A detailed analysis of online pharmacy characteristics to inform safe usage by patients

Background: Evidence suggests that consumers potentially put themselves at risk when purchasing medicines on-line. Whilst logos provided by regulators may provide some level of reassurance there may be other indicators which could be used by consumers to identify those websites which may be safely used. Objectives: Identify characteristics of on-line pharmacies which are related to whether websites are regulated or non-regulated and those characteristics which could be used by patients to increase the likelihood of accessing regulated sites. Setting: Online pharmacies which supply diazepam, fluoxetine and simvastatin. Methods: Using piloted search terms via Google and Yahoo search engines, identified websites were screened for regulatory status, adherence to regulatory standards, administrative requirements, clinical assessment requirements and additional details deemed to be of relevance to a user. Characteristics of regulated and non-regulated (defined as those with an absence of a correctly linked regulatory logo) websites were compared to identify differences which could be used to improve patient safety. Main outcome measure: Regulatory status, adherence to regulatory standards, quality of information provision, barriers to medicines access. Results: 113 websites sold diazepam, fluoxetine and simvastatin; were identified within the first 100 results. Less than quarter were found to be regulated online pharmacies. 80 websites were willing to sell the medication without a prescription. The unregulated internet pharmacy websites (defined as those with an absence of a correctly linked regulatory logo) were found to adhere more closely to the clinical criteria, were less significantly likely to disclose a contact name and address, telephone number of the pharmacy or demand a prescription prior to sale (P\0.05, Fisher’s Exact). Conclusions: The three prescription-only medicines which are liable to abuse, have potentially serious interactions and require counselling to ensure patient safety are readily available via the internet. When purchasing medicines via this route UK consumers should be made aware of the importance of regulatory logos and additionally should ensure that the seller can be meaningfully contacted by the contact details provided. The provision of clinical information should not be used alone as an indication of the seller’s provenance

Temperature dependent photoluminescence of single CdS nanowires

Temperature dependent photoluminescence (PL) is used to study the electronic properties of single CdS nanowires. At low temperatures, both near-band edge (NBE) photoluminescence (PL) and spatially-localized defect-related PL are observed in many nanowires. The intensity of the defect states is a sensitive tool to judge the character and structural uniformity of nanowires. As the temperature is raised, the defect states rapidly quench at varying rates leaving the NBE PL which dominates up to room temperature. All PL lines from nanowires follow closely the temperature-dependent band edge, similar to that observed in bulk CdS.Comment: 11 pages, 4 figure

Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells

Human cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens.This work was funded by a British Medical Research programme grant, grant number G0701279 and Wellcome Research Grant, grant number RG68483. This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2467

Leishmania-specific surface antigens show sub-genus sequence variation and immune recognition.

A family of hydrophilic acylated surface (HASP) proteins, containing extensive and variant amino acid repeats, is expressed at the plasma membrane in infective extracellular (metacyclic) and intracellular (amastigote) stages of Old World Leishmania species. While HASPs are antigenic in the host and can induce protective immune responses, the biological functions of these Leishmania-specific proteins remain unresolved. Previous genome analysis has suggested that parasites of the sub-genus Leishmania (Viannia) have lost HASP genes from their genomes

Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells.

Human cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens.This work was funded by a British Medical Research programme grant, grant number G0701279 and Wellcome Research Grant, grant number RG68483. This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2467

Low temperature photoluminescence imaging and time-resolved spectroscopy of single CdS nanowires

Time-resolved photoluminescence (PL) and micro-PL imaging were used to study single CdS nanowires at 10 K. The low-temperature PL of all CdS nanowires exhibit spectral features near energies associated with free and bound exciton transitions, with the transition energies and emission intensities varying along the length of the nanowire. In addition, several nanowires show spatially localized PL at lower energies which are associated with morphological irregularities in the nanowires. Time-resolved PL measurements indicate that exciton recombination in all CdS nanowires is dominated by non-radiative recombination at the surface of the nanowires.Comment: 9 pages, 3 figures, to be published in Applied Physics Letter

The controversy in the γγ→ρρ\gamma\gamma\to\rho\rho process: potential scattering or qqqˉqˉqq\bar{q}\bar{q} resonance ?

The $\gamma\gamma\to\rho^0\rho^0\to 4 \pi$ reaction shows a broad peak at 1.5 GeV in the $(J^P,J_z)=(2^+,2)$ channel which has no counterpart in the $\rho^+\rho^-$ channel. This "resonance" is considered as a candidate for a $qq\bar q\bar q$ state in the "s-channel". We show, however, that it can also be explained by potential scattering of $\rho^0\rho^0$ via the $\sigma$- exchange in the "t-channel".Comment: 12 pages, latex, 3 postscript figures, to appear in Zeitschrift fur Physi

Spatial and topological organization of DNA chains induced by gene co-localization

Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close-by. This is motivated by recurrent evidence that there exists physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on http://dx.doi.org/10.1371/journal.pcbi.100067

Thermal and electrical conductivity of iron at Earth's core conditions

The Earth acts as a gigantic heat engine driven by decay of radiogenic isotopes and slow cooling, which gives rise to plate tectonics, volcanoes, and mountain building. Another key product is the geomagnetic field, generated in the liquid iron core by a dynamo running on heat released by cooling and freezing to grow the solid inner core, and on chemical convection due to light elements expelled from the liquid on freezing. The power supplied to the geodynamo, measured by the heat-flux across the core-mantle boundary (CMB), places constraints on Earth's evolution. Estimates of CMB heat-flux depend on properties of iron mixtures under the extreme pressure and temperature conditions in the core, most critically on the thermal and electrical conductivities. These quantities remain poorly known because of inherent difficulties in experimentation and theory. Here we use density functional theory to compute these conductivities in liquid iron mixtures at core conditions from first principles- the first directly computed values that do not rely on estimates based on extrapolations. The mixtures of Fe, O, S, and Si are taken from earlier work and fit the seismologically-determined core density and inner-core boundary density jump. We find both conductivities to be 2-3 times higher than estimates in current use. The changes are so large that core thermal histories and power requirements must be reassessed. New estimates of adiabatic heat-flux give 15-16 TW at the CMB, higher than present estimates of CMB heat-flux based on mantle convection; the top of the core must be thermally stratified and any convection in the upper core driven by chemical convection against the adverse thermal buoyancy or lateral variations in CMB heat flow. Power for the geodynamo is greatly restricted and future models of mantle evolution must incorporate a high CMB heat-flux and explain recent formation of the inner core.Comment: 11 pages including supplementary information, two figures. Scheduled to appear in Nature, April 201

Accuracy and repeatability of wrist joint angles in boxing using an electromagnetic tracking system

© 2019, The Author(s). The hand-wrist region is reported as the most common injury site in boxing. Boxers are at risk due to the amount of wrist motions when impacting training equipment or their opponents, yet we know relatively little about these motions. This paper describes a new method for quantifying wrist motion in boxing using an electromagnetic tracking system. Surrogate testing procedure utilising a polyamide hand and forearm shape, and in vivo testing procedure utilising 29 elite boxers, were used to assess the accuracy and repeatability of the system. 2D kinematic analysis was used to calculate wrist angles using photogrammetry, whilst the data from the electromagnetic tracking system was processed with visual 3D software. The electromagnetic tracking system agreed with the video-based system (paired t tests) in both the surrogate ( 0.9). In the punch testing, for both repeated jab and hook shots, the electromagnetic tracking system showed good reliability (ICCs > 0.8) and substantial reliability (ICCs > 0.6) for flexion–extension and radial-ulnar deviation angles, respectively. The results indicate that wrist kinematics during punching activities can be measured using an electromagnetic tracking system