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"Scott, J. C."
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Extended susceptibility testing for refractory Helicobacter pylori infection: regional testing should guide antimicrobial decision making
Background
Helicobacter pylori (H. pylori)
is a Gram-negative bacterium and common cause of gastritis. Antimicrobial treatment typically involves two agents and is prescribed empirically however therapy can be complicated by drug allergies or previous, unsuccessful regimens. Recent data from Europe suggests rising resistance to commonly used agents but contemporary data relevant to UK populations, particularly following the COVID-19 pandemic is limited. This study aimed to report susceptibility testing results in refractory cases of
H. pylori
infections to evaluate local resistance patterns, inform treatment strategies, and compare findings with data from the European Registry on
H. pylori
management.
Methods
A retrospective multi-centre cohort study was conducted between September 2018 and September 2023 at North West London Pathology (London, UK), a central laboratory operating through a hub and spoke model, to assess extended antimicrobial susceptibilities in gastric biopsy samples from patients with refractory
H. pylori
infection. Antimicrobial susceptibilities were assessed using minimum inhibitory concentration methods as per contemporaneous European Committee on Antimicrobial Susceptibility Testing guidelines. Results were compared with European data.
Results
A total of 193 individual isolates were identified. Mean resistance rates were low for tetracycline (2.3%) and amoxicillin (7.3%), moderately low for rifampicin (14.0%), moderate for levofloxacin (27.3%) and high for metronidazole (82.7%) and clarithromycin (75.5%) across the study period. Levofloxacin had a trend of increasing susceptibility (
p =
0.10) and rifampicin of increasing resistance (
p
= 0.31) throughout the study. Resistance rates were significantly higher for the non-naïve North West London cohort compared with the European non-naïve cohort for metronidazole (
p <
0.001), amoxicillin (
p <
0.01), and clarithromycin (
p
= 0.02).
Conclusion
These findings emphasize the necessity of tailored treatment approaches, informed by regional susceptibility patterns. As antimicrobial resistance continues to evolve a proactive and adaptive approach to treatment strategies remains paramount to effectively treat
H. pylori
infection and mitigate associated clinical and financial burdens.
Clinical trial
Not applicable.
Journal Article
The contribution of human conflict to the development of antimicrobial resistance
Human conflict, such as the ongoing conflict in Ukraine, is an important driver of antimicrobial resistance. Here, we describe the challenges when addressing this problem during an ongoing conflict and the opportunities available to reduce the spread of antimicrobial resistance.
Pallett et al. discuss the impact of human conflict on development of antimicrobial resistance. They overview approaches to limit the spread of antimicrobial resistance, using the ongoing conflict in Ukraine as an example of the challenges and opportunities.
Journal Article
The scientific method : a guide to finding useful knowledge
\"I found this book to be a particularly engaging and useful treatment of scientific method and practice whereby the authors' target is to improve practice. There is a lot of subversion out there that they want to avoid with a content-positive approach. The book's themes for improving scientific practice are generated from earthy checklists, all concerned to improve compliance with the substantive content of science. It results in checklists for eleven user categories, from researchers to courts. The checklists all derive from key elements of the scientific method, summarized by eight criteria. I want to apply seven of these elements to my early work in experimental economics that will help me to see how this book can help you, which is its purpose\"-- Provided by publisher.
Book
Overview of candidate device technologies for storage-class memory
Storage-class memory (SCM) combines the benefits of a solid-state memory, such as high performance and robustness, with the archival capabilities and low cost of conventional hard-disk magnetic storage. Such a device would require a solid-state nonvolatile memory technology that could be manufactured at an extremely high effective areal density using some combination of sublithographic patterning techniques, multiple bits per cell, and multiple layers of devices. We review the candidate solid-state nonvolatile memory technologies that potentially could be used to construct such an SCM. We discuss evolutionary extensions of conventional flash memory, such as SONOS (silicon-oxide-nitride-oxide-silicon) and nanotraps, as well as a number of revolutionary new memory technologies. We review the capabilities of ferroelectric, magnetic, phase-change, and resistive random-access memories, including perovskites and solid electrolytes, and finally organic and polymeric memory. The potential for practical scaling to ultrahigh effective areal density for each of these candidate technologies is then compared. [PUBLICATION ABSTRACT]
Journal Article
Risk of Mortality Following Clinical Fractures
To examine the risk of mortality following all clinical fractures, we followed 6459 women age 55-81 years participating in the Fracture Intervention Trial for an average of 3.8 years. All fractures and deaths were confirmed by medical record or death certificate. Clinical fractures were fractures that came to medical attention. Fracture status was used as a time-dependent covariate in proportional hazards models. The 907 women who experienced a fracture were older, had lower bone mineral density and were more likely to report a positive fracture history. A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture. The age-adjusted relative risk (95% confidence intervals) of dying following a clinical fracture was 2.15 (1.36, 3.42). This primarily reflected the higher mortality following a hip fracture, 6.68 (3.08, 14.52); and clinical vertebral fracture, 8.64 (4.45, 16.74). Results were similar after adjusting for treatment assignment, health status and specific common comorbidities. There was no increase in mortality following a forearm or other fracture (non-hip, non-wrist, nonvertebral fracture). In conclusion, clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women.
Journal Article
Tests of Sunspot Number Sequences: 2. Using Geomagnetic and Auroral Data
We compare four sunspot-number data sequences against geomagnetic and terrestrial auroral observations. The comparisons are made for the original Solar Influences Data Center (SIDC) composite of Wolf/Zürich/International sunspot number [
R
ISNv
1
], the group sunspot number [
R
G
] by Hoyt and Schatten (
Solar Phys
.
181
, 491,
1998
), the new “backbone” group sunspot number [
R
BB
] by Svalgaard and Schatten (
Solar Phys
.,
DOI
,
2016
), and the “corrected” sunspot number [
R
C
] by Lockwood, Owens, and Barnard (
J. Geophys. Res
.
119
, 5172,
2014a
). Each sunspot number is fitted with terrestrial observations, or parameters derived from terrestrial observations to be linearly proportional to sunspot number, over a 30-year calibration interval of 1982 – 2012. The fits are then used to compute test sequences, which extend further back in time and which are compared to
R
ISNv
1
,
R
G
,
R
BB
, and
R
C
. To study the long-term trends, comparisons are made using averages over whole solar cycles (minimum-to-minimum). The test variations are generated in four ways: i) using the
IDV
(1d) and
IDV
geomagnetic indices (for 1845 – 2013) fitted over the calibration interval using the various sunspot numbers and the phase of the solar cycle; ii) from the open solar flux (OSF) generated for 1845 – 2013 from four pairings of geomagnetic indices by Lockwood et al. (
Ann. Geophys
.
32
, 383,
2014a
) and analysed using the OSF continuity model of Solanki, Schüssler, and Fligge (
Nature
,
408
, 445,
2000
), which employs a constant fractional OSF loss rate; iii) the same OSF data analysed using the OSF continuity model of Owens and Lockwood (
J. Geophys. Res
.
117
, A04102,
2012
), in which the fractional loss rate varies with the tilt of the heliospheric current sheet and hence with the phase of the solar cycle; iv) the occurrence frequency of low-latitude aurora for 1780 – 1980 from the survey of Legrand and Simon (
Ann. Geophys
.
5
, 161,
1987
). For all cases,
R
BB
exceeds the test terrestrial series by an amount that increases as one goes back in time.
Journal Article
Evaluation of variable new antigen receptors (vNARs) as a novel cathepsin S (CTSS) targeting strategy
Aberrant activity of the cysteine protease Cathepsin S (CTSS) has been implicated across a wide range of pathologies. Notably in cancer, CTSS has been shown to promote tumour progression, primarily through facilitating invasion and migration of tumour cells and augmenting angiogenesis. Whilst an attractive therapeutic target, more efficacious CTSS inhibitors are required. Here, we investigated the potential application of Variable New Antigen Receptors (vNARs) as a novel inhibitory strategy. A panel of potential vNAR binders were identified following a phage display panning process against human recombinant proCTSS. These were subsequently expressed, purified and binding affinity confirmed by ELISA and SPR based approaches. Selected lead clones were taken forward and were shown to inhibit CTSS activity in recombinant enzyme activity assays. Further assessment demonstrated that our lead clones functioned by a novel inhibitory mechanism, by preventing the activation of proCTSS to the mature enzyme. Moreover, using an intrabody approach, we exhibited the ability to express these clones intracellularly and inhibit CTSS activity whilst lead clones were also noted to impede cell invasion in a tumour cell invasion assay. Collectively, these findings illustrate a novel mechanistic approach for inhibiting CTSS activity, with anti-CTSS vNAR clones possessing therapeutic potential in combating deleterious CTSS activity. Furthermore, this study exemplifies the potential of vNARs in targeting intracellular proteins, opening a range of previously “undruggable” targets for biologic-based therapy.
Journal Article