Failure of combined chloroquine and High-Dose primaquine therapy for plasmodium vivax malaria acquired in Guyana, South America

The presence of chloroquine-resistant Plasmodium vivax malaria in the New World has been suspected but not confirmed. We report the cases of three patients who acquired vivax malaria in Guyana, South America, and for whom standard chloroquine therapy (25 mg/kg) failed despite therapeutic blood levels. The optimal treatment of chloroquine-resistant P. vivax malaria is unknown, but recent studies suggest that a combination of chloroquine (25 mg/kg) and high-dose primaquine (2.5 mg/kg over 48 hours) is effective therapy. Two of our patients had recurrences of P. vivax malaria 6–8 weeks after receiving directly observed therapy with this combination. These cases confirm the presence of chloroquine-resistant P. vivax in Guyana and emphasize the need for better treatment regimens for chloroquine-resistant and primaquine-resistant P. vivax malaria

Weight Reduction for Overweight and Obese Adults: Challenges Experienced In a Nigerian Community

Prevalence of overweight and obesity in low/medium income countries is on the increase with associated co-morbidities. This qualitative study was carried out to explore various challenges and barriers experienced by overweight and obese individuals in a sub-Saharan Africa setting. Focus group discussions were conducted in 13 census enumeration areas with a purposive sample size of 83 overweight and obese individuals. The data collected was subjected to thematic analysis after going through rigorous transcriptions from the tape recorder. The three main emerging themes were lack of knowledge about the need to reduce weight and health consequences of overweight, lack of money for consultation and dietary regimen as well as lack of support and motivation from immediate family and friends. This study was able to explore various challenges that impair weight reduction among overweight and obese persons from a low income country. These challenges need to be seriously considered if the increasing tide in the prevalence of overweight and obesity is to be reduced and checked

Reconfiguring global pharmaceutical value networks through targeted technology interventions

Targeting a series of advanced manufacturing technology (AMT) ‘interventions’ provides the potential for significant step changes across the pharmaceutical value chain, from early stage ‘system discovery’ and clinical trials, through to novel service supply models. This research explores future value network configurations which, when aligned with disruptive shifts in technology (process and digital), may enable alternative routes to medicines production and the delivery of additional value to ‘end-users’, i.e. patients and health care providers. We draw on a categorisation of AMTs that may enable a shift from the traditional ‘batch’ and centralised manufacturing paradigm of ‘make-to-stock’, towards more re-distributed ‘continuous’ manufacturing and ‘make-to-order’ models. Despite reported benefits in the academic literature (e.g. reduced footprints, improved quality, enhanced flexibility and inventory savings), current adoption rates of continuous technologies in this sector remain low (c. 5%). This paper presents new data sources, in our study of AMT adoption in a global pharmaceutical context – assessing the barriers to implementation, and the pathways to delivering future continuous manufacturing scenarios. Our findings capture the high level of disparity in viewpoints, highlighting the uncertainties and transformational challenges ahead – in terms of opportunity areas, technological readiness and a future vision for the sector, as a whole

Gatekeeping: A Counselor Educator’s Responsibility to the Counseling Profession and Community

Counseling is one of the few professions practiced in private with vulnerable individuals. Because of this, counselors must be held to high training standards and be deemed competent prior to being allowed to practice independently. The responsibility for ensuring future counselors’ competence rests with counselor educators and clinical supervisors via a process known as gatekeeping. This paper highlights the importance of gatekeeping in the counseling profession and describes models of remediation for supervisors and educators navigating this complex process. Utilizing a case study, the authors demonstrate the protective function gatekeeping serves society by applying a gatekeeping decision-making model. Finally, recommendations are provided to increase adherence to and facilitate implementation of gatekeeping responsibilities by counselor educators and supervisors

The effect of a barnacle-shaped excrescence on the hydrodynamic performance of a tidal turbine blade section

Efficient tidal turbine designs rely upon the hydrodynamic performance of the turbine blade sections. A significant consideration for the likely power generation capacity of a tidal turbine is the effect of biofouling on the blade performance. A turbine blade surface is susceptible to large scale macrofouling, mainly from encrusters, such as barnacles and molluscs, colonising the developing surface. This paper considers the case of when a barnacle attaches to the upper (suction) surface of the blade section. Results of experiments to investigate the unsteady flow characteristics of the blade section are presented, and the modification of the hydrodynamic performance coefficients due to the presence of a barnacle is evaluated. The barnacle has no significant effect upon the lift in steady flow and unsteady flow, but there is a very large increase in the drag. Dependent upon the degree of barnacle encrustation, the effect on a turbine blade drag may be significant and lead to a degradation of a turbine predicted performance

Heavy Carriers and Non-Drude Optical Conductivity in MnSi

Optical properties of the weakly helimagnetic metal MnSi have been determined in the photon energy range from 2 meV to 4.5 eV using the combination of grazing incidence reflectance at 80 degrees (2 meV to 0.8 eV) and ellipsometry (0.8 to 4.5 eV). As the sample is cooled below 100 K the effective mass becomes strongly frequency dependent at low frequencies, while the scattering rate developes a linear frequency dependence. The complex optical conductivity can be described by the phenomenological relation \sigma(\omega,T) \propto (\Gamma(T)+i\omega)^{-1/2} used for cuprates and ruthenates.Comment: 5 pages, ReVTeX 4, 5 figures in eps forma

Coordinated ras and rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria

Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Row-switched states in two-dimensional underdamped Josephson junction arrays

When magnetic flux moves across layered or granular superconductor structures, the passage of vortices can take place along channels which develop finite voltage, while the rest of the material remains in the zero-voltage state. We present analytical studies of an example of such mixed dynamics: the row-switched (RS) states in underdamped two-dimensional Josephson arrays, driven by a uniform DC current under external magnetic field but neglecting self-fields. The governing equations are cast into a compact differential-algebraic system which describes the dynamics of an assembly of Josephson oscillators coupled through the mesh current. We carry out a formal perturbation expansion, and obtain the DC and AC spatial distributions of the junction phases and induced circulating currents. We also estimate the interval of the driving current in which a given RS state is stable. All these analytical predictions compare well with our numerics. We then combine these results to deduce the parameter region (in the damping coefficient versus magnetic field plane) where RS states can exist.Comment: latex, 48 pages, 15 figs using psfi