Molecular and Growth-Based Drug Susceptibility Testing of Mycobacterium tuberculosis Complex for Ethambutol Resistance in the United States.

Ethambutol (EMB) is used as a part of drug regimens for treatment of tuberculosis (TB). Susceptibility of Mycobacterium tuberculosis complex (MTBC) isolates to EMB can be discerned by DNA sequencing to detect mutations in the embB gene associated with resistance. US Public Health Laboratories (PHL) primarily use growth-based drug susceptibility test (DST) methods to determine EMB resistance.

DNA sequencing for confirmation of rifampin resistance detected by Cepheid Xpert MTB/RIF assay.

DNA sequencing of rpoB and culture-based drug susceptibility results were evaluated for samples referred for confirmation of rifampin resistance detected by the Cepheid Xpert MTB/RIF assay. Silent mutations and mutations associated with low-level resistance were found in the study population. These data support CDC recommendations to confirm Xpert rifampin resistance results.

Si⁺-implanted Si-wire waveguide photodetectors for the mid-infrared.

CMOS-compatible Si⁺-implanted Si-waveguide p-i-n photodetectors operating at room temperature and at mid-infrared wavelengths from 2.2 to 2.3 µm are demonstrated.

A 60 Gb/s MDM-WDM Si photonic link with < 0.7 dB power penalty per channel.

Mode-division-multiplexing (MDM) and wavelength-division-multiplexing (WDM) are employed simultaneously in a multimode silicon waveguide to realize on-chip MDM and MDM-WDM transmission. Asymmetric Y-junction MDM multiplexers and demultiplexers are utilized for low coherently suppressed demultiplexed crosstalk at the receiver. We demonstrate aggregate bandwidths of 20 Gb/s and 60 Gb/s for MDM and MDM-WDM on-chip links, respectively, with measured 10(-9) BER power penalties between 0.

Metal-semiconductor-metal ion-implanted Si waveguide photodetectors for C-band operation.

Metal-semiconductor-metal Si waveguide photodetectors are demonstrated with responsivities of greater than 0.5 A/W at a wavelength of 1550 nm for a device length of 1mm. Sub-bandgap absorption in the Si waveguide is achieved by creating divacancy lattice defects via Si(+) ion implantation.

Pulse compression in adiabatically tapered silicon photonic wires.

We present a comprehensive analysis of pulse compression in adiabatically tapered silicon photonic wire waveguides (Si-PhWWGs), both at telecom (λ ∼ 1.55 μm) and mid-IR (λ ≳ 2.1 μm) wavelengths.

Concordance between molecular and phenotypic testing of Mycobacterium tuberculosis complex isolates for resistance to rifampin and isoniazid in the United States.

Multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis complex (MTBC) are defined by resistance to at least rifampin (RMP) and isoniazid (INH). Rapid and accurate detection of multidrug resistance is essential for effective treatment and interruption of disease transmission of tuberculosis (TB). Overdiagnosis of MDR TB may result in treatment with second-line drugs that are more costly, less effective, and more poorly tolerated than first-line drugs.

Integrated optical modulators and switches using coherent perfect loss.

We propose a new type of amplitude modulator for integrated optics based on phase-controllable coherent perfect loss (CPL) from a resonant cavity. Temporal coupled-mode theory is employed to derive a simple set of equations that describe the device operation, and finite-difference time-domain simulations are used to verify these equations. Two examples of CPL modulators are described with this formalism: a ring resonator and a 1D photonic crystal cavity.

Morphology-dependent light trapping in thin-film organic solar cells.

The active layer materials used in organic photovoltaic (OPV) cells often self-assemble into highly ordered morphologies, resulting in significant optical anisotropies. However, the impact of these anisotropies on light trapping in nanophotonic OPV architectures has not been considered. In this paper, we show that optical anisotropies in a canonical OPV material, P3HT, strongly affect absorption enhancements in ultra-thin textured OPV cells.

Generation of parabolic similaritons in tapered silicon photonic wires: comparison of pulse dynamics at telecom and mid-infrared wavelengths.

We study the generation of parabolic self-similar optical pulses in tapered Si photonic nanowires (Si-PhNWs) at both telecom (λ=1.55 μm) and mid-infrared (λ=2.2 μm) wavelengths.

Asymmetric Y junctions in silicon waveguides for on-chip mode-division multiplexing.

Silicon waveguide asymmetric Y junction mode multiplexers and demultiplexers are demonstrated for applications in on-chip mode-division multiplexing (MDM). We measure demultiplexed crosstalk as low as -30 dB, <-9 dB over the C band, and insertion loss <1.5 dB for multimode links up to 1.

Molecular epidemiology of HIV-associated tuberculosis in Dar es Salaam, Tanzania: strain predominance, clustering, and polyclonal disease.

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates.

Width-modulation of Si photonic wires for quasi-phase-matching of four-wave-mixing: experimental and theoretical demonstration.

We experimentally demonstrate quasi-phase-matched (QPM) four-wave-mixing (FWM) in silicon (Si) nanowire waveguides with sinusoidally modulated width. We perform discrete wavelength conversion over 250 nm, and observe 12 dB conversion efficiency (CE) enhancement for targeted wavelengths more than 100 nm away from the edge of the 3-dB conversion bandwidth. The QPM process in Si nanowires is rigorously modeled, with results explaining experimental observations.

Weakly modulated silicon-dioxide-cladding gratings for silicon waveguide Fabry-Pérot cavities.

We show by theory and experiment that silicon-dioxide-cladding gratings for Fabry-Pérot cavities on silicon-on-insulator channel ("wire") waveguides provide a low-refractive-index perturbation, which is required for several important integrated photonics components. The underlying refractive index perturbation of these gratings is significantly weaker than that of analogous silicon gratings, leading to finer control of the coupling coefficient κ. Our Fabry-Pérot cavities are designed using the transfer-matrix method (TMM) in conjunction with the finite element method (FEM) for calculating the effective index of each waveguide section.

Self-phase modulation and nonlinear loss in silicon nanophotonic wires near the mid-infrared two-photon absorption edge.

We report an experimental study of picosecond pulse propagation through a 4-mm-long Si nanophotonic wire with normal dispersion, at excitation wavelengths from 1775 to 2250 nm. This wavelength range crosses the mid-infrared two-photon absorption edge of Si at ~2200 nm. Significant reduction in nonlinear loss due to two-photon absorption is measured as excitation wavelengths approach 2200 nm.

Directionally anisotropic Si nanowires: on-chip nonlinear grating devices in uniform waveguides.

Computational studies are used to show that the crystalline structure of Si causes the waveguide Kerr effective nonlinearity, γ, to vary by 10% for in-plane variation of the orientation of a silicon nanowire waveguide (SiNWG) fabricated on a standard silicon-on-insulator wafer. Our analysis shows that this angular dependence of γ can be employed to form a nonlinear Kerr grating in dimensionally uniform SiNWGs based on either ring resonators or cascaded waveguide bends. The magnitude of the nonlinear index variation in these gratings is found to be sufficient for phase matching in four-wave mixing and other optical parametric processes.

Conversion of 10 Gb/s NRZ-OOK to RZ-OOK utilizing XPM in a Si nanowire.

We have demonstrated for the first time to our knowledge, the conversion of 10 Gb/s non-return-to-zero (NRZ) on-off keying (NRZ-OOK) to RZ-OOK using cross-phase modulation (XPM) in a compact, Silicon (Si) nanowire and a detuned filter. The pulse format conversion resulted in a polarity-preserved, correctly-coded RZ-OOK signal, with no evidence of an error-floor for BER < 10(-11). The advantages of a passive Si nanowire can lead to a compact, power-efficient, highly simplified configuration, amenable to chip-level integration.

Spoligotyping for molecular epidemiology of the Mycobacterium tuberculosis complex.

Spacer oligonucleotide typing, or spoligotyping, is a rapid, polymerase chain reaction (PCR)-based method for genotyping strains of the Mycobacterium tuberculosis complex (MTB). Spoligotyping data can be represented in absolute terms (digitally), and the results can be readily shared among laboratories, thereby enabling the creation of large international databases. Since the spoligotype assay was standardized more than 10 yr ago, tens of thousands of isolates have been analyzed, giving a global picture of MTB strain diversity.

Large longitudinal electric fields (Ez) in silicon nanowire waveguides.

We demonstrate the presence of strong longitudinal electric fields (E(z)) in silicon nanowire waveguides through numerical computation. These waveguide fields can be engineered through choice of waveguide geometry to exhibit amplitudes as high as 97% that of the dominant transverse field component. We show even larger longitudinal fields created in free space by a terminated waveguide can become the dominant electric field component, and demonstrate E(z) has a large effect on waveguide nonlinearity.

The evolution of drug resistance in Mycobacterium tuberculosis: from a mono-rifampin-resistant cluster into increasingly multidrug-resistant variants in an HIV-seropositive population.

We describe the genotypic and phenotypic characteristics of a mono-rifampin-resistant (RIF(R)) Mycobacterium tuberculosis strain cluster (designated AU-RIF(R)) and the acquisition of additional drug resistance. Drug susceptibility, sequences of regions that determine drug resistance, and basic clinical data were examined. A rare codon duplication (514(TTC)) in rpoB conferring high levels of RIF(R) (minimum inhibitory concentration of >256 microg/mL) in 29 isolates was identified.

Application of sensitive and specific molecular methods to uncover global dissemination of the major RDRio Sublineage of the Latin American-Mediterranean Mycobacterium tuberculosis spoligotype family.

The Latin American-Mediterranean (LAM) family of Mycobacterium tuberculosis is believed to be the cause of approximately 15% of tuberculosis cases worldwide. Previously, we defined a prevalent sublineage of the LAM family in Brazil by a single characteristic genomic deletion designated RD(Rio). Using the Brazilian strains, we pinpoint an Ag85C(103) single nucleotide polymorphism (SNP) (screened by restriction fragment length polymorphism [RFLP] analysis) that correctly identified all LAM family strains.

Discrepant results between pyrazinamide susceptibility testing by the reference BACTEC 460TB method and pncA DNA sequencing in patients infected with multidrug-resistant W-Beijing Mycobacterium tuberculosis strains.

Background: Mycobacterium tuberculosis strains belonging to the W-Beijing family have received broad clinical and public health attention because of their rapid worldwide spread and their frequent association with outbreaks, multidrug resistance, and treatment failures and relapses.

Methods: The present study examined a large number of multidrug-resistant strain-W isolates (isolates of 29 patients) by susceptibility testing for pyrazinamide (PZA) using the reference BACTEC 460TB method (Becton Dickinson Diagnostic Instrument Systems; Sparks, MD) and also by DNA sequencing of the pncA gene.

Results: We found that despite of the presence of a strain W-specific Thr47Ala in the pncA gene, all strains showed susceptibility to PZA in the reference BACTEC 460TB system due to their higher minimum inhibitory concentrations (relative to BACTEC 460TB PZA-susceptible strains).

Strain-specific differences in two large Mycobacterium tuberculosis genotype clusters in isolates collected from homeless patients in New York City from 2001 to 2004.

We studied two large Mycobacterium tuberculosis genotype clusters associated with recent outbreaks in homeless persons to determine factors associated with these tuberculosis (TB) strains. Isolates from all culture-positive TB cases diagnosed from 1 January 2001 to 31 December 2004 were genotyped. Patients whose isolates had identical restriction fragment length polymorphism patterns and spoligotypes were considered clustered.

Universal genotyping in tuberculosis control program, New York City, 2001-2003.

In 2001, New York City implemented genotyping to its tuberculosis (TB) control activities by using IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping to type isolates from culture-positive TB patients. Results are used to identify previously unknown links among genotypically clustered patients, unidentified sites of transmission, and potential false-positive cultures. From 2001 to 2003, spoligotype and IS6110-based RFLP results were obtained for 90.

Which patients' factors predict the rate of growth of Mycobacterium tuberculosis clusters in an urban community?

Factors influencing tuberculosis cluster growth are poorly understood. The authors examined clusters of two or more culture-confirmed Mycobacterium tuberculosis cases between January 1, 2001, and December 31, 2003, that had insertion sequence 6110 (IS6110) restriction fragment length polymorphism and spoligotype patterns identical to those of another study case. Genotypes first seen in New York, New York, before or during 1993 were considered historical; recent strains were those first seen after 1993.