Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
258
result(s) for
"Saunders, John Michael"
Sort by:
Evoking through design : contemporary moods in architecture
\"A visually stunning title, 'Evoking Through Design' features built work and speculative projects that highlight how contemporary practices are using devices such as spatial compositing, surface articulation, novel manipulations of matter and computational code in order to constitute spatial conditions radiating in delicate and sophisticated atmospheres. The theoretical foundations of the subject are explored through core essays on key themes: the historical lineage of the evocation of atmosphere and moods in architecture; the more recent preoccupation with speculative realism in architecture; the human body and atmosphere; and picturesque techniques.\"--Back cover.
Book
Factors associated with reporting antibiotic use as STI prophylaxis among HIV PrEP users: findings from a cross-sectional online community survey, May–July 2019, UK
ObjectivesThe use of antibiotics as pre-exposure or postexposure prophylaxis for sexually transmitted infection (STI) prevention (STI prophylaxis) is not currently recommended in the UK, but there is evidence that self-prescribing occurs among those at greatest risk. We present the prevalence and factors associated with STI prophylaxis among a community sample of HIV pre-exposure prophylaxis (PrEP) users.MethodsThe 2019 online PrEP User Survey ran between 17 May and 1 July. Eligible participants included UK residents reporting HIV PrEP use or having tried to obtain HIV PrEP since January 2017. STI prophylaxis use was defined as reporting buying antibiotics to prevent STIs, either privately or through the internet; this question was only asked to HIV PrEP users. Factors associated with STI prophylaxis use were assessed using univariable and multivariable logistic regression.ResultsOverall, 9% (167/1856) of HIV PrEP users reported STI prophylaxis use; 97% were gay or bisexual men, 84% reported white ethnicity, 55% resided in London and 69% were aged ≥35 years. Factors associated with STI prophylaxis included: reporting ≥5 compared with 1–4 condomless sex partners in the past 6 months (12% vs 5.6%, adjusted odds ratio (aOR)=1.80; 95% CI 1.22 to 2.64), reporting chemsex drug use compared with no sexualised drug use in the past 12 months (13% vs 6.0%, aOR=1.88; 95% CI 1.20 to 2.93) and reporting an STI diagnosis in the past 12 months (12% vs 6.6%, aOR=1.54; 95% CI 1.08 to 2.18). Variables not significant in multivariable analyses included: ethnicity, age, residence and HIV PrEP sourcing.ConclusionsApproximately 1 in 10 HIV PrEP users from this community sample reported self-prescribed STI prophylaxis. STI prophylaxis was associated with sexual behaviour known to facilitate STI transmission and with a history of recent STIs acquisition. Given the potential risk of antimicrobial resistance, sexual health clinicians should consider asking attendees, especially HIV PrEP users, about the use of antibiotics as STI prophylaxis, to inform appropriate counselling, testing and management.
Journal Article
Implementation of a national HIV pre-exposure prophylaxis service is associated with changes in characteristics of people with newly diagnosed HIV: a retrospective cohort study
ObjectivesTo review characteristics of individuals newly diagnosed with HIV following implementation of a national pre-exposure prophylaxis (PrEP) programme (comprehensive PrEP services, delivered in sexual health clinics) to inform future delivery and broader HIV prevention strategies.MethodsWe extracted data from national HIV databases (July 2015–June 2018). We compared sociodemographic characteristics of individuals diagnosed in the period before and after PrEP implementation, and determined the proportion of ‘potentially preventable’ infections with the sexual health clinic–based PrEP delivery model used.ResultsThose diagnosed with HIV before PrEP implementation were more likely to be male (342/418, 81.8% vs 142/197, 72.1%, p=0.005), be white indigenous (327/418, 78.2% vs 126/197, 64.0%, p<0.001), report transmission route as sex between men (219/418, 52.4% vs 81/197, 41.1%, p=0.014), and have acquired HIV in the country of the programme (302/418, 72.2% vs 114/197, 57.9% p<0.001) and less likely to report transmission through heterosexual sex (114/418, 27.3% vs 77/197, 39.1%, p=0.002) than after implementation.Pre-implementation, 8.6% (36/418) diagnoses were ‘potentially preventable’ with the PrEP model used. Post-implementation, this was 6.6% (13/197), but higher among those with recently acquired HIV (49/170, 28.8%). Overall, individuals with ‘potentially preventable’ infections were more likely to be male (49/49, 100% vs 435/566, 76.9%, p<0.001), aged <40 years (37/49, 75.5% vs 307/566, 54.2%, p=0.004), report transmission route as sex between men (49/49, 100% vs 251/566, 44.3%, p<0.001), have previously received post-exposure prophylaxis (12/49, 24.5% vs 7/566, 1.2%, p<0.001) and less likely to be black African (0/49, 0% vs 67/566, 11.8%, p=0.010) than those not meeting this definition.ConclusionsThe sexual health clinic–based national PrEP delivery model appeared to best suit men who have sex with men and white indigenous individuals but had limited reach into other key vulnerable groups. Enhanced models of delivery and HIV combination prevention are required to widen access to individuals not benefiting from PrEP at present.
Journal Article
Association between rectal gonorrhoea and HIV incidence in men who have sex with men: a meta-analysis
BackgroundIncidence of rectal gonorrhoea (GC) has been hypothesised as a correlate of HIV exposure in prevention trials of men who have sex with men (MSM). High rectal GC incidence in MSM trials of new biomedical prevention drugs may provide supportive evidence for ongoing HIV risk. Empirical evidence of correlation between rectal GC and HIV incidence is needed to assess whether high rectal GC rates reliably correlate with high risk of HIV.MethodsRectal GC and HIV are routinely tested in sexual health clinics (SHCs) throughout England. Through routine surveillance data collected at visits to SHCs, we assessed HIV incidence and new rectal GC diagnoses in repeat visits by HIV-negative MSM between 2011 and 2018, predating widespread roll-out of pre-exposure prophylaxis. Meta-analysis regression assessed population-level association between HIV and rectal GC incidence over time.FindingsBetween 2011 and 2018, HIV and rectal GC incidence was assessed in 541 056 HIV-negative MSM attending SHCs in England. HIV incidence among MSM attending SHCs fell from 1.26/100 person-years (PYs) in 2011 to 0.28/100 PYs in 2018. Rectal GC rates increased from 3.5/100 PYs to 11.1/100 PYs over the same period. The rate of HIV incidence decreased by 22.3% for each percent increase in rectal GC (95% CI –30.8 to –14.7, p<0.001).InterpretationAmong the population of MSM attending SHCs in England, rectal GC rates increased substantially while HIV incidence rates decreased between 2011 and 2018. HIV incidence likely decreased through expanded HIV testing, prompt antiretroviral treatment (ART) initiation and increased viral suppression in persons living with HIV, interventions that did not decrease rectal GC. Rectal GC may not be an ideal proxy for HIV incidence in trials, as HIV exposure risk is complex and context dependent, given effective HIV prevention interventions in MSM.Introduction
Journal Article
Person-centred care and HIV: challenges and solutions
Person-centred consultations (PCCs) are fundamental to effective healthcare communication, and its use is embedded within key clinical guidance. There are three aspects to PCC: use of the best available research evidence, clinical expertise of the clinician and the patient’s circumstances, goals, values and wishes. Balancing theses three aspects in the context of HIV prevention and management can be challenging, and we use three case examples to highlight these.
Journal Article
No widespread dissemination of Chlamydia trachomatis diagnostic-escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay
ObjectivesA Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants.MethodsFrom June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed.ResultsA total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens.ConclusionsNo widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.
Journal Article
Preparing for PrEP: estimating the size of the population eligible for HIV pre-exposure prophylaxis among men who have sex with men in England
ObjectivesThe size of the population of men who have sex with men (MSM) who may be eligible for HIV pre-exposure prophylaxis (HIV-PrEP) in England remains unknown. To plan for a national PrEP implementation trial, we estimated the number of MSM attending sexual health clinics (SHCs) that may be eligible for HIV-PrEP in England.MethodsSexually transmitted infection (STI) surveillance data from 2010 to 2015 from the GUMCAD surveillance system were used to estimate the annual number of HIV-negative MSM who may be eligible for HIV-PrEP in England. Based on national eligibility criteria, we identified HIV-negative MSM attending SHCs with a HIV-negative test in the past year and used diagnosed bacterial STI (past year) in this group as a proxy for condomless sex and eligibility for HIV-PrEP. We estimated HIV incidence per 100 person-years (py) in these groups in 2014.ResultsDuring 2010–2015, the number of HIV-negative MSM attending SHCs with a HIV-negative test in the past year doubled from 14 643 to 29 023, and HIV incidence in this group was 1.9 (95% CI 1.6 to 2.2) per 100 py in 2014. In the same period, the subgroup with a bacterial STI diagnosis (past year), and therefore considered potentially eligible for HIV-PrEP in this analysis, increased from 4365 (30%) to 10 276 (35%). HIV incidence in this subgroup was 3.3 (95% CI 2.7 to 4.0) per 100 py in 2014.ConclusionsIn 2015, approximately 10 000 HIV-negative MSM were considered potentially eligible for HIV-PrEP based on clinic history in GUMCAD. These data were used to inform the initial recruitment target for the PrEP Impact Trial and will inform future evaluations at a population level.
Journal Article
Optimising opportunities for sti testing for men: exploring the acceptability of different testing venues with a focus on football club-based testing
Background: Chlamydia trachomatis is the commonest curable sexually transmitted infection in the UK. The prevalence is shared equally by men and women. A National Chlamydia Screening Programme (NCSP) has been introduced in England, supported by advances in testing technologies which enable non-invasive sampling methods to be used in non-healthcare settings. The NCSP tests nearly twice as many women as men and is more likely to test men in non-healthcare settings. Men are seen as an important, but difficult to reach group. Little is known about where men prefer to access testing and whether or not nontraditional settings, such as football clubs, are acceptable. Methods: 1) A national stratified random probability sample survey of men aged between 18 and 35 years resident in Great Britain, exploring attitudes to self-collected testing for Chlamydia, acceptability of venues to collect testing kits, health seeking and sexual risk behaviours. 2) Qualitative interviews with men who play amateur football. It explores the acceptability of three different, club-based, testing pathways; Health-care professional promoted; Peer-led promoted; and poster-led promoted. Results: Men are well engaged with existing health services and find selfcollected testing kits for Chlamydia highly acceptable. Healthcare settings are the most acceptable venues to access testing although sports settings are acceptable to a minority. Attitudes to testing in football clubs are influenced by factors relating to men’s characteristics, promoter characteristics and the impact of testing on time and effort involved. Conclusions: Whilst non-healthcare settings can be used to reach some men for Chlamydia testing, existing services are already well accessed and offer considerable opportunities to test more men. More should be done to ensure men are able to access testing within the context of daily living, without significantly impacting on the time needed to pursue their main interests.
Dissertation
Muscle activation and the slow component rise in oxygen uptake
The VO $\\sb2$slow component results in a progressive increase in metabolic energy cost during high-intensity, constant-load exercise. Endurance training reduces the VO $\\sb2$slow component, lowering end-exercise VO $\\sb2.$The purposes of this study were (1) to determine if the VO $\\sb2$slow component was associated with increased muscle use during exercise, and (2) to determine if reduced end-exercise VO $\\sb2$following training was accompanied by reduced muscle use. The VO $\\sb2$slow component was measured in 16 subjects during high- and low-intensity cycling. Exercise-induced contrast shifts in magnetic resonance images were obtained following 3 and 15 minutes at each intensity to determine T $\\sb2$changes (reflective of muscle use). Eight subjects underwent 4 weeks of cycling training, with 7 serving as controls. All procedures were repeated following training. During the low-intensity ride, there were no changes in VO $\\sb2$or muscle use variables from 3 to 15 minutes, except for a small increase (p$<$ .05) in T $\\sb2$of the vastus lateralis. During high-intensity cycling, VO $\\sb2$rose from 3 (2225$\\pm$597 ml) to 15 minutes (2510$\\pm$622 ml). Percent increases in VO $\\sb2$were moderately related (p$<$ .05) with percent increases in muscle T $\\sb2$of the lower extremity (r =.63). Following training, end-exercise VO $\\sb2$was unchanged during low-intensity cycling. However, training reduced (p$<$ .05) end-exercise VO $\\sb2$(58$\\pm$172 ml) and T $\\sb2$of the vastus lateralis (1.2$\\pm$1.5 msec) during high-intensity cycling. Percent changes in end-exercise VO $\\sb2$were moderately related with percent changes in T $\\sb2$of lower extremity muscle (r =.56), vastus lateralis (r =.47), and rectus femoris (r =.49). We conclude that (1) a moderate association exists between muscle use and the VO $\\sb2$slow component and (2) reduction in vastus lateralis activity is associated with reduction in end-exercise VO $\\sb2$following cycling training. These findings support the hypothesis that increased muscle recruitment plays a causal role in the development of the VO $\\sb2$slow component, and provides the first evidence that reduced VO $\\sb2$during heavy submaximal exercise following training is due to reduced muscle use.
Dissertation
BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis
Mitochondrial DNA (mtDNA) is a potent damage-associated molecular pattern that, if it reaches the cytoplasm or extracellular milieu, triggers innate immune pathways. mtDNA signaling has been implicated in a wide range of diseases; however, the mechanisms of mtDNA release are unclear, and the process has not been observed in real time thus far. McArthur et al. used live-cell lattice light-sheet microscopy to look at mtDNA release during intrinsic apoptosis. Activation of the pro-death proteins BAK and BAX resulted in the formation of large macro-pores in the mitochondrial outer membrane. These massive holes caused the inner mitochondrial membrane to balloon out into the cytoplasm, resulting in mitochondrial herniation. This process allowed the contents of the mitochondrial matrix, including mtDNA, to escape into the cytoplasm. Science , this issue p. eaao6047 Mitochondrial DNA is released from mitochondria in apoptotic cells as a result of BAK/BAX-induced mitochondrial herniation. Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce mitochondrial outer membrane permeabilization, leading to cytochrome c release and activation of apoptotic caspases. In the absence of active caspases, mitochondrial DNA (mtDNA) triggers the innate immune cGAS/STING pathway, causing dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains unclear. We used live-cell lattice light-sheet microscopy to examine the mitochondrial network in mouse embryonic fibroblasts. We found that after BAK/BAX activation and cytochrome c loss, the mitochondrial network broke down and large BAK/BAX pores appeared in the outer membrane. These BAK/BAX macropores allowed the inner mitochondrial membrane to herniate into the cytosol, carrying with it mitochondrial matrix components, including the mitochondrial genome. Apoptotic caspases did not prevent herniation but dismantled the dying cell to suppress mtDNA-induced innate immune signaling.
Journal Article