quantum error correction, which starts with tripartite entanglement. Here, using a circuit quantum electrodynamics architecture, we demonstrate deterministic production of three-qubit Greenberger-Horne-Zeilinger (GHZ) states with fidelity of 88 per cent, measured with quantum state tomography. Several entanglement witnesses detect genuine three-qubit entanglement by violating biseparable bounds by 830 ± 80 per cent. We demonstrate the first step of basic quantum error correction, namely the encoding of a logical qubit into a manifold of GHZ-like states using a repetition code. The integration of this encoding with decoding and error-correcting steps in a feedback loop will be the next step for quantum computing with integrated circuits.

Postoperative radiation therapy for patients at high-risk of recurrence after radical prostatectomy: does timing matter?

OBJECTIVE: To evaluate among radical prostatectomy (RP) patients at high-risk of recurrence whether the timing of postoperative radiation therapy (RT) (adjuvant, early salvage with detectable post-RP prostate-specific antigen [PSA], or 'late' salvage with a PSA level of >1.0 ng/mL) is significantly associated with overall survival (OS), prostate-cancer specific survival or metastasis-free survival, in a longitudinal cohort. PATIENTS AND METHODS: Of 6 176 RP patients in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 305 patients with high-risk pathological features (margin positivity, Gleason score 8-10, or pT3-4) who underwent postoperative RT were examined, either in the adjuvant (≤6 months after RP with undetectable PSA levels, 76 patients) or salvage setting (>6 months after RP or pre-RT PSA level of >0.1 ng/mL, 229 patients). Early (PSA level of ≤1.0 ng/mL, 180 patients) or late salvage RT (PSA level >1.0 ng/mL, 49 patients) was based on post-RP, pre-RT PSA level. Multivariable Cox regression examined associations with all-cause mortality and prostate cancer-specific mortality and/or metastases (PCSMM). RESULTS: After a median of 74 months after RP, 65 men had died (with 37 events of PCSMM). Adjuvant and salvage RT patients had comparable high-risk features. Compared with adjuvant, salvage RT (early or late) had an increased association with all-cause mortality (hazard ratio [HR] 2.7, P = 0.018) and with PCSMM (HR 4.0, P = 0.015). PCSMM-free survival differed by further stratification of timing, with 10-year estimates of 88%, 84%, and 71% for adjuvant, early salvage, and late salvage RT, respectively (P = 0.026). For PCSMM-free survival and OS, compared with adjuvant RT, late salvage RT had statistically significantly increased risk; however, early salvage RT did not. CONCLUSION: This analysis suggests that patients who underwent early salvage RT with PSA levels of <1.0 ng/mL may have comparable metastasis-free survival and OS compared with adjuvant RT; however, late salvage RT with a PSA level of >1.0 ng/mL is associated with worse clinical outcomes.

Demonstration of two-qubit algorithms with a superconducting quantum processor.

Quantum computers, which harness the superposition and entanglement of physical states, could outperform their classical counterparts in solving problems with technological impact-such as factoring large numbers and searching databases. A quantum processor executes algorithms by applying a programmable sequence of gates to an initialized register of qubits, which coherently evolves into a final state containing the result of the computation. Building a quantum processor is challenging because of the need to meet simultaneously requirements that are in conflict: state preparation, long coherence times, universal gate operations and qubit readout. Processors based on a few qubits have been demonstrated using nuclear magnetic resonance, cold ion trap and optical systems, but a solid-state realization has remained an outstanding challenge. Here we demonstrate a two-qubit superconducting processor and the implementation of the Grover search and Deutsch-Jozsa quantum algorithms. We use a two-qubit interaction, tunable in strength by two orders of magnitude on nanosecond timescales, which is mediated by a cavity bus in a circuit quantum electrodynamics architecture. This interaction allows the generation of highly entangled states with concurrence up to 94 per cent. Although this processor constitutes an important step in quantum computing with integrated circuits, continuing efforts to increase qubit coherence times, gate performance and register size will be required to fulfil the promise of a scalable technology.

Till receipts--a new approach for investigating outbreaks? Evaluation during a large Salmonella Enteritidis phage type 14b outbreak in a North West London takeaway restaurant, September 2009.

Selecting suitable controls for outbreak investigations is often difficult and if done inappropriately will lead to biased inferences. Till receipts and other sales records are frequently available on food premises, but their applicability has not been fully explored. Using data from an investigation into a Salmonella outbreak affecting 66 individuals exposed in a London takeaway restaurant, this study aimed to evaluate the use of till receipts to assess associations between sales and illness. Cases identified through local case-finding were subjected to a standardised exposure questionnaire. Till receipts over the time period when cases arose were analysed. Estimated food exposures from sales were compared to case reported exposures and till receipts analysis showed strong association between illness and consumption of rotisserie chicken (odds ratio (OR): 2.75; confidence interval (CI): 1.7-4.5). Chicken sales immediately prior to food consumption for cases were compared to two control periods in an ecological case-crossover design. On average there was an estimated increase of 3.7 (CI: 2.2-5.2) extra chickens sold in the hour immediately prior to the consumption in the cases (p<0.0001) and the risk of becoming ill at busy times increased by 5% with each additional chicken quarter sold per hour (OR: 1.05; CI: 1.03-1.08). Microbiological and environmental investigations revealed Salmonella Enteritidis phage type (PT)14b in all available cases' stool samples, two environmental samples and leftover chicken from the takeaway. The feasibility of this novel approach to obtain exposure information in the population at risk has been demonstrated, and its limitations are discussed. Further validation is required, comparing results with those in a concurrent classic case-control study.

Persons with reconstructed ACL exhibit altered knee mechanics during high-speed maneuvers.

Anterior cruciate ligament (ACL) injury is a sports trauma that causes long-term disability. The function of the knee during dynamic activities can be severely limited even after successful surgical reconstruction. This study examined the effects of approach velocity during side-step cutting on knee joint mechanics in persons with reconstructed ACL (ACLR). 22 participants (11 with unilateral ACLR, 11 matched-controls) participated. Knee joint mechanics were tested in 3 approach conditions: counter-movement, one-step, and running. Dependent variables, including peak knee flexion, extension, valgus, varus, internal rotation, external rotation angles and corresponding peak joint moments, were assessed during the stance phase of cutting. Two 2×3 ("group" by "approach condition") mixed MANOVA tests were used to examine the effects of ACLR and approach velocity on knee mechanics. ACLR participants exhibited higher knee internal rotator moment (0.22 vs. 0.13 Nm/kg, p=0.003). Inter-group comparisons revealed that the ACLR participants exhibited significantly higher abductor and internal rotator moments only in the running condition (1.86 vs. 1.16 Nm/kg, p=0.018; 0.28 vs. 0.17 Nm/kg, p=0.010, respectively). Our findings suggested that patients with ACLR may be at increased risk of re-injury when participating in high-demand physical activities. Task demand should be considered when prescribing progressive therapeutic interventions to ACLR patients.

Coupling superconducting qubits via a cavity bus.

Superconducting circuits are promising candidates for constructing quantum bits (qubits) in a quantum computer; single-qubit operations are now routine, and several examples of two-qubit interactions and gates have been demonstrated. These experiments show that two nearby qubits can be readily coupled with local interactions. Performing gate operations between an arbitrary pair of distant qubits is highly desirable for any quantum computer architecture, but has not yet been demonstrated. An efficient way to achieve this goal is to couple the qubits to a 'quantum bus', which distributes quantum information among the qubits. Here we show the implementation of such a quantum bus, using microwave photons confined in a transmission line cavity, to couple two superconducting qubits on opposite sides of a chip. The interaction is mediated by the exchange of virtual rather than real photons, avoiding cavity-induced loss. Using fast control of the qubits to switch the coupling effectively on and off, we demonstrate coherent transfer of quantum states between the qubits. The cavity is also used to perform multiplexed control and measurement of the qubit states. This approach can be expanded to more than two qubits, and is an attractive architecture for quantum information processing on a chip.

Generating single microwave photons in a circuit.

Microwaves have widespread use in classical communication technologies, from long-distance broadcasts to short-distance signals within a computer chip. Like all forms of light, microwaves, even those guided by the wires of an integrated circuit, consist of discrete photons. To enable quantum communication between distant parts of a quantum computer, the signals must also be quantum, consisting of single photons, for example. However, conventional sources can generate only classical light, not single photons. One way to realize a single-photon source is to collect the fluorescence of a single atom. Early experiments measured the quantum nature of continuous radiation, and further advances allowed triggered sources of photons on demand. To allow efficient photon collection, emitters are typically placed inside optical or microwave cavities, but these sources are difficult to employ for quantum communication on wires within an integrated circuit. Here we demonstrate an on-chip, on-demand single-photon source, where the microwave photons are injected into a wire with high efficiency and spectral purity. This is accomplished in a circuit quantum electrodynamics architecture, with a microwave transmission line cavity that enhances the spontaneous emission of a single superconducting qubit. When the qubit spontaneously emits, the generated photon acts as a flying qubit, transmitting the quantum information across a chip. We perform tomography of both the qubit and the emitted photons, clearly showing that both the quantum phase and amplitude are transferred during the emission. Both the average power and voltage of the photon source are characterized to verify performance of the system. This single-photon source is an important addition to a rapidly growing toolbox for quantum optics on a chip.