Assessment of function and clinical utility of alcohol and other drug web sites: An observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent

Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge

We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratrache

The Effect of Influenza Virus on the Human Oropharyngeal Microbiome

BACKGROUND: Secondary bacterial infections are an important cause of morbidity and mortality associated with influenza infections. As bacterial disease can be caused by a disturbance of the host microbiome, we examined the impact of influenza on the upper respiratory tract microbiome in a human challenge study. METHODS: The dynamics and ecology of the throat microbiome were examined following an experimental influenza challenge of 52 previously-healthy adult volunteers with influenza A/Wisconsin/67/2005 (H3N2) by intranasal inoculation; 35 healthy control subjects were not subjected to the viral challenge. Serial oropharyngeal samples were taken over a 30-day period, and the V1-V3 region of the bacterial 16S ribosomal RNA sequences were amplified and sequenced to determine the composition of the microbiome. The carriage of pathogens was also detected. RESULTS: Of the 52 challenged individuals, 43 developed proven influenza infections, 33 of whom became symptomatic. None of the controls developed influenza, although 22% reported symptoms. The diversity of bacterial communities remained remarkably stable following the acquisition of influenza, with no significant differences over time between individuals with influenza and those in the control group. Influenza infection was not associated with perturbation of the microbiome at the level of phylum or genus. There was no change in colonization rates with Streptococcus pneumoniae or Neisseria meningitidis. CONCLUSIONS: The throat microbiota is resilient to influenza infection, indicating the robustness of the upper-airway microbiome

Breakingtheice: A protocol for a randomised controlled trial of an internet-based intervention addressing amphetamine-type stimulant use

Background: The prevalence of amphetamine-type stimulant use is greater than that of opioids and cocaine combined. Currently, there are no approved pharmacotherapy treatments for amphetamine-type stimulant problems, but some face-to-face psychotherapies are of demonstrated effectiveness. However, most treatment services focus on alcohol or opioid disorders, have limited reach and may not appeal to users of amphetamine-type stimulants. Internet interventions have proven to be effective for some substance use problems but none has specifically targeted users of amphetamine-type stimulants. Design/method: The study will use a randomized controlled trial design to evaluate the effect of an internet intervention for amphetamine-type stimulant problems compared with a waitlist control group. The primary outcome will be assessed as amphetamine-type stimulant use (baseline, 3 and 6 months). Other outcomes measures will include ‘readiness to change’, quality of life, psychological distress (K-10 score), days out of role, poly-drug use, help-seeking intention and help-seeking behavior. The intervention consists of three modules requiring an estimated total completion time of 90 minutes. The content of the modules was adapted from face-to-face clinical techniques based on cognitive behavior therapy and motivation enhancement. The target sample is 160 men and women aged 18 and over who have used amphetamine-type stimulants in the last 3 months. Discussion: To our knowledge this will be the first randomized controlled trial of an internet intervention specifically developed for users of amphetamine-type stimulants. If successful, the intervention will offer greater reach than conventional therapies and may engage clients who do not generally seek treatment from existing service providers

Six-month outcomes of a web-based intervention for users of amphetamine-type stimulants: Randomized controlled trial

Background: The use of amphetamine-type stimulants (ATS) places a large burden on health services.Objective: The aim was to evaluate the effectiveness of a self-guided Web-based intervention (“breakingtheice”) for ATS users over 6 months via a free-to-access site.Methods: We conducted a randomized trial comparing a waitlist control with a fully automated intervention containing 3 modules derived from cognitive behavioral therapy and motivation enhancement. The main outcome was self-reported ATS use in the past 3 months assessed at 3- and 6-month follow-ups using the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Secondary outcomes were help-seeking intentions (general help-seeking questionnaire), actual help seeking (actual help-seeking questionnaire), psychological distress (Kessler 10), polydrug use (ASSIST), quality of life (European Health Interview Survey), days out of role, and readiness to change. Follow-up data were evaluated using an intention-to-treat (ITT) analysis with a group by time interaction.Results: We randomized 160 people (intervention: n=81; control: n=79). At 6 months, 38 of 81 (47%) intervention and 41 of 79 (52%) control participants provided data. ATS scores significantly declined for both groups, but the interaction effect was not significant. There were significant ITT time by group interactions for actual help seeking (rate ratio [RR] 2.16; d=0.45) and help-seeking intentions (RR 1.17; d=0.32), with help seeking increasing for the intervention group and declining for the control group. There were also significant interactions for days completely (RR 0.50) and partially (RR 0.74) out of role favoring the intervention group. However, 37% (30/81) of the intervention group did not complete even 1 module.Conclusions: This self-guided Web-based intervention encouraged help seeking associated with ATS use and reduced days out of role, but it did not reduce ATS use. Thus, this program provides a means of engaging with some sections of a difficult-to-reach group to encourage treatment, but a substantial minority remained disengaged.Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12611000947909;https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=343307 (Archived by WebCite athttp://www.webcitation.org/6Y0PGGp8q).URL http://dx.doi.org/10.2196/jmir.3778</a

The effective rate of influenza reassortment is limited during human infection

We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which reassortment is observed. Our results do not contradict previous findings of high rates of viral reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of reassortment may be substantially more limited.CJRI is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 101239/Z/13/Z) and received support from the National Science Foundation Research Coordination Network on Infectious Disease Evolution Across Scales. KK, ASL, CWW, and MTM were funded by NIGMS U54-GM111274, the MIDAS Center for Inference and Dynamics of Infectious Disease. ASL acknowledges support from the MSTP training grant number T32 GM007171. GJDS was supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore and by contract HHSN272201400006C from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, USA. DEW, RAH, XL, AR, TBS, SRD and also the influenza whole genome sequencing were supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200900007C. GSG was funded by the Defense Advanced Research Projects Agency under grant number DARPA-N66001-07-C-2024. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Evolution Across Scales. KK, ASL, CWW, and MTM were funded by NIGMS U54- GM111274, the MIDAS Center for Inference and Dynamics of Infectious Disease. DEW, RAH, XL, AR, TBS, and SRD were supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200900007C. GSG was funded by the Defense Advanced Research Projects Agency under grant number DARPA-N66001-07-C-2024. This work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council

Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate

Background Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. Results The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. Conclusions ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components

Excitonic recombination dynamics in shallow quantum wells

We report a comprehensive study of carrier-recombination dynamics in shallow AlxGa1-xAs/GaAs quantum wells. At low crystal temperature (2 K), the excitonic radiative recombination time is shown to be strongly enhanced in shallow quantum wells with x>0.01, consistently with a model that takes into account the thermal equilibrium between the three-dimensional exciton gas of the barrier and the two-dimensional exciton gas, which are closer in energy as x decreases. Furthermore, we demonstrate the existence of a thermally activated escape mechanism due to the low effective barrier height in these structures. The nonradiative recombination is shown to dominate the carrier dynamics for temperatures as low as 10 K for x≈0.01. Our experimental observations are analyzed using three different variational exciton calculations. In particular, we study the crossover from the two-dimensional to the three-dimensional behavior of the exciton, which occurs for x as low as 0.01 and affects mainly the oscillator strength, whereas the transition energies in shallow quantum wells can be calculated, to a large extent, using the same approximations as for conventional quantum wells. The peculiar behavior of the oscillator strength at the crossover to the weak confinement regime is obtained by expansion in a large basis