Dissertations / Theses: 'Diagnostic pathway'

1

Martin, Laura. "Insights into the tuberculosis diagnostic pathway." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/33125.

Full text

Abstract:

Background: Early identification of patients with drug-resistant tuberculosis (DR-TB) is important. Existing first and second-line drug (SLD) susceptibility testing (DST) strategies can be slow, unreliable and inaccessible. Methods and Findings: SLD DST on the MODS platform (MODS+): 97 drug-naïve and on-treatment patients provided sputum samples for analysis by MODS+ for SLDs. Agreement of MODS+ results with proportions method was >80% for fluoroquinolones and second-line injectables but suboptimal for ethambutol, pyrazinamide, streptomycin, cycloserine, ciprofloxacin and ethionamide. Performance of MODS kit for TB and multi-drug resistant TB (MDR-TB) diagnosis: Sputum samples (N=2446) were cultured in parallel by standard methods and MODS kit. Compared to conventional MODS, MODS kit sensitivity and specificity for TB detection was 99.3% (95%CI:98.3-99.8%) and 99.0% (95%CI:97.8-99.6%) respectively, for detection of rifampicin resistance 98.9% (95%CI:94.2-100.0%) and 99.0% (95%CI:97.8-99.6%) respectively and for detection of isoniazid resistance 96.0% (95%CI:90.8-98.7%) and 99.5% (95%CI:98.4-99.9%) respectively. Can changes in culture time to detection of TB (TTD-TB) predict MDR-TB? 95 patients provided sequential sputum samples before and during treatment for culture by MODS. TTD-TB increased during treatment but TTD-TB distribution at each time point did not differ between MDR and drug-susceptible strains (p=0.4, during eight weeks first-line treatment). Should TB DSTs be rationed to 'high risk' TB suspects? Clinico-epidemiological data from TB suspects (N=1545) underwent multivariate analysis for DR-TB predictors. 17 selective testing strategies were based on significant predictors and international guidelines. The proportions of DR-TB patients captured by each strategy were calculated. 147 patients had culture-positive TB (DR-TB, n=31). If only those with a MDR-TB risk factor were tested 53.1% of DR-TB patients would not have undergone DST. Most strategies performed similarly poorly or tested 80% of the population to detect 90% of DR-TB patients. Conclusion: The MODS+ assay and MODS kit are promising diagnostic tools, likely to aid important universal access to early TB DST.

APA, Harvard, Vancouver, ISO, and other styles

2

Laird, Madeleine Mackay. "Parental perceptions of a pre-school diagnostic pathway for autism." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/parental-perceptions-of-a-pre-school-diagnostic-pathway-for-autsim(85bcad79-fa33-4b62-95f3-45662cda7021).html.

Full text

Abstract:

There is a recognition that services for people with autism and their families need to improve. Although a number of good practice documents and clinical guidance have been published there is continued concern that services are still not providing optimum support. Despite many of the documents focussing upon the diagnostic procedures there is little information available on the quality of the diagnostic process from the parents’ perspective. This qualitative study aims to explore parents’ perceptions of a diagnostic pathway for pre-school children, with autism, in a Local Authority in the North West of England. It considers the factors which, parents perceive, contribute to the success of the local pathway and aims to identify any areas of unmet need for the parents and their families. It also investigates what, if any, feelings of grief and loss are experienced by the parents when their children are diagnosed with autism. It seeks to determine whether the existing pathway supports parents through feelings of grief and loss which may accompany a diagnosis. An interpretivist paradigm was adopted. Eight semi structured interviews were conducted with an opportunity sample of parents drawn from the Multi Agency Autism Team’s database. The interviews were recorded and transcribed and a thematic analysis was made of the data. Two core themes, Knowledge and Loss, emerged from the data which conceptualised the parent’s perception of the diagnostic process. Both of the themes contained sub themes: Knowledge - acquisition of knowledge: communication of knowledge: and quality of knowledge Loss - feelings of grief and loss: being supported through loss: and loss of normal familyThe results of the research are discussed within the context of the existing literature and illustrated with pertinent quotations made by the parents. The findings are supportive of previous research that the diagnosis of autism is a complex and emotionally challenging experience. The results suggest that communication with professionals, the manner in which the diagnosis is disclosed and the support available to families, are pivotal factors in the local pathway. The personal attributes of the professionals who support families, for example, ability to be flexible and have empathy, were more important to the sample than their knowledge of autism. Parents identified areas of unmet need in the existing pathway including having a clear understanding of the possible outcome of their child’s assessment, being provided with information about autism and access to post diagnostic support. The entire sample reported feelings of grief and loss when their child was diagnosed with autism. Their descriptions of these feelings suggest that they experience an ambiguous loss. The implications of the findings for practice are discussed and areas for future research are suggested in response to the findings.

APA, Harvard, Vancouver, ISO, and other styles

3

Johns, Christopher. "Improving the diagnostic pathway of pulmonary hypertension using cardio-pulmonary magnetic resonance imaging." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/20207/.

Full text

Abstract:

Whilst pulmonary hypertension is a relatively uncommon condition, it is associated with a poor quality of life and poor survival. It is therefore important that we correctly identify patients who suffer from pulmonary hypertension, assess the underlying cause (an essential step for treatment) and seek those who are at risk of death. Current guidelines centre on right heart catheterisation as the recommended tool to answer these important clinical questions. Since it was first described in the mid-1950s, there have been significant improvements in the survival of patients with pulmonary hypertension, mainly due to the introduction of vasodilator therapies and surgical procedures. There have been parallel improvements in imaging technologies, the most tangible of which is cardiac MRI, allowing time resolved assessment of cardiac structure and function. Despite these improvements in non-invasive methodologies, there remains heavy reliance upon invasively measured pressures and flow for the diagnosis, phenotyping and assessment of risk in patients with pulmonary hypertension. The aim of this PhD thesis is to evaluate, and hopefully increase, the role of cardio pulmonary vascular MRI in the non-invasive assessment of pulmonary hypertension. I show that cardiac MRI metrics, particularly when combined in a regression model, are able to predict mean pulmonary arterial pressure. Such models are able to identify with reasonable accuracy the presence of pulmonary hypertension in patients referred to a tertiary referral centre. The role of cardio-pulmonary MRI in the assessment of the underlying group of pulmonary hypertension, such as chronic thrombo-embolic pulmonary hypertension and PH-left heart disease, is then explored as identification of patients who may respond to PH specific therapy is an important step. Finally, the role of MRI in the assessment of prognosis, concentrating specifically on patients with PH left heart disease and PH in patients with chronic obstructive pulmonary disease is assessed.

APA, Harvard, Vancouver, ISO, and other styles

4

Vignali, Giulia. "The Bell Tower: the facts-finding pathway and good practice for the structural diagnostic analysis." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018.

Find full text

Abstract:

Specific characteristics of single heritage constructions pose a challenge at the moment of the formulation of a judgement on the preservation state and safety of the object. In Italy, the guidelines on assessment and reduction of seismic risk to heritage constructions have provided a procedure for gaining an adequate level of knowledge of masonry constructions. Such operative methodology is presented as a path made of many aspects that, at different levels and from many viewpoints, should bring together a detailed qualitative and quantitative knowledge of the artifact under analysis. Knowledge steps include the search for documents and information from various sources, visual inspections, surveys and non-invasive diagnostic approaches, structural numerical modelling. Nevertheless, these guidelines are necessarily a generic document and cannot detail many practical aspects so that the professional dealing with real cases has to rely on extensive knowledge and experience. This is particularly true in the case of peculiar typologies of constructions, such as ancient masonry towers, which – due to their geometry - present extra problems of accessibility, inspection and survey. This thesis looks at a number of medieval masonry towers with steeple masonry spires located in Piacenza and Ravenna, Italy, to test on-site a multidisciplinary, coherent facts-finding path that keeps into account the characteristics and problematics of the single constructions in order to reach a reliable evaluation, drawing from the examination of the collected info and produced data. At the same time, this thesis aims to consolidate the author’s knowledge about the most correct choice and procedural application of various techniques according to the specific aims, in view of her professional future, keeping in mind both the engineer’s viewpoint of building safety and the architect respect for the heritage value.

APA, Harvard, Vancouver, ISO, and other styles

5

Dickinson, C. L. "The integration of magnetic resonance imaging in the diagnostic and therapeutic pathway for localised prostate cancer." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1464111/.

Full text

Abstract:

The current clinical pathway for localised prostate cancer firstly involves serum PSA testing, through screening programmes or ad hoc testing in highrisk or symptomatic men. If the PSA is raised, a transrectal-ultrasound guided biopsy is performed for histological diagnosis for suspected cancer. However, serum Prostate Specific Antigen (PSA) levels are inaccurate in selecting an ‘at-risk’ group for malignancy, and transrectal-ultrasound guided biopsy is a morbid procedure in which approximately 30% of men are under-diagnosed (through missing the disease) or misdiagnosed (through underestimating the true disease burden), therefore misinforming on appropriate management. A proportion of men are ‘over-diagnosed’ with low risk cancers on biopsy that may have little to no metastatic potential. The current management options of low- to intermediate-risk disease includes active surveillance with regular repeat serum PSA and biopsy tests and their inherent limitations. The alternative, which is radical treatment, may cause significant morbidity and reduce quality of life, despite considerable technical advances. An imaging test that is able to detect, characterise and localise prostate cancer may allow better diagnosis through improved risk stratification to the current standard tests, and targeted sampling of any suspicious areas, with more effective grading of disease burden. Additionally, the morbidity associated with the current therapeutic options could be reduced through the identification and targeted treatment of cancer lesions (‘focal therapy’), rather than the whole prostate. This thesis addresses the adoption of multi-parametric (mp)MRI for these diagnostic and therapeutic purposes. Whilst mpMRI has already demonstrated high accuracy rates for the detection of clinically significant prostate cancer, the current lack of standardisation of conduct and reporting has reduced comparability between studies and resulted in poor external validity. I present the rationale for the use of a new prostate mpMRI scoring system and the consensus outputs from a European expert group on standardising conduct and reporting, and their applications to date. I also present studies that apply the information obtained from mpMRI on the location and burden of clinically significant disease, to plan, conduct and follow-up focal treatment.

APA, Harvard, Vancouver, ISO, and other styles

6

Eliasson, Madeleine. "Recurrent macroscopic hematuria after anegative investigation – diagnostic yield ofrepeat investigation." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-93341.

Full text

Abstract:

Introduction: Macroscopic hematuria is an important alarm symptom of cancer in theurinary tract. One single episode in patients over the age of 50 fulfills the criteria for referralto the standardized care pathway. Several patients included in the pathway with a negativeresult of the investigation will return with recurrent macroscopic hematuria for repeatinvestigation. Aim: To evaluate the diagnostic yield of repeat investigation in patients presenting withrecurrent macroscopic hematuria after a previous negative investigation and to estimate theincidence of false negative investigations in the standardized care pathway for cancer in theurinary tract. Material and Methods: A retrospective review of medical records was performed at theDepartment of Urology in Örebro County, including all patients investigated in thestandardized care pathway for cancer in the urinary tract during 2016 with a negative result ofthe investigation. Individuals with repeat investigation were identified. Results of theseinvestigations and the time interval between investigations were documented. Results: Repeat investigation was performed in 96 out of 627 patients (15.3%). Two (2.1%)were diagnosed with cancer, at a time interval from initial investigation of 4 and 27 months,respectively. Other results were benign urological conditions (n = 62) and normalinvestigations (n = 30). Conclusions: It appears that few tumors are missed when macroscopic hematuria isinvestigated in the standardized care pathway. We observed a very low number of newlydiagnosed cancers after repeat investigation of recurrent macroscopic hematuria. A moreselective approach regarding repeat investigations should be considered.

APA, Harvard, Vancouver, ISO, and other styles

7

Kanthabalan, Ana Abhiramy. "The evaluation of a novel imaging-based complex diagnostic and therapeutic pathway intervention for men who fail radiotherapy for prostate cancer." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10057034/.

Full text

Abstract:

Background: One-third of men may experience biochemical failure by 8 years following radical radiotherapy for prostate cancer. Focal salvage therapy (FST) may offer further curative treatment. Before FST, distant disease must be ruled-out and intra-prostatic disease must be accurately detected and characterised. Aim: The aim of this thesis was to evaluate novel diagnostic and staging techniques and outcomes of focal salvage treatments for radiorecurrent prostate cancer. Methods: Both retrospective and prospective data will be presented. A retrospective analysis was conducted to compare a) Bone scan with Choline PET/CT in the detection of distant metastases b) Accuracy of MRI-Targeted Biopsy (MRI-TB) with whole-gland template mapping biopsy (TPM) c) the outcomes of focal salvage HIFU (FS-HIFU). These retrospective analyses provided important inputs into the design and conduct of the prospective trial FORECAST - Focal RECurrent Assessment and Salvage Treatment. Key trial outcomes were a) detection rate of distant metastatic disease of Whole Body MRI compared to other staging scans b) detection rate of MRI for clinically significant prostate cancer and c) Short-term outcomes of focal salvage therapies. Outcomes: Within the retrospective analyses, there was poor concordance with bone scan and Choline PET/CT in the detection of metastatic disease (kappa value 0.024). MRI-TB had lower detection rates of clinically significant cancer compared with TPM biopsy; 77.9% vs. 85.7% (p=0.146). The b-DFS rate post FS-HIFU was 48% (95% CI 39–59) and composite end free survival was 40% (95% CI 31–50). In the prospective analyses, there was moderate agreement between WB-MRI and Choline PET/CT for bony metastatic disease (Kappa=0.411 (p < 0.0001)). MRI (PIRADS 4) had a high sensitivity, specificity, PPV and NPV for the detection of clinically significant cancer 90%, 81.3%, 85.7% and 86.7%. b-DFS rates post FS-HIFU and FS-cryotherapy was 73% (95% CI 51-100) and 67% (95% CI 30-100) at 12 months (p=0.95).

APA, Harvard, Vancouver, ISO, and other styles

8

Bauffe, Frédérique. "Etude de protéines parasitaires pour l'amélioration des tests de diagnostic rapide du paludisme." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5068.

Full text

Abstract:

Le paludisme est un problème de santé public dans de nombreux pays. Cinq espèces infectent l'homme : P. falciparum, responsable de la grande majorité des décès, et P. vivax, P. ovale, P. malariae et P. knowlesi qui provoquent des formes bénignes de la maladie. Le diagnostic qui fait partie des moyens de lutte, est une urgence médicale. Les tests de diagnostic rapides (TDRs) dont l'usage est recommandés par l'OMS, sont donc de plus en plus employés. Cependant, la détection et l'identification des espèces non P. falciparum par ces tests est insuffisante. Le besoin en nouveaux couples « antigènes-anticorps » est une nécessité pour améliorer les TDRs. Au cours de ce travail, de nouveaux anticorps anti LDH de P.malariae ont été produits.Une recherche de nouveaux antigènes a également été entreprise. Pour cela, certaines enzymes de la voie de la glycolyse ont été étudiées. Pour la première fois des séquences des enzymes de cette voie ont été obtenues pour P. ovale et P. malariae. Elles ont permis de déterminer de nombreux épitopes cibles potentiels spécifiques et ceux communs à toutes les espèces. Dans un deuxième temps, une recherche en protéomique a été menée pour identifier des biomarqueurs parasitaires. L'étude du culot globulaire et du plasma de patients infectés a permis la sélection de 8 protéines cibles originales. Ces travaux préparent la fabrication et la commercialisation par la société Whidiag d'une nouvelle génération de TDRs pour le paludisme
Malaria is a public health problem in many countries. Five species infect humans: P. falciparum, responsible for the vast majority of deaths, and P. vivax, P. ovale, P. malariae and P. knowlesi causing mild forms of the disease. The diagnostic is a means of control and a medical emergency. The rapid diagnostic tests (RDT) whose are recommended by WHO, are increasingly used. However, the detection and identification of not P. falciparum species is insufficient. New "antigen-antibody" couples are a need to improve the RDTs performance. In this work, new anti LDH antibodies from P. malariae were produced. A search for new antigens was also undertaken. For this purpose, some enzyme of glycolysis pathway were studied. For the first time the sequences of the enzymes from this pathway were obtained for P. ovale and P. malariae. We identified many potential target epitopes specific and common to all those species. In a second step, a proteomics approches has been conducted to identify parasites biomarkers. The study of red blood cells and plasma of infected patients has led to the selection of 8 original target proteins. This work prepares the manufacturing and marketing of a new generation of RDTs for malaria by the company Whidiag

APA, Harvard, Vancouver, ISO, and other styles

9

Phyu, Su Myat. "Targeting of the PI3K/AKT/mTOR signalling pathway and associated kinases in breast and colon cancer cells and response evaluation by molecular imaging techniques." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=238576.

Full text

Abstract:

The phosphatidylinositol-3-kinase/AKT (Protein Kinase B)/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway, downstream of tyrosine kinase receptors, is upregulated in human cancers including breast and colon cancers. Glycogen synthase kinase 3 (GSK 3) is a serine/threonine protein kinase plays important role in various cellular processes including glycogen synthesis mediated by insulin signalling pathway. Moreover, 5' adenosine monophosphate activated protein kinase (AMPK), a crucial cellular energy sensor, has regulatory role in cell growth and proliferation through mTOR pathway. Phosphatidylcholine (PtdCho) is the major phospholipid in the mammalian cell membranes and is mainly synthesized by the CDP-choline pathway. Malignant transformation has been reported to be associated with altered choline metabolism. Hyperactivation of the PI3K/AKT signalling pathway upregulates the key enzymes of phospholipid metabolism. The first line antidiabetic drug, metformin, modulates glucose and concomitant lipid metabolism through AMPK activation. Studies suggest phosphatidylcholine biosynthesis and breakdown through CDP-choline pathway are modulated by glucose metabolism and de novo fatty acid synthesis. Cancer cell growth inhibitory effect of PI3K/AKT/mTOR/GSK3 pathway inhibitors and metformin were investigated by cytotoxic assay, western blot and cell cycle analysis in breast and colon cancer cells. IC50 values of anticancer drugs and combination indices between drug combinations were determined. 31P-NMR was carried out on cell extracts after drug treatments. [14C (U)] glucose and [3H] choline incorporation into lipids were also determined. All inhibitors targeting PI3K/AKT/mTOR signaling pathway, GSK3 and metformin have cancer cell growth inhibition. By 31P-NMR, PI3K/AKT/mTOR pathway inhibition induced agent-specific changes in PCho intensity. Increased UDP-sugars observed in breast and colon cancer cell extracts treated with LY294002 and AZD8055, an effect abrogated by inclusion of a GSK3 inhibitor. A link between glycolytic intermediates and phosphatidylcholine biosynthesis was investigated by metformin and GSK3 inhibitor in breast and colon cancer cells.

APA, Harvard, Vancouver, ISO, and other styles

10

Mohanty, Sujit Kumar. "A. Genetic characterization of the caffeine C-8 oxidation pathway in Pseudomonas Sp. CBB1 B. Validation of caffeine dehydrogenase as a suitable enzyme for a rapid caffeine diagnostic test." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/4879.

Full text

Abstract:

Pseudomonassp. CBB1 degraded caffeine via C-8 oxidation. Previously, a novel quinone-dependent caffeine dehydrogenase (Cdh) was shown to catalyze the oxidation of caffeine to 1,3,7-trimethyluric acid (TMU). Initial metabolite analysis using resting cells and partially purified extract of CBB1 identified transient accumulation 1,3,7-trimethyl-5-hydroxyisourate (TM-HIU), and 3,6,8-trimethylallantoin (TMA). TMA structure was confirmed; chiral analysis revealed that it was racemic. In contrast, a time-course reaction showed that one of the enantiomers of TMA accumulated nine times, and racemized in three hours. Based on this, it was proposed that TMU was converted to TM-HIU and enantiomeric TMA. A 43-kDa NADH-dependent TMU mononxygenase (TmuM) was purified and shown to convert TMU to unstable TM-HIU. The enzyme belonged to a new family of FAD-dependent monooxygenases. The enzyme was specific for methyluric acid with no activity on uric acid. Homology model of TmuM revealed a larger, more hydrophobic active site compared to analogous uricase in the uric acid pathway. Genes encoding heterotrimeric Cdh (cdhA,B,C) and TmuM (tmuM), were located on a 25.2-kb fragment in CBB1 genome. Gene cluster analysis relative to similar cluster in uric acid degrading organisms identified five more putative genes of the C-8 oxidation pathway, namely tmuH, tmuD, orf1, orf2, and orf3. First three genes were assigned encoding TM-HIU hydrolase (TM-HIU to TM-OHCU), TM-OHCU decarboxylase (TM-OHCU to stereospecific TMA (proposed S-(+)-TMA)), and trimethylallantoinase (stereospecific TMA to TMAA), respectively. Further, orf2 and orf3 are proposed to encode for YlbA and ArgE like hydrolase and deacetylase, which convert TMAA to glyoxylate, di- and monomethylurea. This is the first report of (a) TMA structure (b) TMU monooxygenase and TM-HIU (hydroxylation product of TMU), and (c) complete delineation of C-8 oxidation pathway by a combination of enzymology and cluster analysis. Excessive consumption of caffeine in various forms has created a need for a rapid diagnostic test, esp. for nursing mothers and infants. Cdh was hypothesized to be suitable for this test. Sensitivity of the test was shown to be 1 ppm. A colorimetric test with partially purified Cdh and INT-dye was optimized to detect within a minute, caffeine in drugs, nursing mother's milk, and differentiate decaffeinated beverages.

APA, Harvard, Vancouver, ISO, and other styles

11

Dhillon, Ravinder. "Diagnostic imaging pathways." University of Western Australia. School of Medicine and Pharmacology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0126.

Full text

Abstract:

[Truncated abstract] Hypothesis: There is deficiency in the evidence base and scientific underpinning of existing diagnostic imaging pathways (DIP) for diagnostic endpoints. Objective: a) To carry out systematic review of literature in relation to use of diagnostic imaging tests for diagnosis and investigation of 78 common clinical problems, b) To identify deficiencies and controversies in existing diagnostic imaging pathways, and to develop a new set of consensus based pathways for diagnostic imaging (DIP) supported by evidence as an education and decision support tool for hospital based doctors and general practitioners, c) To carry out a trial dissemination, implementation and evaluation of DIP. Methods: 78 common clinical presentations were chosen for development of DIP. For general practitioners, clinical topics were selected based on the following criteria: common clinical problem, complex in regards to options available for imaging, subject to inappropriate imaging resulting in unnecessary expenditure and /or radiation exposure, and new options for imaging of which general practitioners may not be aware. For hospital based junior doctors and medical students, additional criteria included: acute presentation when immediate access to expert radiological opinion may be lacking and clinical problem for which there is a need for education. Systematic review of the literature in relation to each of the 78 topics was carried out using Ovid, Pubmed and Cochrane Database of Systematic Reviews. ... The electronic environment and the method of delivery provided a satisfactory medium for dissemination. Getting DIP implemented required vigorous effort. Knowledge of diagnostic imaging and requesting behaviour tended to become more aligned with DIP following a period of intensive marketing. Conclusions: Systematic review of literature and input and feedback from various clinicians and radiologists led to the development of 78 consensus based Diagnostic Imaging Pathways supported by evidence. These pathways are a valuable decision support tool and are a definite step towards incorporating evidence based medicine in patient management. The clinical and academic content of DIP is of practical use to a wide range of clinicians in hospital and general practice settings. It is source of high level knowledge; a reference tool for the latest available and most effective imaging test for a particular clinical problem. In addition, it is an educational tool for medical students, junior doctors, medical imaging technologists, and allied health care personnel.

APA, Harvard, Vancouver, ISO, and other styles

12

Dhillon, Ravinder. "Diagnostic imaging pathways /." Connect to this title, 2006. http://theses.library.uwa.edu.au/adt-WU2007.0126.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Saville, Christina. "Modelling pathways to diagnosis of breast conditions." Thesis, University of Southampton, 2018. https://eprints.soton.ac.uk/422238/.

Full text

Abstract:

This thesis describes how logistic regression and discrete-event simulation (DES) can be combined to predict patient risk and evaluate the potential operational impact of implementing risk-based pathways. We test whether using diagnostic information provided by non-specialists to plan diagnostic tests offers benefits in operational performance. We demonstrate our approach on an application area in breast diagnostics with data from the Whittington Hospital breast diagnostic clinic. Specifically we assess whether GP referral information is complete and accurate enough for use in predicting the risk of an abnormal result (i.e. an abnormality being detected from mammogram, ultrasound or biopsy). The construction of a unique dataset for this purpose is described; it links GP referral information to in-clinic tests and results. This dataset is used to develop two alternative logistic regression scorecards that predict a patient’s risk of abnormal breast diagnostic results from their GP referral data (n=179). The simple scorecard uses two referral characteristics while the full scorecard uses seven. It is usual to base the decision of where to set the cut-off score between low and high risk patients on a scorecard’s predictive performance. In contrast, we show how a discreteevent simulation can be used to optimise the cut-off in terms of operational performance. In our example, the performance measure is the daily average proportion of patients’ time at the clinic that adds value, called the clinic efficiency. We simulate the potential impacts of introducing the following risk-based pathways. High-risk patients are sent straight for imaging tests and then to a clinician for their results. Low-risk patients are sent to a clinician first (as today) who decides whether imaging is needed. The set of labels that determines a patient’s progress through the simulation is modelled empirically for the simple scorecard, since all possible label combinations are present in our sample. However for the full scorecard this is not the case, so using the empirical distribution is not appropriate. Instead we introduce a novel method using Poisson loglinear models to generate representative sets of patient labels.

APA, Harvard, Vancouver, ISO, and other styles

14

Brechbiel, Julia. "Pathways Linking Clinician Demographics to Mental Health Diagnostic Accuracy: An International Perspective." VCU Scholars Compass, 2017. https://scholarscompass.vcu.edu/etd/5120.

Full text

Abstract:

Significant research efforts have focused on examining the effect of patient factors on providing diagnoses across clinical settings; however, the influence of clinician demographics have received less attention. This study aimed to understand the impact of nonclinical factors such as clinician characteristics and response time on diagnostic accuracy. The study used data from a WHO field study of the ICD-11 development (n = 1822) that required clinicians to diagnose two case vignettes. Clinicians’ slower response times had a significant positive impact on their rates of diagnostic accuracy. However, there was no evidence that clinicians’ demographic features were directly related to their diagnostic accuracy. Rather, clinicians’ age, years of experience, world region, and their clinical profession indirectly predicted accuracy through their overall response time. Contradictory to decision-making theories, older clinicians and clinicians with more years of experience had higher rates of diagnostic accuracy when they spent more time completing the study. Additionally, clinicians in South America with slower response times had higher accuracy compared to clinicians in North America. Clinicians in Asia had faster response times that negatively impacted their accuracy rates compared to North America clinicians. These findings suggest differences in response time and the applicability of the ICD-11 across cultures. Consistent with previous research, medical professionals with quicker response times had the lowest rates of accuracy compared to psychologists and other clinical professionals. These findings highlight the need for researchers and clinicians to consider the role their dispositional features have in the diagnostic process. Moreover, it is crucial that future research into diagnostic decision-making and accuracy should consider additional mediating factors such as response style, culture, and experience.

APA, Harvard, Vancouver, ISO, and other styles

15

Tamburrino, Federica <1980&gt. "I disordini del pathway RAS-MAPK o Rasopatie: aspetti diagnostici, clinici e terapeutici." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7435/.

Full text

Abstract:

Le “RASopatie” includono un gruppo di patologie congenito-malformative a trasmissione autosomica-dominante causate da mutazioni eterozigoti germinali in geni che codificano per proteine del pathway RAS-MAPKinasi. Sono caratterizzate da dismorfismi faciali, iposomia, cardiopatia congenita, anomalie ectodermiche e scheletriche, coinvolgimento cognitivo e suscettibilità tumorale. La bassa statura è uno dei principali elementi distintivi sul quale si può agire sotto il profilo terapeutico, mediante somministrazione di Ormone della Crescita biosintetico (GH). In questo studio è stato analizzato l’andamento accrescitivo in un ampio gruppo di 88 pazienti affetti da Rasopatia con diagnosi molecolare confermata. Sono stati valutati: distribuzione per genotipo, prevalenza delle caratteristiche fenotipiche e correlazione genotipo-fenotipo sull’intero gruppo di studio ed in particolare andamento accrescitivo spontaneo, proporzioni corporee, sviluppo puberale, e dati di statura finale (FH) in 33 soggetti, di cui 16 trattati con GH per deficit secretivo (GHD). Valutati inoltre efficacia e sicurezza della terapia con GH, definito il rischio oncologico e quantificato il coinvolgimento psico-cognitivo. 33 pazienti hanno mostrato GHD e sono stati trattati con GH per 6,8 ± 4,8 anni. Prima dell’ inizio della terapia, la velocità di crescita era - 2.6 ± 1.3 SDS e i livelli basali di IGF1 pari a - 2.0 ± 1.1 SDS. La terapia con GH a lungo termine, iniziata precocemente durante l’infanzia, ha determinato un guadagno staturale positivo rispetto ai pazienti non trattati (+1,3 SDS), normalizzando la FH per gli standards di condizione ma non per la popolazione generale e il Target staturale parentale. Il timing di sviluppo puberale ha influenzato negativamente lo scatto di crescita puberale. 1/88 soggetti, non sottoposta a terapia con GH, ha sviluppato neoplasia. Sono emersi ritardo mentale (41.1%), deficit visuo-spaziali (41.8%), ADHD (38.8%), anomalie del SNC (24.4%) e anomalie del tracciato elettroencefalografico (6.7%).
RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. These conditions share facial dysmorphism, failure to thrive, congenital heart disease, ectodermal, and skeletal anomalies, variable cognitive involvement, and susceptibility to certain malignancies as major characteristics. This study analized clinical features, growth trend and body proportions in 88 patients affected by RASopathies with molecularly confirmed diagnosis, and FH reached in 33, including 16 treated with GH therapy for proven GH deficiency. Clinically, 69 patients (78.4%) had a diagnosis of Noonan syndrome (NS), seven of NS/Loose anagen hair (8.0%), six of CFC syndrome (6.8%), and two of Costello syndrome, Noonan syndrome with multiple lentigines (NSML) and Legius syndrome. Among them, 52 (59.1%) had PTPN11 mutations, while the other genotypes were less than 10%. Most patients were born at term, after a physiological pregnancy and presented regular neonatal adaptation. 75.9% patients had cardiac anomalies and 20.2% needed surgery for cardiac involvement. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8±4.8 years. Before starting therapy, HV was -2.6±1.3 SDS, and mean basal IGF1 levels were -2.0±1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. The delayed pubertal development and the inadequate pubertal catch-up growth could explain the impaired FH. Our patients on GH-therapy benefitted from the pharmacological treatment if started in pre-puberty and given for a long time. Probably, the prepubertal start of GH-treatment could compensate the lack of a pubertal growth. 1/88 patient had cancer, but she didn’t received GH. The patients presented cognitive impairment (41.1%), ADHD (38.8%), SNC anomalies (24.4%) and EEG alterations (6.7%).

APA, Harvard, Vancouver, ISO, and other styles

16

Jager-Hyman, Shari Gail. "Nonsuicidal Self-Injury in a College Sample: Risk Factors, Pathways, and Diagnostic Correlates." Diss., Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/201201.

Full text

Abstract:

Psychology
Ph.D.
As research on nonsuicidal self-injury (NSSI) is in its beginning stages, relatively little is known about the variables that confer risk for this class of behaviors. Although recent work has implicated the role of childhood maltreatment in the development of NSSI, this body of literature is hampered by several important limitations. These limitations include either grouping together all forms of maltreatment (i.e., emotional, physical, and sexual abuse) or focusing on only one form of maltreatment. In addition, there is a paucity of research exploring the mechanisms by which maltreatment experiences relate to NSSI. Furthermore, although a great deal of attention has focused on the relation between self-harm (both suicidal and nonsuicidal) and specific psychological diagnoses, particularly borderline personality disorder (BPD), the vast majority of this research has been conducted with severe clinical samples. As a result, there is a dearth of knowledge about the risk factors, pathways, and diagnostic correlates of NSSI in non-clinical samples. Given that recent research has suggested that NSSI is increasingly common in college samples, the current study aimed to address these limitations in a diverse sample of 1,819 college students. Participants completed assessments of childhood maltreatment experiences, NSSI, as well as two potential mediators, emotion dysregulation and cognitive vulnerability, and one potential moderator, impulsivity. In addition, a subset of participants (n = 140) were administered diagnostic interviews for BPD and depression. Results provided support for the role of childhood maltreatment in the development in NSSI. Controlling for other forms of maltreatment, emotional maltreatment was most predictive of NSSI. Both emotion dysregulation and negative cognitive style partially mediated the relationship between childhood maltreatment and NSSI. In contrast, impulsivity did not significantly moderate the childhood maltreatment - NSSI relation. As expected, borderline personality features significantly predicted NSSI. However, contrary to expectations, impulsivity and affective instability were not the strongest borderline criteria in the prediction of NSSI. Treatment implications of these results, strengths and limitations, as well as areas of future research are discussed.
Temple University--Theses

APA, Harvard, Vancouver, ISO, and other styles

17

Hussin, Duratul 'Ain. "Development and evaluation of optometrist-led referral pathways in Ampang, Malaysia." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/98401/8/98401.pdf.

Full text

Abstract:

Screening for eye diseases is currently performed by ophthalmologists in most public hospitals in Malaysia, which increases workloads for ophthalmology eye-care personnel in hospitals. Optometrists also practise at hospital eye clinics in Malaysia; however, their main role currently focuses on refractive care. This study is the first in Malaysia and Asia to investigate, from a public health context, two optometry-led service pathways for triaging referrals to the hospitals and diabetic retinopathy screening in both hospital and community care. The thesis comprehensively evaluates the optometric pathways quantitatively and qualitatively considering clinical care outcomes, patient access, satisfaction and costs.

APA, Harvard, Vancouver, ISO, and other styles

18

Vergaro, Giuseppe. "Galectin-3 and aldosterone profibrotic pathways in the failing heart." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC235.

Full text

Abstract:

La galectine-3 (Gal-3) est biologiquement liée au processus d'inflammation et de fibrose dans l’insuffisance cardiaque (IC). Le système rénine-angiotensine-aldostérone (SRAA) a été largement démontré comme exerçant des effets profibrotiques, prohypertrophiques et pro-inflammatoires dans la pathophysiologie de l’IC. En outre, il existe des preuves expérimentales que Gal-3 et SRAA peuvent interagir dans le développement des dommages cardiovasculaires dans des modèles d’hypertension. Cependant, une telle interaction n'a pas été étudiée dans un contexte de dysfonction ventriculair gauche (VG). Nous avons donc cherché à tester les hypothèses suivantes: 1. La Gal-3 participe aux mécanismes de la fibrose cardiaque et du remodelage tissulaire médiés par l'aldostérone dans un modèle murin de dysfonction du VG; 2. Le niveau de Gal-3 est associé au développement du remodelage du VG et de la fibrose et peut prédire les effets des l'antagonistes neurohormonaux chez les patients atteints d'IC chronique due à une cardiomyopathie dilatée non ischémique (CMDNI). Méthode 1. Des souris mâles adultes atteintes d'hyperaldostéronisme cardiaque spécifique ont été soumises à des injections sous-cutanées d'isoprotérénol (200 mg/kg x 2/jour pendant deux jours), puis randomisées pour recevoir un placebo, un inhibiteur de Gal-3 (modified citrus pectin, MCP), un antagoniste de récepteurs aux minéralocortïcoides (canrenoate de potassium) ou l’association de deux (MCP+canrenoate) pendant 14 jours. 2. Nous avons recruté 150 patients avec un diagnostic de CMDNI. Tous les patients ont bénéficié d'une évaluation clinique et biohumorale, incluant le dosage de Gal-3, l'échocardiographie, et une imagerie par résonance magnétique cardiaque (IRM) contrastée pour l'évaluation des volumes et de la fibrose par le late gadolinium enhancement (LGE). Une plus petite cohorte de 70 patients a également reçu un dosage de soluble suppression of tumorigenicity protein 2 (sST2) à l’inclusion, et une IRM de suivi à 24 mois pour l'évaluation du remodelage inverse du VG, définie comme une augmentation de >10% de la fraction d’ejection du VG ou une diminution de 10% du volume diastolique du VG indexé. Résultats L’isoprotérénol a induit une diminution rapide et persistante de la fonction systolique du VG chez la souris, qui a été nettement améliorée par le traitement au MCP ou canrenoate. Le MCP et le canrenoate ont également prévenue l'hypertrophie et la fibrose cardiaques ainsi que l’augmentation de l'expression de gènes impliqués dans la fibrogénèse (Coll-1 et Coll-3) et l'infiltration de macrophages (CD-68 et MCP-1). L'utilisation combinée du MCP et canrenoate a entraîné des effets additifs sur l'hypertrophie cardiaque, l'inflammation et la fibrose, comparativement au MCP ou au canrenoate seul. Dans notre cohorte de patients avec CMDNI, la valeur médiane de Gal-3 était de 14,4 ng/mL; le LGE a été observée chez 106 patients. Les patients ayant un LGE positif avaient un taux de Gal-3 plus élevée que ceux qui n'en avaient pas (p=0,006). Après analyse multivariée suel la Gal-3, le sexe, l’ancienneté del la cardiopathie et la fraction d’éjection du ventricule droit sont des facteurs prédicteurs indépendants de la présence de LGE. L’IRM de suivi a montrée que 35 patients présentaient un remodelage inverse. L’analyse multivariée met en evidence Gal-3 comme un prédicteur indépendant du remodelage inverse contrairement au sST2. Conclusion La Gal-3 participe à des mécanismes de lésions myocardiques médiées par l'aldostérone dans un modèle murin de IC. De même, dans un cadre clinique de CMDNI, Gal-3 semble être associée à la fibrose du VG et à l'évolution du remodelage cardiaque, en identifiant éventuellement le sous-ensemble de patients avec une réponse plus prononcée à l'antagonisme neuro-hormonal pharmacologique
BackgroundGalectin-3 (Gal-3) is biologically linked to the process of inflammation and fibrosis in heart failure (HF). The renin-angiotensin-aldosterone system (RAAS) has been largely demonstrated to exert profibrotic, prohypertrophic and proinflammatory effects in the pathophysiology of HF. Further, there is initial experimental evidence that Gal-3 and RAAS may interplay in the development of cardiovascular damage in hypertensive models. However, such interaction has not been investigated in the setting of left ventricular (LV) dysfunction and HF. We aimed therefore to test the following hypotheses:1. Gal-3 participates in the mechanisms of aldosterone mediated cardiac fibrosis and tissue remodeling in a murine model of LV dysfunction;2. Gal-3 level is associated with the development of LV remodeling and fibrosis and can predict the effects of neurohormonal antagonism in patients with chronic HF due to non-ischemic dilated cardiomyopathy (NIDCM).Methods1. Adult male mice with cardiac-specific hyperaldosteronism (AS) underwent isoproterenol subcutaneous injections (200 mg/kg x 2/day over two days), to be then randomized to receive placebo, a Gal-3 inhibitor (modified citrus pectin, MCP), an aldosterone antagonist (potassium canrenoate), or MCP+canrenoate for 14 days.2. We enrolled 150 patients with a diagnosis of NIDCM. All patients underwent a comprehensive clinical and biohumoral evaluation, including Gal-3 assay, 2-D echocardiography, and a contrast-enhanced cardiac magnetic resonance (CMR) for the assessment of LV volumes and fibrosis by the late gadolinium enhancement (LGE) technique. A smaller cohort of 70 patients also received soluble suppression of tumorigenicity protein 2 (sST2) assay at baseline as well as a follow-up CMR after 24 months for the evaluation of LV reverse remodeling, defined as a >10 percentage units increase in LV ejection fraction or a >10% decrease in LV end-diastolic volume indexed.ResultsIsoproterenol induced a rapid and persistent decrease in LV systolic function which was markedly improved by treatment with either MCP or canrenoate. MCP and canrenoate also reduced cardiac hypertrophy and fibrosis and the expression of genes involved in fibrogenesis (Coll-1 and Coll-3) and macrophage infiltration (CD-68 and MCP-1). The combined use of antagonists of Gal-3 and aldosterone resulted in enhanced effects on cardiac hypertrophy, inflammation, and fibrosis, when compared to MCP or canrenoate alone. In our cohort of NIDCM patients, median Gal-3 value was 14.4 ng/mL; LGE was detected in 106. Patients with LGE had higher Gal-3 than those without (p=0.006). Among univariate predictors of LGE, Gal-3 maintained its predictive value at multivariate analysis, together with sex, hypertension, disease duration and right ventricular ejection fraction. At follow-up CMR, 35 patients showed reverse remodeling. Gal-3, but not sST2 resulted as an independent predictor of LV reverse remodeling at multivariate analysis.ConclusionGal-3 participates in mechanisms of aldosterone-mediated myocardial damage in murine model of HF. Likewise, in the clinical setting of NIDCM, Gal-3 seems to be associated with LV fibrosis and to the evolution of cardiac remodeling, possibly identifying the subset of patients with a more pronounced response to pharmacological neurohormonal antagonism

APA, Harvard, Vancouver, ISO, and other styles

19

Perez, Jalessa Ivelis. "DEPRESSION AND ADDICTION: ALONG THE PATHWAY TOWARDS SUICIDE." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1546606105783207.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Ho, Ka-yan Rebecca Lucinda, and 何嘉茵. "Mutations of epidermal growth factor receptor (EGFR) pathway genes andMET in primary lung adenocarcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48333906.

Full text

Abstract:

This study completed the analysis of mutational frequencies and clinicopathological patterns of six EGFR pathway-related genes (EGFR, HER2, HER4, KRAS, BRAF and MET) in 212 resected lung adenocarcinomas (AD) from 98 male and 114 female Chinese patients without prior chemotherapy or tyrosine kinase inhibitor (TKI) therapy. Genomic DNA and cDNA sequencing, quantitative PCR and fluorescence in-situ hybridization (FISH) were employed to investigate mutation and amplification status of the relevant genes. Overall, more than 75% of tumours were detected to harbour mutations or amplification in one of these six genes. The commonest mutation was found to involve EGFR, comprising 60.38% of cases, followed by KRAS (9.43%), HER2 (2.36%), MET (2.36%), BRAF (1.42%) and HER4 (0.47%). Four somatic mutations in MET exon 14 splicing region were found, leading to alternative splicing and a transcript lacking exon 14. Two of the MET mutant tumours and one MET wild-type tumour showed MET amplification of more than 3.5 fold increase in copy number. Mutations of EGFR were significantly more frequent in female (p = 0.0196), non-smokers (p < 0.001) and well differentiated tumours (p = 0.0209). KRAS mutations showed significant association with male (p = 0.0099) and smoking history (p = 0.0011). A novel HER2 D769Y mutation was found and HER2 mutations were associated with smokers (p = 0.0013) and poorly differentiated tumours (p = 0.0147). BRAF, MET mutations and MET amplification were not associated with clinicopathological factors. Mutations were mutually exclusive except for two cases with KRAS and HER4/BRAF. MET amplification was co-existent with MET mutations in two cases. MET amplification was found to negatively correlate with disease-free and cancer-specific survivals. The results suggested that MET amplification may contribute to disease progression and could be a therapeutic target in primary lung AD in Hong Kong Chinese patients.
published_or_final_version
Pathology
Master
Master of Medical Sciences

APA, Harvard, Vancouver, ISO, and other styles

21

Elakad, Omar [Verfasser]. "Functional and diagnostic relevance of FGFR1-dependent signaling pathways in squamous cell lung cancer / Omar Elakad." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1218299207/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Harman, David J. "The identification of chronic liver disease in primary care using non-invasive diagnostics within a novel pathway." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/36459/.

Full text

Abstract:

Introduction: Deaths due to chronic liver disease have increased significantly in recent decades. This is due to increases in alcohol consumption and obesity during this time period, and insensitive screening tests (liver function blood tests) utilised in primary care. This thesis describes a new liver disease community diagnostic pathway which focussed upon defined risk factors for chronic liver disease and uses Transient Elastography (TE) as the primary investigation modality. The aims of the thesis are to assess the feasibility of this pathway for detecting liver disease due to alcohol or non-alcoholic fatty liver disease within the United Kingdom healthcare system, to quantify the number of new cases detected with this approach and to evaluate patient experience of these investigations. Methods: Following a systematic review of the literature, an investigation pathway was derived and piloted in 4 general practice sites in Nottinghamshire in two phases between February 2012 and September 2014. Patients with hazardous alcohol use, type 2 diabetes or persistently raised alanine aminotransferase (ALT) level and negative liver serology were eligible for study. TE was performed in the community; a liver stiffness reading of ≥8 kilopascals defined clinically significant liver disease and subsequent review in a consultant led community clinic. Risk factors for new diagnoses of liver disease and cirrhosis were identified and the association with obesity investigated. A qualitative interview substudy was conducted to explore the experiences of 20 patients undergoing investigation. Results: In a total adult population of 20,868 patients, 2,022 patients were eligible for study of whom 909 (45%) underwent TE. Valid liver stiffness measurements were possible in 98% of patients. Overall, 230 cases of elevated liver stiffness and 27 new cases of cirrhosis were identified. Minimum cirrhosis prevalence in patients with type 2 diabetes was 2%. Obesity was significantly associated with diagnosis of cirrhosis in type 2 diabetics (odds ratio 9.4 (95% CI 2.2-40.9)) and hazardous alcohol users (OR 5.6 (95% CI 1.6-19.7)). The majority of new cases of liver disease had normal ALT levels. From the initial pilot phase in two general practices in Rushcliffe (Nottingham), in which liver function test data from 378 patients undergoing TE was analysed, 72.4% with elevated liver stiffness measurement, 60% with biopsy proven cirrhosis and 90% with cirrhosis diagnosis had normal ALT. Patients felt that TE was a useful adjunct to lifestyle change and described a positive experience of liver disease investigation. Conclusion: A new non-invasive diagnostic pathway for liver disease was feasible to implement in Nottinghamshire primary care and resulted in significantly increased diagnosis of chronic liver disease and cirrhosis. These findings warrant exploration of the pathway in a larger primary care population.

APA, Harvard, Vancouver, ISO, and other styles

23

Burkitt, Wright Emma Mary Milborough. "De novo germline disorders of the Ras-MAPK pathway : clinical delineation, molecular diagnosis and pathogenesis." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/de-novo-germline-disorders-of-the-rasmapk-pathwayclinical-delineation-molecular-diagnosis-and-pathogenesis(9688dc20-7b1b-46f1-a638-b4d1809f430b).html.

Full text

Abstract:

This work sought to investigate the clinical phenotypes and molecular basis of cardio-facio-cutaneous syndrome (CFC), a germline disorder of the Ras-MAPK pathway, like Noonan syndrome (NS) and neurofibromatosis type I, caused by mutations in genes encoding proteins that act within this signal transduction pathway. CFC is most commonly due to mutation in BRAF, and less commonly MAP2K1, MAP2K2 or KRAS. A proportion of patients currently have no mutation identified. Mutations and clinical features of patients with a molecular diagnosis of CFC were investigated, which demonstrated a wide range of causative mutations, and some unclassified variants. Both known and novel clinical features of CFC were identified. A strong association between severe contractures and the p.(Tyr130Cys) mutation in MAP2K1 was found, which has not previously been reported. In contrast to the large number of patients with a confirmed molecular diagnosis, several with a highly suggestive clinical phenotype have been found to have no mutationin any of the known CFC genes. The molecular basis of these presentations was investigated by conventional Sanger sequencing of candidate genes. Fourteen patients with the p.(Ser2Gly) mutation in SHOC2 were identified, with clinical presentations consistent with CFC, NS or CS. Target enrichment and massively parallel sequencing of selected genes was undertaken in ten patients. Mutations in known genes were identified in four patients (including the positive control). Candidate causative variants in novel genes were suggested in two further patients, one of which was confirmed on Sanger sequencing. Whole exome sequencing of patient-parent trios was also undertaken to identify de novo variants. Three trios were analysed, and in one patient with a clinical diagnosis of CFC, a frameshift mutation in NF1 was identified, which was confirmed by Sanger sequencing to be present and de novo. The molecular effects of CFC-associated mutations in BRAF on Ras-MAPK pathway signalling were studied in cell culture systems, using Western blotting for ERK1/2 phosphorylation, in vitro kinase assays and luciferase assays, to assess activity of downstream targets of the Ras-MAPK pathway. Altered pathway activity was demonstrated for novel variants that had not previously been characterised at the molecular level, which was in keeping with the findings of the effects of previously studied mutations. The cardiac phenotype in animal models of CFC, CS and NS/CFC was explored using expression microarrays to identify potentially important genes and pathways in the pathogenesis of hypertrophic cardiomyopathy (a progressive but potentially treatable disease feature) in these conditions. A signature of increased expression of Myh7, the embryonic form of myosin, was identified in the heart of the mouse model of CFC due to a B-Raf mutation at four weeks postnatal age, but comparative analysis suggested significant differences in either the mechanisms causing cardiac phenotypes, or the timescales over which these may exert their effects, in the three models. In summary, the most significant findings of this work were that SHOC2 mutation is a frequent cause of a severe NCFC presentation, and massively parallel sequencing can be an effective means of molecular investigation of this group of disorders. Novel features of CFC syndrome that were identified include severe contractures in association with p.(Tyr130Cys) mutations in MAP2K1. The analysis of mouse models of the NCFCs was hampered by heterogeneity within the expression microarray results, and low levels of expression of the H-Ras mutant allele in the mouse model of Costellosyndrome.

APA, Harvard, Vancouver, ISO, and other styles

24

Canatsey, Ryan Douglas. "Combination Therapeutic Strategies Targeting Growth and Metabolic Pathways in Prostate Cancer." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/613236.

Full text

Abstract:

Despite recent advances, prognosis in metastatic prostate cancer remains poor. As with other cancers, tumor heterogeneity is an increasingly evident contributor in prostate tumorigenesis and developed resistance. Using in vitro and in vivo model systems, we examined novel diagnostic and therapeutic strategies in prostate cancer. In these studies, combination treatment with amuvatinib, a receptor tyrosine kinase inhibitor, and erlotinib, an epidermal growth factor inhibitor, was assessed for its ability to differentially modulate growth signaling in pathway diverse LNCaP (PTEN⁻) and DU-145 (PTEN⁺) human prostate cancer cell and mouse xenograft models. Our results suggest both individual mechanistic signaling activities, as well as benefits of the combination therapy though modulations of MAPK (pERK) and 4EBP1/cyclin D1 in growth signaling divergent PTEN+ and PTEN- prostate cancer cells. Additionally, despite the importance preanalytical tissue preservation on downstream diagnostic assays, exact protocols are not well defined and highly variable clinically and, as such, critical diagnostic information is lost. We show that a novel 2+2 fixation method induces target- and cell-specific alterations in immunostain intensity and efficacy. Importantly, cyclin D1 is increasingly utilized for as a clinical prognostic/diagnostic marker and demonstrated improved immunohistochemical staining efficacy with 2+2 fixation compared with treatment-matched xenograft protein alterations as assessed by western analysis. Finally, pentoxifylline (PTX) is a clinically utilized and well tolerated PDE inhibitor that has shown promise as a radio-/chemo-sensitization and anti-cancer agent against a variety of cancers. In these studies, we demonstrate that PTX induces cell and tumor growth inhibition in LNCaP prostate cancer cells. Mechanistically, PTX induces transient cellular signaling modulations of both the AMPK metabolic and AKT/mTOR growth pathways, while inducing autophagy. Also, PTX sensitizes LNCaP prostate cancer to cytotoxicity induced by first line chemotherapy docetaxel, inducing significant cellular apoptosis and reducing effective docetaxel concentrations by >10 fold for equivalent toxicity in viability assays. These findings nominate PTX as an adjunct therapy for the treatment of prostate cancer. In summary, these studies characterize the targeted signaling modulation by combination erlotinib and amuvatinib therapy, as well as pentoxifylline, for their use as therapies for prostate cancer. A novel fixation protocol was also assessed for improved diagnostic tissue preservation of critical signaling proteins. Further understanding in these areas will aid and expand the development of effective diagnostics, as well as emphasize the benefits of these and similar therapeutics for the treatment of prostate cancer.

APA, Harvard, Vancouver, ISO, and other styles

25

Bungay, Hilary. "Pathways in the diagnosis and treatment of breast cancer : the significance of delay." Thesis, University of Kent, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369686.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Humphrys, Elka Suzanne. "Understanding the pathways to oesophageal and stomach cancer diagnosis : a multi-methods approach." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289397.

Full text

Abstract:

Increasing symptom awareness, encouraging help-seeking, and facilitating timely referral are key for improving cancer outcomes, particularly for cancers such as oesophageal and gastric (stomach), where five-year survival is less than 20%. In this research, I used multiple methods to explore factors that influence timely diagnosis of these cancers from a patient's perspective, with a particular focus on health literacy (accessing, understanding and using health information, and navigating healthcare systems). I started by exploring current knowledge in this field before conducting a systematic review investigating health literacy in the timely diagnosis of symptomatic cancer. Literature was searched from January 1990-May 2017 using six bibliographic databases. I screened 2304 titles/abstracts, assessed 26 full-text papers and included three, although they were methodologically weak, therefore limiting the conclusions. To examine pathways to diagnosis for oesophageal and gastric cancer, I conducted a questionnaire study of newly diagnosed patients across two hospitals in the East and North East of England. 127 participants were recruited (39.6% recruitment rate), aged 44-96 (median 71); 102 male (80%). Most had oesophageal cancer (n=102, 80%); 64 (50%) of the total cohort were late-stage at diagnosis. Common pre-diagnostic symptoms varied between cancers (oesophageal: difficulty swallowing (n=66, 65%), painful swallowing (n=55, 54%); gastric: fatigue/tiredness (n=20, 80%), weight loss (n=13, 52%)). The questionnaire included two domains (engagement, understanding) of the Health Literacy Questionnaire with participants demonstrating high health literacy (mean 4.18 and 4.28, score 1-5). The median time from noticing the trigger symptom (prompting help-seeking) to diagnosis was 81 days (IQR 45-137.5, n=107). Twenty-six participants were purposively sampled, from questionnaire respondents, for face-to-face interviews (aged 55-88, 18 male, 15 with oesophageal cancer). I undertook thematic analysis to explore participant accounts of their pathways to diagnosis, identifying that the symptom nature was important for appraisal, while health literacy ability influenced the health system interval. Descriptions of 'heartburn', 'reflux' and 'indigestion' differed between participants, suggesting these terms may introduce uncertainty in relation to symptom experience. This is the first study to explore the role of health literacy in the timely diagnosis of symptomatic cancer, and pathways to diagnosis for oesophageal and gastric cancers, from a patient's perspective. Findings provide important insights for the development of targeted awareness campaigns and strategies enhancing GP symptom exploration.

APA, Harvard, Vancouver, ISO, and other styles

27

Wilne, Sophie Helen. "The Pathways Project : developing guidelines to facilitate the diagnosis of childhood brain tumours." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/2881/.

Full text

Abstract:

The Pathways project was undertaken to devise guidelines to facilitate rapid diagnosis of paediatric brain tumours. Methods: A systematic review and meta-analysis of published data on paediatric brain tumour presentation and analysis of the presentation of children newly diagnosed with a brain tumour at four oncology centres was undertaken. The results informed a professional consensus process. Results: 74 papers met the inclusion criteria for the meta-analysis. 56 symptoms and signs at diagnosis were identified. The most frequent symptoms and signs at diagnosis were: headache (33%), nausea and vomiting (32%), abnormalities of gait and coordination (27%), and papilloedema (13%). 139 patients were recruited to a multi-centre cohort study. Symptoms and signs at disease onset and at diagnosis and factors associated with a long and short symptom interval were determined. A shorter symptom interval was associated with nausea and vomiting and motor system abnormalities. A longer symptom interval was associated with head tilt, cranial nerve palsies, endocrine and growth abnormalities and reduced visual acuity. A multi-disciplinary workshop and Delphi consensus voting were used to translate the evidence into a clinical guideline comprising 76 statements advising on the identification and assessment of children who may have a brain tumour.

APA, Harvard, Vancouver, ISO, and other styles

28

Wikström, Git. "Women’s Perspectives on Pathway to Diagnosis of Pulmonary Tuberculosis : Women Voices from Community Level in Uganda." Thesis, Nordic School of Public Health NHV, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:norden:org:diva-3116.

Full text

Abstract:

Objectives: A qualitative study to explore the perceptions and ideas of women at community level in Uganda, about factors influencing their health care-seeking behaviour when symptoms that could indicate pulmonary tuberculosis. To let the women identify barriers to health care-seeking and to let them present ideas how to overcome barriers. Method: Focus Group Discussions (72 informants) and In Depth Interviews (19 informants) were conducted in rural Uganda with women of reproductive age. For triangulation purposes discussions and interviews also included health care providers, traditional healers and a few men. Main Results: The data showed a wide range of health care-seeking behaviours including no action at all, self-treatment using traditional herbs or western medicines, consulting traditional healers and consulting various formal or informal healthcare facilities. The data also identified many barriers that could prevent women from getting a proper diagnosis, including lack of financial resources, lack of power, male supremacy in decision-making, lack of knowledge, perceived corruption in healthcare facilities, fear of stigma and this fear heavily boosted by the idea that PTB equates HIV/AIDS. Conclusion: These data support the idea that successfully fighting PTB among Ugandan women and increasing case finding, demands recognition that tuberculosis is a multifaceted disease: economical, social, psychological and medical. Therefore, approaches to eradicating tuberculosis must target different sectors and reach all levels of society

ISBN 978-91-86739-19-5

APA, Harvard, Vancouver, ISO, and other styles

29

Ayre, Colin A. "Delay to diagnosis and specialist consultation following anterior cruciate ligament injury : a study investigating the nature of, and factors associated with, pathway delay." Thesis, University of Bradford, 2016. http://hdl.handle.net/10454/14627.

Full text

Abstract:

Background: Historically the identification of ACL injuries upon initial presentation is low and considerable diagnostic delays have been reported. However, specific evidence on the individual elements of, and factors which influence delay, is lacking. Aims: The overarching aim was to provide a comprehensive picture of delay to diagnosis and specialist consultation, including factors which influence delay. An additional aim was to determine whether the approach to examining acute knee injuries varied as a consequence of varying patient presentation or experience of the assessing clinician. Methods: Study 1: Cross -sectional survey. Study 2: Non-participant direct observation methodology. Results: Data from 194 patients were analysed in the survey. Only 15.5% of patients were given a correct diagnosis of ACL rupture at the initial consultation. Median delay to diagnosis was 67.5 days (IQR= 15 to 178 days) and specialist consultation 108 days (IQR= 38 to 292 days). The factors most influential on delay were whether a follow-up appointment was arranged after attending A&E, whether the site of attendance operated an acute knee clinic and whether MRI was performed. The direct observation study showed wide variation in approach to injury assessment. Specialist clinicians performed the most comprehensive examination. A&E clinicians were more likely to assess for bony, neurovascular and gross tendon injuries as opposed to ligamentous or meniscal injury. Conclusions: The diagnostic rate of ACL injury at initial presentation remains low. Considerable delays to diagnosis and specialist consultation are apparent following ACL injury, the majority of which is attributable to health system delay.

APA, Harvard, Vancouver, ISO, and other styles

30

Karnam, Anupama. "Role of Wnt/β-catenin pathway in the anti-inflammatory mechanism of therapeutic normal immunoglobulins Wuchereria bancrofti filaria activates human dendritic cells and polarizes T helper 1 and regulatory T cells via toll-like receptor 4 Regulatory T cells induce activation rather than suppression of human basophils." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS642.

Full text

Abstract:

Les immunoglobulines polyclonales intraveineuses (IVIG) sont préparées à partir de plasmas provenant de plusieurs milliers de donneurs sains et utilisées comme traitement dans de nombreuses maladies inflammatoires et autoimmunes. Lors de ma thèse, j’ai investigué si cette thérapie pouvait interférer avec la détection sérique du virus Zika chez des patients atteints du syndrome de Guillain-Barré (GBS). J’ai démontré que la thérapie par IVIG n’interférait pas avec la détection sérique du virus dans le plasma des patients atteints de GBS suivant un traitement aux IVIG. Contrairement aux souris, les IVIG peuvent activer les basophiles humains par une voie différente que celle de l’IL-33. Les IVIG induisent la sécrétion d’Il-4, IL-6 et IL-8 par interaction directe avec les IgE à la surface des basophiles. Cette fonction est dépendante de la fraction F(ab’)2 et implique l’activation de Syk. Ces résultats montrent un nouveau mécanisme dans l’activation des basophiles humains par les IVIG. La dernière partie de ma thèse m’a permis d’étudier le rôle de la voie de signalisation β-caténine sur les effets anti-inflammatoires médiées pars les IVIG. La β-caténine, composante de la voie Wnt, joue un rôle important dans la tolérogénicité des cellules dendritiques (DC) et dans la protection contre l’encéphalomyélite auto-immune expérimentale (EAE). Les données générées montrent que les IVIG activent la voie β-caténine chez les DC humains en plus de la production de Wnt 5a nécessitant une IgG complète ainsi que les co-récepteurs LRP5/6. En dépit de l’induction de β-caténine par les IVIG, cette voie est dispensable pour ses actions anti-inflammatoires in vitro et in vivo dans le modèle EAE
Intravenous immunoglobulin (IVIG) is a therapeutic preparation of pooled normal IgG obtained from the several thousand healthy donors. It is established as first-line therapy for many autoimmune and inflammatory diseases. In the first part of my thesis, I have investigated if IVIG therapy interferes with the serological detection of Zika virus infection in Guillain–Barré syndrome (GBS) patients. By analyzing the plasma of GBS patients treated with IVIG for anti-Zika IgG, I have demonstrated that IVIG therapy in GBS patients does not interfere with the serological Zika detection. The second part addresses the immunoregulatory role of IVIG on human basophil function. Unlike in mice, IVIG does not require DC-SIGN-dependent IL-33 for the activation of human basophils. IVIG directly induces the activation of IL-3-primed human basophils and secretion of IL-4, IL-6, and IL-8 by directly interacting with the basophil surface-bound IgE. This function was F(ab’)2-dependent and involves Syk activation. These results demonstrate a novel mechanism of human basophil activation by IVIG. The last part unravels the signaling pathways associated with IVIG-mediated anti-inflammatory effects specifically the Wnt/β-catenin pathway, which imparts tolerogenic properties to dendritic cells (DCs) and protection against experimental autoimmune encephalomyelitis (EAE). My data shows that IVIG activates β-catenin in human DC along with upregulation of Wnt 5a. Activation of β-catenin requires intact IgG and LRP5/6 co-receptors. However, despite the activation of β-catenin by IVIG, this pathway is dispensable for its anti-inflammatory actions both in vitro and in vivo in the EAE model

APA, Harvard, Vancouver, ISO, and other styles

31

Adair, Carole. "Parental perceptions of the efficacy of diagnostic and educational pathways for children with autistic spectrum disorder in Northern Ireland." Thesis, University of East London, 2010. http://roar.uel.ac.uk/3139/.

Full text

Abstract:

Services for children with autism in Northern Ireland, over the past decade, have been reviewed and developed. The purpose of this study was to explore parental perceptions of the efficacy of resource allocation within education, and to highlight areas for further improvement. Two groups of parents were surveyed, in 1994 and in 2009. Parental opinions in relation to assessment, diagnosis, education and support services were examined across both years, to evaluate the match between the parental definition of effective service delivery and the aims, intentions and actions of the strategic planners. A mixed method design was used, incorporating descriptive and inferential statistics,content analysis of open-ended responses, and a thematic analysis of final comments. The aim was to identify general trends across the participant parent populations (1994 and 2009), in relation to their perceptions of service delivery, but also to record detailed accounts of parents' personal experiences of the present systems. Findings indicated that although assessment and diagnostic procedures for children with autism appear to have improved, following diagnosis, there was still a distinct lack of support, advice and guidance for parents in relation to educational issues. Parents in both years felt that the Special Educational Needs (SEN) system did not cater specifically for children with autistic spectrum disorder, and that a Statement of SEN was a legal necessity to safeguard educational provision and resources. In both 1994 and 2009 parents suggested that schools needed to equip themselves more thoroughly, through training of teachers, and translation of learned skills into classroom practice, to work with the strengths of the children with autism, rather than the deficits. More attention needed to be given to the development of a social skills curriculum and extra-curricular activities. In addition to highlighting parental opinions on the efficient use of scarce resources, this study adds to growing research, illustrating the importance of developing parent professional partnerships in Northern Ireland.

APA, Harvard, Vancouver, ISO, and other styles

32

Yilma, Lemma. "Pathways to diagnosis and treatment : TB patients' experiences in London : a narrative enquiry and analysis." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2011. http://researchonline.lshtm.ac.uk/1379947/.

Full text

Abstract:

The purpose of this study was to understand TB patients' experiential accounts of access to TB diagnosis and treatment and more specifically about their experiences of medical help from health care professionals. METHOD: This narrative enquiry was undertaken in three boroughs of London, including two boroughs with the highest TB notification rates in the UK. The study involved pilot interviews with ten patients to develop the research question. In-depth narrative interviews with 32 additional patients were then undertaken. All participants were over eighteen years of age. The analysis of narratives involved descriptive; holistic-form and categorical content (themes) approaches to identify story 'plot' and 'subplots' and themes covering the whole of the patients' journeys to treatment. RESULTS: Seven narrative plots and thirty subplots were grouped into six categories of medical help and specific themes embedded in them were grouped in three stages of patients' pathways 'before' 'during' and 'after' diagnosis. These themes are listed below sequentially to illustrate these patients' pathways. 1. Symptoms were misinterpreted and misdiagnosed. 2. Kept on ineffective antibiotics/painkillers for many visits. 3. Referred quickly for suspected TB or other serious illnesses. 4. Referred only when critically ill. 5. Referred when antibiotics and pain killers not helping. 6. Referred only after pushing for referral. 7. Sought help from A&E. 8. Diagnosed immediately after TB testing. 9. Referred to wrong specialist and waited too long. 10. Had to fight for TB test. 11. Had lots of tests but no results. 12. Doubts about diagnosis. 13. Felt ignored and had no information. 14. Felt listened and cared for. 15. Quickly began my treatment. 16. Felt better after treatment, no side-effects. 17. Felt better after treatment with side-effects. 18. Felt needed longer treatment. CONCLUSIONS: The accounts of two thirds of the study participants suggest that their doctors' misunderstanding of their illness and miscommunication with them contributed to delayed diagnosis and treatment ranging from one month to twelve months. TB service providers and commissioners need to raise clinical staff awareness about TB and review the factors hindering doctor-patient communication about TB care. The findings in this research indicate that health service related delay is likely to contribute to increased TB transmission rates in the two research settings in London.

APA, Harvard, Vancouver, ISO, and other styles

33

Marinskis, Germanas. "Tachikardijų elektrofiziologinė diagnostika ir nemedikamentinis gydymas." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2009. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2009~D_20090408_085250-65904.

Full text

Abstract:

Šiame darbe apžvelgiama Vilniaus Universiteto Širdies ligų ir kraujagyslių klinikoje 1991−2008 metais sukaupta patirtis taikant nemedikamentinį gydymą pacientams su supraventrikulinėmis tachikardijomis ir skilveliniais ritmo sutrikimais. Apibendrinome nemedikamentinio gydymo rezultatus 1693 pacientams: 753 pacientams su atrioventrikulinio mazgo paroksizmine tachikardija, 657 pacientams su papildomais laidumo takais, 169 pacientams su skilvelinėmis tachikardijomis. Be to, apibendrinome kardioverterių defibriliatorių implantavimo rezultatus 118 pacientų. Nustatėme, kad atrioventrikulinio mazgo tachikardijos kateterinės abliacijos efektyvumas 99,2%, komplikacijų dažnis 0,53%. Įrodėme, kad saugu atlikti „lėtos“ zonos abliaciją pacientams su ilgu PQ intervalu. Papildomų laidumo takų kateterinė abliacija buvo efektyvi 98,1% atvejų, komplikacijų dažnis 1,7%. Papildomų laidumo takų grupėje sudėtingiausios lokalizacijos yra užpakalinė pertvarinė dalis ir vidurinė pertvarinė dalis (pastaroji – dėl rizikos sukelti III laipsnio AV blokadą). Skilvelinių tachikardijų kateterinės abliacijos rezultatas priklauso nuo etiologijos. „Idiopatinių“ skilvelinių tachikardijų atvejais kateterinės abliacijos efektyvumas viršija 90%. Koronarinės širdies ligos ir kardiomiopatijų atvejais kateterinė abliacija mažiau efektyvi (~60%). Kardioverterių defibriliatorių grupėje iki 11 m. stebint pacientus, defibriliatorius suveikė 68,6% atvejų.
This paper reviews the 1991−2008 experience with non-pharmacological treatment of supraventricular and ventricular tachycardias in the Clinic of Heart and vessel diseases of Vilnius University. We summarized the results of managing 1693 patients: 753 patients with atrioventricular nodal tachycardia, 657 patients with accessory pathways, 169 patients with ventricular tachycardias, and 118 patients with implanted cardioverter defibrillators. We have shown that the success rate of catheter ablation for atrioventricular nodal tachycardia is 99.2% with complication rate 0.53%. The safety of ablating the “slow” pathway in patients with prolonged PQ interval has been shown. The success rate of catheter ablation of accessory pathways is 98.1% with 1.7% complication rate. The most complex accessory pathway localization for ablation was posteroseptal area and midseptal area (the latter because of the risk to induce a complete atrioventricular block). The result of catheter ablation for ventricular tachycardia depends on etiology. For “idiopathic” ventricular tachycardias success rate exceeds 90%. In patients with coronary heart disease and cardiomyopathies, catheter ablation is less effective (60%). During the follow-up with duration up to 11 years, 68.6% of patients with implanted cardioverter defibrillators have experienced therapy delivered by the device.

APA, Harvard, Vancouver, ISO, and other styles

34

Jagoret, Patrick. "Analyse et évaluation de systèmes agroforestiers complexes sur le long terme : application aux systèmes de culture à base de cacaoyer au Centre Cameroun." Thesis, Montpellier, SupAgro, 2011. http://www.theses.fr/2011NSAM0012.

Full text

Abstract:

La cacaoculture est aujourd'hui considérée comme un des principaux facteurs de déforestation en milieu tropical. Dans de nombreux pays, elle repose en effet sur un modèle technique peu durable de monoculture intensive impliquant le déplacement des zones de production. Souvent délaissés par la recherche en raison de leurs faibles rendements en cacao marchand, les systèmes agroforestiers à base de cacaoyer apparaissent aujourd'hui comme une alternative crédible pour faire face aux nouveaux enjeux de la cacaoculture mondiale. Au Centre-Sud du Cameroun, la cacaoculture repose en grande partie sur des cacaoyères agroforestières anciennes, ce qui pose l'hypothèse qu'un modèle de cacaoculture durable basé sur des systèmes de culture agroforestiers est possible. Notre objectif est de mieux comprendre le fonctionnement de ces systèmes agroforestiers à base de cacaoyer, à travers leurs caractéristiques, leurs évolutions et leurs déterminants, ainsi que les conditions de leur production en cacao marchand sur le long terme. Notre démarche articule à la fois une évaluation des systèmes agroforestiers complexes à l'échelle de la parcelle et une analyse compréhensive des pratiques techniques sur le temps long. La thèse repose sur un dispositif de recherche mis en place dans la région du Centre, dans trois zones de culture différenciables par leurs conditions pédo-climatiques (Bokito, Zima et Ngomedzap). Une enquête d'agriculteurs a été réalisée à grande échelle (1 171 exploitations regroupant 1 638 cacaoyères), complétée par des observations spécifiques réalisées dans un réseau de 61 cacaoyères exploitées par 40 agriculteurs. Résultats. (1) Nos résultats d'enquête, complétés par des observations spécifiques, ont confirmé la durabilité des systèmes agroforestiers à base de cacaoyer aux plans agro-écologique et socio-économique. (2) Dans la zone de transition forêt-savane, considérée comme sub-optimale pour la cacaoculture, nous avons montré que le modèle technique adopté par les agriculteurs leur permet d'installer sur savane des cacaoyères viables sur le long terme. (3) Une méthode participative de quantification de la valeur d'usage des espèces par les agriculteurs, appliquée sur le réseau d'observation, a confirmé la multifonctionnalité des systèmes agroforestiers et mesuré la place qu'y occupe la composante cacaoyère. (4) L'évaluation des peuplements cacaoyers, réalisée en adaptant la méthode de diagnostic agronomique régional aux systèmes complexes, a permis d'identifier les facteurs limitant le rendement en cacao marchand. Celui-ci s'avère étroitement lié à la structure des peuplements cacaoyers et à celle des peuplements associés. (5) Enfin, l'analyse compréhensive des pratiques des agriculteurs sur le long terme, en lien avec l'évolution technique des peuplements cacaoyers a confirmé la flexibilité des systèmes agroforestiers à base de cacaoyer. Cette flexibilité peut être traduite par des trajectoires d'évolution des pratiques et des trajectoires de structures spécifiques. Ce travail fournit une nouvelle base méthodologique pour l'analyse et l'évaluation des systèmes agroforestiers complexes. L'ensemble des résultats et des connaissances produites dans ce travail permet de formuler des propositions pour la mise au point d'un nouveau modèle technique en cacaoculture
Cocoa cultivation is generally considered as one of the main deforestation factors in the Tropics. Indeed, in many countries it is based on a low-sustainability technical model of intensive monocrops with shifting production zones. Cocoa agroforests, which are often neglected by research due to their low fermented dried cocoa yields, now appear to be a credible alternative for taking up the new challenges facing world cocoa production. In Centre-South Cameroon, cocoa cultivation is largely based on old cocoa agroforests, which suggests that a sustainable cocoa growing model based on agroforestry systems is possible. Our aim was to more effectively understand how these cocoa agroforests function, through their characteristics, their evolution and their determinants, along with the conditions for their long-term fermented dried cocoa production. Our approach consisted of an evaluation of cocoa agroforests on a plot scale and a comprehensive analysis of technical practices over the long term. The thesis is based on an experimental design set up in the Centre region, in three growing zones that could be differentiated through their pedo climatic conditions (Bokito, Zima and Ngomedzap). A large-scale survey was undertaken (1,171 farms grouping 1,638 cocoa plantations) completed by specific observations collected in a network of 61 cocoa agroforests managed by 40 farmers. Results. (1) Our survey results, completed by specific observations, confirmed the sustainability of the cocoa agroforestry systems from an agro ecological and socio-economic viewpoint. (2) In the forest-savannah transition zone, which is considered sub-optimum for cocoa cultivation, we confirmed that the technical model adopted by the farmers enabled them to set up cocoa agroforests on savannah that were viable over the long term. (3) In the network, a participatory method applied to quantify the use value given to the species by the farmers confirmed the multi-functionality of cocoa agroforests and measured the place occupied in it by cocoa. (4) The evaluation of the cocoa tree stands, achieved by adapting the regional agronomic diagnosis method to complex systems, revealed the factors limiting cocoa yield. It was proved that cocoa yield is closely linked to the structure of the cocoa tree stand and that of the intercropped stands. (5) Lastly, a comprehensive analysis of farmer practices over the long term, in association with the evolution of the technical management of the cocoa tree stands, confirmed the flexibility of cocoa agroforestry systems. This flexibility was reflected in the evolution pathways for specific practices and structures. This work provides a new methodological basis to assess the performance of complex agroforestry systems. All the results and knowledge produced by this work make it possible to draw up proposals for developing a new technical model for cocoa growing

APA, Harvard, Vancouver, ISO, and other styles

35

Namaki, Araghi Sina. "A methodology for business process discovery and diagnosis based on indoor location data : Application to patient pathways improvement." Thesis, Ecole nationale des Mines d'Albi-Carmaux, 2019. http://www.theses.fr/2019EMAC0014.

Full text

Abstract:

Dans chaque organisation, les processus métier sont aujourd’hui incontournables. Cette thèse vise à développer une méthode pour les améliorer. Dans le domaine de la santé, les organisations hospitalières déploient beaucoup d’efforts pour mettre leurs processus sous contrôle, notamment à cause de la très faible marge d’erreur admise. Les parcours des patients au sein des structures de santé constituent l’application qui a été choisie pour démontrer les apports de cette méthode. Elle a pour originalité d’exploiter les données de géolocalisation des patients à l’intérieur de ces structures. Baptisée DIAG, elle améliore les parcours de soins grâce à plusieurs sous-fonctions : (i) interpréter les données de géolocalisation pour la modélisation de processus, (ii) découvrir automatiquement les processus métier, (iii) évaluer la qualité et la performance des parcours et (iv) diagnostiquer automatiquement les problèmes de performance des processus. Cette thèse propose donc les contributions suivantes : la méthode DIAG elle-même qui, grâce à quatre différents états, extrait les informations des données de géolocalisation ; le méta-modèle DIAG qui a deux utilités : d’une part, interpréter les données de géolocalisation et donc passer des données brutes aux informations utilisables, et, d’autre part contribuer à vérifier l’alignement des données avec le domaine grâce à deux méthodes de diagnostic décrites plus bas ; deux algorithmes de découverte de processus qui utilisent la stabilité statistique des logs d’évènements ; une nouvelle approche de process mining utilisant SPC (Statistical Process Control) pour l’amélioration ; l’algorithme proDIST qui mesure les distances entre les modèles de processus ; deux méthodes de diagnostic automatique de processus pour détecter les causes des déviations structurelles dans des cas individuels et pour des processus communs. Le contexte de cette thèse confirme la nécessité de proposer de telles solutions. Une étude de cas dans le cadre de ce travail de recherche illustre l’applicabilité de la méthodologie DIAG et des fonctions et méthodes mentionnées
Business processes are everywhere and, as such, we must acknowledge them. Among all of them, hospital processes are of vital importance. Healthcare organizations invest huge amount of efforts into keeping these processes under control, as the allowed margin of error is so slight. This research work seeks to develop a methodology to endorse improvement of patient pathways inside healthcare organizations. It does so by using the indoor location data of patients. This methodology is called DIAG (Data state, Information state, Awareness, Governance). It is constructed of several different functions. The most important ones are as follows: (i) location data interpreting, (ii) automatic discovery of business process models, (iii) business process analyzing for evaluating the performance and quality of processes, and finally, (iv) automatic diagnosing of business processes. Along the former functions, the contribution of this thesis are: The DIAG methodology which, through four different states, extracts knowledge from location data; the DIAG meta-model which supports both the interpretation of location data (from raw data to usable information) and the alignment of the domain knowledge (which are used for the diagnosing methods); two process discovery algorithms which explore statistical stability in event logs, application of Statistical Process Control (SPC) for the “enhancement notation” of Process Mining; the ProDIST algorithm for measuring the distance between process models; two automatic process diagnosing methods to detect causes of structural deviations in individual cases and common processes. The state of the art in this dissertation endorses the necessity for proposing such solutions. A case study within this research work illustrates the applicability of the DIAG methodology and its mentioned functions and methods

APA, Harvard, Vancouver, ISO, and other styles

36

Yeung, Yuet-wah, and 楊月華. "Role of social networks in the pathway to care of Chinese people living with a diagnosis of severe mental illness in England." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50662314.

Full text

Abstract:

Background: Current literature suggests that there is an underutilisation of mental health services among Chinese people in England and that most Chinese people only come into contact with mental health services when a crisis occurs. However, there is limited evidence to enhance understanding of how they enter and navigate through the mental health systems. Objectives: This study aimed to examine the pathway experience of Chinese people living with a diagnosis of severe mental illness and the experience of their social networks who became involved in this journey. Methodology: Adopting a phenomenological approach, this study involved 55 interviews relating to 16 Chinese people with severe mental illness. Participants included Chinese people with severe mental illness, their families and Chinese speaking workers working in different service settings. Data was analysed with the aid of the QSR Nvivo software program. Findings: This was the first qualitative study to help understand the experience of Chinese people with severe mental illness in England. It confirmed that language difference, a lack of knowledge about how to access mainstream services and different conceptualisation of the experience of mental illness were significant barriers to seeking help. However, contrary to existing literature, this study found that not all Chinese people with severe mental illness experienced delays in receiving professional support. The health beliefs and attitude of their social networks towards mental illness were the main factors shaping the duration and direction of individual journey. Family played an important role throughout this journey but most families did not have adequate resources to meet the mental health needs of their relatives. Therefore, they had to seek help from mental health professionals, Chinese speaking workers and their overseas connections. Discussion: The stigma attached to mental illness was reported as the key explanation for delays in help-seeking. The impact of stigma was felt more strongly by Chinese male than female family members. The worry that mental illness would ruin the family name and the family would lose face in the community explained the reluctance of Chinese men to seek help for their close relatives with severe mental illness. Chinese speaking workers provided vital resources for Chinese people to access mainstream mental health services. However, the strong belief in self-reliance and the perception that Chinese people held a more stigmatising attitude towards people with mental illness explained why some participants were resistant to seek help from outsiders, especially people from the Chinese community. Additionally, Chinese people living in remote areas were unable to reach and access these resources because of the unavailability of such resources in rural areas. Conclusion: This study expands our conceptual understanding of how the stigma associated with mental illness impacts on the utilisation of mental health services among Chinese people in England. Chinese speaking workers play an important role in facilitating access to mental health services. Hence, it is important to explore and develop different strategies to de-stigmatise mental illness so that Chinese people living in different parts of England can utilise resources from the Chinese and wider community.
published_or_final_version
Social Work and Administration
Doctoral
Doctor of Philosophy

APA, Harvard, Vancouver, ISO, and other styles

37

Oliveira, Elaine Aparecida de. "Desenvolvimento e avaliação de uma ferramenta para diagnostico da literacia visual, contextualizada no estudo de vias metabolicas." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314741.

Full text

Abstract:

Orientador: Eduardo Galembeck
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-15T17:08:58Z (GMT). No. of bitstreams: 1 Oliveira_ElaineAparecidade_M.pdf: 4028860 bytes, checksum: 12a75ba90b00d8eded4dc1107cc6168a (MD5) Previous issue date: 2010
Resumo: Representações externas são muito utilizadas no ensino de bioquímica. As vias metabólicas constituem um tipo de representação externa e envolvem habilidades visuais; estão, portanto, intimamente relacionados à literacia visual (capacidade de interpretar imagens). Há uma preocupação crescente em diagnosticar a dificuldade dos estudantes com a bioquímica. Este tipo de diagnóstico é importante para poder propor soluções pedagógicas que possam facilitar o aprendizado. O presente trabalho tem como objetivo descrever o desenvolvimento e a aplicação de um teste informatizado para diagnosticar a literacia visual, relacionada ao estudo de vias metabólicas, de estudantes de cursos das áreas biológica e da saúde. Inicialmente foram desenvolvidos testes piloto com itens (modelos e questões) que contemplavam habilidades visuais para a compreensão de vias metabólicas mais frequentemente representadas em livros didáticos de bioquímica. Os testes piloto foram aplicados em 2007 e 2008 com turmas de graduação de cursos da área biológica e da saúde. Os resultados obtidos serviram de subsídio para que alguns itens fossem reformulados e outros adicionados. Os resultados obtidos foram tratados com uso do modelo de Rasch, tanto no processo de equalização dos testes piloto (para definir os itens do teste final), como para o tratamento dos resultados obtidos com a calibração de itens-respondentes após as aplicações do teste final. Três grupos participaram da aplicação do teste final e compreenderam 79 estudantes distribuídos entre os cursos de educação física (UNICAMP), enfermagem (UNICAMP) e fisioterapia/nutrição (FAJ). A partir dos dados obtidos utilizou-se o processo de calibração de itens-respondentes, proposta pelo modelo de Rasch, obtendo-se a dificuldade dos itens e as habilidades visuais apresentadas pelos grupos. Os resultados observados sugerem que entre as dificuldades apresentadas pelos estudantes no aprendizado de metabolismo pode ser incluída a dificuldade em se compreender as representações externas de vias metabólicas. Essa dificuldade pode ser minimizada com explicações dos modelos antes de se entrar nos conteúdos específicos. O teste produzido permite o diagnóstico de estudantes ou de grupos. A necessidade de desenvolver práticas de visualização para melhorar a compreensão de conceitos bioquímicos pelos estudantes mostrou-se um aspecto importante no estudo de vias metabólicas
Abstract: External representations are used in teaching of biochemistry. The metabolic pathways are a type of external representation and involve visual skills, are therefore closely related to visual literacy (ability to interpret images). There is an increasing concern regarding the diagnosis of students with difficulty to the biochemistry, this type of diagnosis is important to be able to propose solutions that would facilitate learning. This paper aims to describe the development and implementation of a computerized test to diagnose the visual literacy, related to the study of metabolic pathways for undergraduate students enrolled in courses in the biological and health. Initially, pilot tests have been developed with (models and items) that looked visual skills for the understanding of metabolic pathways most often represented in textbooks of biochemistry. The pilot tests were applied in 2007 and 2008 on undergraduate classes of various courses in the biological and health. The results served as a subsidy for some items were reformulated and others added. The results are processed using the Rasch model, both in the process of equalizing the pilot tests (for set of the final test) and for the treatment of the results obtained with calibration of items-respondents the applications for the final test. Three groups participated in the implementation of the final test and included 79 students distributed among the courses of physical education (UNICAMP), nursing (UNICAMP) and physiotherapy/nutrition (FAJ). From the data we used the calibration of items-respondents proposed by Rasch model resulting in the difficulty of items and visual skills presented by the groups. The results suggest that among the difficulties presented by the students in the learning of metabolism may be included the difficulty in understanding the external representations of metabolic maps. This difficulty can be minimized with the explanations of the models before they enter the specific content. The test produced allows the diagnosis of students or groups. The need of developing imagery to improve the understanding of biochemical concepts by students were an important aspect in the study of metabolic pathways
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular

APA, Harvard, Vancouver, ISO, and other styles

38

Jordan, Sumanas W. "A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33907.

Full text

Abstract:

A mathematical model of blood coagulation under defined flow conditions, initiated and modulated by spatially discrete regions of surface bound tissue factor (TF) and thrombomodulin (TM), respectively, is presented. The model incorporates fluid phase and surface-associated reactions of the extrinsic, intrinsic, and common pathways, as well as three inhibitory pathways. The spatially heterogeneous model is formulated by finite element method, and an effective prothrombotic zone, which quantifies the spatial propagation of thrombin generation is defined. Characteristic features of coagulation are simulated under physiologic conditions, and the behavior of the system in response to perturbations in TF and TM surface densities, TF site dimensions, and wall shear rate is explored. The major findings of these studies include: (i) The model system responds in an 'all-or-none', threshold-like manner to changes in model parameters. (ii) It was found that prothrombotic effects may extend significantly beyond the dimensions of the spatially discrete site of TF expression in both axial and radial directions. (iii) The relationship between the length of the effective prothrombotic zone and the interval distance between tandem sites of TF expression dictate the net response of the system. Additive prothrombotic effects of sub-clinical lesions as well as suppressive antithrombotic effects of intervening TM-containing regions were observed. Secondly, the computational model is applied to calculate an individualized, systems-based metric of clotting potential for 210 pre-menopausal women in the Leiden Thrombophilia Study (LETS). The simulated variable was found to be a highly predictive parameter for deep venous thrombosis risk.

APA, Harvard, Vancouver, ISO, and other styles

39

Bailey, Janelle Lee. "Language Pathways Defined in a Patient with Left Temporal Lobe DamageSecondary to Traumatic Brain Injury: A QEEG & MRI Study." BYU ScholarsArchive, 2014. https://scholarsarchive.byu.edu/etd/4363.

Full text

Abstract:

Though the current understanding of language processing is incomplete, it has been established that the left hemisphere is dominant for language in the majority of the population. Damage to language centers of the brain and to white matter tracts connecting these language centers results in a language deficit known as aphasia. Neuroplasticity in the brain can often compensate for these language deficits by strengthening neuronal connections between the right and left hemisphere, or by enhancing the neuronal connectivity of undamaged areas in the left hemisphere. Thus the brain can compensate for damaged language centers by using alternative cortical areas. These compensatory language areas may be homologous areas of the right hemisphere, or other undamaged portions of the left hemisphere. Various imaging techniques have been used to demonstrate this phenomenon. The current neuroimaging technique known as quantitative electroencephalographic brain imaging allows investigators to evaluate the functional anatomical location of language processing. When this mapping is overlaid on a magnetic resonance image, investigators are able to locate areas in the brain of the participant that are electrically activated during elicited speech tasks. This method was used in a single case study to examine the brain of an individual with a unique traumatic brain injury in which the anterior portion of the individual's left temporal lobe was surgically removed and considerable recovery of language subsequently occurred. The stimulus for the quantitative electroencephalography included identifying syntactically incorrect sentences. Imaging results from the participant with traumatic brain injury were compared to imaging results obtained from an age-matched control. Differences in quantitative electroencephalography between the two participants included a delayed P1-N1-P2 response and an absent P600 in the participant with traumatic brain injury. Behavioral results include an increased number of incorrect responses from the participant with traumatic brain injury as compared to the control participant. These results imply an interesting cortical distribution of language processing that could be further assessed by functional magnetic resonance imaging.

APA, Harvard, Vancouver, ISO, and other styles

40

Powell, Tim. "Investigating the molecular underpinnings of major depressive disorder and the utility of biomarkers in the inflammatory cytokine pathway as aids for clinical diagnosis and treatment selection." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/investigating-the-molecular-underpinnings-of-major-depressive-disorder-and-the-utility-of-biomarkers-in-the-inflammatory-cytokine-pathway-as-aids-for-clinical-diagnosis-and-treatment-selection(c75d417f-13f8-4618-91de-96ce798a8336).html.

Full text

Abstract:

Major depressive disorder (MDD) is a complex, heterogeneous disorder characterised by a pathological distortion of emotional mood. There is evidence of both genetic and environmental risk factors for MDD, and gene-environment interactions may play a particularly important role. Clinically, MDD is defined by patients meeting a number of diagnostic criteria. However, the heterogeneous nature of the disorder can make MDD difficult to diagnose, especially as it shares close similarities with other psychiatric illnesses such as bipolar disorder. Another clinical problem is that antidepressants, the first line of treatment for MDD, are ineffective in a significant proportion of patients. The projects in this thesis address four aims: (i) the identification of novel gene-environment interactions which may increase risk for MDD; (ii) the identification of diagnostic biomarkers for MDD; (iii) the identification of biomarkers for the prediction of treatment response to antidepressants; and (iv) the identification of transcriptional changes associated with antidepressant treatment and successful therapeutic response. Utilising a model of early life stress in two inbred mouse strains, we investigated the transcriptional effects of maternal separation. The top stress by strain interaction was found in the telomerase RNA component gene (Terc). We also found that a single nucleotide polymorphism in TERC (rs10936599), previously identified as a predictor of telomere length, interacted with childhood neglect to predict MDD in a human case-control cohort. A study investigating differences in the transcription of inflammatory cytokines in the blood of MDD patients, bipolar disorder patients and controls, revealed disorder-specific differences in chemokine (C-C motif) ligand 24 and CC chemokine receptor type 6 which specifically differentiated MDD patients. Furthermore, we found that transcription of tumour necrosis factor and its targets in the inflammatory cytokine pathway, and DNA methylation in interleukin-11 could be used to predict antidepressant response amongst MDD patients. Moreover, transcription of ATP-binding cassette sub-family F member 1 was found to increase on antidepressant treatment, with the magnitude of change corresponding to clinical response.

APA, Harvard, Vancouver, ISO, and other styles

41

Porchet, Nicolas. "Role of signaling pathays in cell-fate specification in the early mouse embryo." Thesis, Université de Paris (2019-....), 2019. http://www.theses.fr/2019UNIP7096.

Full text

Abstract:

Lors du développement précoce de l’embryon de souris, divers évènements de spécification des destins cellulaires induisent la formation du blastocyste pré-implantatoire. Ces évènements sont majoritairement contrôlés par l’action de voies de signalisation activées via la fixation de molécules signal à la membrane de la cellule. L’activité de ces voies de signalisation permet la régulation de la transcription de gènes cible responsable de l’acquisition d’une identité cellulaire et de son arrangement sous forme de tissu. Ici je m’intéresse aux rôles des voies ACTIVINE/NODAL et βCATENIN dans la spécification de ces identités cellulaires lors de la formation du blastocyste de souris
During the early mouse embryogenesis, cell-fate specification events result in the formation of the pre-implantation blastocyst. Those events are mainly regulated by the action of signaling cascades activated upon fixation of the signaling molecules at the cell membrane. The activity of these signaling pathways allow the transcriptional regulation of a specific pool of genes responsible for cell-fate decisions and the formation of tissues. Here, I am interested in the roles of both ACTIVIN/NODAL and βCATENIN signaling pathways in the specification of cell identities during the maturation of the mouse blastocyst

APA, Harvard, Vancouver, ISO, and other styles

42

O'Donnell, Melissa. "Towards prevention - a population health approach to child abuse and neglect : health indicators and the identification of antecedent causal pathways." University of Western Australia. School of Paediatrics and Child Health, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0029.

Full text

Abstract:

[Truncated abstract] The primary aims of this thesis were to investigate health indicators of child maltreatment, as well as pathways into the child protection system using routinely collected government databases, enabling a preventative health approach to child abuse and neglect. This thesis aims to improve understanding of the trends in child maltreatment and the factors, at the child and family level, which increase or reduce vulnerability to child maltreatment so more effective prevention policies and practices can be developed. This project uses longitudinal de-identified population data from the Western Australian Government Departments of Child Protection, Health and Disability Services. These data contained information on demographic, clinical, social and child protection outcomes of children and their families. Record linkage of administrative data was undertaken to: investigate health indicators of abuse and neglect using Hospital Morbidity data to enable the monitoring of population trends in abuse and neglect; compare proportion of cases obtained using health indicators with the Department of Child Protection data, and describe the physical, psychological and social characteristics of abused and/or neglected children and families. Statistical techniques utilised include logistic and Cox regression to investigate risk of adverse child outcomes, taking into account potential confounding and time to event. The main findings include: There has been an increase in assault and maltreatment related hospital admissions over the last 25 years. ... There has been a marked increase in the birth prevalence of Neonatal Withdrawal Syndrome (NWS) in Western Australia over the last 25 years, from 1 per 10,000 live births in 1980, to 31 per 10,000 live births in 2005. Specific maternal characteristics associated with having a child with NWS are identified and these children have an increased risk of child protection involvement. A population level analysis of child and parental factors determined the estimated increase in risk of substantiated child maltreatment for child intellectual disability, parental admissions for mental health, substance use, and assault, as well as greater socio-economic disadvantage. Conclusions This is the first body of research which has extensively used longitudinal, population level linked health and child protection data to investigate health indicators of child abuse and neglect and antecedent causal pathways. Monitoring injuries and conditions associated with child abuse and neglect in routinely collected data and using multiple sources of ascertainment are important initiatives in child maltreatment surveillance. Health indicators of child abuse and neglect are not subject to the same definitional and policy issues as child protection data and therefore provide a more valid comparison over time and between jurisdictions. The identification of factors which increase vulnerability for children and families to child maltreatment is essential in the implementation of prevention strategies including universal public health approaches as well as the identification of at-risk families for targeted intervention.

APA, Harvard, Vancouver, ISO, and other styles

43

Petkova, Hristina. "How gene tests travel : bi-national comparison of the institutional pathways taken by diagnostic genetic testing for Maturity Onset Diabetes of the Young (MODY) through the British and the German health care system." Thesis, University of Exeter, 2008. http://hdl.handle.net/10036/47558.

Full text

Abstract:

Scientific developments in genetics receive great public and political attention. However, genetic tests as medical innovations need to travel from the laboratory to the individual patient in order to fulfil the goal that makes the science so attractive. A medical innovation has to pass through the institutions of diverse health care systems. This thesis compares how the structures of two very different health care systems in Europe (Germany and the UK) foster or hinder the diffusion of genetic technologies. It presents a detailed analysis of the institutional pathways involved in order to discuss whether and in which way the kind of medical innovation that genetic testing represents is accommodated. The case study used for analysing the passage of a genetic test in both countries is diagnostic testing for Maturity Onset Diabetes of the Young (MODY). This example has the idiosyncratic dimension that it had strong support by scientists and government when the UK Government prioritized genetics in health policy. However, MODY testing was chosen for this study because MODY is a ‘simple’ monogenetic test, and it is one of the few at present that are both reliable and lead to altered treatment with a better quality of life for the patient. MODY represents, according to the current state of genomic knowledge, a prime example of what genetics is likely to deliver at best over the coming decades. In brief, the comparison of the pathways MODY travelled and the degree to which it reached patients successfully shows that both systems are not optimally set up to exploit what MODY genetic testing has to offer, but that the vertical structure and centralization in the UK system fit the needs of genetic medical innovations better than the horizontal, diversified and market oriented structures dominating the German health care system.

APA, Harvard, Vancouver, ISO, and other styles

44

Hill, Owen T. "Improving prostate cancer detection in veterans through the developement of a clinical decision rule for prostate biopsy." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001575.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Oliveira, Joana Isabel Remoaldo. "Lesões endo-perio." Master's thesis, [s.n.], 2014. http://hdl.handle.net/10284/4586.

Full text

Abstract:

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
Introdução: Este trabalho teve como objetivo a realização de uma revisão de literatura sobre a doença endo-perio. Nesta medida, foram exploradas as relações biológicas entre a polpa e o periodonto, nomeadamente as vias de comunicação existentes, os fatores que contribuem para o seu aparecimento, persistência e/ou agravamento, tendo sido sublinhados os factores etiológicos e a influência da patologia pulpar no periodonto e viceversa. Foram, também, referidas as principais classificações das lesões endo-perio e a problemática do diagnóstico, tratamento e prognóstico dos dentes envolvidos. Materiais e métodos: Esta revisão foi realizada com o limite temporal de 1975 a 2014, recorrendo ao motor de busca Google e às bases de dados Medline/ PubMed, B-on, Science direct, utilizando as seguintes palavras-chave: endo-perio lesions, classification of endo-perio lesion, microbiology, pathways of communication, diagnosis in endoperio lesions, treatment of endo-perio lesions. Após a leitura dos resumos, a seleção dos artigos foi efectuada de acordo com a especificidade do tema e com os limites temporais acima referidos. Foram, ainda, consultados livros na área de Endodontia na biblioteca da FCS-UFP. Os critérios de exclusão dos artigos foram os artigos pagos e aos quais não se obteve resposta por parte dos seus autores e os que não abordassem directamente o tema em estudo. Resultados: Na literatura consultada, a principal causa apontada para as lesões é de origem microbiana: a microbiologia de lesões endo-perio combinadas, dominada por anaeróbios facultativos e/ou obrigatórios, reflete a microbiota da lesão endodôntica e periodontal em separado e permite infeção cruzada entre o canal radicular e a bolsa periodontal. Os tratamentos endodônticos inadequados, as infiltrações coronais, o atraso da colocação da restauração definitiva, as características anátomo-morfológicas do sistema de canais radiculares, as obturações anteriores, as técnicas de instrumentação e de obturação e a escolha dos materiais, são factores amplamente referidos na literatura que influenciam as falhas do tratamento. Enquanto a polpa mantém funções vitais, mesmo com infeção, a probabilidade desta causar problemas no periodonto é baixa; pelo contrário, a necrose pulpar já é, frequentemente, associada a inflamação do tecido periodontal. Conclusões: Como principal conclusão, deve ser salientado o facto da polpa e do periodonto se constituírem como uma unidade biológica contínua, com múltiplas vias de comunicação, pelo que as doenças pulpares e as doenças periodontais podem influenciarse mutuamente. Pode, igualmente, ser realçado que as doenças endodôntica, periodontal e endodôntica- -periodontal podem apresentar os mesmos sintomas, aspectos radiográficos e sinais clínicos muito semelhantes, sendo que o tratamento e o prognóstico dependem, em primeiro lugar, do diagnóstico da doença endodôntica e/ou periodontal específica, pelo que os principais fatores a considerar na tomada de decisão do tratamento devem ser a vitalidade pulpar e também o tipo e extensão da doença periodontal. A classificação mais utilizada pela maioria dos autores e nos livros da área é a de Simon et al. 1972, que se baseia nos fatores etiológicos e descreve o desenvolvimento deste tipo de lesões; no entanto, os seus fatores etiológicos e os seus padrões patológicos são muito diversos, facto que, ainda, não permitiu o aparecimento de uma classificação totalmente satisfatória. Introduction: This study aimed to conduct a literature review regarding the perio-endo disease. To this extent, the biological relationship between the pulp and the periodontium were explored, including the existing means of communication, the factors that contribute to its onset, persistence and / or worsening, and highlighting the etiological factors and the influence of pulp pathology in the periodontium and vice versa. The main classifications of endo-perio lesions were presented along with the problem of diagnosing, treating and the prognosis of teeth involved. Materials and Methods: This review was performed with the time limit of 1975 to 2014, using the search engine Google and several databases such as Medline / PubMed, B-on, ScienceDirect using the following keywords: endo-perio lesions, classification of endoperio lesion, microbiology, pathways of communication, diagnosis in endo-perio lesions, treatment of endo-perio lesions. After reading the abstracts, the selection of articles was performed according to the specificity of the topic and the time limits mentioned above. Books in the field of endodontics were also consulted in the FCSUFP library. Excluding criteria was used on articles that needed purchase and to which there was no response on the part of their authors and on the ones that didn’t directly address the topic under study. Results: In this review, the main reason given for the lesions is of microbial origin: the microbiology of combined endo-perio lesions that are dominated by facultative and / or strict anaerobes, reflects the microbiota of endodontic and periodontal lesion separately and allows cross-infection between the root canal and the periodontal pocket. Inadequate endodontic treatment, coronal leakage, delay placing the final restoration, the anatomical and morphological characteristics of the root canal system, previous fillings, technical instrumentation and obturation, and the choice of materials, are widely referred to factors in literature that influence treatment failures. As long as the pulp retains vital functions, even when infected, the likelihood of this infection causing problems in the periodontium is low; in contrast, pulp necrosis is often associated with tissue inflammation of the periodontium. Conclusions: As the main conclusion, it should be emphasized that the pulp and periodontium are constituted as a continuous biological unit, with multiple communication paths, so the pulp diseases and periodontal diseases can have a mutual influence. It may also be noted that the endodontic, periodontal and endodontic-periodontal diseases may present the same symptoms, radiographic features and similar clinical signs, therefore the treatment and prognosis depend, firstly on the diagnosis of the specific endodontic and/or periodontal disease, and the main factors to consider in making the decision to treat should be the pulp vitality and also the type and extent of periodontal disease. The classification used by the majority of authors and books in the area is that of Simon et al. 1972, which is based on etiological factors and describes the development of such injuries; however, their etiological factors and their pathological patterns are very diverse, which makes it difficult to have a fully satisfactory classification.

APA, Harvard, Vancouver, ISO, and other styles

46

Hajdarevic, Senada. "Patient and health care delays in malignant melanoma." Doctoral thesis, Umeå universitet, Dermatologi och venereologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-54392.

Full text

Abstract:

Background: Unlike other cancers, malignant melanoma (MM) is generally visible and can be easily and effectively cured if treated in time. Optimal cure of MM requires early detection, diagnosis, and treatment, which improves prognosis. However, patients as well as the health care organization and its professionals contribute to delayed treatment in various ways. Aims and objectives: The general aim of this PhD thesis was to explore reasons for delay in care seeking, diagnosis, and treatment of malignant melanoma. The specific objectives to be addressed were To explore patients’ decision making about seeking care for malignant melanoma To identify specific patterns in the decision-making process to seek care for suspect melanoma, as narrated by women and men To compare self-reported decision making coping styles between men and women in various ages, who live with or without a partner and are diagnosed with various stages of malignant melanoma in northern Sweden. To describe and compare patients diagnosed with MM, depending on their initial contact with care, and with regard to age, sex, and MM type and thickness, and to explore pathways and time intervals between clinics from the initial contact to diagnosis and treatment. Methods: In studies I and II, 21 and 30 patients, respectively, were interviewed about their decision making to seek care for MM. Study II focused on gender patterns in this decision making. The interviews were analysed using Grounded Theory (I) and qualitative content analysis (II). Study III included 270 people with MM who completed a translated questionnaire (Melbourne Decision Making Questionnaire) about coping styles in decision making. In study IV the pathways and time delay in health care for 71 people with MM were explored. Studies I and II were qualitative, whereas studies III and IV were quantitative. Results: In study I, the insights into severity and feelings of fear and existential threat were identified as key motivators for patients to decide to seek care for a suspected melanoma. Results in study II showed that gender constructions influenced the care-seeking behaviour. Women acknowledged the skin changes and attempted self-care first. They delayed care seeking due to family responsibilities. Men seldom acknowledged the suspicious skin change, but sought care immediately after prompting, and most often complied with relatives’ advice to seek care. Study III showed that men generally scored higher in buck-passing, while women and those living without a partner scored higher in hypervigilance. Participants with nodular melanoma (NM), a rapid-growing form of MM, scored higher in vigilance than those diagnosed as in situ melanoma. No correlation was found between tumour thickness and coping styles. Some differences concerning treatment of MM were found in study IV between people who initially had sought care at primary health care centres (PHC) and those who had sought care at dermatological and specialist clinics (Derm). Thicker tumours as well as NM were more common in the PHC group. A larger proportion of patients from PHCs were primarily excided within the primary health care; however, almost all of them were later referred to surgical clinics for wide excision. Patients within the PHC group also had to wait longer for the registered results of histopathological assessments. In general, women waited a shorter time for primary excision, and older people waited longer for wide excision. Conclusions: Time delay of diagnosis and treatment of MM is still common, and crucial to decrease. Future interventions should include gender aspects to influence people to seek care earlier. In health care, time delay could be decreased by facilitating access for patients with suspected skin melanomas, but also by reducing unnecessary referrals. Moreover, organizational changes whereby general practitioners and primary health care nurses are supported in using new technology for faster diagnoses and management of MM in collaboration with specialist clinics should be considered. Easy access and frequently used guidelines for MM could further decrease delay. Lastly, more efficient transfer and registration of laboratory results and referrals could decrease delay and improve patient safety.
Bakgrund: Malignt melanom (MM) är till skillnad från andra cancerformer ofta synlig och kan enkelt och kostnadseffektivt botas om det behandlas i tid. En optimal prognos av MM förutsätter tidig upptäckt, diagnos och behandling. Patienter, samt hälso- och sjukvården, dess organisation och dess personal kan på olika sätt bidra till fördröjning av behandlingen av MM. Syfte: Det övergripande syftet med denna avhandling var att undersöka orsaker till fördröjning att söka vård, diagnosticera och behandla malignt melanom. Specifika delsyften var: Att utforska patienternas beslutsfattande process att söka vård för MM Att identifiera specifika mönster i beslutsfattande-processen att söka vård för misstänkt MM utifrån kvinnors och mäns egna berättelser Att jämföra självrapporterade coping-stilar i den beslutsfattande processen mellan män och kvinnor i olika åldrar, boende med eller utan partner, och diagnosticerade med MM i olika stadier från norra Sverige Att beskriva och jämföra patienter med MM utifrån deras primära vårdkontakt samt utifrån ålder, kön, MM-typ och tjocklek. Ytterligare att utforska vård- och remissvägar samt tidsintervaller mellan olika kliniker från första kontakt till diagnos och behandling. Metod: I studie I och II, intervjuades 21 respektive 30 patienter om den beslutsfattande processen att söka vård för MM. Genuskonstruktioner i relation till den beslutsfattande processen var i fokus i studie II. Intervjuerna analyserades med hjälp av Grounded Theory (I) och kvalitativ innehållsanalys (II). I studie III inkluderades 270 patienter med MM som besvarade ett instrument (MDMQ) avseende coping-stilar i beslutsfattande processen. I studie IV undersöktes övergångar mellan olika kliniker och remissvägar för 71 patienter med MM samt eventuell tidsfördröjning inom hälso- och sjukvården. Resultat: I studie I, identifierades insikt i allvarlighetsgrad samt rädsla och existentiellt hot till följd av tillståndet vara nyckel-motivatorer för att bestämma sig för att söka vård för misstänkt hudmelanom. Resultat från studie II påvisade att genuskonstruktioner påverkar hur personer söker vård för MM. Kvinnor upptäckte själv sina melanom och försökte tillämpa egenvård i början. De kunde dröja att söka vård pga. ansvar för familjen. Män upptäckte sällan suspekta melanom själva men följde oftast anhörigas råd att söka vård och sökte vård omedelbart efter påstötning. Resultaten från studie III visade att män i högre grad använde en avvaktande startegi (buck-passing) medan kvinnor och de som bodde utan partner var överdrivet vaksamma (hypervigilance). Deltagare med nodulärt melanom (NM), en snabbt växande form av MM, var mer vaksamma (vigilance) jämfört med de med melanom in situ, en mycket tidig form av melanom. Några korrelationer mellan tumörtjocklek och coping-stilar hittades ej. Vissa skillnader avseende typer av MM samt vårdens handläggning beroende på var patienter initialt sökt vård identifierades i studie IV. Bland patienter som initialt sökt vård på hälsocentralerna var tjockare tumörer vanligare jämfört med dem som hade sökt vård på hud- och andra specialistklinker. Dessa patienter hade också som regel genomgått den primära excisionen på hälsocentralerna och en majoritet blev senare remitterade till kirurgisk klinik för utvidgad excision. Hälsocentralernas patienter fick vänta längre på att det histopatologiska svaret registrerades i journalen än sjukhusklinikernas patienter. Kvinnor fick generellt vänta kortare tid på primär excision och äldre patienter fick vänta längre för utvidgad excision. Slutsatser: Tidsfördröjning av diagnos och behandling av MM är fortfarande vanlig och därför viktig att minska. Framtida interventioner för att påverka människor att söka vård tidigare bör inkludera genusaspekter. Inom hälso- och sjukvården kan tidsfördröjning minskas genom förbättrad tillgänglighet för patienter med misstänkta hudmelanom, men också genom minskning av onödig remittering. En förändrad organisation där sjuksköterskor och primärvårdsläkare i samarbete med specialistkliniker stöttas att använda ny teknologi för snabbare diagnosticering och omhändertagande av MM bör övervägas. Ökad kännedom bland hälso- och sjukvårdspersonal om riktlinjer for MM-vård kan vidare minska fördröjning. Till sist, mer effektiva och förbättrade arbetssätt kring registrering och överföring av laboratoriska svar och remisser skulle kunna minska fördröjning och därmed öka patientsäkerheten.

APA, Harvard, Vancouver, ISO, and other styles

47

Sanches, Seisse Gabriela Gandolfi. ""Efeito de supressão das emissões otoacústicas transientes em crianças com distúrbio de processamento auditivo"." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-18042006-162330/.

Full text

Abstract:

Com o objetivo de analisar o efeito de supressão das emissões otoacústicas transientes com a apresentação de ruído branco contralateral, foram avaliadas 51 crianças de 7 a 11 anos, sendo 15 sem queixas auditivas (grupo controle) e 36 com distúrbio de processamento auditivo (divididas em dois grupos experimentais). Foram determinados, para cada grupo, a média e o desvio padrão dos valores de supressão em cada condição de estímulo: clique linear e clique não linear. Verificou-se que a proporção de ausência do efeito de supressão foi significativamente maior nos grupos de crianças com distúrbio de processamento auditivo, comparados ao grupo controle
This study concerns the suppression of transient evoked otoacoustic emissions by contralateral white noise in children with auditory processing disorder. Fifty-one children between 7 and 11 years old were assessed, being 15 children without auditory complaints (control group) and 36 with auditory processing disorder (divided in two experimental groups). The mean suppression of otoacoustic emissions and standard deviation were determined for each group, both in linear and nonlinear acquisition mode. The results provided evidence that proportion of absence of otoacoustic emissions suppression was significantly higher in auditory processing disorder groups, when compared to control group

APA, Harvard, Vancouver, ISO, and other styles

48

Travers, Simon. "Stéroïdomique corticosurrénalienne par LC-MS/MS : applications en endocrinologie pédiatrique Multiplexed Steroid Profiling of Gluco- and Mineralocorticoids Pathways Using a Liquid Chromatography Tandem Mass Spectrometry Method Urinary Steroidomic Profiles by LC-MS/MS to Monitor Classic 21-Hydroxylase Deficiency Interaction between Accumulated 21-Deoxysteroids and Mineralocorticoid Signaling in 21-Hydroxylase Deficiency Comparative Profiling of Adrenal Steroids in Maternal and Umbilical Cord Blood Alterations of Adrenal Steroidomic Profiles in Preterm Infants at Birth." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL019.

Full text

Abstract:

La corticostéroïdogénèse correspond à la synthèse de l’aldostérone, hormone régulant l’homéostasie hydrosodée, et du cortisol hormone du stress, impliquée, dans de nombreux processus physiologiques. Son exploration exhaustive nécessite un dosage précis des précurseurs de synthèse, dont certains, en pathologie, peuvent être déficitaires ou au contraire s’accumuler entrainant des conséquences cliniques graves. Grâce à la chromatographie liquide à la spectrométrie de masse en tandem (LC-MS/MS), nous avons développé deux méthodes permettant de cartographier les stéroïdomes plasmatique et urinaire et de doser la fludrocortisone à partir d’un faible volume d’échantillon. Nous avons démontré le potentiel de cette méthode dans le dépistage et le suivi du bloc en 21-hydroxylase, et décrit une accumulation prolongée de précurseurs de synthèse dont les dérivés 21-désoxystéroïdes chez les patients mal équilibrés. Nous avons montré l’action antagoniste partielle de ces composés conduisant à une interférence potentielle avec la signalisation minéralocorticoïde et risquant d’aggraver la symptomatologie. Dans un deuxième temps, notre méthode de dosage en LC-MS/MS nous a permis d’explorer la corticostéroïdogenèse périnatale. La comparaison des stéroïdomes maternel et foetal de grossesses menées à terme a permis de préciser la coopération existant entre les stéroïdogenèses materno-fœto-placentaire et l’étude du stéroïdome des 152 nouveau-nés de la cohorte PREMALDO a confirmé l’existence d’un déficit global de la synthèse corticostéroïdienne au cours de la grande prématurité et identifié pour la première fois un déficit partiel en enzyme P450c11b; responsable de la synthèse du cortisol chez ces nouveau-nés.Enfin, avons identifié un nouveau régulateur potentiel de la sécrétion stéroïdienne : l’adrénomédulline (ADM). Négativement corrélé à l’âge gestationnel dans la cohorte PREMALDO et à la concentration de cortisol, l’ADM inhibe la voie glucocorticoïde dans les cellules humaines surrénaliennes HAC15.L’analyse du stéroïdome par LC-MS/MS est désormais le gold-standard de l’investigation endocrinienne, tant en biologie clinique qu’en recherche fondamentale
Corticosteroidogenesis is the synthesis of aldosterone, a hydroelectrolytic homeostasis regulatory hormone, and the stress hormone cortisol involved in many physiological processes. Its exhaustive exploration requires a precise dosing of the steroid precursors, some of which, in pathology, may be deficient or, on the contrary, accumulate with serious deletorious clinical consequences. Thanks to liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we have developed two methods for mapping plasma and urinary steroidomic and for the determination of fludrocortisone from a small sample volume. We have demonstrated the usefulness of this method in screening and monitoring of 21-hydroxylase block and have described a prolonged accumulation of synthetic precursors including 21-deoxysteoid derivatives in patients with poorly controlled disease. We showed the partial antagonistic action of these compounds leading to an interference with mineralocorticoid signaling and potentially worsening the symptomatology.In a second step, our LC-MS/MS assay method allowed us to explore perinatal corticosteroidogenesis. The comparison of maternal and fetal steroidomes of term pregnancies clarified the cooperation existing between maternal-fetal-placental steroidogenesis and the study of the steroidomic profiles of 152 newborns of the PREMALDO cohort confirmed the existence of a overall defect in corticosteroid synthesis during prematurity and identified for the first time a partial deficiency in the P450c11b; enzyme, responsible for cortisol synthesis, in these newborns.Finally, we identified a new potential regulator of steroid secretion: adrenomedullin (ADM). Negatively correlated with gestational age in the PREMALDO cohort and cortisol concentrations, ADM inhibits the glucocorticoid pathway in human adrenal HAC15 cells.Steroidomic analysis by LC-MS/MS is now the gold-standard in endocrine investigation, in both clinical biology and fundamental research

APA, Harvard, Vancouver, ISO, and other styles

49

Stewart, Heather G. "Amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase 1 (SOD1) mutations in British Columbia, Canada : clinical, neurophysiological and neuropathological features." Doctoral thesis, Umeå : Dept. of Pharmacology and Clinical Neurosciences, Umeå University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-638.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Agarwala, Sandip. "System Support for End-to-End Performance Management." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16171.

Full text

Abstract:

This dissertation introduces, implements, and evaluates the novel concept of "Service Paths", which are system-level abstractions that capture and describe the dynamic dependencies between the different components of a distributed enterprise application. Service paths are dynamic because they capture the natural interactions between application services dynamically composed to offer some desired end user functionality. Service paths are distributed because such sets of services run on networked machines in distributed enterprise data centers. Service paths cross multiple levels of abstraction because they link end user application components like web browsers with system services like http providing communications with embedded services like hardware-supported data encryption. Service paths are system-level abstractions that are created without end user, application, or middleware input, but despite these facts, they are able to capture application-relevant performance metrics, including end-to-end latencies for client requests and the contributions to these latencies from application-level processes and from software/hardware resources like protocol stacks or network devices. Beyond conceiving of service paths and demonstrating their utility, this thesis makes three concrete technical contributions. First, we propose a set of signal analysis techniques called ``E2Eprof' that identify the service paths taken by different request classes across a distributed IT infrastructure and the time spent in each such path. It uses a novel algorithm called ``pathmap' that computes the correlation between the message arrival and departure timestamps at each participating node and detect dependencies among them. A second contribution is a system-level monitoring toolkit called ``SysProf', which captures monitoring information at different levels of granularity, ranging from tracking the system-level activities triggered by a single system call, to capturing the client-server interactions associated with a service paths, to characterizing the server resources consumed by sets of clients or client behaviors. The third contribution of the thesis is a publish-subscribe based monitoring data delivery framework called ``QMON'. QMON offers high levels of predictability for service delivery and supports utility-aware monitoring while also able to differentiate between different levels of service for monitoring, corresponding to the different classes of SLAs maintained for applications.

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Diagnostic pathway'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles