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

Editorial: a New Era of GR2P

This year, a new editorial team has stepped in to take the reins of Global Responsibility to Protect (GR2P). In light of the tremendous contributions this journal has made in pioneering and shaping a generation of scholarship on R2P, we recognise that continuing this legacy is both an exciting and challenging prospect. We are indebted to the outgoing editors, Alex Bellamy, Sara Davies and Luke Glanville for their dedication to high-quality scholarship from a diverse set of scholars as well as their impressive achievements in chaperoning this journal from new entry to established and respected outlet. We also wish to thank the Editorial Board for their notable contributions to GR2P over the past eleven years; we are pleased to work with a team of such highly reputed and experienced individuals. We will strive to live up to the high standards they have all set while seeking to innovate and push GR2P to new heights

Pattern analysis of vegan eating reveals healthy and unhealthy patterns within the vegan diet

Objective: This study aimed to identify the types of foods that constitute a vegan diet and establish patterns within the diet. Dietary pattern analysis, a key instrument for exploring the correlation between health and disease was used to identify patterns within the vegan diet. Design: A modified version of the EPIC-Norfolk food frequency questionnaire (FFQ) was created and validated to include vegan foods and launched on social media. Setting: UK participants, recruited online Participants: A convenience sample of 129 vegans voluntarily completed the FFQ. Collected data was converted to reflect weekly consumption to enable factor and cluster analyses. Results: Factor analysis identified four distinct dietary patterns including: 1) convenience, (22%); 2) health conscious, (12%); 3) unhealthy, (9%); and 4) traditional vegan (7%). Whilst two healthy patterns were defined, the convenience pattern was the most identifiable pattern with a prominence of vegan convenience meals and snacks, vegan sweets and desserts, sauces, condiments and fats. Cluster analysis identified three clusters, cluster one ‘convenience’ (26.8%), cluster two, ‘traditional’ (22%) and cluster 3 ‘health conscious’ (51.2%). Clusters one and two consisted of an array of ultra-processed vegan food items. Together, both clusters represent almost half of participants and yielding similar results to the predominant dietary pattern, strengthens the factor analysis. Conclusions: These novel results highlight a need for further dietary pattern studies with full nutrition and blood metabolite analysis in larger samples of vegans to enhance and ratify these results

Results of the Patient-Related Outcomes of Mechanical lead Extraction Techniques (PROMET) study: a multicentre retrospective study on advanced mechanical lead extraction techniques.

AIMS: Several large studies have documented the outcome of transvenous lead extraction (TLE), focusing on laser and mechanical methods. To date there has been no large series addressing the results obtained with rotational lead extraction tools. This retrospective multicentre study was designed to investigate the outcomes of mechanical and rotational techniques. METHODS AND RESULTS: Data were collected on a total of 2205 patients (age 66.0 ± 15.7 years) with 3849 leads targeted for extraction in six European lead extraction centres. The commonest indication was infection (46%). The targeted leads included 2879 pacemaker leads (74.8%), 949 implantable cardioverter-defibrillator leads (24.6%), and 21 leads for which details were unknown; 46.6% of leads were passive fixation leads. The median lead dwell time was 74 months [interquartile range (IQR) 41-112]. Clinical success was obtained in 97.0% of procedures, and complete extraction was achieved for 96.5% of leads. Major complications occurred in 22/2205 procedures (1%), with a peri-operative or procedure-related mortality rate of 4/2205 (0.18%). Minor complications occurred in 3.1% of procedures. A total of 1552 leads (in 992 patients) with a median dwell time of 106 months (IQR 66-145) were extracted using the Evolution rotational TLE tool. In this subgroup, complete success was obtained for 95.2% of leads with a procedural mortality rate of 0.4%. CONCLUSION: Patient outcomes in the PROMET study compare favourably with other large TLE trials, underlining the capability of rotational TLE tools and techniques to match laser methods in efficacy and surpass them in safety

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud \ud Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Performance and outcomes of transvenous rotational lead extraction: Results from a prospective, monitored, international clinical study.

BACKGROUND: Transvenous lead extraction (TLE) plays a critical role in managing patients with cardiovascular implantable electronic devices. Mechanical TLE tools, including rotational sheaths, are used to overcome fibrosis and calcification surrounding leads. Prospective clinical data are limited regarding the safety and effectiveness of use of mechanical TLE devices, especially rotational tools. OBJECTIVE: To prospectively investigate the safety and effectiveness of mechanical TLE in real-world usage. METHODS: Patients were enrolled at 10 sites in the United States and Europe to evaluate the use of mechanical TLE devices. Clinical success, complete procedural success, and complications were evaluated through follow-up (median, 29 days). Patient data were source verified and complications were adjudicated by an independent clinical events committee (CEC). RESULTS: Between October 2018 and January 2020, mechanical TLE tools, including rotational sheaths, were used to extract 460 leads with a median indwell time of 7.4 years from 230 patients (mean age 64.3 ± 14.4 years). Noninfectious indications for TLE were more common than infectious indications (61.5% vs 38.5%, respectively). The extracted leads included 305 pacemaker leads (66.3%) and 155 implantable cardioverter-defibrillator leads (33.7%), including 85 leads with passive fixation (18.5%). A bidirectional rotational sheath was needed for 368 leads (88.0%). Clinical success was obtained in 98.7% of procedures; complete procedural success was achieved for 96.3% of leads. CEC-adjudicated device-related major complications occurred in 6 of 230 (2.6%) procedures. No isolated superior vena cava injury or procedural death occurred. CONCLUSION: This prospective clinical study demonstrates that use of mechanical TLE tools, especially bidirectional rotational sheaths, are effective and safe

The RNA Chaperone Hfq Is Important for Growth and Stress Tolerance in Francisella novicida

The RNA-binding protein Hfq is recognized as an important regulatory factor in a variety of cellular processes, including stress resistance and pathogenesis. Hfq has been shown in several bacteria to interact with small regulatory RNAs and act as a post-transcriptional regulator of mRNA stability and translation. Here we examined the impact of Hfq on growth, stress tolerance, and gene expression in the intracellular pathogen Francisella novicida. We present evidence of Hfq involvement in the ability of F. novicida to tolerate several cellular stresses, including heat-shock and oxidative stresses, and alterations in hfq gene expression under these conditions. Furthermore, expression of numerous genes, including several associated with virulence, is altered in a hfq mutant strain suggesting they are regulated directly or indirectly by Hfq. Strikingly, we observed a delayed entry into stationary phase and increased biofilm formation in the hfq mutant. Together, these data demonstrate a critical role for Hfq in F. novicida growth and survival

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Low-temperature magnetization of (Ga,Mn) As semiconductors

Journals published by the American Physical Society can be found at http://journals.aps.org/We report on a comprehensive study of the ferromagnetic moment per Mn atom in (Ga,Mn)As ferromagnetic semiconductors. Theoretical discussion is based on microscopic calculations and on an effective model of Mn local moments antiferromagnetically coupled to valence band hole spins. The validity of the effective model over the range of doping studied is assessed by comparing with microscopic tight-binding/coherent-potential approximation calculations. Using the virtual crystal k center dot p model for hole states, we evaluate the zero-temperature mean-field contributions to the magnetization from the hole kinetic and exchange energies, and magnetization suppression due to quantum fluctuations of Mn moment orientations around their mean-field ground state values. Experimental low-temperature ferromagnetic moments per Mn are obtained by superconducting quantum interference device and x-ray magnetic circular dichroism measurements in a series of (Ga,Mn)As semiconductors with nominal Mn doping ranging from similar to 2 to 8%. Hall measurements in as-grown and annealed samples are used to estimate the number of uncompensated substitutional Mn moments. Based on our comparison between experiment and theory we conclude that all these Mn moments in high quality (Ga,Mn)As materials have nearly parallel ground state alignment