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"Davies, Helen"
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Rome, global dreams and the international origins of an empire
\"In Rome, Global Dreams, and the International Origins of an Empire, Sarah Davies explores how the Roman Republic evolved, in ideological terms, into an 'Empire without end.' This work stands out within Roman imperialism studies by placing a distinct emphasis on the role of international-level norms and concepts in shaping Roman imperium. Using a combination of literary, epigraphic, and numismatic evidence, Davies highlights three major factors in this process. First is the development, in the third and second centuries BCE, of a self-aware international community with a cosmopolitan vision of a single, universalizing world-system. Second is the misalignment of Rome's polity and concomitant diplomatic practices with those of its Hellenistic contemporaries. And third is contemporary historiography, which inserted Rome into a cyclical (and cosmic) rise-and-fall of great power.\" -- Provided by publisher.
Book
Management of pleural infection in adults: British Thoracic Society pleural disease guideline 2010
Historical perspective The Egyptian physician Imhotep initially described pleural infection around 3000 BC, although Hippocrates has been more famously credited with its recognition in 500 BC. [...]the 19th century open thoracic drainage was the recommended treatment for this disorder but carried an associated mortality of up to 70%. Age-adjusted incidence rates also increased in their cohort by almost 13% during the 8-year period. 3 Risk factors for pleural infection mirror those for pneumonia although independent considerations for developing empyema include diabetes mellitus, immunosuppression including corticosteroid use, gastro-oesophageal reflux, alcohol misuse and intravenous drug abuse. 2 A history of aspiration or poor oral hygiene is often elicited in anaerobic infection.
Journal Article
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
HRDetect represents a model integrating whole-genome sequencing mutation signatures associated with
BRCA1
and
BRCA2
deficiency. The implementation of this predictor across different tumor types identifies a larger proportion of patients displaying ‘BRCAness’ than previously recognized; they might derive benefit from platinum and PARP-inhibitor therapies.
Approximately 1–5% of breast cancers are attributed to inherited mutations in
BRCA1
or
BRCA2
and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in
BRCA1
and/or
BRCA2
(
BRCA1
/
BRCA2
) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect
BRCA1
/
BRCA2
-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with
BRCA1
/
BRCA2
dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of
BRCA1
/
BRCA2
deficiency. A weighted model called HRDetect was developed to accurately detect
BRCA1
/
BRCA2
-deficient samples. HRDetect identifies
BRCA1
/
BRCA2
-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline
BRCA1
or
BRCA2
mutation, allowed us to identify an additional 22 tumors with somatic loss of
BRCA1
or
BRCA2
and 47 tumors with functional
BRCA1
/
BRCA2
deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring
BRCA1
/
BRCA2
deficiency (up to 22%) than hitherto appreciated (∼1–5%) who could have selective therapeutic sensitivity to PARP inhibition.
Journal Article
Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection
Slowly clearing infections in the pleural space are a source of substantial morbidity. This study showed that instillation of recombinant DNase and tissue plasminogen activator (t-PA) is more effective than placebo in clearing radiographic pleural effusions.
Pleural infection affects more than 65,000 patients each year in the United States and the United Kingdom,
1
and the incidence is increasing in both countries — in both children
2
–
4
and adults.
5
,
6
The mortality rate from pleural infection is between 10% and 20%,
5
,
7
–
9
and drainage through a chest tube and administration of antibiotics fail in approximately one third of patients, who then require surgical drainage.
5
,
9
The median duration of the hospital stay for these patients is 12 to 15 days,
5
,
6
,
8
,
9
with 25% hospitalized for more than a month. Care of each patient costs . . .
Journal Article
General practice at the core of neighbourhoods
[...]we need population based service delivery. [...]the small business model of general practice is no longer appropriate for an integrated healthcare system. [...]one might consider GPs being employed by Integrated Care Systems (ICS).
Journal Article
Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study
Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network–Breast (SCAN-B) project (ClinicalTrials.gov ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2–0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13–0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.
Journal Article
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA—potentially capable of being translated to produce viral proteins—persist in tissue as a ‘reservoir’. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.
Proal and colleagues review the evidence for long-term persistence of coronavirus SARS-CoV-2 in tissues of infected individuals and discuss how this viral reservoir may contribute to the pathogenesis of post-acute sequelae of COVID-19 (PASC).
Journal Article
Characterisation of ovine lymphatic vessels in fresh specimens
The development and use of experimental models using lymphatic cannulation techniques have been hampered by the lack of high-quality colour imaging of lymphatic vessels in situ. Most descriptions of lymphatic anatomy in sheep have historically depended on schematic diagrams due to limitations in the ability to publish colour images of the lymphatic vessels with decent resolution. The aim of this work was to encourage more widespread use of the ovine cannulation model by providing clear photographic images identifying the location and anatomical layout of some major lymphatic ducts and their in situ relationship to surrounding tissues.
The cadavers of the sheep were collected after they had been euthanized at the end of animal trials not associated with this study. The lymphatics were dissected and exposed to show their appearance in the surrounding tissues and their relationship to other organs. Patent Blue was used to locate lymphatic vessels in exploratory preparations. However, in order to present the natural appearance of the vessels, we used minimal dissection and dye was not used for the photographed examples. Instead, we have indicated the course of the vessels with lines where their position is less clear.
In this paper, we have used sheep specimens as examples to show characteristic images of lymphatic vessels. The images of in situ lymphatics and lymph nodes combined with schematic summaries provide a concise illustration of the lymphatic drainage scheme in sheep.
Journal Article
The influence of equine limb conformation on the biomechanical responses of the hoof: An in vivo and finite element study
Hoof conformation plays a key role in equine locomotion. Toe-in conformation is an abnormal condition characterized by inward deviation of the limb from its frontal axis. Several studies have documented differences in hoof deformation and hoof kinematics in horses with toe-in and normal hoof conformations. However, the reason behind this has yet to be understood. The present study hypothesizes that a different center of pressure (COP) path underneath the hoof is the cause of different deformation patterns and hoof kinematics in toe-in hooves. In vivo measurements and finite element (FE) analysis were conducted to test the hypothesis. A normal and a toe-in limb were considered for in vivo strain measurements. Strains were measured at three different sites on the hoof wall, and the stride characteristics were investigated using video recording. The magnitude of the minimum principal strain measured at the medial aspect of the toe-in hoof was much lower relative to the normal hoof. Furthermore, the toe-in hoof had a different movement pattern (plaiting) compared to the normal hoof. In the second study, an entire hoof model was simulated from computed tomography (CT) scans of an equine left forelimb. The Neo-Hookean hyperelastic material model was used, and the hoof was under dynamic loading over a complete stride at the trot. Two different COP paths associated with normal and toe-in conformations were assigned to the model. The FE model produced the same in vivo minimum principal strain distributions and successfully showed the different kinematics of the toe-in and normal hooves.
Journal Article
Passive Dynamics of the Head, Neck and Forelimb in Equine Foetuses—An Observational Study
Passive dynamics is an aspect of locomotion which is entirely dependent on the mechanical configuration and linkages of adjacent body segments. Tension distribution along mechanical linkages enables the execution of movement patterns with reduced need for complex neurological pathways and may play a role in reestablishing postural stability following external disturbances. Here we demonstrate a uni-directional mechanical relationship between the equine forelimb, head and neck, which may have implications for balance and forelimb loading in the horse. These observations suggest that forelimb, head and neck movement coordination (observed in the horse during unrestrained locomotion) is significantly influenced by the mechanical linkages between body segments, rather than being entirely dependent on neurological input as previously thought. This highlights the potential significance of research directed at investigating passively induced movements in understanding common locomotory patterns. Additionally, it suggests a mode of postural control which may provide instantaneous adjustments to postural disturbances, thus promoting rapid and efficient locomotion.
Journal Article