Temporal fluctuation of multidrug resistant salmonella typhi haplotypes in the mekong river delta region of Vietnam.

BACKGROUND: typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. PRINCIPAL FINDINGS: the population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. SIGNIFICANCE: the H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam

Linear and nonlinear PSE for compressible boundary layers

Compressible stability of growing boundary layers is studied by numerically solving the partial differential equations under a parabolizing approximation. The resulting parabolized stability equations (PSE) account for nonparallel as well as nonlinear effects. Evolution of disturbances in compressible flat-plate boundary layers are studied for freestream Mach numbers ranging from 0 to 4.5. Results indicate that the effect of boundary-layer growth is important for linear disturbances. Nonlinear calculations are performed for various Mach numbers. Two-dimensional nonlinear results using the PSE approach agree well with those from direct numerical simulations using the full Navier-Stokes equations while the required computational time is less by an order of magnitude. Spatial simulation using PSE were carried out for both the fundamental and subharmonic type breakdown for a Mach 1.6 boundary layer. The promising results obtained show that the PSE method is a powerful tool for studying boundary-layer instabilities and for predicting transition over a wide range of Mach numbers

Impact of brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom Inventory

Background: Psoriasis symptoms have a significant negative impact on health-related quality of life, impairing physical functioning and well-being. Objective: To evaluate the impact of brodalumab, a human anti-interleukin-17R monoclonal antibody, on psoriasis symptom severity as measured by a novel patient-reported outcome measure, the Psoriasis Symptom Inventory, and dermatology-specific health-related quality of life as measured by the Dermatology Life Quality Index (DLQI). Methods: This was a secondary analysis of a phase II, randomized, double-blind, placebo-controlled clinical study of patients with moderate-to-severe psoriasis (n = 198) treated with brodalumab or placebo. This analysis assessed Psoriasis Symptom Inventory scores and DLQI scores over time. Analyses were conducted on all patients who were randomized and received one or more injections of the study drug according to intention to treat using last observation carried forward to impute missing data. Results: At week 12, subjects in the brodalumab groups had significant improvements in mean Psoriasis Symptom Inventory total scores [8·5 (70 mg), 15·8 (140 mg), 16·2 (210 mg) and 12·7 (280 mg)] compared with placebo (4·8). Mean improvements in DLQI were clinically meaningful (≥ 5·7) in the brodalumab groups (6·2, 9·1, 9·6 and 7·1, respectively) and significantly greater than placebo (3·1). Improvements in Psoriasis Symptom Inventory were observed as early as week 2 and in DLQI by week 4. All eight Psoriasis Symptom Inventory item scores improved significantly among the brodalumab groups by week 12. Conclusions: Results were from a single randomized clinical trial and may not generalize to broader patient populations. However, treatment with brodalumab provided significant improvement in psoriasis symptoms in patients with moderate-to-severe psoriasis

Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)

Background HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. Methods A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits. Results Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment. Conclusions HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load

Wilson Loops in N=4 SYM and Fermion Droplets

The matrix models which are conjectured to compute the circle Wilson loop and its correlator with chiral primary operators are mapped onto normal matrix models. A fermion droplet picture analogous to the well-known one for chiral primary operators is shown to emerge in the large N limit. Several examples are computed. We find an interesting selection rule for the correlator of a single trace Wilson loop with a chiral primary operator. It can be non-zero only if the chiral primary is in a representation with a single hook. We show that the expectation value of the Wilson loop in a large representation labelled by a Young diagram with a single row has a first order phase transition between a regime where it is identical to a large column representation and a regime where it is a large wrapping number single trace Wilson loop.Comment: 32 pages, 2 figure

Three-party qutrit-state sharing

A three-party scheme for securely sharing an arbitrary unknown single-qutrit state is presented. Using a general Greenberger-Horne-Zeilinger (GHZ) state as the quantum channel among the three parties, the quantum information (i.e., the qutrit state) from the sender can be split in such a way that the information can be recovered if and only if both receivers collaborate. Moreover, the generation of the scheme to multi-party case is also sketched.Comment: 7 page

Tidal disruption of satellites and formation of narrow rings

In this paper we investigate the formation of narrow planetary rings such as those found around Uranus and Saturn through the tidal disruption of a weak, gravitationally bound satellite that migrates within its Roche limit. Using $N$-body simulations, we study the behaviour of rubble piles placed on circular orbits at different distances from a central planet. We consider both homogeneous satellites and differentiated bodies containing a denser core. We show that the Roche limit for a rubble pile is closer to the planet than for a fluid body of the same mean density. The Roche limit for a differentiated body is also closer to the planet than for a homogeneous satellite of the same mean density. Within its Roche limit, a homogeneous satellite totally disrupts and forms a narrow ring. The initial stages of the disruption are similar to the evolution of a viscous fluid ellipsoid, which can be computed semi-analytically. On the other hand, when a differentiated satellite is just within the Roche limit only the mantle is disrupted. This process is similar to Roche-lobe overflow in interacting binary stars and produces two narrow rings on either side of a remnant satellite. We argue that the Uranian rings, and possibly their shepherd satellites, could have been formed through the tidal disruption of a number of protomoons that were formed inside the corotation radius of Uranus and migrated slowly inwards as a result of tidal interaction with the planet.Comment: Accepted for publication in MNRAS. Some figures have been compressed to fit into astro-ph size guidelines. Please contact authors if full resolution images are require

Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)

Background: HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. Methods: A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits. Results: Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment. Conclusions: HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load

Proof of Principle of Ocular Sparing in Dogs with Sinonasal Tumors Treated with Intensity-Modulated Radiation Therapy

Intensity modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared to a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT treated and 2D treated dogs was 420 days and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared to historical controls treated with 2D-RT