Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections

Background: Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. Methods: A prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. Results: Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. Conclusions: Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi.Publisher PDFPeer reviewe

Genetic variability and differentiation of common Kilka fish (Clupeonella cultriventris Nordmann, 1840) in the southern coasts of Caspian Sea

A total of 120 samples of adult common Kilka fish (Clupeonella cultriventris) were collected during spring and summer from the southern coasts of Caspian Sea (Bandar Anzali and Babolsar). Fifteen sets of microsatellite primers were developed from Clupeidae being tested on genomic DNA of common Kilka. Allele frequency, observed and expected heterozygosity, FST, RST, FIS index were determined. Five primer sets as polymorphic loci were used to analyze the genetic variation in adults of the common Kilka population. Results revealed that average alleles per locus was 13.1 (range 5 to 22 alleles per locus in regions, Ne=9.5). All sampled regions contained private alleles. Average observed and expected heterozygosity was 0.348 and 0.877, respectively. Deviations from Hardy Weinberg equilibrium were observed in most cases. FST, RST and gene flow estimates in AMOVA and the genetic distance between populations indicated that the genetic difference among the studied populations was pronounced. The data generated in this study provide primary information on the genetic variation and differentiation in populations of Caspian common Kilka

Damping Reduction Factors for Crustal, Inslab, and Interface Earthquakes Characterizing Seismic Hazard in Southwestern British Columbia, Canada

High-damping displacement spectra and corresponding damping reduction factors ( η) are important ingredients in seismic design and analysis of structures equipped with seismic protection systems, as well as in displacement-based design methodologies. In this study, we investigated η factors for three types of earthquake characterizing seismic hazard in southwestern British Columbia, Canada: shallow crustal, deep inslab, and interface subduction. We used a large and comprehensive database including records from recent relevant earthquakes, such as the 2011 Tohoku event. Our key observations were as follows: (1) there is negligible dependence of η on soil class; (2) there is significant dependence of η on the frequency content and duration of ground motions that characterize the different record types, and (3) η is dependent on period, particularly for inslab events. Period-dependent equations were proposed to predict η for damping ratios between 5% and 30% corresponding to the three event types.</jats:p

Unusual conductance collapse in one-dimensional quantum structures

We report an unusual insulating state in one-dimensional quantum wires with a non-uniform confinement potential. The wires consist of a series of closely spaced split gates in high mobility GaAs/AlGaAs heterostructures. At certain combinations of wire widths, the conductance abruptly drops over three orders of magnitude, to zero on a linear scale. Two types of collapse are observed, one occurring in multi-subband wires in zero magnetic field and one in single subband wires in an in-plane field. The conductance of the wire in the collapse region is thermally activated with an energy of the order of 1 K. At low temperatures, the conductance shows a steep rise beyond a threshold DC source-drain voltage of order 1 mV, indicative of a gap in the density of states. Magnetic depopulation measurements show a decrease in the carrier density with lowering temperature. We discuss these results in the context of many-body effects such as charge density waves and Wigner crystallization in quantum wires.Comment: 5 pages, 5 eps figures, revte

Highly Anisotropic Transport in the Integer Quantum Hall Effect

At very large tilt of the magnetic (B) field with respect to the plane of a two-dimensional electron system the transport in the integer quantum Hall regime at $\nu$ = 4, 6, and 8 becomes strongly anisotropic. At these filling factors the usual {\em deep minima} in the magneto-resistance occur for the current flowing {\em perpendicular} to the in-plane B field direction but develop into {\em strong maxima} for the current flowing {\em parallel} to the in-plane B field. The origin of this anisotropy is unknown but resembles the recently observed anisotropy at half-filled Landau levels.Comment: 4 pages, 4 figure

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

Magnetic Anisotropy in Quantum Hall Ferromagnets

We show that the sign of magnetic anisotropy energy in quantum Hall ferromagnets is determined by a competition between electrostatic and exchange energies. Easy-axis ferromagnets tend to occur when Landau levels whose states have similar spatial profiles cross. We report measurements of integer QHE evolution with magnetic-field tilt. Reentrant behavior observed for the $\nu = 4$ QHE at high tilt angles is attributed to easy-axis anisotropy. This interpretation is supported by a detailed calculation of the magnetic anisotropy energy.Comment: 12 pages, 3 figures, submitted to Phys. Rev. Let

Magnetoresistivity in a Tilted Magnetic Field in p-Si/SiGe/Si Heterostructures with an Anisotropic g-Factor: Part II

The magnetoresistance components $\rho_{xx}$ and $\rho_{xy}$ were measured in two p-Si/SiGe/Si quantum wells that have an anisotropic g-factor in a tilted magnetic field as a function of temperature, field and tilt angle. Activation energy measurements demonstrate the existence of a ferromagnetic-paramagnetic (F-P) transition for a sample with a hole density of $p$=2$\times10^{11}$\,cm$^{-2}$. This transition is due to crossing of the 0$\uparrow$ and 1$\downarrow$ Landau levels. However, in another sample, with $p$=7.2$\times10^{10}$\,cm$^{-2}$, the 0$\uparrow$ and 1$\downarrow$ Landau levels coincide for angles $\Theta$=0-70$^{\text{o}}$. Only for $\Theta$ > 70$^{\text{o}}$ do the levels start to diverge which, in turn, results in the energy gap opening.Comment: 5 pages, 6 figure

Interaction Effects in a One-Dimensional Constriction

We have investigated the transport properties of one-dimensional (1D) constrictions defined by split-gates in high quality GaAs/AlGaAs heterostructures. In addition to the usual quantized conductance plateaus, the equilibrium conductance shows a structure close to $0.7(2e^2/h)$, and in consolidating our previous work [K.~J. Thomas et al., Phys. Rev. Lett. 77, 135 (1996)] this 0.7 structure has been investigated in a wide range of samples as a function of temperature, carrier density, in-plane magnetic field $B_{\parallel}$ and source-drain voltage $V_{sd}$. We show that the 0.7 structure is not due to transmission or resonance effects, nor does it arise from the asymmetry of the heterojunction in the growth direction. All the 1D subbands show Zeeman splitting at high $B_{\parallel}$, and in the wide channel limit the $g$-factor is $\mid g \mid \approx 0.4$, close to that of bulk GaAs. As the channel is progressively narrowed we measure an exchange-enhanced $g$-factor. The measurements establish that the 0.7 structure is related to spin, and that electron-electron interactions become important for the last few conducting 1D subbands.Comment: 8 pages, 7 figures (accepted in Phys. Rev. B