Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types

In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12–13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12–13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%. To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV. From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated. This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake

Design and simulation of a high-gain organic operational amplifier for use in quantification of cholesterol in low-cost point-of-care devices

© The Institution of Engineering and Technology. This paper presents circuit design and simulations of a high gain organic Op-Amp, for use in quantification of real cholesterol, in the range of 1-9 mM. A 7-stage inverter chain is added onto the design so as to enhance the amplifier gain. The circuit adapts p-channel transistors only (PMOS) design architecture with saturated loads, simulated on a conventional platform, using appropriate OTFT model and associated parameters. The effect of variation in threshold voltage on circuit operation is also examined. For a supply voltage of ±15 V, the DC output voltage is found to be within an acceptable range of -1 V to -12.5 V, with a highest open loop gain of 83 dB. The closed loop gain is also in agreement with theoretical values, in the range of 1.5 dB to 39 dB, with corresponding bandwidths of 770 Hz to 275 Hz respectively. The latter gain of 39 dB and/or gain-bandwidth product of 10.63 kHz is currently the highest reported in the literature, for this lower supply voltage. The amplifier offers adequate quantification factor, with linear sensitivity of -0.7 V/mM. This paper is the first to adapt organic circuit designs in quantification of cholesterol, with promising outputs, for implementation in low-cost sensor systems

The social cognition of medical knowledge, with special reference to childhood epilepsy

This paper arose out of an engagement in medical communication courses at a Gulf university. It deploys a theoretical framework derived from a (critical) sociocognitive approach to discourse analysis in order to investigate three aspects of medical discourse relating to childhood epilepsy: the cognitive processes that are entailed in relating different types of medical knowledge to their communicative context; the types of medical knowledge that are constituted in the three different text types analysed; and the relationship between these different types of medical knowledge and the discursive features of each text type. The paper argues that there is a cognitive dimension to the human experience of understanding and talking about one specialized from of medical knowledge. It recommends that texts be studied in medical communication courses not just in terms of their discrete formal features but also critically, in terms of the knowledge which they produce, transmit and reproduce

Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer’s disease: a cross-sectional metabolomic analysis

Copyright \ua9 2024 Pan, Donaghy, Roberts, Chouliaras, O’Brien, Thomas, Heslegrave, Zetterberg, McGuinness, Passmore, Green and Kane.Background: In multifactorial diseases, alterations in the concentration of metabolites can identify novel pathological mechanisms at the intersection between genetic and environmental influences. This study aimed to profile the plasma metabolome of patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), two neurodegenerative disorders for which our understanding of the pathophysiology is incomplete. In the clinical setting, DLB is often mistaken for AD, highlighting a need for accurate diagnostic biomarkers. We therefore also aimed to determine the overlapping and differentiating metabolite patterns associated with each and establish whether identification of these patterns could be leveraged as biomarkers to support clinical diagnosis. Methods: A panel of 630 metabolites (Biocrates MxP Quant 500) and a further 232 metabolism indicators (biologically informative sums and ratios calculated from measured metabolites, each indicative for a specific pathway or synthesis; MetaboINDICATOR) were analyzed in plasma from patients with probable DLB (n = 15; age 77.6 \ub1 8.2 years), probable AD (n = 15; 76.1 \ub1 6.4 years), and age-matched cognitively healthy controls (HC; n = 15; 75.2 \ub1 6.9 years). Metabolites were quantified using a reversed-phase ultra-performance liquid chromatography column and triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode, or by using flow injection analysis in MRM mode. Data underwent multivariate (PCA analysis), univariate and receiving operator characteristic (ROC) analysis. Metabolite data were also correlated (Spearman r) with the collected clinical neuroimaging and protein biomarker data. Results: The PCA plot separated DLB, AD and HC groups (R2 = 0.518, Q2 = 0.348). Significant alterations in 17 detected metabolite parameters were identified (q ≤ 0.05), including neurotransmitters, amino acids and glycerophospholipids. Glutamine (Glu; q = 0.045) concentrations and indicators of sphingomyelin hydroxylation (q = 0.039) distinguished AD and DLB, and these significantly correlated with semi-quantitative measurement of cardiac sympathetic denervation. The most promising biomarker differentiating AD from DLB was Glu:lysophosphatidylcholine (lysoPC a 24:0) ratio (AUC = 0.92; 95%CI 0.809–0.996; sensitivity = 0.90; specificity = 0.90). Discussion: Several plasma metabolomic aberrations are shared by both DLB and AD, but a rise in plasma glutamine was specific to DLB. When measured against plasma lysoPC a C24:0, glutamine could differentiate DLB from AD, and the reproducibility of this biomarker should be investigated in larger cohorts

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

In Scotland, a national HPV immunisation programme began in 2008 for 12-13 year olds, with a catch-up campaign from 2008-2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.  We analysed colposcopy data from a cohort of women born between 1988-1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012.  By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1) (RR 0.71, 95% CI 0.58 to 0.87, p=0.0008), CIN 2 (RR 0.5, 95% CI 0.4, 0.63, p<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58, p< 0.0001) for women who received 3 doses of vaccine compared with unvaccinated women.  To our knowledge, this is one of the first studies to show a reduction of low and high grade cervical intraepithelial neoplasia associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake

Correlative Analysis of GRBs detected by Swift, Konus and HETE

Swift has now detected a large enough sample of gamma-ray bursts (GRBs) to allow correlation studies of burst parameters. Such studies of earlier data sets have yielded important results leading to further understanding of burst parameters and classifications. This work focuses on seventeen Swift bursts that have also been detected either by Konus-Wind or HETE-II, providing high energy spectra and fits to E(sub peak). Eight of these bursts have spectroscopic redshifts and for others we can estimate redshifts using the variability/luminosity relationship. We can also compare E(sub peak) with E(sub iso), and for those bursts for which a jet break was observed in the afterglow we can derive E(sub g) and test the relationship between E(peak) and E(sub gamma). For all bursts we can derive durations and hardness ratios from the prompt emission

Plants Modify Biological Processes to Ensure Survival following Carbon Depletion: A Lolium perenne Model

BACKGROUND: Plants, due to their immobility, have evolved mechanisms allowing them to adapt to multiple environmental and management conditions. Short-term undesirable conditions (e.g. moisture deficit, cold temperatures) generally reduce photosynthetic carbon supply while increasing soluble carbohydrate accumulation. It is not known, however, what strategies plants may use in the long-term to adapt to situations resulting in net carbon depletion (i.e. reduced photosynthetic carbon supply and carbohydrate accumulation). In addition, many transcriptomic experiments have typically been undertaken under laboratory conditions; therefore, long-term acclimation strategies that plants use in natural environments are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Perennial ryegrass (Lolium perenne L.) was used as a model plant to define whether plants adapt to repetitive carbon depletion and to further elucidate their long-term acclimation mechanisms. Transcriptome changes in both lamina and stubble tissues of field-grown plants with depleted carbon reserves were characterised using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The RT-qPCR data for select key genes indicated that plants reduced fructan degradation, and increased photosynthesis and fructan synthesis capacities following carbon depletion. This acclimatory response was not sufficient to prevent a reduction (P<0.001) in net biomass accumulation, but ensured that the plant survived. CONCLUSIONS: Adaptations of plants with depleted carbon reserves resulted in reduced post-defoliation carbon mobilization and earlier replenishment of carbon reserves, thereby ensuring survival and continued growth. These findings will help pave the way to improve plant biomass production, for either grazing livestock or biofuel purposes

Using digital technologies to facilitate social inclusion during the COVID-19 pandemic: Experiences of co-resident and non-co-resident family carers of people with dementia from DETERMIND-C19

Background The COVID-19 pandemic triggered rapid and unprecedented changes in the use of digital technologies to support people's social inclusion. We examined whether and how co-resident and non-co-resident family carers of people with dementia engaged with digital technologies during this period. Methods Throughout November 2020-February 2021, we interviewed 42 family carers of people with dementia from our DETERMIND-C19 cohort. Preliminary analysis was conducted through Framework analysis, followed by an inductive thematic analysis. Findings Digital technologies served as a Facilitator for social inclusion by enabling carers to counter the effects of the differing restrictions imposed on them so they could remain socially connected and form a sense of solidarity, access resources and information, engage in social and cultural activities and provide support and independence in their caring role. However, these experiences were not universal as carers discussed some Challenges for tech inclusion, which included preferences for face-to-face contact, lack of technological literacy and issues associated with the accessibility of the technology. Conclusion Many of the carers engaged with Information and Communication Technologies, and to a lesser extent Assistive Technologies, during the pandemic. Whilst carers experienced different challenges due to where they lived, broadly the use of these devices helped them realise important facets of social inclusion as well as facilitated the support they provided to the person with dementia. However, to reduce the ‘digital divide’ and support the social inclusion of all dementia carers, our findings suggest it is essential that services are attuned to their preferences, needs and technological abilities

HPV type-specific prevalence using a urine assay in unvaccinated male and female 11- to 18-year olds in Scotland

We conducted a baseline prevalence survey of unvaccinated 11- to 18-year olds to inform effectiveness studies for the new human papillomavirus (HPV) immunisation programme in Scotland

X-ray Flashes or soft Gamma-ray Bursts? The case of the likely distant XRF 040912

In this work, we present a multi-wavelength study of XRF 040912, aimed at measuring its distance scale and the intrinsic burst properties. We performed a detailed spectral and temporal analysis of both the prompt and the afterglow emission and we estimated the distance scale of the likely host galaxy. We then used the currently available sample of XRFs with known distance to discuss the connection between XRFs and classical Gamma-ray Bursts (GRBs). We found that the prompt emission properties unambiguously identify this burst as an XRF, with an observed peak energy of E_p=17+/-13 keV and a burst fluence ratio S(2-30keV)/S(30-400keV)>1. A non-fading optical source with R~24 mag and with an apparently extended morphology is spatially consistent with the X-ray afterglow, likely the host galaxy. XRF 040912 is a very dark burst since no afterglow optical counterpart is detected down to R>25 mag (3 sigma limiting magnitude) at 13.6 hours after the burst. The host galaxy spectrum detected from 3800A to 10000A, shows a single emission line at 9552A. The lack of any other strong emission lines blue-ward of the detected one and the absence of the Ly alpha cut-off down to 3800A are consistent with the hypothesis of the [OII] line at redshift z=1.563+/-0.001. The intrinsic spectral properties rank this XRF among the soft GRBs in the E_peak-E_iso diagram. Similar results were obtained for most XRFs at known redshift. Only XRF 060218 and XRF 020903 represent a good example of instrinsic XRF(i-XRF) and are possibly associated with a different progenitor population. This scenario may calls for a new definition of XRFs.Comment: 10 pages, 7 figures, accepted for publication in Astronomy & Astrophysic