6,887 research outputs found
Supersymmetric geometries of IIA supergravity I
IIA supergravity backgrounds preserving one supersymmetry locally admit four
types of Killing spinors distinguished by the orbits of on the
space of spinors. We solve the Killing spinor equations of IIA supergravity
with and without cosmological constant for Killing spinors representing two of
these orbits, with isotropy groups and .
In both cases, we identify the geometry of spacetime and express the fluxes in
terms of the geometry. We find that the geometric constraints of backgrounds
with a invariant Killing spinor are identical to
those found for heterotic backgrounds preserving one supersymmetry.Comment: 21 page
HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer
Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial.
Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro.
Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors.
Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group
Computer aided synthesis: a game theoretic approach
In this invited contribution, we propose a comprehensive introduction to game
theory applied in computer aided synthesis. In this context, we give some
classical results on two-player zero-sum games and then on multi-player non
zero-sum games. The simple case of one-player games is strongly related to
automata theory on infinite words. All along the article, we focus on general
approaches to solve the studied problems, and we provide several illustrative
examples as well as intuitions on the proofs.Comment: Invitation contribution for conference "Developments in Language
Theory" (DLT 2017
Rapidly rotating Rayleigh-Bénard convection with a tilted axis
We numerically explore the dynamics of an incompressible fluid heated from below, bounded by free-slip horizontal plates and periodic lateral boundary conditions, subject to rapid rotation about a distant axis that is tilted with respect to the gravity vector. The angle ϕ between the rotation axis and the horizontal plane measures the tilting of the rotation axis; it can be taken as a proxy for latitude if we think of a local Cartesian representation of the convective dynamics in a rotating fluid shell. The results of the simulations indicate the existence of three different convective regimes, depending on the value of ϕ: (1) sheared, intermittent large-scale winds in the direction perpendicular to the plane defined by the gravity and rotation vectors, when rotation is “horizontal” (ϕ=0∘); (2) a large-scale cyclonic vortex tilted along the rotation axis, when the angle between the rotation axis and the gravity vector is relatively small (ϕ between about 45∘ and 90∘); and (3) a new intermediate regime characterized by vertically sheared large-scale winds perpendicular to both gravity and rotation. In this regime, the winds are organized in bands that are tilted along the rotation axis, with unit horizontal wave number in the plane defined by gravity and rotation at values of ϕ less than about 60∘. This intermediate solution, studied for the first time in this work, is characterized by weaker vertical heat transport than the cases with large-scale vortices. For intermediate values of ϕ (between about 45∘ and 60∘), the banded, sheared solution coexists with the large-scale vortex solution, with different initial conditions leading to one or the other dynamical behavior. A discussion of the possible implications of these results for the dynamics of rapidly rotating planetary atmospheres is provided
Asthma Prevalence, Knowledge, and Perceptions among Secondary School Pupils in Rural and Urban Costal Districts in Tanzania.
Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A >= 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. The mean age of participants was 16.8 (+/-1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools
Socio-Economic Instability and the Scaling of Energy Use with Population Size
The size of the human population is relevant to the development of a sustainable world, yet the forces setting growth or declines in the human population are poorly understood. Generally, population growth rates depend on whether new individuals compete for the same energy (leading to Malthusian or density-dependent growth) or help to generate new energy (leading to exponential and super-exponential growth). It has been hypothesized that exponential and super-exponential growth in humans has resulted from carrying capacity, which is in part determined by energy availability, keeping pace with or exceeding the rate of population growth. We evaluated the relationship between energy use and population size for countries with long records of both and the world as a whole to assess whether energy yields are consistent with the idea of an increasing carrying capacity. We find that on average energy use has indeed kept pace with population size over long time periods. We also show, however, that the energy-population scaling exponent plummets during, and its temporal variability increases preceding, periods of social, political, technological, and environmental change. We suggest that efforts to increase the reliability of future energy yields may be essential for stabilizing both population growth and the global socio-economic system
The impact of obesity on time spent with the provider and number of medications managed during office-based physician visits using a cross-sectional, national health survey
<p>Abstract</p> <p>Background</p> <p>Obesity is associated with morbidity, mortality, and increased health care costs. Few studies have examined the impact of obesity on outpatient office visits. The purpose of this study was to determine if outpatient visits by obese persons required more time with the provider and more prescription medication management compared to visits made by non-obese persons.</p> <p>Methods</p> <p>Obesity status was determined for 9,280 patient visits made by persons aged 18 years or older in the 2006 National Ambulatory Medical Care Survey. Multivariate analyses compared obese and non-obese visits, stratified by sex, for duration of the visit and the number of medications mentioned at the visit.</p> <p>Results</p> <p>Average duration of visit was higher among visits with patients determined to be obese. However, these differences were not considered significant after statistical testing. Visits made by obese female patients were significantly more likely to involve more than two prescription medications (OR 1.26, 95% CI 1.05 - 1.51) and visits made by obese male patients were significantly more likely to involve more than two prescription medications (OR 1.46, 95% CI 1.16 - 1.83) as compared to visits made by non-obese patients.</p> <p>Conclusion</p> <p>Time spent with the provider was found to be greater among visits with obese patients, but not significantly different from visits with non-obese patients. The number of medications for each visit was found to be significantly greater for visits where the patient was considered to be obese. Increased time for the visit and increased numbers of medication for each visit translate into increased costs. These findings document the impact of obesity on our health care system and have great implications on medical care cost and planning.</p
Valley-spin blockade and spin resonance in carbon nanotubes
Manipulation and readout of spin qubits in quantum dots made in III-V
materials successfully rely on Pauli blockade that forbids transitions between
spin-triplet and spin-singlet states. Quantum dots in group IV materials have
the advantage of avoiding decoherence from the hyperfine interaction by
purifying them with only zero-spin nuclei. Complications of group IV materials
arise from the valley degeneracies in the electronic bandstructure. These lead
to complicated multiplet states even for two-electron quantum dots thereby
significantly weakening the selection rules for Pauli blockade. Only recently
have spin qubits been realized in silicon devices where the valley degeneracy
is lifted by strain and spatial confinement. In carbon nanotubes Pauli blockade
can be observed by lifting valley degeneracy through disorder. In clean
nanotubes, quantum dots have to be made ultra-small to obtain a large energy
difference between the relevant multiplet states. Here we report on
low-disorder nanotubes and demonstrate Pauli blockade based on both valley and
spin selection rules. We exploit the bandgap of the nanotube to obtain a large
level spacing and thereby a robust blockade. Single-electron spin resonance is
detected using the blockade.Comment: 31 pages including supplementary informatio
A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.
BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care
Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs
Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability
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