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"Hudson, Benjamin"
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Conformations of peptoids in nanosheets result from the interplay of backbone energetics and intermolecular interactions
The conformations adopted by the molecular constituents of a supramolecular assembly influence its large-scale order. At the same time, the interactions made in assemblies by molecules can influence their conformations. Here we study this interplay in extended flat nanosheets made from nonnatural sequence-specific peptoid polymers. Nanosheets exist because individual polymers can be linear and untwisted, by virtue of polymer backbone elements adopting alternating rotational states whose twists oppose and cancel. Using molecular dynamics and quantum mechanical simulations, together with experimental data, we explore the design space of flat nanostructures built from peptoids. We show that several sets of peptoid backbone conformations are consistent with their being linear, but the specific combination observed in experiment is determined by a combination of backbone energetics and the interactions made within the nanosheet. Our results provide a molecular model of the peptoid nanosheet consistent with all available experimental data and show that its structure results from a combination of intraand intermolecular interactions.
Journal Article
Foreign policy analysis : classic and contemporary theory
\"Forereign Policy Analysis: Classic and Contemporary Theoryis a succinct yet comprehensive introduction to Foreign Policy Analysis (FPA) geared toward advanced undergraduate and beginning graduate students. Cogently written, clearly organized, and filled with illuminating examples, the third edition has been thoroughly revised and updated. Beginning with an overview of this broad field of study, Hudson and Day consider theory and research at multiple levels of analysis, including personality and psychology of foreign policy decision makers, small group dynamics, the organizational process, bureaucratic politics, domestic politics, cultural and societal influences, national attributes, and system-level effects on foreign policy. The authors also examine the promise and frustration of theoretical integration in FPA and review promising new work by non - North American scholars\"--Back cover.
Book
Automated calculation of the right ventricle to left ventricle ratio on CT for the risk stratification of patients with acute pulmonary embolism
Objectives
To assess the feasibility and reliability of the use of artificial intelligence post-processing to calculate the RV:LV diameter ratio on computed tomography pulmonary angiography (CTPA) and to investigate its prognostic value in patients with acute PE.
Methods
Single-centre, retrospective study of 101 consecutive patients with CTPA-proven acute PE. RV and LV volumes were segmented on 1-mm contrast-enhanced axial slices and maximal ventricular diameters were derived for RV:LV ratio using automated post-processing software (IMBIO LLC, USA) and compared to manual analysis in two observers, via intraclass coefficient correlation analysis. Each CTPA report was analysed for mention of the RV:LV ratio and compared to the automated RV:LV ratio. Thirty-day all-cause mortality post-CTPA was recorded.
Results
Automated RV:LV analysis was feasible in 87% (
n
= 88). RV:LV ratios ranged from 0.67 to 2.43, with 64% (
n
= 65) > 1.0. There was very strong agreement between manual and automated RV:LV ratios (ICC = 0.83, 0.77–0.88). The use of automated analysis led to a change in risk stratification in 45% of patients (
n
= 40). The AUC of the automated measurement for the prediction of all-cause 30-day mortality was 0.77 (95% CI: 0.62–0.99).
Conclusion
The RV:LV ratio on CTPA can be reliably measured automatically in the majority of real-world cases of acute PE, with perfect reproducibility. The routine use of this automated analysis in clinical practice would add important prognostic information in patients with acute PE.
Key Points
•
Automated calculation of the right ventricle to left ventricle ratio was feasible in the majority of patients and demonstrated perfect intraobserver variability.
•
Automated analysis would have added important prognostic information and altered risk stratification in the majority of patients.
•
The optimal cut-off value for the automated right ventricle to left ventricle ratio was 1.18, with a sensitivity of 100% and specificity of 54% for the prediction of 30-day mortality.
Journal Article
Chest X-ray in suspected lung cancer is harmful
Objectives
The aim of this study was to analyse the use of the chest radiograph (CXR) as the first-line investigation in primary care patients with suspected lung cancer.
Methods
Of 16,945 primary care referral CXRs (June 2018 to May 2019), 1,488 were referred for suspected lung cancer. CXRs were coded as follows: CX1, normal but a CT scan is recommended to exclude malignancy; CX2, alternative diagnosis; or CX3, suspicious for cancer. Kaplan-Meier survival analysis was undertaken by stratifying patients according to their CX code.
Results
In the study period, there were 101 lung cancer diagnoses via a primary care CXR pathway. Only 10% of patients with a normal CXR (CX1) underwent subsequent CT and there was a significant delay in lung cancer diagnosis in these patients (
p
< 0.001). Lung cancer was diagnosed at an advanced stage in 50% of CX1 patients, 38% of CX2 patients and 57% of CX3 patients (
p
= 0.26). There was no survival difference between CX codes (
p
= 0.42).
Conclusion
Chest radiography in the investigation of patients with suspected lung cancer may be harmful. This strategy may falsely reassure in the case of a normal CXR and prioritises resources to advanced disease.
Key Points
• Half of all lung cancer diagnoses in a 1-year period are first investigated with a chest X-ray.
• A normal chest X-ray report leads to a significant delay in the diagnosis of lung cancer.
• The majority of patients with a normal or abnormal chest X-ray have advanced disease at diagnosis and there is no difference in survival outcomes based on the chest X-ray findings.
Journal Article
The Picts
The Picts is a survey of the historical and cultural developments in northern Britain between AD 300 and AD 900. Discarding the popular view of the Picts as savages, they are revealed to have been politically successful and culturally adaptive members of the medieval European world.
* Re-interprets our definition of 'Pict' and provides a vivid depiction of their political and military organization
* Offers an up-to-date overview of Pictish life within the environment of northern Britain
* Explains how art such as the 'symbol stones' are historical records as well as evidence of creative inspiration.
* Draws on a range of transnational and comparative scholarship to place the Picts in their European context
eBook
Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis
Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis.
Journal Article
Artificial intelligence to improve the detection and risk stratification of acute pulmonary embolism (AID-PE): protocol for a pragmatic quasi-experimental comparator study
IntroductionPulmonary embolism (PE) is a potentially fatal condition requiring timely diagnosis and treatment. CT pulmonary angiography (CTPA) is the gold standard for diagnosis and indicates PE severity through radiological markers of right heart strain. However, accurate interpretation and communication of these findings is often suboptimal in real-world practice. Artificial intelligence (AI) could alleviate pressure on radiology services by supporting PE identification, risk stratification and worklist prioritisation. Before widespread adoption, AI tools must be rigorously validated for diagnostic accuracy, safety and clinical impact.Methods and analysisThis pragmatic single-centre, non-randomised quasi-experimental study will evaluate the diagnostic accuracy, feasibility, and clinical-cost impact of AI-assisted PE detection and risk stratification using AIDOC and IMBIO software. We will recruit two consecutive cohorts of adult patients undergoing CTPAs for suspected PE: a comparator cohort (12 months pre-AI implementation) and an intervention cohort (12 months post-AI implementation). AI will be applied retrospectively to the comparator cohort, while in the intervention cohort, radiologists will have contemporaneous access to the AI’s interpretation of CTPA images.A subset of retrospective scans, both PE-positive and PE-negative, will undergo expert thoracic radiologist review to establish a reference standard. Data on patient demographics, clinical management and outcomes will be collected. Clinical management pathways and patient outcomes will be compared between cohorts to assess AI’s influence on acute PE management. Health economic modelling will assess the cost-effectiveness of integrating AI technology within the diagnostic workflow of acute PE.Ethics and disseminationThis study was approved by the UK Healthcare Research authority (IRAS 311735, 10 May 2023). Ethical approval was granted by West of Scotland Research Ethics Service (23/WS/0067, 3 May 2023). Results will be shared with stakeholders, presented at national and international conferences, and published in open-access peer-reviewed journals.Trial registration numberNCT06093217.
Journal Article
Increased sediment load during a large-scale dam removal changes nearshore subtidal communities
The coastal marine ecosystem near the Elwha River was altered by a massive sediment influx-over 10 million tonnes-during the staged three-year removal of two hydropower dams. We used time series of bathymetry, substrate grain size, remotely sensed turbidity, scuba dive surveys, and towed video observations collected before and during dam removal to assess responses of the nearshore subtidal community (3 m to 17 m depth). Biological changes were primarily driven by sediment deposition and elevated suspended sediment concentrations. Macroalgae, predominantly kelp and foliose red algae, were abundant before dam removal with combined cover levels greater than 50%. Where persistent sediment deposits formed, macroalgae decreased greatly or were eliminated. In areas lacking deposition, macroalgae cover decreased inversely to suspended sediment concentration, suggesting impacts from light reduction or scour. Densities of most invertebrate and fish taxa decreased in areas with persistent sediment deposition; however, bivalve densities increased where mud deposited over sand, and flatfish and Pacific sand lance densities increased where sand deposited over gravel. In areas without sediment deposition, most invertebrate and fish taxa were unaffected by increased suspended sediment or the loss of algae cover associated with it; however, densities of tubeworms and flatfish, and primary cover of sessile invertebrates increased suggesting benefits of increased particulate matter or relaxed competition with macroalgae for space. As dam removal neared completion, we saw evidence of macroalgal recovery that likely owed to water column clearing, indicating that long-term recovery from dam removal effects may be starting. Our results are relevant to future dam removal projects in coastal areas and more generally to understanding effects of increased sedimentation on nearshore subtidal benthic communities.
Journal Article
Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis
Nucleotide hydrolysis is essential for many aspects of cellular function. In the case of 3′,5′-bisphosphorylated nucleotides, mammals possess two related 3′-nucleotidases, Golgi-resident 3′-phosphoadenosine 5′-phosphate (PAP) phosphatase (gPAPP) and Bisphosphate 3′-nucleotidase 1 (Bpnt1). gPAPP and Bpnt1 localize to distinct subcellular compartments and are members of a conserved family of metal-dependent lithium-sensitive enzymes. Although recent studies have demonstrated the importance of gPAPP for proper skeletal development in mice and humans, the role of Bpnt1 in mammals remains largely unknown. Here we report that mice deficient for Bpnt1 do not exhibit skeletal defects but instead develop severe liver pathologies, including hypoproteinemia, hepatocellular damage, and in severe cases, frank whole-body edema and death. Accompanying these phenotypes, we observed tissue-specific elevations of the substrate PAP, up to 50-fold in liver, repressed translation, and aberrant nucleolar architecture. Remarkably, the phenotypes of the Bpnt1 knockout are rescued by generating a double mutant mouse deficient for both PAP synthesis and hydrolysis, consistent with a mechanism in which PAP accumulation is toxic to tissue function independent of sulfation. Overall, our study defines a role for Bpnt1 in mammalian physiology and provides mechanistic insights into the importance of sulfur assimilation and cytoplasmic PAP hydrolysis to normal liver function.
Journal Article