47 research outputs found
A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach
No full textCarriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric adenocarcinoma. To our knowledge, we are the
first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the
first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA+ background
American trout-stream insects; a guide to angling flies and other aquatic insects alluring to trout, selected and painted for each month of the trout season from nearly one hundred living specimens native to the rivers and lakes of the temperate zone of North America, with notes on and reproductions of artificial imitation flies tied by the author, and a chapter on the mode of tying artificial flies, with assisting charts and illustrations in the text, together with descriptions and illustrations of a complete set of new artificial nature-lures copied exactly from carefully colored life-pictures of all creatures that bass and other game fishes consume as food
No full textWorking towards an international ANPR Standard — An initial investigation into the UK standard
No full textThis paper examines the use of the UK National ACPO ANPR Standard (NAAS) as the “de facto” technical standard applied in many international countries. It considers the requirement for a standard and examines the effectiveness of the current NAAS and questions its fitness for purpose. The need for accuracy is discussed in terms of both tackling terrorism, serious crime and other law enforcement investigations alongside the need to protect citizens from unwarranted infringement of their privacy as a result of ANPR misreads. The causes of inaccurate ANPR read data are examined in more detail and recommendations made as to how improvements could be introduced to minimise the risk of misreads and “missed” reads. This paper recommends future parameters of measurement and provides examples of gaps between the current standards and existing legislation. Laboratory and field testing was carried out to gain a better understanding of the factors that affect the performance of ANPR systems. These tests were carried out under a variety of weather and lighting conditions. The results of this work have led to further testing to better understand the optimum conditions for number plate capture by a variety of ANPR systems. Additional testing has been carried out using "hard to read" number plates with a number of differing characteristics such as illegally spaced characters, illegal fonts, screw caps that interfere with infrared imaging and defects in the construction of the number plate itself (whether created inadvertently at the point of manufacture or subsequently caused by damage / wear and tear / weather conditions). The first author is a UK police officer and, like his senior analyst colleague who is the second author, has wide experience in testing and developing ANPR systems. The authors have been commissioned by the UK Home Office to carry out post graduate ANPR research at the University of Hertfordshire
My Dear Horace Kephart: Letters from George Mac Reynolds and Louise Rhead
No full textHorace Kephart was a renaissance man of his day. A librarian, author, and impassioned outdoorsman, he maintained a career at the St. Louis Mercantile Library before moving to North Carolina in 1904. Kephart wrote extensively on camping, woodcraft, and wildlife. He also worked to establish the smoky mountain national park. To offer a sense of his personality and appreciation for both the human-made and the natural world, he wrote the following in a letter dated Oct. 2, 1888 to friend Harry Koopman: “Imagine Boston or Florence set in the midst of the Yellowstone Park with no suburbs or even a farm within 200 miles – that’s my idea of paradise! When a fellow wanted to he could go to the public library or the opera, when he wanted to, he could walk right out into the primeval truth of things and cuss the universe of shams – be Samuel Jonson and Daniel Boone by turns!”(26). The ensuing letters from 1916 reflect Kephart’s foothold in both the professional and natural worlds
Ordering of organic molecules on templated surfaces
No full textThis thesis describes the controlled growth of molecular nanostructures using modified metallic and semiconductor surfaces. The Ag/Si(lll)-(root3 x root3),the Sn/Cu(100) surface alloy system and the Bi/Si(100) nanolines and (2xn) surfaces were all investigated as suitable substrates for the controlled growth of pentacene, (C22H14) or trimesic acid, (C6H3(COOH)3) organic molecules. The following techniques were used in this study; Scanning Tunnelling Microscopy (STM), Low Energy Electron Diffraction (LEED), Normal Incident X-Ray Standing Waves (NIXSW) and Temperature Programmed Desorption (TPD).
The room temperature growth and ordering of trimesic acid on the AgfSi(ll1)-(root3 x root3) surface was investigated. An oblique unit cell was determined and a model proposed for the highly ordered close-packed domains.
The discovery of a new submonolayer phase on Sn/Cu(100) and the re-examined known phase are discussed. New models for these reconstructions are proposed. Adsorption of trimesic acid at room temperature on the clean substrate the lowest Sn coverage phase were studied. Two new Sn coverage dependent structures were discovered and bonding schemes in upright and flat orientations are discussed.
BifSi(100)-(2xn) surface was exploited as a template for the ordered growth of pentacene, which exhibited orientation specific adsorption. The Bi/Si(100)-(2xn) single domain surface created on vicinal silicon was used to test the suitable of Daresbury 4.2 beamline for NIXSW Imaging experiments and the quality of the results are discussed
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6-17 years: a preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial.
No full textBACKGROUND: Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults. METHODS: COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6-17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12-17 years were enrolled before those aged 6-11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12-17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344). FINDINGS: Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12-17 years and 112 [43%] aged 6-11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6-11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12-17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685-91 733] and 299 half-maximal inhibitory concentration [IC50; 95% CI 230-390]) compared with those aged 12-17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852-52 246] and 150 IC50 [95% CI 116-194]). Humoral responses were higher in those aged 6-11 years than in those aged 12-17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07-2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89-4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination. INTERPRETATION: ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6-17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial. FUNDING: AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research
Spatial patterns of HIV prevalence and Service Use in East Zimbabwe: implications for future targeting of interventions
No full textIntroduction: Focusing resources for HIV control on geographic areas of greatest need in countries with generalised epidemics has been recommended to increase cost-effectiveness. However, socio-economic inequalities between areas of high and low prevalence could raise equity concerns and have been largely overlooked. We describe spatial patterns in HIV prevalence in east Zimbabwe and test for inequalities in accessibility and uptake of HIV services prior to the introduction of spatially-targeted programmes.
Methods: 8092 participants in an open-cohort study were geo-located to 110 locations. HIV prevalence and HIV testing and counselling (HTC) uptake were mapped with ordinary kriging. Clusters of high or low HIV prevalence were detected with Kulldorff statistics, and the socio-economic characteristics and sexual risk behaviours of their populations, and levels of local HIV service availability (measured in travel distance) and uptake were compared. Kulldorff statistics were also determined for HTC, antiretroviral therapy (ART), and voluntary medical male circumcision (VMMC) uptake.
Results: One large and one small high HIV prevalence cluster (relative risk [RR]=1.78, 95% confidence interval [CI]=1.53–2.07; RR=2.50, 95% CI=2.08–3.01) and one low-prevalence cluster (RR=0.70, 95% CI=0.60–0.82) were detected. The larger high-prevalence cluster was urban with a wealthier population and more high-risk sexual behaviour than outside the cluster. Despite better access to HIV services, there was lower HTC uptake in the high-prevalence cluster (odds ratio [OR] of HTC in past 3 years: OR=0.80, 95% CI=0.66–0.97). The low-prevalence cluster was predominantly rural with a poorer population and longer travel distances to HIV services; however, uptake of HIV services was not reduced.
Conclusions: High-prevalence clusters can be identified to which HIV control resources could be targeted. To date, poorer access to HIV services in the poorer low-prevalence areas has not resulted in lower service uptake, while there is significantly lower uptake of HTC in the high-prevalence cluster where health service access is better. Given the high levels of risky sexual behaviour and lower uptake of HTC services, targeting high-prevalence clusters may be cost-effective in this setting. If spatial targeting is introduced, inequalities in HIV service uptake may be avoided through mobile service provision for lower prevalence areas
Author Correction: A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus
No full textDurability of ChAdOx1 nCov-19 vaccination in people living with HIV
No full textDuration of protection from SARS-CoV-2 infection in people with HIV (PWH) following vaccination is unclear. In a sub-study of the phase 2/3 the COV002 trial (NCT04400838), 54 HIV positive male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and MesoScale Discovery (MSD)), neutralisation, ACE-2 inhibition, gamma interferon ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that 6 months after vaccination the majority of measurable immune responses were greater than pre-vaccination baseline, but with evidence of a decline in both humoral and cell mediated immunity. There was, however, no significant difference compared to a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although were lower than wild type. Pre-existing cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater post-vaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the on-going policy to vaccinate PWH against SARS-CoV-2, and underpin the need for long-term monitoring of responses after vaccination
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Author Correction: A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus
No full textAn amendment to this paper has been published and can be accessed via a link at the top of the paper
