Functional derivatives of meta-generalized gradient approximation (meta-GGA) type exchange-correlation density functionals.

Meta-generalized gradient approximation (meta-GGA) exchange-correlation density functionals depend on the Kohn-Sham (KS) orbitals through the kinetic energy density. The KS orbitals in turn depend functionally on the electron density. However, the functional dependence of the KS orbitals is indirect, i.e., not given by an explicit expression, and the computation of analytic functional derivatives of meta-GGA functionals with respect to the density imposes a challenge. The practical solution used in many computer implementations of meta-GGA density functionals for ground-state calculations is abstracted and generalized to a class of density functionals that is broader than meta-GGAs and to any order of functional differentiation. Importantly, the TDDFT working equations for meta-GGA density functionals are presented here for the first time, together with the technical details of their computer implementation. The analysis presented here also uncovers the implicit assumptions in the practical solution to computing functional derivatives of meta-GGA density functionals. The connection between the approximation that is invoked in taking functional derivatives of density functionals, the non-uniqueness with respect to the KS orbitals, and the non-locality of the resultant potential is also discussed.

Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia.

BACKGROUND: Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. METHODS: Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. RESULTS: Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. CONCLUSIONS: This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.

Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation.

A novel influenza A(H1N1)2009 variant with mildly reduced oseltamivir and zanamivir sensitivity has been detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia during the early months of 2011. The variant, which has also been detected in other regions of the Asia-Pacific, contains a S247N neuraminidase mutation. When combined with the H275Y mutation, as detected in an oseltamivir-treated patient, the dual S247N+H275Y mutant had extremely high oseltamivir resistance.

Digital controller design for absolute value function constrained nonlinear systems via scalar sign function approach.

In this paper, a scalar sign function-based digital design methodology is developed for modeling and control of a class of analog nonlinear systems that are restricted by the absolute value function constraints. As is found to be not uncommon, many real systems are subject to the constraints which are described by the non-smooth functions such as absolute value function. The non-smooth and nonlinear nature poses significant challenges to the modeling and control work. To overcome these difficulties, a novel idea proposed in this work is to use a scalar sign function approach to effectively transform the original nonlinear and non-smooth model into a smooth nonlinear rational function model. Upon the resulting smooth model, a systematic digital controller design procedure is established, in which an optimal linearization method, LQR design and digital implementation through an advanced digital redesign technique are sequentially applied. The example of tracking control of a piezoelectric actuator system is utilized throughout the paper for illustrating the proposed methodology.

Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109).

Thirty-eight human immunodeficiency virus-1 (HIV-1)-infected pregnant women were administered tenofovir disoproxil fumarate (TDF; 300 mg)-emtricitabine (FTC; 200 mg) tablets: two at labor initiation and one daily for 7 days postpartum. Maternal, umbilical, and neonatal plasma tenofovir concentrations were measured by high-performance liquid chromatography and analyzed using a population approach. Data were described using a two-compartment model for the mother, an effect compartment linked to maternal circulation for cord, and a neonatal compartment disconnected after delivery. Absorption was greater for women delivering by caesarian section than for those delivering vaginally. The maternal 600 mg TDF administration before delivery produces the same concentrations as 300 mg administration in other adults. If the time elapsed between maternal administration and delivery is >or=12 h, two tablets of TDF-FTC should be readministered. Tenofovir showed good placental transfer (60%). Administering 13 mg/kg of TDF as soon as possible after birth should produce neonatal concentrations comparable with those observed in adults.

A simple recursive method for stationary receiver position estimation using GPS difference measurements.

This paper presents a simple recursive method to estimate the position of a stationary receiver using the difference of Global Positioning System (GPS) pseudorange measurements. In contrast to conventional Differential GPS (DGPS), the proposed simple method uses the difference of pseudorange measurements corresponding to a single receiver itself without requiring a fixed station with known location. The use of difference measurements reduces the effects of the various noise terms involved in pseudorange measurements. According to the proposed method, the position of the receiver is estimated recursively using an optimal linear approximation of the pseudorange nonlinear equations. The effectiveness of the proposed method is demonstrated on the estimation of the position of a stationary receiver, and its performance is compared to the performance of a classical approach. The results show that the proposed method outperforms the classical approach.

[Severe pulmonary and meningeal cryptococcosis in an immunocompetent Cambodian]. / Cryptococcose grave, pulmonaire et méningée, chez un cambodgien non-immunodéprimé.

A chest x-ray showing a large tumor-like opacity in the left lower lobe and endoscopy visualizing a budding mass suggested a diagnosis of bronchial carcinoma in a 55-year old, tobacco-smoking Cambodian who consulted for hemoptysis and altered general status. Histological study of bronchial biopsies allowed differential diagnosis of cryptococcosis. Serologic tests for human immunodeficiency virus were negative and there was no other cause of immunodepression. Left lower lobectomy was performed at the German hospital of the APRONUC in Phnom Penh. Examination of the surgical specimen confirmed massive bronchopulmonary cryptococcosis. Two months after the procedure the patient was readmitted for neuromeningial cryptococcosis that responded well to fluconazole. Another relapse occurred 5 months later and was treated using the same drug. The patient is currently in remission. An increasingly common deep mycosis that is serious but curable with proper treatment, cryptococcosis deserves the full attention of physicians working in Cambodia where, as in other tropical zones, it is likely that this infection will progress with the incidence of AIDS. Symptoms can be misleading, suggesting neuromeningial or pulmonary tuberculosis. The value of India ink smear which should be performed in all patients presenting lymphocytic meningitis with hypoglycorrhachia must be emphasized. In the present case bronchoscopy was useful to distinguish from bronchopulmonary cancer.