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

Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations

The semiparametric accelerated failure time model is not as widely used as the Cox relative risk model mainly due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations provide promising tools to make the accelerate failure time models more attractive in practice. For semiparametric multivariate accelerated failure time models, we propose a generalized estimating equation approach to account for the multivariate dependence through working correlation structures. The marginal error distributions can be either identical as in sequential event settings or different as in parallel event settings. Some regression coefficients can be shared across margins as needed. The initial estimator is a rank-based estimator with Gehan's weight, but obtained from an induced smoothing approach with computation ease. The resulting estimator is consistent and asymptotically normal, with a variance estimated through a multiplier resampling method. In a simulation study, our estimator was up to three times as efficient as the initial estimator, especially with stronger multivariate dependence and heavier censoring percentage. Two real examples demonstrate the utility of the proposed method

Quantum interference and Klein tunneling in graphene heterojunctions

The observation of quantum conductance oscillations in mesoscopic systems has traditionally required the confinement of the carriers to a phase space of reduced dimensionality. While electron optics such as lensing and focusing have been demonstrated experimentally, building a collimated electron interferometer in two unconfined dimensions has remained a challenge due to the difficulty of creating electrostatic barriers that are sharp on the order of the electron wavelength. Here, we report the observation of conductance oscillations in extremely narrow graphene heterostructures where a resonant cavity is formed between two electrostatically created bipolar junctions. Analysis of the oscillations confirms that p-n junctions have a collimating effect on ballistically transmitted carriers. The phase shift observed in the conductance fringes at low magnetic fields is a signature of the perfect transmission of carriers normally incident on the junctions and thus constitutes a direct experimental observation of ``Klein Tunneling.''Comment: 13 pages and 6 figures including supplementary information. The paper has been modified in light of new theoretical results available at arXiv:0808.048

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

Anyonic interferometry and protected memories in atomic spin lattices

Strongly correlated quantum systems can exhibit exotic behavior called topological order which is characterized by non-local correlations that depend on the system topology. Such systems can exhibit remarkable phenomena such as quasi-particles with anyonic statistics and have been proposed as candidates for naturally fault-tolerant quantum computation. Despite these remarkable properties, anyons have never been observed in nature directly. Here we describe how to unambiguously detect and characterize such states in recently proposed spin lattice realizations using ultra-cold atoms or molecules trapped in an optical lattice. We propose an experimentally feasible technique to access non-local degrees of freedom by performing global operations on trapped spins mediated by an optical cavity mode. We show how to reliably read and write topologically protected quantum memory using an atomic or photonic qubit. Furthermore, our technique can be used to probe statistics and dynamics of anyonic excitations.Comment: 14 pages, 6 figure

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ

It’s all about the money? A qualitative study of healthcare worker motivation in urban China

Background China’s healthcare reform programme continues to receive much attention. Central to these discussions has been how the various financial incentives underpinning reform efforts are negatively impacting on the healthcare workforce. Research continues to document these trends, however, qualitative analysis of how these incentives impact on the motivation of healthcare workers remains underdeveloped. Furthermore, the application of motivational theories to make sense of healthcare worker experiences has yet to be undertaken. Methods The purpose of our paper is to present a comparative case study account of healthcare worker motivation across urban China. It draws on semi structured interviews (n = 89) with a range of staff and organisations across three provinces. In doing so, the paper analyses how healthcare worker motivation is influenced by a variety of financial incentives; how motivation is influenced by the opportunities for career development; and how motivation is influenced by the day to day pressures of meeting patient expectations. Results The experience of healthcare workers in China highlights how a reliance on financial incentives has challenged their ability to maintain the values and ethos of public service. Our findings suggest greater attention needs to be paid to the motivating factors of improved income and career development. Further work is also needed to nurture and develop the motivation of healthcare workers through the building of trust between fellow workers, patients, and the public. Conclusions Through the analysis of healthcare worker motivation, our paper presents a number of ways China can improve its current healthcare reform efforts. It draws on the experience of other countries in calling for policy makers to support alternative approaches to healthcare reform that build on multiple channels of motivation to support healthcare workers

Abortive Lytic Reactivation of KSHV in CBF1/CSL Deficient Human B Cell Lines

Since Kaposi's sarcoma associated herpesvirus (KSHV) establishes a persistent infection in human B cells, B cells are a critical compartment for viral pathogenesis. RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular DNA binding factors including CBF1/CSL as DNA adaptors. In addition, the viral factors LANA1 and vIRF4 are known to bind to CBF1/CSL and modulate RTA activity. To analyze the contribution of CBF1/CSL to reactivation in human B cells, we have successfully infected DG75 and DG75 CBF1/CSL knock-out cell lines with recombinant KSHV.219 and selected for viral maintenance by selective medium. Both lines maintained the virus irrespective of their CBF1/CSL status. Viral reactivation could be initiated in both B cell lines but viral genome replication was attenuated in CBF1/CSL deficient lines, which also failed to produce detectable levels of infectious virus. Induction of immediate early, early and late viral genes was impaired in CBF1/CSL deficient cells at multiple stages of the reactivation process but could be restored to wild-type levels by reintroduction of CBF1/CSL. To identify additional viral RTA target genes, which are directly controlled by CBF1/CSL, we analyzed promoters of a selected subset of viral genes. We show that the induction of the late viral genes ORF29a and ORF65 by RTA is strongly enhanced by CBF1/CSL. Orthologs of ORF29a in other herpesviruses are part of the terminase complex required for viral packaging. ORF65 encodes the small capsid protein essential for capsid shell assembly. Our study demonstrates for the first time that in human B cells viral replication can be initiated in the absence of CBF1/CSL but the reactivation process is severely attenuated at all stages and does not lead to virion production. Thus, CBF1/CSL acts as a global hub which is used by the virus to coordinate the lytic cascade