Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): A feasibility study

Background: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. Patients and Methods: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m(2)). This was to be followed by 2 cycles of cisplatin/vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. Results: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. Conclusion: Oral vinorelbine 50 mg/m(2) (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy

Quantum memory for entangled two-mode squeezed states

A quantum memory for light is a key element for the realization of future quantum information networks. Requirements for a good quantum memory are (i) versatility (allowing a wide range of inputs) and (ii) true quantum coherence (preserving quantum information). Here we demonstrate such a quantum memory for states possessing Einstein-Podolsky-Rosen (EPR) entanglement. These multi-photon states are two-mode squeezed by 6.0 dB with a variable orientation of squeezing and displaced by a few vacuum units. This range encompasses typical input alphabets for a continuous variable quantum information protocol. The memory consists of two cells, one for each mode, filled with cesium atoms at room temperature with a memory time of about 1msec. The preservation of quantum coherence is rigorously proven by showing that the experimental memory fidelity 0.52(2) significantly exceeds the benchmark of 0.45 for the best possible classical memory for a range of displacements.Comment: main text 5 pages, supplementary information 3 page

Performance of the DNA-citoliq liquid-based cytology system compared with conventional smears

To evaluate the performance of a new, manual, simplified liquid-based system, DNA-Citoliq (Digene Brasil), employed under routine conditions as compared to conventional smears collected from six collaborating private laboratories. Methods: A panel of cytopathologists, who served as the gold standard diagnosis, adjudicated discordant opinions. Results: Of 3206 pairs of slides considered valid for comparison, there were 3008 in full agreement (93.8%), 112 (3.5%) with one diagnostic category discrepancies, and 86 (2.7%) discordant cases. Among the 288 borderline+ by either method, DNA-Citoliq detected abnormalities in 243 (84.4%), and conventional smears (CS) detected abnormalities in 178 (61.8%) (McNemar test, P < 0.000), a 36.5% increased detection of borderline+ cases. Conclusions: For mild dyskaryosis, DNA-Citoliq detected 176 cases and CS 125 cases (McNemar test, P < 0.000); and for moderate+severe dyskaryosis 66 versus 32 cases respectively (McNemar test, P < 0.000)

Vortices in polariton OPO superfluids

This chapter reviews the occurrence of quantised vortices in polariton fluids, primarily when polaritons are driven in the optical parametric oscillator (OPO) regime. We first review the OPO physics, together with both its analytical and numerical modelling, the latter being necessary for the description of finite size systems. Pattern formation is typical in systems driven away from equilibrium. Similarly, we find that uniform OPO solutions can be unstable to the spontaneous formation of quantised vortices. However, metastable vortices can only be injected externally into an otherwise stable symmetric state, and their persistence is due to the OPO superfluid properties. We discuss how the currents charactering an OPO play a crucial role in the occurrence and dynamics of both metastable and spontaneous vortices.Comment: 40 pages, 16 figure

International comparison of health spending and utilization among people with complex multimorbidity.

OBJECTIVE: The objective of this study was to explore cross-country differences in spending and utilization across different domains of care for a multimorbid persona with heart failure and diabetes. DATA SOURCES: We used individual-level administrative claims or registry data from inpatient and outpatient health care sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States (US). DATA COLLECTION/EXTRACTION METHODS: Data collected by ICCONIC partners. STUDY DESIGN: We retrospectively analyzed age-sex standardized utilization and spending of an older person (65-90 years) hospitalized with a heart failure exacerbation and a secondary diagnosis of diabetes across five domains of care: hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, and outpatient drugs. PRINCIPAL FINDINGS: Sample sizes ranged from n = 1270 in Spain to n = 21,803 in the United States. Mean age (standard deviation [SD]) ranged from 76.2 (5.6) in the Netherlands to 80.3 (6.8) in Sweden. We observed substantial variation in spending and utilization across care settings. On average, England spent $10,956 per person in hospital care while the United States spent$30,877. The United States had a shorter length of stay over the year (18.9 days) compared to France (32.9) and Germany (33.4). The United States spent more days in facility-based rehabilitative care than other countries. Australia spent $421 per person in primary care, while Spain (Aragon) spent$1557. The United States and Canada had proportionately more visits to specialist providers than primary care providers. Across almost all sectors, the United States spent more than other countries, suggesting higher prices per unit. CONCLUSION: Across 11 countries, there is substantial variation in health care spending and utilization for a complex multimorbid persona with heart failure and diabetes. Drivers of spending vary across countries, with the United States being the most expensive country due to high prices and higher use of facility-based rehabilitative care

Differences in health outcomes for high-need high-cost patients across high-income countries.

ObjectiveThis study explores variations in outcomes of care for two types of patient personas-an older frail person recovering from a hip fracture and a multimorbid older patient with congestive heart failure (CHF) and diabetes.Data sourcesWe used individual-level patient data from 11 health systems.Study designWe compared inpatient mortality, mortality, and readmission rates at 30, 90, and 365 days. For the hip fracture persona, we also calculated time to surgery. Outcomes were standardized by age and sex.Data collection/extraction methodsData was compiled by the International Collaborative on Costs, Outcomes and Needs in Care across 11 countries for the years 2016-2017 (or nearest): Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Principal findingsThe hip sample across ranged from 1859 patients in Aragon, Spain, to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia, and the majority of hip patients across countries were female. The congestive heart failure (CHF) sample ranged from 742 patients in England to 21,803 in the United States. Mean age ranged from 77.2 in the United States to 80.3 in Sweden, and the majority of CHF patients were males. Average in-hospital mortality across countries was 4.1%. for the hip persona and 6.3% for the CHF persona. At the year mark, the mean mortality across all countries was 25.3% for the hip persona and 32.7% for CHF persona. Across both patient types, England reported the highest mortality at 1 year followed by the United States. Readmission rates for all periods were higher for the CHF persona than the hip persona. At 30 days, the average readmission rate for the hip persona was 13.8% and 27.6% for the CHF persona.ConclusionAcross 11 countries, there are meaningful differences in health system outcomes for two types of patients

Differences in health care spending and utilization among older frail adults in high-income countries: ICCONIC hip fracture persona.

ObjectiveThis study explores differences in spending and utilization of health care services for an older person with frailty before and after a hip fracture.Data sourcesWe used individual-level patient data from five care settings.Study designWe compared utilization and spending of an older person aged older than 65 years for 365 days before and after a hip fracture across 11 countries and five domains of care as follows: acute hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, and outpatient drugs. Utilization and spending were age and sex standardized..Data collection/extraction methodsThe data were compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries as follows: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Principal findingsThe sample ranged from 1859 patients in Spain to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia. The majority of patients across countries were female. Relative to other countries, the United States had the lowest inpatient length of stay (11.3), but the highest number of days were spent in post-acute care rehab (100.7) and, on average, had more visits to specialist providers (6.8 per year) than primary care providers (4.0 per year). Across almost all sectors, the United States spent more per person than other countries per unit ($13,622 per hospitalization,$233 per primary care visit, $386 per MD specialist visit). Patients also had high expenditures in the year prior to the hip fracture, mostly concentrated in the inpatient setting.ConclusionAcross 11 high-income countries, there is substantial variation in health care spending and utilization for an older person with frailty, both before and after a hip fracture. The United States is the most expensive country due to high prices and above average utilization of post-acute rehab care

ALMA observations of the η Corvi debris disc: Inward scattering of CO-rich exocomets by a chain of 3-30 M⊕ planets?

While most of the known debris discs present cold dust at tens of astronomical unit (au), a few young systems exhibit hot dust analogous to the Zodiacal dust. η Corvi is particularly interesting as it is old and it has both, with its hot dust significantly exceeding the maximum luminosity of an in situ collisional cascade. Previous work suggested that this system could be undergoing an event similar to the Late Heavy Bombardment (LHB) soon after or during a dynamical instability. Here, we present ALMA observations of η Corvi with a resolution of 1.2 arcsec (~22 au) to study its outer belt. The continuum emission is consistent with an axisymmetric belt, with a mean radius of 152 au and radial full width at half-maximum of 46 au, which is too narrow compared to models of inward scattering of an LHB-like scenario. Instead, the hot dust could be explained as material passed inwards in a rather stable planetary configuration. We also report a 4σ detection of CO at ~20 au. CO could be released in situ from icy planetesimals being passed in when crossing the H2O or CO2 ice lines. Finally, we place constraints on hidden planets in the disc. If a planet is sculpting the disc's inner edge, this should be orbiting at 75-100 au, with a mass of 3-30M⊕ and an eccentricity < 0.08. Such a planet would be able to clear its chaotic zone on a time-scale shorter than the age of the system and scatter material inwards from the outer belt to the inner regions, thus feeding the hot dust.ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada) and NSC and ASIAA (Taiwan) and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. MCW, LM, AB and QK acknowledge the support of the European Union through ERC grant number 279973. LM also acknowledges support by STFC through a graduate studentship. The work of OP is supported by the Royal Society Dorothy Hodgkin Fellowship. GMK is supported by the Royal Society as a Royal Society University Research Fellow

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Comparison of Longitudinal CA125 Algorithms as a First-Line Screen for Ovarian Cancer in the General Population

Purpose: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening(UKCTOCS) women in the multimodal (MMS) arm had a serum CA125 test (first-line), with those at increased risk, having repeat CA125/ultrasound (second-line test). CA125 was interpreted using the 'Risk of Ovarian Cancer Algorithm'(ROCA). We report on performance of other serial algorithms and a single CA125 threshold as a first line screen in the UKCTOCS dataset. // Experimental Design: 50,083 post-menopausal women who attended 346,806 MMS screens were randomly split into training and validation sets, following stratification into cases (ovarian/tubal/peritoneal cancers) and controls. The two longitudinal algorithms, a new serial algorithm, method of mean trends (MMT) and the parametric empirical Bayes (PEB) were trained in the training set and tested in the blinded validation set and the performance characteristics, including that of a single CA125 threshold, were compared. // Results The area under receiver operator curve (AUC) was significantly higher (p=0.01) for MMT (0.921) compared to CA125 single threshold (0.884). At a specificity of 89.5%, sensitivities for MMT (86.5%;95%CI:78.4-91.9) and PEB (88.5%;95%CI:80.6-93.4) were similar to that reported for ROCA (sensitivity 87.1%; specificity 87.6%; AUC 0.915) and significantly higher than the single CA125 threshold (73.1%;95%CI:63.6-80.8). // Conclusions: These findings from the largest available serial CA125 data set in the general population provide definitive evidence that longitudinal algorithms are significantly superior to simple cut-offs for ovarian cancer screening. Use of these newer algorithms requires incorporation into a multimodal strategy. The results highlight the importance of incorporating serial change in biomarker levels in cancer screening/early detection strategies