cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
The role of CKS proteins in cancer development
Creators: name: Luft, Christin
Publisher: name: Imperial College London
Year: 2013

description: The mammalian CKS family consists of two highly conserved proteins, CKS1 and CKS2. Both are able to bind to cyclin dependent kinases 1 and 2 (CDK1 and CDK2) with high affinity and were suggested to modulate CDK activity and thus cell cycle control. CKS proteins have also been reported to facilitate the ubiquitination of cyclin A by the anaphase promoting complex (APC). Additionally CKS1 has been shown to have an important role in the recognition of the cyclin dependent kinase inhibitor p27Kip1 by the SCFSkp2 (Skp1-Cul1-F-box-protein) ubiquitin ligase. Elevated expression of both CKS proteins is often found in a variety of tumours and is correlated with poor prognosis. This might indicate an involvement of CKS proteins in the process of transformation from normal to cancer cells. Previously it was shown that down-regulation of CKS proteins in cancer derived cell lines results in a loss of their high proliferative capacity. I surmise, that a possible oncogenic effect of CKS proteins might be due to the deregulation of replication. To study the role of CKS proteins as oncogenes, different stages of cancer development were modelled in the human diploid fibroblast cell line, IMR90. Over-expression of CKS proteins was combined with defined genetic events known to be associated with transformation such as activation of telomerase (hTERT) and blockage of the p53 and RB pathways. Over-expression of CKS variants in IMR90 cells led to checkpoint activation and growth arrest reminiscent of oncogenic stress. Down-regulation of the checkpoint proteins p53 and RB however could alleviate the growth arrest and led to a slight growth advantage of the CKS over-expressing fibroblasts. Analyses to understand the molecular mechanisms behind the checkpoint activation in primary IMR90 were performed addressing, in particular, the involvement of an altered CDK activity.
Temporal expression of neurochemical markers in primary sensory neurones in traumatic and non-traumatic models of neuropathic pain
Creators: name: Boateng, Edward
Publisher: name: Imperial College London
Year: 2013

description: Introduction: Expression of neurochemical markers in dorsal root ganglion (DRG) has been shown to underlie nerve injury induced neuropathic pain and are usually examined once post injury in rodent models. Here I hypothesize that neurochemical markers are expressed differentially at various time points post nerve injury and that expression of these markers differ between traumatic and non-traumatic models of neuropathic pain, thus reflecting variations in pathophysiology. In two different rat models of neuropathic pain, namely, the tibial nerve transection (TNT) and the d4T (HIV antiretroviral drug) associated toxic neuropathy; immunohistochemical labelling was used to determine the expression of various neurochemical markers across time. Double labelling with peripherin or NF-200 (labels small and large neurons respectively) and a cell size analysis were conducted to validate cellular phenotype. Pain behaviour was measured in vivo using mechanical and thermal hypersensitivity assays. To confirm tibial nerve distribution in the DRGs, Fluorogold retrograde labelling was performed. I also explored the effect of the omega-3 polyunsaturated fatty acid dicosahexonoic acid (DHA) on TNT associated mechanical hypersensitivity and inflammation, as previous studies have shown DHA to be both anti-inflammatory and neuroprotective in animal models of spinal cord injury and stroke, and therefore could be relevant in peripheral nerve injury. Results: [Table of results appears here. To view, please open pdf attachment] From day 7, TNT rats developed mechanical hypersensitivity (↓62% from baseline at peak, day 28). Rats injected with d4T exhibited bilateral hind paw mechanical hypersensitivity (↓~47% from baseline at peak, day 22), but failed to exhibit any neurochemical changes in the DRG such as that observed in TNT injury. Seven days following Fluorogold injection into the tibial nerve of naive rats, labelling was identified in the L4 (38.5%) and L5 (27.5%) DRGs. Since DHA did not alter TNT induced mechanical hypersensitivity, key neurochemical markers were not evaluated. Investigations examined the potential of DHA to modulate the DRG macrophage response, and revealed no differences compared to saline controls at day 28 post TNT injury. Conclusion: The results of the study demonstrate completely different expression patterns of neurochemical markers following TNT injury and treatment with d4T, and highlight the mechanistic difference between nerve trauma and antiretroviral associated neuropathic pain.
SIA 2051 Building Information Modelling – Grundlagen zur Anwendung der BIM-Methode
Creators: name: Huber, Manfred
Publisher: name: Institut für Schweizerisches und Internationales Baurecht
Year: 2018
Subjects: BIM
SIA
Normierung

description: Der Schweizerische Ingenieur- und Architektenverein SIA veröffentlichte Ende 2017 das Merkblatt SIA 2051. SIA Merkblätter sind Bestandteil des SIA-Normenwerkes und haben den Charakter von Verständigungsnormen. Ergänzt wird die SIA 2051 durch eine Reihe von SIA-Dokumentationen (SIA D 0270 ff), welche in der Form von Leitfäden die Anwendung der BIM-Methode erläutern.
Investigating the role and regulation of the AMPK-related kinase NUAK1
Creators: name: Bull, Duncan
Publisher: name: Imperial College London
Year: 2013

description: AMP-activated protein kinase (AMPK) is a well characterised central regulator of energy homeostasis with many downstream substrates and potential therapeutic targets. Recently several kinases related to AMPK have been identified which are activated by the same upstream kinase, LKB1, and share significant sequence homology with the catalytic α subunit of AMPK. Previous studies have implicated NUAK1, one of these related kinases, in cell cycle regulation and other studies have identified various partner proteins but as yet there is no consensus model of its regulation or physiological role. This aim of this study was to investigate the regulation and interactions of NUAK1 using an in vitro system and also use an in vivo tissue specific mouse knockout system to investigate its function in two different tissues. The results of these studies reveal new insights into the regulation of NUAK1 in vitro and suggest that the kinase is capable of activation by autophosphorylation, in the absence of LKB1. NUAK1 is shown to interact with 14-3-3 proteins and evidence that this interaction may be important for the function of the kinase is presented. Cell based studies in mouse embryonic fibroblasts (MEFs) lacking NUAK1 show that it is involved in proliferation and there are suggestions of pathways involved in regulating this effect. NUAK1 liver-specific knockout mice were generated and extensive metabolic phenotyping analyses were carried out. In young animals deletion of NUAK1 in liver did not lead to any obvious changes in whole body metabolism. However, preliminary studies revealed a possible role for NUAK1 in metabolic regulation in older mice and in response to liver damage. Mice with heart-specific deletion of NUAK1 were generated and these mice were found to have a cardiac hypertrophy phenotype in response to angiotensin II treatment. Potential signalling pathways downstream of NUAK1 in the heart were then investigated in this model.
title: Aufnahmegrund Makrohämaturie bei „geriatrischen“ Patienten in der Urologie: „Lohnt“ eine Abklärung und welche Rolle spielen Blutverdünner, Infekt und Katheter?
Creators: name: Wiedemann, A.
name: Küper, L.
name: Heppner, H.-J.
Publisher: name: German Medical Science GMS Publishing House
Year: 2020
Subjects: subject: 610 Medical sciences; Medicine

description: Hintergrund: Häufig werden in der Urologie hochbetagte Patienten mit einer Makrohämaturie aufgenommen. Unklar ist die Rolle eines einliegende suprapubischen oder transurethralen Katheters, einer Harnwegsinfektion und die Einnahme von gerinnungsaktiven Medikamenten. Methodik: 162 stationäre[zum vollständigen Text gelangen Sie über die oben angegebene URL]
description: 46. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie
SPECT imaging and Automatic Classification Methods in Movement Disorders
Creators: name: Towey, David John
Publisher: name: Imperial College London
Year: 2013

description: This work investigates neuroimaging as applied to movement disorders by the use of radionuclide imaging techniques. There are two focuses in this work: 1) The optimisation of the SPECT imaging process including acquisition and image reconstruction. 2) The development and optimisation of automated analysis techniques The first part has included practical measurements of camera performance using a range of phantoms. Filtered back projection and iterative methods of image reconstruction were compared and optimised. Compensation methods for attenuation and scatter are assessed. Iterative methods are shown to improve image quality over filtered back projection for a range of image quality indexes. Quantitative improvements are shown when attenuation and scatter compensation techniques are applied, but at the expense of increased noise. The clinical acquisition and processing procedures were adjusted accordingly. A large database of clinical studies was used to compare commercially available DaTSCAN quantification software programs. A novel automatic analysis technique was then developed by combining Principal Component Analysis (PCA) and machine learning techniques (including Support Vector Machines, and Naive Bayes). The accuracy of the various classification methods under different conditions is investigated and discussed. The thesis concludes that the described method can allow automatic classification of clinical images with equal or greater accuracy to that of commercially available systems.
Robust estimators for additive models using backfitting
Creators: name: Boente, Graciela
name: Martínez, Alejandra
name: Salibián-Barrera, Matías
Publisher: name: Taylor & Francis
Year: 2017
Subjects: subject: Medicine
subject: Molecular Biology
subject: Neuroscience
subject: Physiology
subject: FOS: Biological sciences
subject: Evolutionary Biology
subject: Ecology
subject: Sociology
subject: FOS: Sociology
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: Computational Biology

description: Additive models provide an attractive setup to estimate regression functions in a nonparametric context. They provide a flexible and interpretable model, where each regression function depends only on a single explanatory variable and can be estimated at an optimal univariate rate. Most estimation procedures for these models are highly sensitive to the presence of even a small proportion of outliers in the data. In this paper, we show that a relatively simple robust version of the backfitting algorithm (consisting of using robust local polynomial smoothers) corresponds to the solution of a well-defined optimisation problem. This formulation allows us to find mild conditions to show Fisher consistency and to study the convergence of the algorithm. Our numerical experiments show that the resulting estimators have good robustness and efficiency properties. We illustrate the use of these estimators on a real data set where the robust fit reveals the presence of influential outliers.
Exploring the potential role of CRTH2 agonists in the prevention of inflammation induced preterm labour
Creators: name: Sykes, Lynne
Publisher: name: Imperial College London
Year: 2013

description: Introduction: Preterm labour occurs in 76,000 women in England and Wales each year and accounts for 75% of neonatal mortality. Infection and inflammation are key triggers of preterm labour. The transcription factor NF-ĸB plays a key regulatory role in the expression of the labour associated genes such as COX-2, prostaglandins and MMPs, as well as pro-inflammatory cytokines such as IL-8, IL-1β, IFN-γ and TNF-α. The anti-inflammatory prostaglandin 15-deoxyΔ-12,14 Prostaglandin J2, a CRTH2 agonist can inhibit NF-ĸB and delay preterm labour in a murine model of inflammation induced preterm labour. It is well recognised that the immunology of pregnancy is biased towards a Th2 rather than Th1 response. CRTH2 agonists induce the production of the anti-inflammatory cytokines IL-4 and IL-10 in T-helper 2 cells in vitro, thus have potential to further alter the Th1:Th2 ratio in favour of the Th2 bias. Aims: This thesis examines the role of the CRTH2 receptor and its agonists in pregnancy and parturition, and its potential as a therapeutic target for the prevention of preterm labour. Methods: PCR, western analysis and flow cytometry were used for CRTH2 expression studies. To examine the effect of CRTH2 agonists on NF-ĸB activation, western analysis of p65 and phospho-p65 was performed. The effect of the agonists on interleukin profiles was demonstrated by flow cytometry. Myometrial contractility response to agonists was measured using a myograph. To determine the in vivo effect of a small molecule CRTH2 agonist on inflammation induced preterm labour, CD1 mice were given an intrauterine injection of LPS and the CRTH2 agonist. Delivery outcome and the effect on labour associated genes and interleukins were determined by PCR, western analysis and ELISA. Results: Amniocytes and myocytes show low CRTH2 mRNA levels however do not express the protein at detectable levels. The small molecule CRTH2 agonist Pyl A does not inhibit NF-ĸB in amniocytes and myocytes, indicating that the inhibition of NF-ĸB by 15dPGJ2 is independent of CRTH2. Although 15dPGJ2 was able to inhibit the production of pro-inflammatory cytokines in peripheral blood mononuclear cells, Pyl A was unable to alter the Th2 cytokine profile. Pyl A inhibits myometrial contractility, although in a mechanism independent of CRTH2. In the murine model of inflammation induced preterm labour fetal viability was significantly increased by Pyl A, however, preterm labour was augmented rather than prevented. Conclusion: 15dPGJ2 inhibits NF-ĸB and inflammation induced preterm labour in the mouse in a mechanism independent of CRTH2. Contrary to anticipated, Pyl A does not modulate the Th1:Th2 bias or delay preterm labour in vivo. However, 15dPGJ2 suppresses the Th1 response in vitro, thus represents a potential anti-inflammatory therapeutic target for both the prevention of preterm labour and inflammation induced brain injury.
Additional file 4: of Combination of lymphovascular invasion and the AJCC TNM staging system improves prediction of prognosis in N0 stage gastric cancer: results from a high-volume institution
Creators: name: Lu, Jun
name: Dai, Yun
name: Xie, Jian-Wei
name: Wang, Jia-Bin
name: Lin, Jian-Xian
name: Chen, Qi-Yue
name: Cao, Long-Long
name: Lin, Mi
name: Tu, Ru-Hong
name: Zheng, Chao-Hui
name: Li, Ping
name: Huang, Chang-Ming
Publisher: name: figshare
Year: 2019
Subjects: subject: Space Science
subject: Medicine
subject: Molecular Biology
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Mathematical Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: Figure S1. Comparison of the 8th edition of the TNM classification alone and the 8th edition of the TNM classification combined with LVI. LVI: lymphovascular invasion, LVIâ /+: negative/positive LVI. (DOCX 83 kb)
Use of high-throughput sequencing technologies to study the genetic basis of monogenic and complex diseases
Creators: name: Thomas, Ellen Rachel Amy
Publisher: name: Imperial College London
Year: 2013

description: The study of Mendelian and complex diseases has accelerated rapidly over the last decade, due to developments in knowledge and understanding of the human genome, and the application of high-throughput technologies to a wide range of questions. In this project, the common treatable Mendelian disease familial hypercholesterolaemia (FH) and the polygenic autoimmune disease systemic lupus erythematosus (SLE) were studied by targeted resequencing of small genomic regions and larger exome sequencing experiments. The targeted resequencing protocols were developed in the course of the project against a background of rapid technological advances in the commercial and academic sectors in this field. In FH, known and novel genes were studied in patient cohorts from two lipid clinics, and families with no identifiable mutation were followed up using linkage analysis and exome sequencing. Functional data were also generated to establish a novel variant in APOB as the likely cause of hypercholesterolaemia in one such family. The relationship between polymorphisms in SLCO1B1 and adverse reactions to statin drugs used to treat FH was also investigated, and the application of novel protocols in diagnostic testing and screening was also considered. In SLE, targeted resequencing was applied to the ITGAM gene which encodes a component of complement receptor 3 (CR3); ITGAM had previously been associated with the disease in multiple genome-wide association studies. Two rare variants were detected in a patient with SLE, and these have been found to have an effect on the phagocytic capability of CR3, which is likely to have contributed to these patients’ disease process. This project has compared the strengths and limitations of experiments employing high-throughput sequencing protocols in Mendelian and complex disease, and has contributed to protocol development as well as increasing understanding of the genetic basis of FH and SLE.
The use of soluble and surface TREM-1 as markers of Ventilator-associated pneumonia in Intensive Care
Creators: name: Grover, Vimal
Publisher: name: Imperial College London
Year: 2013

description: Ventilator-associated pneumonia (VAP) is the commonest nosocomial infection in Intensive Care and is associated with significant morbidity and mortality. Biomarkers offer the potential to speed up diagnosis and differentiate pulmonary from nonpulmonary infection. We postulated that measurement of cell surface receptors in addition to soluble proteins, in dual sites (blood and BAL) and calculation of an index ratio of BAL / blood would increase the discriminative utility and differentiate pulmonary from non-pulmonary infection. Our body of work included paired blood and BALF obtained from 91 patients in a pilot study: 27 with VAP, 15 ventilated patients with non-pulmonary sepsis, 18 ventilated patients with no evidence of infection and 31 non-ventilated non-infected patients. In each sample, the monocytic and neutrophilic surface proteins TREM-1, CD11b and CD62L were assessed using flow cytometry. Soluble proteins (IL-1β, IL- 6, IL-8) were assayed using ELISA in addition to Procalcitonin, CRP and white cell count. The levels of soluble TREM-1, IL-1β and IL-8 were significantly raised in the BAL of patients with VAP. BAL monocytic surface TREM-1 was also significantly higher in VAP. The BAL / blood ratio increased the discrimination of patients with VAP from non-VAP. Furthermore, the BAL / blood ratio of patients differentiated VAP from non-pulmonary infection. Monocytic and neutrophilic TREM-1 were assessed during the development and resolution phases of VAP. Monocytic surface TREM-1 and its BAL / blood ratio accurately mirrored the changes with infection, indicating them to be putative biomarkers of infection. Finally, we constructed and validated a biomarker panel to discriminate patients with VAP from non-VAP. The panel comprised the BAL / blood ratios of monocytic TREM-1 and CD11b, the BAL levels of soluble TREM-1, IL-8 and IL-1β together with the blood levels of IL-6 and CRP. It had high utility in identifying patients with VAP.
The use of geodetic and geophysical observations and modelling to interpret ground deformation at the Okataina Volcanic Centre, North Island, New Zealand
Creators: name: LUCAS DANIEL HOLDEN
Publisher: name: Monash University
Year: 2017
Subjects: subject: 49999 Earth Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: Geology
subject: Geophysics

description: The Okataina Volcanic Centre (OVC) is one of two large active rhyolite centres located in the Taupo Rift in New Zealand. Limited geodetic studies do not provide a clear understanding of the deformation patterns preceding renewed volcanic activity at the OVC. This knowledge is essential to ensure that geodetic signals from volcanic processes at the OVC are correctly identified and distinguished from non-volcanic signals. This study uses geodetic and geophysical modelling techniques to investigate this problem. The results have important implications for how any future observed ground deformation at the OVC is observed and interpreted.
Ketamine - Molecule of the Month April 2003[Archived version]
Creators: name: Aldridge, Tim
Publisher: name: figshare
Year: 2017
Subjects: subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences

description: This is the Molecule of the Month entry for April 2003 about ketamine. It is a pdf archive version of the HTML webpage.
Additional file 1: of Low-dose aspirin in the prevention of pre-eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial
Creators: name: Lin, Li
name: Zhu, Yuchun
name: Li, Boya
name: Yang, Huixia
Publisher: name: figshare
Year: 2018
Subjects: Medicine
Cell Biology
Pharmacology
Mathematical Sciences not elsewhere classified
Developmental Biology
Cancer

description: SPIRIT 2013 checklist: Low-dose aspirin in the prevention of pre-eclampsia in China (APPEC study): protocol for a multicentre randomized controlled trial. (DOCX 52 kb)
MicroRNA implications in chemotherapy-induced cardiac toxicity
Creators: name: Roca-Alonso, Laura
Publisher: name: Imperial College London
Year: 2014

description: The use of anthracyclines such as doxorubicin (DOX) has improved mortality and morbidity in cancer patients, yet associated risks of cardiomyopathy have limited their clinical application. DOX-associated cardiotoxicity typically progresses to heart failure (HF). The knowledge of the mechanisms underlying DOX-related cardiac dysfunction is currently limited, hampering the development of cardioprotective strategies. MicroRNAs (miRNAs) are gene expression regulators that play potent roles in both cardiovascular disease and cancer. We wished to investigate DOX-induced changes in cardiac miRNA expression and the potential alteration of cellular processes downstream. Myocardial miRNA profiling was performed after DOX injury, either via acute administration to cardiomyocytes in vitro or chronic exposure in vivo, and compared to miRNA profiles from infarcted hearts. We identified an overlapping down-regulation of several members of the miR-30 family. Subsequent experimental validation of a bioinformatically predicted subset of target genes allowed us to confirm four novel miR-30 targets: β1- and β2-adrenoceptors (β1AR, β2AR), Gi alpha 2 (Giα-2) and the pro-apoptotic gene BNIP3L, all of which are essential in cardiomyocytes. The implications of the β-adrenergic pathway in HF are extensively described. Importantly, we show a preferential βAR inhibition by miR-30, having a β-blocker like effect. Additionally, we demonstrate that high miR-30 levels are protective against DOX insults and correlate with lower reactive oxygen species generation in cardiac cultures. Upstream of these mechanisms, we describe the transcription factor GATA-6 to be involved in mediating DOX-induced miR-30 down-regulation. Finally, when assessing the implications of miR-30 in breast cancer, we observed an inverse correlation between miR-30 expression levels and breast cancer cell migration in vitro. Moreover, bioinformatic analyses revealed reduced miR-30 levels in breast cancer patients. Taken together, our findings encourage a potential translational use for miR-30 as an early biomarker as well as a therapeutic strategy, combining a cardioprotective action with pleiotropic anti-cancer effects.
title: Besonderheiten bei geriatrischen Patienten mit Verdacht auf symptomatischen Harnwegsinfekt
Creators: name: Manseck, S.
name: Otto, W.
name: Schnabel, M. J.
name: Denzinger, S.
name: Burger, M.
name: Spachmann, P. J.
Publisher: name: German Medical Science GMS Publishing House
Year: 2020
Subjects: subject: 610 Medical sciences; Medicine

description: Einleitung: Geriatrische Patienten mit symptomatischen Harnwegsbeschwerden sind aufgrund des demographischen Wandels, der steigenden Lebenserwartung und der zunehmenden Komorbiditäten ein überproportional wachsender Teil des urologischen Patientenkollektivs. Material und Methoden: Anhand[zum vollständigen Text gelangen Sie über die oben angegebene URL]
description: 46. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie
Measuring the quality and safety of hospital care using specialty-specific indicators based on routinely collected administrative data: a feasibility study
Creators: name: Palmer, William
Publisher: name: Imperial College London
Year: 2014

description: Using administrative data to measure the quality and safety of hospital care offers many opportunities. However, progress has been limited to few countries and predominantly to a small subset of broad measures, such as Hospital Standardised Mortality Rates. In this thesis, I investigate the potential advantages and feasibility – in terms of validity and applicability – of specialty-specific indicators. In the first part of my PhD work, I examine the case for specialty-specific indicators. I also present potential applications which overcome some of the existing shortcomings of previous uses of indicators based on administrative data. In the next stage of the project I focus on assessing feasibility by focusing on two specialties – stroke and obstetric care – conducting systematic reviews and consulting with experts to develop two indicator sets. As part of this, I identified the shortcomings in current use of indicators in these specialties. To investigate the limitations of these indicators, I applied the indicator definitions to English hospital administrative data (Hospital Episode Statistics, HES) and evaluated whether they can be used to discriminate between hospitals based on their performance and, importantly, to understand the effect of differences in coding practice. The final aspect of the research was to investigate alternative applications for the indicators which can overcome some of the shortcomings highlighted in both the prior analyses and existing literature. In doing so, I raise serious, robust shortcomings on the quality and safety of weekend care.
Evaluation of a National Cardiovascular Risk Assessment Programme (NHS Health Check)
Creators: name: Artac, Macide
Publisher: name: Imperial College London
Year: 2013

description: Background: The NHS Health Check, the largest systematic cardiovascular disease (CVD) primary prevention programme globally, aims to reduce CVD burden and health inequalities by assessing and managing CVD risk among 40 to 74 year old individuals without existing vascular diseases. I evaluated the impact of the programme at local and national levels. Methods: Using electronic medical record data from general practices in Hammersmith and Fulham, I assessed CVD risk factor recording before the programme, the programme uptake in the first two years and the impact of the programme on CVD risk. National coverage of the programme in one financial year was assessed using data from Primary Care Trusts (PCTs). Results: There was good recording of smoking status (86.1%) and blood pressure (82.5%), with lower BMI (59.5%) and cholesterol (47.5%) recording among Health Check eligible patients before the programme in Hammersmith and Fulham. Uptake of the Health Check was lower than the national target (75%) at 39.2% among patients with an estimated high CVD risk, but matched the national required rate at 20.0% among all remaining eligible patients. There was significant reduction in mean global CVD risk score (28.2% to 26.2%) after one year among patients with estimated high risk that had a complete Health Check. The programme uptake was higher in patients living in more deprived areas among those not at estimated high risk (adjusted odds ratio = 0.88 (0.73-106)). Mean national coverage of the programme was lower (8.1%) than anticipated (18%), with large PCT-level variation (0% to 29.8%). Coverage was significantly greater in PCTs in more deprived areas (coefficient = -0.51 (-1.88-0.00), p-value: 0.035). Conclusions: Population-wide impact of the NHS Health Check may be limited by poor uptake of the programme. This and other limitations to the programme suggest that a targeted screening approach along with population-wide strategies may be a better option for more cost-effective prevention of CVD.
Patients’ online descriptions of their experiences as a measure of healthcare quality
Creators: name: Greaves, Felix Edward Clovis
Publisher: name: Imperial College London
Year: 2013

description: Introduction Patients are describing their healthcare experiences online using rating websites. There has been substantial professional opposition to this, but the government in England has promoted the idea as a mechanism to improve healthcare quality. Little is known about the content and effect of healthcare rating and review sites. This thesis aims to look at comments left online and assess whether they might be a useful measure of healthcare quality. Method I used a variety of different approaches to examine patients’ comments and ratings about care online. I performed an examination of the comments left on the NHS Choices website, and analysed whether there was a relationship between the comments and traditional patient surveys or other measures of clinical quality. I used discrete choice experiments to look at the value patients place on online care reviews when making decisions about which hospital to go to. I used natural language processing techniques to explore the comments left in free text reviews. I analysed the tweets sent to NHS hospitals in England over a year to see if they contained useful information for understanding care quality. Results The analysis of ratings on NHS Choices demonstrates that reviews left online are largely positive. There are associations between online ratings and both traditional survey methods of patient experience and outcome measures. There is evidence of a selection bias in those who both read and contribute ratings online – with younger age groups and those with higher educational attainment more likely to use them. Discrete choice experiments suggest that people will use online ratings in their decisions about where to seek care, and the effect is similar to that of a recommendation by friends and family. I found that sentiment analysis techniques can be used classify free text comments left online into meaningful information that relates to data in the national patient surveys. However, the analysis of comments on Twitter found that only 11% of tweets were related to care quality. Conclusions Patients rating their care online may have a useful role as a measure of care quality. It has some drawbacks, not least the non-random group of people who leave their comments. However, it provides information that is complementary to current approaches to measuring quality and patient experiences, may be used by patients in their decision-making, and provides timely information for quality improvement. I hypothesise that it is possible to measure a ‘cloud of patient experience’ from all of the sources where patients describe their care online, including social media, and use this to make inferences about care quality. I find this idea has potential, but there are many technical and practical limitations that need to be overcome before it is useful.
EXPLORING THE USE OF PARTICIPATORY PRACTICES IN GREEK MUSEUM EDUCATION THROUGH THE PRISM OF IDENTITY
Creators: name: Giampili, Ioanna Danai
Publisher: name: Apollo - University of Cambridge Repository
Year: 2019
Subjects: education
museums
identity
local identity
community
participation
museum education

description: [Restricted]
description: The Vergottis Foundation though Cambridge European Trusts The School of Humanities and Social Sciences
Mass transfer analysis and kinetic modeling for process design of countercurrent membrane supported reactive extraction of carboxylic acids
Creators: name: Schuur, Boelo
name: Gössi, Angelo
name: Riedl, Wolfgang
Publisher: name: Elsevier
Year: 2021
Subjects: subject: Reactive extraction
subject: Product recovery
subject: Carboxylic acid
subject: Membrane extraction
subject: 500 - Naturwissenschaften

description: Countercurrent membrane supported reactive extraction (MSRE) was studied for removal of carboxylic acids from aqueous streams with a PTFE capillary membrane. Analysis of the mass transfer rates was per- formed to support modeling of the process. Total mass transfer coefficients ranging from 2.0 10-7 to 4.0 10-7 m/s were obtained when extracting lactic acid with 20 wt% tri-N-octyl amine in 1-decanol with membrane thicknesses of 260 mm and 80 mm. The limiting mass transfer resistance in all experiments was in the membrane phase. The developed model based on mass transfer and reaction in parallel allows to predict countercurrent extraction. Experimental validation with 5, 7 and 12 m long membrane modules showed excellent accordance for two acids, validating the model simulations. Simulated membrane con- tactor lengths required for single, two and three countercurrent stages varied between 10 and 39 m/stage for lactic, mandelic, succinic, itaconic and citric acid, depending on acid, membrane, and diluent.
Review and Hypothesis: A Potential Common Link Between Glial Cells, Calcium Changes, Modulation of Synaptic Transmission, Spreading Depression, Migraine, and Epilepsy—H+
Creators: name: Malchow, Robert Paul
name: Tchernookova, Boriana
name: Choi, Ji-in Vivien
name: Smith, Peter JS
name: Kramer, Richard H
name: Kreitzer, Matthew A
Publisher: name: University of Illinois at Chicago
Year: 2022
Subjects: Uncategorized

description: There is significant evidence to support the notion that glial cells can modulate the strength of synaptic connections between nerve cells, and it has further been suggested that alterations in intracellular calcium are likely to play a key role in this process. However, the molecular mechanism(s) by which glial cells modulate neuronal signaling remains contentiously debated. Recent experiments have suggested that alterations in extracellular H+ efflux initiated by extracellular ATP may play a key role in the modulation of synaptic strength by radial glial cells in the retina and astrocytes throughout the brain. ATP-elicited alterations in H+ flux from radial glial cells were first detected from Müller cells enzymatically dissociated from the retina of tiger salamander using self-referencing H+-selective microelectrodes. The ATP-elicited alteration in H+ efflux was further found to be highly evolutionarily conserved, extending to Müller cells isolated from species as diverse as lamprey, skate, rat, mouse, monkey and human. More recently, self-referencing H+-selective electrodes have been used to detect ATP-elicited alterations in H+ efflux around individual mammalian astrocytes from the cortex and hippocampus. Tied to increases in intracellular calcium, these ATP-induced extracellular acidifications are well-positioned to be key mediators of synaptic modulation. In this article, we examine the evidence supporting H+ as a key modulator of neurotransmission, review data showing that extracellular ATP elicits an increase in H+ efflux from glial cells, and describe the potential signal transduction pathways involved in glial cell-mediated H+ efflux. We then examine the potential role that extracellular H+ released by glia might play in regulating synaptic transmission within the vertebrate retina, and then expand the focus to discuss potential roles in spreading depression, migraine, epilepsy, and alterations in brain rhythms, and suggest that alterations in extracellular H+ may be a unifying feature linking these disparate phenomena.
BOSH MIYA KATTA YARIM SHARLARINING FUNKSIONAL ASSIMETRIYASINI TASHXIS QO'YISHDA  AHAMIYATI
Creators: name: Umarov, Faxriddin
name: Toʻxtarov, Baxrom
name: Xoliqov, Dilbek
Publisher: name: Zenodo
Year: 2024

description: Bosh miya o'ng va chap katta yarimsharlardan iborat. Bu yarim sharlarning har birida tashqi kulrang modda, bosh miya po‘stlog‘i, uning ostida esa ichki oq modda qavati bor.Yarimsharlar oldingi komissiya, orqa komissura kabi kichikroq komissuralar  va forniks (gumbaz) yordamida ham bog'lanadi va bu komissuralar mahalliy funktsiyalarni koordinatsiya qilish uchun ikkala yarimshardagi axborotlar almashinuvini ta'minlaydi.
Distinct functional roles of microRNA-23b and microRNA-26a in breast cancer pathogenesis
Creators: name: Pellegrino, Loredana
Publisher: name: Imperial College London
Year: 2013

description: Tumour formation and metastasis are distinct processes that arise from cumulative alterations of genomic and epigenetic regulation. Uncontrolled modulation of cell cycle-related genes is crucial to tumour growth and additional genetic modifications provide cancer cells with motile and invasive phenotypes, leading to metastatic dissemination. The cytoskeleton constitutes the structural support to cell motility, invasion and adhesion. Among the best-characterised cytoskeletal modulators are the p21-activated kinases (PAKs). In breast cancer (BC), the HER2 pathway controls the cytoskeletal dynamics and cell motility via PAK activation, through distinct downstream signaling mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that modulate gene expression post-transcriptionally. MiRNAs dysregulation can contribute to tumorigenicity, cell motility and metastasis by affecting relevant signaling pathways. We identified PAK2 as target of both miR-23b and miR-26a, implicating a direct role for these miRNAs in cytoskeletal remodeling. Experimentally, expression of miR-23b and miR-26a in BC cells promotes focal adhesions and cell spreading on substrates, but miR-23b alone controls cell-cell junctions and lamellipodia formation. Despite sharing the same target, the two miRNAs show additional distinct functions. MiR-26a overexpression in BC leads to formation of aneuploid cells associated with higher tumorigenicity. On the other hand, miR-23b inhibition enhances BC cell migration, invasion and metastasis in vivo. Clinically, low miR-23b levels correlate with metastatic development in BC patients. Mechanistically, growth factor-mediated signal transductions activate the transcription factor AP-1 and we show that this transcriptionally reduces miR-23b expression thus releasing PAK2 from its translational inhibition. The distinct cellular phenotypes described by the two miRNAs indicate that their global functions depend upon all the genes they regulate. Using RNA-sequencing and luciferase reporter assays, we validated a subset of genes as direct targets of either the two miRNAs. These genes are crucial to distinct molecular pathways and contribute to elucidate the observed phenotypes induced by miR-23b and miR-26a modulation.
Literature Review
Creators: name: Trivedi-Bateman, Neema
Publisher: name: OSF Registries
Year: 2022
Subjects: Situational Action Theory
antisocial behaviour
crime
delinquency
empathy
guilt
intervention programme
morality
psychological strategies
randomised controlled trial RCT
shame
youth development

description: A literature review of empathy, emotion, and morality interventions has been carried out (150+ studies) to identify what has and has not been effective in achieving positive behavioural outcomes.
Additional file 3: of A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveals that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes
Creators: name: Youn, Ahrim
name: In Kim, Kyung
name: Rabadan, Raul
name: Tycko, Benjamin
name: Shen, Yufeng
name: Wang, Shuang
Publisher: name: figshare
Year: 2018
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Environmental Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer

description: Text S1. Details with some modified steps for identifying EDGs.; Results of MDGs in LGG; Results from stratified analysis in all other cancers other than LGG. (DOCX 68 kb)
Normas para teses e dissertações
Creators: name: Menezes, Isabel Bueno Santos
name: Andréia Cristina Feitosa Do Carmo
Publisher: name: figshare
Year: 2017
Subjects: subject: 80706 Librarianship
subject: FOS: Media and communications
subject: Library and Information Studies
subject: 80799 Library and Information Studies not elsewhere classified

description: The primary purpose of a thesis or dissertation is to train the student in the processes of scholarly research and writing under the direction of members of the Graduate Faculty. After the student has graduated and the work is published, it serves as a contribution to human knowledge, useful to other scholars and perhaps even to a more general audience.Therefore, the University Library, and the Universidade Federal de São Paulo have established format standards that theses and dissertations must meet before receiving final approval as fulfillment of graduate requirements. This publication sets forth those standards. Some of these requirements are purely technical; others have been established to ensure that certain vital information is presented in an orderly, uniform manner.
The impact and cost of ivermectin control strategies against River Blindness in Africa
Creators: name: Turner, Hugo
Publisher: name: Imperial College London
Year: 2013

description: River Blindness (onchocerciasis) has been identified by the World Health Organization as potentially eliminable. Until recently, the African Programme for Onchocerciasis Control focused on annual distribution of ivermectin to reduce morbidity, but encouraged by success in some foci, it has embarked on eliminating the infection from the continent. To this end, increasing the treatment frequency to twice yearly (biannual) has been suggested. However, this may not be cost-effective everywhere in Africa, so it is necessary to assess under which epidemiological scenarios it would be advisable. The central aim of this thesis is to develop further an onchocerciasis transmission model (EpiOncho) to evaluate the impact and cost of biannual vs. annual ivermectin treatment in a range of scenarios typical of savannah onchocerciasis foci in Africa. The analyses and methods are divided into three main components. First, a mathematical model of the dynamics of onchocercal disease was developed and linked to infection output from EpiOncho. Results indicate that although long-term annual ivermectin treatment reduces dramatically onchocerciasis related disease burden, its overall impact on infection depends strongly on baseline levels of endemicity. Second, a study was conducted in Ghana to assess the economic cost of biannual relative to annual ivermectin distribution. Results indicate that the (per year) cost of biannual ivermectin treatment is approximately 60% higher than that of annual treatment (and not simply double, as assumed by others). Third, the health impact, programmatic cost, and projected duration of biannual vs. annual ivermectin treatment were evaluated. Findings indicate that although biannual treatment yields only small additional health benefits over those of annual treatment, its benefit is pronounced in the context of elimination goals, shortening timeframes to reach proposed operational thresholds for stopping treatment and potentially generating programmatic cost savings. Notwithstanding these conclusions, the feasibility of increasing from one to two treatments yearly will vary with the specific programmatic circumstances.
Human Cellular Genetics of Innate Immunity
Creators: name: Rostom, Raghd
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Single cell RNA-sequencing
Single cell genomics
Type I interferon response
Innate immunity

description: The type I interferon response is a key part of the innate immune system, responding to infection and inducing an antiviral intracellular state. While there is known to be variability in this signalling pathway between individuals, alongside cell-to-cell heterogeneity in a genetically identical cell population, the basis of this variation is not fully understood. In this PhD, I established large-scale single-cell RNA sequencing experiments to study cellular variation in the innate immune response in fibroblasts of 70 healthy human individuals from the HipSci initiative. Chapter 2 describes optimisation of stimulation conditions to induce an antiviral response, and the experimental work carried out on the panel of donors. In Chapter 3, I analyse heterogeneity in resting (unstimulated) fibroblasts. By comparing to ex vivo skin data containing multiple cell types, I confirm the relative homogeneity of the in vitro cultured fibroblasts used, mapping to one sub-population of ex vivo skin fibroblasts. Using matched whole exome sequencing data, somatic mutations in sub-populations of cells within each donor were detected, and clonal populations identified. A novel computational method, cardelino, was developed for inference of the clonal tree configuration and the clone of origin of individual cells that have been assayed using scRNA-seq. Applying cardelino to 32 fibroblast lines identifies hundreds of differentially expressed genes between cells from different somatic clones, with cell cycle and proliferation pathways frequently enriched. Returning to innate immunity, Chapters 4 and 5 centre on variability in the type I interferon response. I first describe work linking variability in the innate immune response and evolutionary divergence across mammalian species. Focusing on human variability, the large dataset described above is used to characterise the innate immune response at single cell resolution, elucidating the dynamics of the response across donors in Chapter 4. Chapter 5 describes the application of quantitative trait loci approaches to innate immune phenotypes. This work characterises both inter- and intra-individual heterogeneity in innate immunity.
Devī Māhātmya – FREE ONLINE COURSE – Ācārya dr. Sthaneshwar Timalsina
Creators: name: Timalsina, Staneshwar
Publisher: name: Zenodo
Year: 2022
Subjects: Kali
mahadeva
agama
Mahakali
advaita vedanta
Kubjika
Shiva Sutra
Kashmir Shaivism
Kula
sarvamnaya
Saundaryalahari
krama
Camunda
Shiva
vimarsha-foundation
tantraloka
Spanda
Sadāśiva
Tripura Rahasya
vedanta
Abhinavagupta
saivadvaita
shakti
Guhyakālī
sthaneshwar timalsina
Durga
Bhairava
trika
Divine Mother
shambhava
Tantra
Devi Mahatmya
Tripurasundari
Sarvamnaya
timalsina
tripura
Mālinīvijayottaratantra
consciousness
Kaula
anava upaya
yantra
Īśāna
Vasugupta
shakta upāya
Chandi
Shaiva
sarvamnaya-oral-tradition-archive
Tantric philosophy
amnaya

description: REGISTRATION to the Devī Māhātmya FREE online course: https://www.vimarshafoundation.org/registration

Original YouTube video: https://www.youtube.com/watch?v=iasXZ3aQ0sc

This presentation is part of the Sarvāmnāya Oral Tradition Archive.
Vimarsha Foundation. (2025). The Sarvāmnāya Oral Tradition Archive [Data set]. Zenodo. https://doi.org/10.5281/zenodo.15188107
The role of Steroid Receptor Coactivator-1 in human metabolic disease
Creators: name: Cacciottolo, Tessa
Publisher: name: Apollo - University of Cambridge Repository
Year: 2019
Subjects: Steroid Receptor Coactivator-1
SRC-1
obesity
metabolism
adipose tissue fibrosis
liver fibrosis
coactivators
nuclear hormone receptors

description: Addenbrooke's Charitable Trust Wellcome Trust Research Training Fellowship