Quasi-Exact Solvability and the direct approach to invariant subspaces

We propose a more direct approach to constructing differential operators that preserve polynomial subspaces than the one based on considering elements of the enveloping algebra of sl(2). This approach is used here to construct new exactly solvable and quasi-exactly solvable quantum Hamiltonians on the line which are not Lie-algebraic. It is also applied to generate potentials with multiple algebraic sectors. We discuss two illustrative examples of these two applications: an interesting generalization of the Lam\'e potential which posses four algebraic sectors, and a quasi-exactly solvable deformation of the Morse potential which is not Lie-algebraic.Comment: 17 pages, 3 figure

Noncommutative effective theory of vortices in a complex scalar field

We derive a noncommutative theory description for vortex configurations in a complex field in 2+1 dimensions. We interpret the Magnus force in terms of the noncommutativity, and obtain some results for the quantum dynamics of the system of vortices in that context

Biologically active Phytophthora mating hormone prepared by catalytic asymmetric total synthesis

A Phytophthora mating hormone with an array of 1,5-stereogenic centers has been synthesized by using our recently developed methodology of catalytic enantioselective conjugate addition of Grignard reagents. We applied this methodology in a diastereo- and enantioselective iterative route and obtained two of the 16 possible stereoisomers of Phytophthora hormone α1. These synthetic stereoisomers induced the formation of sexual spores (oospores) in A2 mating type strains of three heterothallic Phytophthora species, P. infestans, P. capsici, and P. nicotianae but not in A1 mating type strains. The response was concentration-dependent, and the oospores were viable. These results demonstrate that the biological activity of the synthetic hormone resembles that of the natural hormone α1. Mating hormones are essential components in the sexual life cycle of a variety of organisms. For plant pathogens like Phytophthora, sexual reproduction is important as a source of genetic variation. Moreover, the thick-walled oospores are the most durable propagules that can survive harsh environmental conditions. Sexual reproduction can thus greatly affect disease epidemics. The availability of synthetic compounds mimicking the activity of Phytophthora mating hormone will be instrumental for further unravelling sexual reproduction in this important group of plant pathogens.

Oscillatons revisited

In this paper, we study some interesting properties of a spherically symmetric oscillating soliton star made of a real time-dependent scalar field which is called an oscillaton. The known final configuration of an oscillaton consists of a stationary stage in which the scalar field and the metric coefficients oscillate in time if the scalar potential is quadratic. The differential equations that arise in the simplest approximation, that of coherent scalar oscillations, are presented for a quadratic scalar potential. This allows us to take a closer look at the interesting properties of these oscillating objects. The leading terms of the solutions considering a quartic and a cosh scalar potentials are worked in the so called stationary limit procedure. This procedure reveals the form in which oscillatons and boson stars may be related and useful information about oscillatons is obtained from the known results of boson stars. Oscillatons could compete with boson stars as interesting astrophysical objects, since they would be predicted by scalar field dark matter models.Comment: 10 pages REVTeX, 10 eps figures. Updated files to match version published in Classical and Quantum Gravit

Diagnosis and treatment outcomes of adult tuberculosis in an urban setting with high HIV prevalence in Sierra Leone: A retrospective study

OBJECTIVE: To assess the diagnosis, treatment outcomes, and predictors of mortality in adult tuberculosis (TB) patients in an urban setting with a high HIV prevalence. METHODS: A retrospective study was conducted of adult TB patients aged >/=15 years who were treated at Connaught Hospital in Freetown, Sierra Leone from January through December 2017. Multivariate logistic regression was used to identify predictors of mortality. RESULTS: Of 1127 TB cases notified in 2017, 1105 (98%) were tested for HIV, yielding a TB/HIV co-infection rate of 32.0%. Only HIV-tested cases (n=1105) were included in the final analysis. The majority were male (69.3%), aged 25-34 years (29.2%), and had pulmonary TB (96.3%). Treatment outcomes were as follows: 29.0% cured, 29.0% completed, 0.5% treatment failure, 24.2% lost to follow-up, 12.8% transferred/not evaluated, and 4.5% died. The majority of deaths (80.0%, 40/50) occurred within 2 months of TB treatment initiation. Age 65 years or older (adjusted odds ratio 3.48, 95% confidence interval 1.15-10.56; p=0.027) and HIV-positive status (adjusted odds ratio 3.50, 95% confidence interval 1.72-7.12; p=0.001) were independent predictors of mortality. CONCLUSIONS: Suboptimal TB treatment outcomes were observed in Sierra Leone in 2017. More local and international action is warranted to help achieve the 2035 global TB elimination targets

Galactic Collapse of Scalar Field Dark Matter

We present a scenario for galaxy formation based on the hypothesis of scalar field dark matter. We interpret galaxy formation through the collapse of a scalar field fluctuation. We find that a cosh potential for the self-interaction of the scalar field provides a reasonable scenario for galactic formation, which is in agreement with cosmological observations and phenomenological studies in galaxies.Comment: 4 pages, 3 figue

Diagnostic and prognostic value of B4GALT1 hypermethylation and its clinical significance as a novel circulating cell-free DNA biomarker in colorectal cancer

Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan-Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592-0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC

Cost-Effectiveness Analysis of Apixaban Versus Edoxaban in Patients with Atrial Fibrillation for Stroke Prevention

OBJECTIVE: Our objective was to assess the cost effectiveness of apixaban versus edoxaban in the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) in Spain. METHODS: We customized a Markov model with ten health states to estimate the lifetime economic and clinical outcomes in 6-week cycles. The efficacy (clinical event rates per 100 patient-years) and safety data were derived from a pairwise indirect treatment comparison. The analysis was conducted from both the national health service (NHS) and societal perspectives, and included pharmaceutical costs (retail price plus value-added tax (VAT) and applicable national deductions) according to daily dosages (apixaban 10 mg (5 mg twice daily (bid)) and edoxaban 60 or 30 mg) and complications and disease-management costs, obtained from national databases. Utilities for quality-adjusted life-year (QALY) calculations reflected EuroQoL 5-Dimension scores in patients with AF. An annual discount rate of 3% was applied for costs (euro, year 2019 values) and outcomes. RESULTS: In a 1000-patient cohort, apixaban 5 mg bid versus edoxaban 60 mg could avoid five strokes, six major bleedings and 29 clinically relevant non-major bleedings (CRNMBs). Compared with edoxaban 30 mg, apixaban could avoid 21 strokes and two SEs. An increase in bleedings was observed with apixaban (seven haemorrhagic strokes, 48 major bleedings and 17 CRNMBs). Apixaban yielded 0.04 additional QALYs compared with edoxaban 60 mg or 30 mg. Incremental costs/QALY were euro9639.33 and euro354.22 for apixaban versus edoxaban 60 mg and edoxaban 30 mg, respectively, from the NHS perspective and euro7756.62 for apixaban versus edoxaban 60 mg from the societal perspective. Apixaban was dominant versus edoxaban 30 mg from the societal perspective. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This study suggests that apixaban 5 mg bid is a cost-effective alternative to edoxaban for stroke prevention in the AF population in Spain

Identification of a novel synthetic lethal vulnerability in non-small cell lung cancer by co-targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

Pass a Law, Any Law, Fast! State Legislative Responses to the Kelo Backlash

The Supreme Court in Kelo v. City of New London left protection of property against takings for economic development to the states. Since Kelo, thirty-seven states have enacted legislation to update their eminent domain laws. This paper is the first to theoretically and empirically analyze the factors that influence whether, in what manner, and how quickly states change their laws through new legislation. Fourteen of the thirty-seven new laws offer only weak protections against development takings. The legislative response to Kelo was responsive to measures of the backlash but only in the binary decision whether to pass any new law. The decision to enact a meaningful restriction was more a function of relevant political economy measures. States with more economic freedom, greater value of new housing construction, and less racial and income inequality are more likely to have enacted stronger restrictions, and sooner. Of the thirteen states that have not updated, Arkansas, Oklahoma and Mississippi are highly likely to do so in the future. Hawaii, Massachusetts and New York are unlikely to update ever if at all