Dissertations / Theses on the topic 'Familial aggregation'
To see the other types of publications on this topic, follow the link: Familial aggregation.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 41 dissertations / theses for your research on the topic 'Familial aggregation.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Tahir, Hassaan. "Familial Aggregation of Severe Preeclampsia." Thesis, Linköpings universitet, Statistik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-73266.
Full textAbstract:
It has been proved from several studies that the genetic influence has been the most significant factor for having preeclampsia (PE). Still there are many uncertainties about origin and magnitude of the genetic effects as no specific inheritance patterns have been established. In this study, heritage risk of PE is in both the woman’s family and her partner’s family to her risk of PE is examined, along women and men own history with same and different partners. Moreover it is also examined whether timing of onset of PE is also has any impact on familial clustering of PE. Here, we used the population based Danish birth and multi generation registers to identify a cohort of women who have given birth during 1978 to 2008; which consisted of 1,79,69,28 singleton deliveries. This information is linked with pedigree information from the Danish Family Relation Database to define both maternal and paternal relationships. Risk ratios were estimated comparing women with and without various PE histories. It is found that the recurrence risk of a woman suffering from PE is 12.4 with 95% confidence limits (11.9, 12.8). Woman's recurrence risk diminishes only slightly when she changes partner means that particularly maternal genetic factors play the largest role, compared to male partner whose recurrence risk almost diminishes if he changes his female partner. Women and men from families with PE contribute to risk of PE in pregnancies they are involved in. The woman’s family history is still more important compared to man family history of PE; except for increased rick in pregnancies fathered by men who were born to preeclamptic mothers. The recurrence risk of a women suffering from PE, if she already has suffered from this condition before 34 weeks is found to be very high (RR=25.4 with 95% confidence limits (21.8, 29.1)) with same male partner. It is found that early-onset PE and later-onset varieties have a clear genetic component but the intensity of early onset is stronger than late onset varieties. There are both maternal and paternal genetic contributions to early-onset PE, with the maternal ones seeming to be stronger.
2
Pappas, Sylvie Rachelle. "The familial aggregation of agoraphobia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0017/MQ47079.pdf.
Full text
3
Beaujeux, Timothy Paul. "Protein aggregation in a mouse model of familial motor neurone disease." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427349.
Full text
4
Seeley, John Robert. "Comorbidity between conduct disorder and major depression : phenomenology, correlates, course, and familial aggregation /." view abstract or download file of text, 2001. http://wwwlib.umi.com/cr/uoregon/fullcit?p3035576.
Full textAbstract:
Thesis (Ph. D.)--University of Oregon, 2001."Based on data collected from the Oregon Adolescent Depresssion Project (OADP)."--Abstract. Typescript. Includes vita and abstract. Includes bibliographical references (leaves 73-84). Also available for download via the World Wide Web; free to University of Oregon users.
5
Brauer, Paula Mae. "Familial aggregation of diabetes, hypertension and cardiovascular conditions in a case-control study of colorectal neoplasia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0023/NQ49836.pdf.
Full text
6
Tisler, Andras. "Analysis of the familial aggregation of hypertension among patients with different types of kidney stone disease." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0022/MQ40818.pdf.
Full text
7
Räsänen, Maija. "Familial aggregation and risk factors for asthma and hay fever among Finnish adolescent twins : a twin family study." Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/laa/kansa/vk/rasanen/.
Full text
8
Andersson, Karin, M. Pokrzywa, Ingrid Dacklin, and Erik Lundgren. "Inhibition of TTR aggregation-induced cell death : a new role for serum amyloid P component." Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-65622.
Full textAbstract:
BACKGROUND: Serum amyloid P component (SAP) is a glycoprotein that is universally found associated with different types of amyloid deposits. It has been suggested that it stabilizes amyloid fibrils and therefore protects them from proteolytic degradation. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we show that SAP binds not only to mature amyloid fibrils but also to early aggregates of amyloidogenic mutants of the plasma protein transthyretin (TTR). It does not inhibit fibril formation of TTR mutants, which spontaneously form amyloid in vitro at physiological pH. We found that SAP prevents cell death induced by mutant TTR, while several other molecules that are also known to decorate amyloid fibrils do not have such effect. Using a Drosophila model for TTR-associated amyloidosis, we found a new role for SAP as a protective factor in inhibition of TTR-induced toxicity. Overexpression of mutated TTR leads to a neurological phenotype with changes in wing posture. SAP-transgenic flies were crossed with mutated TTR-expressing flies and the results clearly confirmed a protective effect of SAP on TTR-induced phenotype, with an almost complete reduction in abnormal wing posture. Furthermore, we found in vivo that binding of SAP to mutated TTR counteracts the otherwise detrimental effects of aggregation of amyloidogenic TTR on retinal structure. CONCLUSIONS/SIGNIFICANCE: Together, these two approaches firmly establish the protective effect of SAP on TTR-induced cell death and degenerative phenotypes, and suggest a novel role for SAP through which the toxicity of early amyloidogenic aggregates is attenuated.Epub 2013 Feb 4.
9
de, Zwaan Sally Elizabeth. "The Genetics of Basal Cell Carcinoma of the Skin." Thesis, The University of Sydney, 2008. http://hdl.handle.net/2123/3878.
Full textAbstract:
BCC is the commonest cancer in European-derived populations and Australia has the highest recorded incidence in the world, creating enormous individual and societal cost in management of this disease. The incidence of this cancer has been increasing internationally, with evidence of a 1 to 2% rise in incidence in Australia per year over the last two decades. The main four epidemiological risk factors for the development of BCC are ultraviolet radiation (UVR) exposure, increasing age, male sex, and inability to tan. The pattern and timing of UVR exposure is important to BCC risk, with childhood and intermittent UVR exposure both associated with an increased risk. The complex of inherited characteristics making up an individual’s ‘sun sensitivity’ is also important in determining BCC risk. Very little is known about population genetic susceptibility to BCC outside of the rare genodermatosis Gorlin syndrome. Mutations in the tumour suppressor gene patched (PTCH) are responsible for this BCC predisposition syndrome and the molecular pathway and target genes of this highly conserved pathway are well described. Derangments in this pathway occur in sporadic BCC development, and the PTCH gene is an obvious candidate to contribute to non-syndromic susceptibility to BCC. The melanocortin 1 receptor (MC1R) locus is known to be involved in pigmentary traits and the cutaneous response to UVR, and variants have been associated with skin cancer risk. Many other genes have been considered with respect to population BCC risk and include p53, HPV, GSTs, and HLAs. There is preliminary evidence for specific familial aggregation of BCC, but very little known about the causes. 56 individuals who developed BCC under the age of 40 in the year 2000 were recruited from the Skin and Cancer Foundation of Australia’s database. This represents the youngest 7 – 8% of Australians with BCC from a database that captures approximately 10% of Sydney’s BCCs. 212 of their first degree relatives were also recruited, including 89 parents and 123 siblings of these 56 probands. All subjects were interviewed with respect to their cancer history and all reports of cancer verified with histopathological reports where possible. The oldest unaffected sibling for each proband (where available) was designated as an intra-family control. All cases and control siblings filled out a questionnaire regarding their pigmentary and sun sensitivity factors and underwent a skin examination by a trained examiner. Peripheral blood was collected from these cases and controls for genotyping of PTCH. All the exons of PTCH for which mutations have been documented in Gorlin patients were amplified using PCR. PCR products were screened for mutations using dHPLC, and all detectable variants sequenced. Prevalence of BCC and SCC for the Australian population was estimated from incidence data using a novel statistical approach. Familial aggregation of BCC, SCC and MM occurred within the 56 families studied here. The majority of families with aggregation of skin cancer had a combination of SCC and BCC, however nearly one fifth of families in this study had aggregation of BCC to the exclusion of SCC or MM, suggesting that BCCspecific risk factors are also likely to be at work. Skin cancer risks for first-degree relatives of people with early onset BCC were calculated: sisters and mothers of people with early-onset BCC had a 2-fold increased risk of BCC; brothers had a 5-fold increased risk of BCC; and sisters and fathers of people with early-onset BCC had over four times the prevalence of SCC than that expected. For melanoma, the increased risk was significant for male relatives only, with a 10-fold increased risk for brothers of people with early-onset BCC and 3-fold for fathers. On skin examination of cases and controls, several phenotypic factors were significantly associated with BCC risk. These included increasing risk of BCC with having fair, easyburning skin (ie decreasing skin phototype), and with having signs of cumulative sun damage to the skin in the form of actinic keratoses. Signs reflecting the combination of pigmentary characteristics and sun exposure - in the form of arm freckling and solar lentigines - also gave subjects a significantly increased risk BCC. Constitutive red-green reflectance of the skin was associated with decreased risk of BCC, as measured by spectrophotometery. Other non-significant trends were seen that may become significant in larger studies including associations of BCC with propensity to burn, moderate tanning ability and an inability to tan. No convincing trend for risk of BCC was seen with the pigmentary variables of hair or eye colour, and a non-significant reduced risk of BCC was associated with increasing numbers of seborrhoeic keratoses. Twenty PTCH exons (exons 2, 3, 5 to 18, and 20 to 23) were screened, accounting for 97% of the coding regions with published mutations in PTCH. Nine of these 20 exons were found to harbour single nucleotide polymorphisms (SNPs), seen on dHPLC as variant melting curves and confirmed on direct sequencing. SNPs frequencies were not significantly different to published population frequencies, or to Australian general population frequencies where SNP database population data was unavailable. Assuming a Poisson distribution, and having observed no mutations in a sample of 56, we can be 97.5% confident that if there are any PTCH mutations contributing to early-onset BCC in the Australian population, then their prevalence is less than 5.1%. Overall, this study provides evidence that familial aggregation of BCC is occurring, that first-degree relatives are at increased risk of all three types of skin cancer, and that a combination of environmental and genetic risk factors are likely to be responsible. The PTCH gene is excluded as a major cause of this increased susceptibility to BCC in particular and skin cancer in general. The weaknesses of the study design are explored, the possible clinical relevance of the data is examined, and future directions for research into the genetics of basal cell carcinoma are discussed.
10
de, Zwaan Sally Elizabeth. "The Genetics of Basal Cell Carcinoma of the Skin." University of Sydney, 2008. http://hdl.handle.net/2123/3878.
Full textAbstract:
Doctor of Philosophy(PhD)BCC is the commonest cancer in European-derived populations and Australia has the highest recorded incidence in the world, creating enormous individual and societal cost in management of this disease. The incidence of this cancer has been increasing internationally, with evidence of a 1 to 2% rise in incidence in Australia per year over the last two decades. The main four epidemiological risk factors for the development of BCC are ultraviolet radiation (UVR) exposure, increasing age, male sex, and inability to tan. The pattern and timing of UVR exposure is important to BCC risk, with childhood and intermittent UVR exposure both associated with an increased risk. The complex of inherited characteristics making up an individual’s ‘sun sensitivity’ is also important in determining BCC risk. Very little is known about population genetic susceptibility to BCC outside of the rare genodermatosis Gorlin syndrome. Mutations in the tumour suppressor gene patched (PTCH) are responsible for this BCC predisposition syndrome and the molecular pathway and target genes of this highly conserved pathway are well described. Derangments in this pathway occur in sporadic BCC development, and the PTCH gene is an obvious candidate to contribute to non-syndromic susceptibility to BCC. The melanocortin 1 receptor (MC1R) locus is known to be involved in pigmentary traits and the cutaneous response to UVR, and variants have been associated with skin cancer risk. Many other genes have been considered with respect to population BCC risk and include p53, HPV, GSTs, and HLAs. There is preliminary evidence for specific familial aggregation of BCC, but very little known about the causes. 56 individuals who developed BCC under the age of 40 in the year 2000 were recruited from the Skin and Cancer Foundation of Australia’s database. This represents the youngest 7 – 8% of Australians with BCC from a database that captures approximately 10% of Sydney’s BCCs. 212 of their first degree relatives were also recruited, including 89 parents and 123 siblings of these 56 probands. All subjects were interviewed with respect to their cancer history and all reports of cancer verified with histopathological reports where possible. The oldest unaffected sibling for each proband (where available) was designated as an intra-family control. All cases and control siblings filled out a questionnaire regarding their pigmentary and sun sensitivity factors and underwent a skin examination by a trained examiner. Peripheral blood was collected from these cases and controls for genotyping of PTCH. All the exons of PTCH for which mutations have been documented in Gorlin patients were amplified using PCR. PCR products were screened for mutations using dHPLC, and all detectable variants sequenced. Prevalence of BCC and SCC for the Australian population was estimated from incidence data using a novel statistical approach. Familial aggregation of BCC, SCC and MM occurred within the 56 families studied here. The majority of families with aggregation of skin cancer had a combination of SCC and BCC, however nearly one fifth of families in this study had aggregation of BCC to the exclusion of SCC or MM, suggesting that BCCspecific risk factors are also likely to be at work. Skin cancer risks for first-degree relatives of people with early onset BCC were calculated: sisters and mothers of people with early-onset BCC had a 2-fold increased risk of BCC; brothers had a 5-fold increased risk of BCC; and sisters and fathers of people with early-onset BCC had over four times the prevalence of SCC than that expected. For melanoma, the increased risk was significant for male relatives only, with a 10-fold increased risk for brothers of people with early-onset BCC and 3-fold for fathers. On skin examination of cases and controls, several phenotypic factors were significantly associated with BCC risk. These included increasing risk of BCC with having fair, easyburning skin (ie decreasing skin phototype), and with having signs of cumulative sun damage to the skin in the form of actinic keratoses. Signs reflecting the combination of pigmentary characteristics and sun exposure - in the form of arm freckling and solar lentigines - also gave subjects a significantly increased risk BCC. Constitutive red-green reflectance of the skin was associated with decreased risk of BCC, as measured by spectrophotometery. Other non-significant trends were seen that may become significant in larger studies including associations of BCC with propensity to burn, moderate tanning ability and an inability to tan. No convincing trend for risk of BCC was seen with the pigmentary variables of hair or eye colour, and a non-significant reduced risk of BCC was associated with increasing numbers of seborrhoeic keratoses. Twenty PTCH exons (exons 2, 3, 5 to 18, and 20 to 23) were screened, accounting for 97% of the coding regions with published mutations in PTCH. Nine of these 20 exons were found to harbour single nucleotide polymorphisms (SNPs), seen on dHPLC as variant melting curves and confirmed on direct sequencing. SNPs frequencies were not significantly different to published population frequencies, or to Australian general population frequencies where SNP database population data was unavailable. Assuming a Poisson distribution, and having observed no mutations in a sample of 56, we can be 97.5% confident that if there are any PTCH mutations contributing to early-onset BCC in the Australian population, then their prevalence is less than 5.1%. Overall, this study provides evidence that familial aggregation of BCC is occurring, that first-degree relatives are at increased risk of all three types of skin cancer, and that a combination of environmental and genetic risk factors are likely to be responsible. The PTCH gene is excluded as a major cause of this increased susceptibility to BCC in particular and skin cancer in general. The weaknesses of the study design are explored, the possible clinical relevance of the data is examined, and future directions for research into the genetics of basal cell carcinoma are discussed.
11
Knight, Ann. "Clinical and Epidemiological Studies of Wegener´s Granulomatosis." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7887.
Full textAbstract:
Wegener´s granulomatosis (WG) is an unusual, serious, systemic vasculitis with specific clinical findings. The studies in this thesis aim at broadening our understanding of the aetiology and outcome of WG.
Patients with WG were identified in the In-patient Register 1975-2001. During this time the incidence increased three-fold, and neither ANCA-related increased awareness, nor diagnostic drift, seem to fully explain this trend, but it is still unclear if a true rise in incidence exists.
Anti- neutrophil cytoplasmic antibodies (ANCA) have been presented as highly specific for vasculitis. In a series of consecutive cANCA/PR3-ANCA positive patients, we investigated the positive predictive value for ANCA, and the outcome of patients with a positive cANCA/PR3-ANCA but not vasculitis. These patients have a low future risk of developing vasculitis, possibly indicating that ANCA, in this setting, reflects neutrophil activating properties not specific to vasculitis.
By linkage of the WG-cohort, and randomly selected population controls, to the Multi-generation register, we identified all first-degree relatives and spouses of patients and controls, totally encompassing some 2,000 patients and 70,000 relatives. Familial aggregation of WG was the exception, with absolute risks of < 1 per 1000.However, relative risks in first-grade relatives amounted to 1.56 (95% CI 0.35-6.90) such that a moderate familial aggregation cannot be excluded.
In the WG-cohort, cancer occurrence and risk was compared to that of the general population. Patients with WG have an overall doubled risk of cancer, with particularly increased risks of bladder-cancer, haematopoietic cancers including lymphomas and squamous skin-cancer. In a case-control study nested within the WG-cohort, treatment with cyclophosphamide was compared among bladder-cancer patients and matched cancer-free controls. Absolute risk of bladder cancer as high as 10% some years after diagnosis were found, and this risk can partly be attributed to cyclophosphamide-treatment, with a dose-response relationship.
12
Jones, Luke D. "Early knee arthritis : symptoms and structure." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:fafe8d46-9ad5-4d1e-b8f5-b2ea3757b3fb.
Full textAbstract:
Knee osteoarthritis (OA) is the commonest form of lower limb OA with a lifetime risk of over 40%. It is a disease characterised by symptoms such as pain and loss of function. In addition there are typical structural features on both radiographs and MRI. Knee OA represents a spectrum of disease, ranging from early preclinical cartilage change to established full thickness disease. Anteromedial knee OA is a particular phenotype of knee OA where disease is confined to the medial compartment. Whilst end stage arthritis is treated reliably with joint arthroplasty, those with early stage disease are treated with a variety of non- surgical interventions with varying success. This thesis is concerned with understanding the disease of patients that have early radiographic changes but symptoms not controlled by conservative measures. Up to 150 of these patients a year present to the Nuffield Orthopaedic Centre, Oxford. They have been described as being in the “Treatment Gap”. A series of validation studies were performed to determine the optimal method for diagnosing cartilage defects within the knee. The three commonest diagnostic methods were examined for their validity. Arthroscopic assessments of cartilage lesions demonstrated a moderate level of intra and inter observer reliability. In contrast, radiographs and MRI demonstrated high levels of reliability. When using MRI as a criterion standard, both radiographs and arthroscopic assessment were found to have poor accuracy. Based on the work in this thesis a formal definition of the cartilage changes exhibited in early knee OA was proposed. A cross sectional cohort of 100 patients with the symptoms and radiological features of early knee OA were identified. Their pain and function profile was compared to two comparison groups of patients at the end stage of knee OA (defined by the need for partial or total arthroplasty). In up to 78% of individual cases those with early OA had pain and function profiles as bad as those with end stage disease. The cross sectional symptoms of early knee OA demonstrate a marked discordance with their mild radiographic changes. The same cohort was extended to 125 patients. They were followed over one year with monthly PROM assessments to determine how symptoms change over time. 43% of patients experience a clinical improvement over 12 months, 31% experience a clinical deterioration and 26% remain unchanged. The range in OKS variation over 12 months was on average 12 points, with clinically relevant variation occurring on 45% of monthly measurements. Patients with early knee OA can expect to experience considerable variation in their symptoms over 12 months and this must be considered when planning interventions. A number of patients with early knee OA were noticed to demonstrate medial meniscal extrusion. Using data from the Osteo Arthritis Initiative (OAI) a nested case control study was designed to determine how the presence of meniscal extrusion in an otherwise normal knee affects the risk of developing knee OA over the next 48 months. This demonstrated an Odds Ratio of 3.5, suggesting that meniscal extrusion is a considerable risk factor for the development of OA. The presence of a knee injury or operative intervention to the index meniscus was shown to increase this risk. Many phenotypes of OA are known to demonstrate familial aggregation. In an attempt to determine where the earliest structural changes occur in medial compartment knee OA, a cohort of patients selected only for their family history of the disease were developed. This cohort was compared to spouse controls for the presence of knee OA, as well as meniscal extrusion and long leg alignment. In addition, a functional analysis of their cartilage was performed. This cohort was not shown to be at increased risk of disease compared to controls. Discussion of the possible reasons for this finding is presented. Early knee osteoarthritis is a considerable clinical problem. This thesis has aided the understanding of the condition by firstly defining the radiological description of these patients. Secondly, their cross sectional and longitudinal symptom profile have been described for the first time. In addition, the presence of an extruded meniscus has been demonstrated as a substantial risk factor for the disease. Finally, family history has not been demonstrated as a risk factor for the disease within the limits of the study described here. Future work has been proposed.
13
Schreier, Andrea, Michael Höfler, Hans-Ulrich Wittchen, and Roselind Lieb. "Clinical characteristics of Major Depressive Disorder run in families – A community study of 933 mothers and their children." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-110222.
Full textAbstract:
The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother–offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children’s sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.
14
Bergström, Joakim. "Apolipoprotein A-IV and Transthyretin in Swedish Forms of Systemic Amyloidosis." Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4535.
Full textAbstract:
Over 20 different plasma proteins have been shown to have the capacity to undergo conformational changes and self-assemble into highly stable and insoluble amyloid fibrils.
One, transthyretin (TTR), consists of 127 amino acid residues arranged in eight β-strands (named A to H) and is involved in two different clinical forms of amyloidosis. In familial amyloidotic polyneuropathy (FAP), mutated TTR is found in the amyloid deposits while in senile systemic amyloidosis (SSA) only wild type TTR is present in the amyloid deposits.
In this study, we have identified a novel form of amyloidosis that is caused by the deposition of an N-terminal fragment of apolipoprotein A-IV (apoA-IV). Interestingly, apoA-IV amyloid was found deposited in a patient that also suffered from SSA. Thus, this patient had two biochemically distinct and concurrent forms of amyloidosis that were derived from apoA-IV and TTR.
We have also discovered that two different morphological deposition patterns (identified as patterns A and B) exist in TTR-derived amyloidosis. Pattern A, observed in all SSA patients studied and in half of the FAP patients examined contained large homogenous deposits that were composed of short randomly oriented fibrils. In contrast, pattern B was observed in the remaining FAP patients and was represented by smaller-sized deposits that consisted of longer fibrils that were arranged in parallel bundles. The predominant TTR component deposited also differed between the two amyloid patterns. Amyloid pattern A contained mainly C-terminal TTR fragments while pattern B amyloid consisted of full-length TTR. Our findings suggest that two different mechanisms of fibril formation may exist in TTR-derived amyloidosis.
We have found two epitopes, corresponding to strand C and H that are surface-exposed in TTR-derived amyloid fibrils but hidden and part of the hydrophobic core in the native molecular structure. This indicates that TTR undergoes partial unfolding during fibril formation.
15
Schreier, Andrea, Michael Höfler, Hans-Ulrich Wittchen, and Roselind Lieb. "Clinical characteristics of Major Depressive Disorder run in families – A community study of 933 mothers and their children." Technische Universität Dresden, 2006. https://tud.qucosa.de/id/qucosa%3A26822.
Full textAbstract:
The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother–offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children’s sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.
16
Militão, Elza da Silva. "Caracterização da agroindústria artesanal familiar na região de Jales-SP /." Ilha Solteira: [s.n.], 2008. http://hdl.handle.net/11449/98896.
Full textAbstract:
Orientador: Silvia Maria Almeida Lima CostaBanca: Antonio Lázaro Sant'Ana
Banca: Rosângela Aparecida de Medeiros Hespanhol.
Resumo: As estratégias de agregação de valor aos produtos, incluindo a agroindustrialização da produção, têm sido buscadas e vêm ganhando importância no período recente como alternativa para aumentar o grau de inserção aos mercados dos agricultores familiares. O presente trabalho analisou algumas iniciativas de agregação de valor agropecuário como opções estratégicas de geração complementar de renda para produtores rurais organizados em grupos na região de Jales. A pequena agroindústria é entendida como geradora de renda de caráter complementar para os constituintes dos grupos e ainda guardam grande dependência do poder público municipal para viabilizar principalmente a comercialização e exposição dos produtos. Entretanto, dentro de uma concepção de desenvolvimento endógeno, o poder público há que investir por mais tempo tanto para propiciar a consolidação e legalização dos grupos, quanto para criar uma cultura, junto aos consumidores locais/regionais, de valorização dos aspectos e competências produtivas locais.
Abstract: The strategies of aggregation of value to products, including agroindustry of production, have been searched and are gaining importance in the recent period as an alternative to increasing the degree of integration of markets for family farmers. This study examined some initiatives of aggregation of agricultural value as strategic options for generating additional income for farmers organized into groups in the region of Jales. The small agribusiness is seen as income-generating complement to the character of the constituent groups and still retain high reliance on public power to make municipal mainly the marketing and exhibition of products. However, within a concept of endogenous development, the public should be able to invest more time both to facilitate the consolidation and legalization of the groups, how to create a culture along to consumers local / regional, capitalizing on local issues and productive skills.
Mestre
17
Militão, Elza da Silva [UNESP]. "Caracterização da agroindústria artesanal familiar na região de Jales–SP." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/98896.
Full textAbstract:
Made available in DSpace on 2014-06-11T19:29:45Z (GMT). No. of bitstreams: 0
Previous issue date: 2008-09-04Bitstream added on 2014-06-13T19:59:39Z : No. of bitstreams: 1
militao_es_me_ilha.pdf: 984980 bytes, checksum: 355398d8fe6a97fb608da1d0ed631782 (MD5)As estratégias de agregação de valor aos produtos, incluindo a agroindustrialização da produção, têm sido buscadas e vêm ganhando importância no período recente como alternativa para aumentar o grau de inserção aos mercados dos agricultores familiares. O presente trabalho analisou algumas iniciativas de agregação de valor agropecuário como opções estratégicas de geração complementar de renda para produtores rurais organizados em grupos na região de Jales. A pequena agroindústria é entendida como geradora de renda de caráter complementar para os constituintes dos grupos e ainda guardam grande dependência do poder público municipal para viabilizar principalmente a comercialização e exposição dos produtos. Entretanto, dentro de uma concepção de desenvolvimento endógeno, o poder público há que investir por mais tempo tanto para propiciar a consolidação e legalização dos grupos, quanto para criar uma cultura, junto aos consumidores locais/regionais, de valorização dos aspectos e competências produtivas locais.
The strategies of aggregation of value to products, including agroindustry of production, have been searched and are gaining importance in the recent period as an alternative to increasing the degree of integration of markets for family farmers. This study examined some initiatives of aggregation of agricultural value as strategic options for generating additional income for farmers organized into groups in the region of Jales. The small agribusiness is seen as income-generating complement to the character of the constituent groups and still retain high reliance on public power to make municipal mainly the marketing and exhibition of products. However, within a concept of endogenous development, the public should be able to invest more time both to facilitate the consolidation and legalization of the groups, how to create a culture along to consumers local / regional, capitalizing on local issues and productive skills.
18
Bezerra, Patr?cia Costa Fonseca Meirelles. "Agrega??o familiar e resultados maternos e perinatais da pr?-ecl?mpsia severa em popula??o do Rio Grande do Norte." Universidade Federal do Rio Grande do Norte, 2007. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13114.
Full textAbstract:
Made available in DSpace on 2014-12-17T14:13:21Z (GMT). No. of bitstreams: 1
PatriciaCFMB.pdf: 373126 bytes, checksum: 359c5249b6f868d7e2bf1418acaf9bec (MD5)
Previous issue date: 2007-11-28To determine whether there is familiar aggregation of severe preeclampsia in a Brazilian population from Rio Grande do Norte and to characterize the maternal and perinatal outcomes in the studied population. Methods: A case control study was performed with 412 participants who were admitted at Maternidade Escola Janu?rio Cicco (MEJC) for medical care. Of these, 264 subjects presented normal blood pressure and 148 were cases. Cases were composed of eclampsia (n=47), HELLP Syndrome (n=85) and Eclampsia associated with HELLP syndrome (n=16). The diagnosis of these illness were based on the citeria developed by National High Blood Pressure Education Program Working (2000). An interview was performed with each subject and questions related to personal and familiar history of hypertension, preeclampsia, HELLP syndrome and eclampsia. Statistical analysis was performed and comparison of median and mean between cases and controls were performed, with the level of significance of 5%. The Odds-Ratio was determined to estimate the risk of preeclampsia within the families. Results: There were no difference in the demographic data between cases and controls. Previous history of chronic hypertension and preeclampsia was more frequent in the case group. Headaches were more frequent in eclampsia and epigastric pain in the HELLP syndrome cases. Bleeding and oliguria were more frequently found in the eclampsia associated with HELLP syndrome cases. Acute Renal insufficiency was a common complication in the case group, but these cases did not evolve to chronic renal insufficiency. The maternal mortality was 0.4% and the perinatal mortality was high, 223 per 1,000 live births. The 111 risk of a woman to develop preeclampsia whose mother has hypertension or had preeclampsia was respectively 2.5 and 3.5. This risk was increased 5 times, when a sibling has hypertension and 6 times when both sibling and mother had previous history of preeclampsia. Conclusions: This study confirms that there is familiar aggregation of preeclampsia in this Brazilian population. The potential for cardiovascular complications due to development of chronic hypertension indicates the need of closely follow up of women who develop preeclampsia
Determinar a agrega??o familiar na pr?-ecl?mpsia severa em popula??o brasileira do Rio Grande do Norte e caracterizar os resultados maternos e perinatais desta popula??o. M?todos: Estudo de caso controle, no qual foram arroladas 412 pacientes internadas na Maternidade Escola Janu?rio Cicco (MEJC). Dessas, 264 pacientes normotensas, grupo controle, e 148 com pr?-ecl?mpsia severa, grupo dos casos. Os casos foram compostos por ecl?mpsia (n=47), s?ndrome HELLP (n=85) e por ambas, ecl?mpsia e s?ndrome HELLP (n=16). O diagn?stico, destas doen?as, foram baseados nos crit?rios adotados pelo National High Blood Pressure Education Program Working (2000). Foi realizado inqu?rito familiar quanto ? agrega??o familiar, sendo questionadas informa??es a respeito de antecedentes de hipertens?o cr?nica, pr?-ecl?mpsia, ecl?mpsia e s?ndrome HELLP. An?lise estat?stica foi realizada para avaliar associa??es e correla??es entre vari?veis, bem como compara??o de m?dias ou medianas, adotando-se um n?vel de signific?ncia de 5%. O Odds-Ratio foi calculado para estimar o risco da pr?-ecl?mpsia severa nas fam?lias. Resultados: N?o houve diferen?a nos par?metros demogr?ficos entre casos e controles. A hist?ria pr?via de hipertens?o cr?nica e pr?-ecl?mpsia foram mais frequentes nas pacientes com pr?-ecl?mpsia severa. A cefal?ia foi o sintoma mais freq?ente na ecl?mpsia e a epigastralgia na s?ndrome HELLP. A hemorragia e a olig?ria foram mais presentes quando associado ecl?mpsia e s?ndrome HELLP. A insufici?ncia renal aguda foi uma complica??o freq?ente, sem, no entanto, evoluir para a insufici?ncia renal cr?nica. A mortalidade xii materna foi baixa 0,4% e a mortalidade perinatal alta de 223 por 1000 nascidos vivos. O risco de uma mulher, cuja m?e teve hipertens?o ou pr?-ecl?mpsia, vir a ter pr?-ecl?mpsia ?, respectivamente, 2,5 e 3,5 vezes. Esse risco aumenta para cinco vezes, quando a irm? tem antecedente de hipertens?o e seis vezes quando, tanto a m?e quanto a irm? t?m antecedentes de pr?-ecl?mpsia. Conclus?es: Este estudo confirma a agrega??o familiar da pr?-ecl?mpsia em popula??o brasileira. O risco aumentado para doen?as cardiovasculares e hipertens?o cr?nica nestas mulheres, indica a necessidade de seguimento das pacientes que desenvolvem pr?-ecl?mpsia
19
Raupp, Ivan Decker. "Redes de cooperação: um estudo sobre a criação e captura de valor por produtores de hortaliças no Oeste do Paraná." Universidade Estadual do Oeste do Parana, 2012. http://tede.unioeste.br:8080/tede/handle/tede/2294.
Full textAbstract:
Made available in DSpace on 2017-07-10T18:33:55Z (GMT). No. of bitstreams: 1
Ivan Decker Raupp.pdf: 2198527 bytes, checksum: e59bf59bb1a7bf236791775e606d2cfb (MD5)
Previous issue date: 2012-03-30Fundação Araucária
The participation in horizontal cooperation networks is suggested by several authors as an important strategy so that low economic status farmers under family management can keep or improve the profitability of their entrepreneurships. In this context, the issue that guides this study is to answer whether the horizontal cooperation networks which are set up among the family producers of vegetables really allow them to aggregate value to production and whether the values occasionally aggregated are captured by them as well. In order to answer it, a theoretical matrix was used, where it is discussed the importance of the collective action and the cooperation networks as a governance structure which encourage the family agriculture and, thus, the rural development. In the empirical approach, a study of multi-case of two organizations was carried out, a cooperative and an association of producers that gathers vegetable producers. As a result, it is noticed that the strategies developed by means of both organizations allowed the farmers to have the aggregation and the value capture. The participation in the cooperative provided to the producers gains resulting from the transference of technology and scale extension in vegetable production. In regard to the association, the value aggregation mainly resulted from the access to more profitable distribution channels and from processes of product differentiation. In both cases, it is also evidenced the value capture translated by the extension of the farmers average income and other indicators described in this study as well. However, it was possible to identify that, in spite of the gains provided to the farmers, the studied organizations face problems of economic competitiveness and viability of the same ones which were pointed out in this study. On the basis of such information, at the end of this essay, some suggestions were formulated in order to contribute with the improvement of the farmers income and the sustainability of the studied organizations.
A participação em redes de cooperação horizontal é sugerida por diversos autores como uma importante estratégia para que produtores rurais de pequeno porte econômico sob gestão familiar possam manter ou melhorar a rentabilidade de seus empreendimentos. Neste contexto, a questão que norteia esse estudo é responder se as redes de cooperação horizontal estabelecidas entre produtores familiares de hortaliças realmente lhes permitem agregar valor à produção e também se os valores eventualmente agregados são capturados pelos mesmos. Para respondê-la utilizou-se uma matriz teórica que discute a relevância da ação coletiva e das redes de cooperação como estrutura de governança que estimula a agricultura familiar e, assim, o desenvolvimento rural. Na aproximação empírica efetuou-se um estudo de multicaso de duas organizações, uma cooperativa e uma associação de produtores que congregam produtores de hortaliças. Como resultado, observa-se que as estratégias desenvolvidas por intermédio de ambas as organizações permitiram aos agricultores a agregação e captura de valor. A participação na cooperativa proporcionou aos produtores ganhos decorrentes da transferência de tecnologia e ampliação de escala na produção de hortaliças. No caso da associação, a agregação de valor derivou principalmente do acesso a canais de distribuição mais rentáveis e de processos de diferenciação dos produtos. Nos dois casos evidencia-se também a captura de valor traduzida pela ampliação da renda média dos agricultores e também por outros indicadores descritos neste trabalho. Entretanto foi possível identificar que, apesar dos ganhos proporcionados aos agricultores, as organizações estudadas deparam-se com problemas de competitividade e viabilidade econômica. Com base em tais informações, no final desta dissertação, formularam-se algumas sugestões no sentido de contribuir com a melhoria da renda dos produtores e também com a sustentabilidade das organizações estudadas.
20
Chang, Huan-Jan, and 張晃禎. "Bayesian Analysis of Familial Aggregation." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/13058779530639644046.
Full textAbstract:
碩士國立臺灣大學
流行病學研究所
88
Familial aggregation can be expressed by correlation coefficient. There are several methods to estimate the correlation, including one-way random effects model, method of maximum likelihood and Pearson’s product-moment correlation. These methods estimate a fixed value of correlation, and does not contain any prior information. My research is using Bayesian analysis to make statistical inference about the correlation based on observations and prior information. A real application, the data of continuous performance test score of schizophrenic and their families are used to test if there exists familial aggregation. I also compare one-way random effects model, method of maximum likelihood and Bayesian analysis with data simulated under different true values of correlation and various familial sizes. The estimation correlation of continuous performance test score in schizophrenic families by one-way random effects model, method of maximum likelihood and Bayesian analysis are all over 0.16. It means that there exists aggregation of gene or environments in schizophrenic families. For simulated familial data, Bayesian analysis has small standard error than the other methods.
21
Wang, Mei-Jan, and 王美珍. "Familial aggregation of nonsmoking female lung cancer patients." Thesis, 1996. http://ndltd.ncl.edu.tw/handle/86065729983266507768.
Full textAbstract:
碩士高雄醫學院
公共衛生學研究所
84
ABSTRACT A case control study matched on sex and age (1:1 ratio)was performed to explore the pedigree aggregation of femalelung cancer. A total of 120 female subjects with lung cancerwere collected from The Hospital attached to KaohsiungMedical College during the hospitalized period from Jan 1992to Mar 1996, all these subjects (probands) were cigarrettenosmoking and well diagnosed as primary lung cancer. Wecollected the first-degree relatives'' data by telephone orinterviewing with them, and 85.8% (103) of these subjectsand their 1117 first degree relatives and 103 partners werecomplete collected. The control subjects (probands) were thefemale patients with unrelated to smoking-causal disease fromKMC, who composing 103 persons, and their 1130 first degreerelatives and 103 partners. The social demographic data,environmental and occupational, industrial explosures, historyof disease (such as lung disease and all types of cancer) werecollected. The results found that the first degree relatives hadhigher rate of lung cancer in case group than control group(2.3%; 26/1117 vs 0.6%; 7/1130), and with 2.8 of exccessrisk (OR=3.8; 95%CI 1.75 - 8.35) in relative to lung cancer.With the same results, the case group had higher risk in allcancer and other cancers ( excluding lung cancer) thancontrol''s first degree relatives (OR=2.7 and 2.2; 95%CI = 1.68 - 4.23 and 1.22 - 10.18). The partners in case groupdidn''t have higher risk in relative to lung cancer, allcancer and other cancers than control group (P>0 .05). All of the risk factors of lung cancer were consideredin this study, such as smoking, second smoking, environmentalexposure, occupational exposure, couldn''t make significantstatistically difference between the case and control groupsin first degree relatives, but with the age greater than 65had higher risk in relative to lung cancer (adjusted OR=4.3,95%CI= 1 .87 - 10.13) in case group than control group. Inthe mean time, the partners living the same environment withthe proband, couldn''t show high risk in relative to lung cancer.
22
Tsai, Ping-Yun, and 蔡秉芸. "A Multi-level Model for Familial Aggregation of Obesity." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/94933372592890664352.
Full textAbstract:
碩士國立臺灣大學
預防醫學研究所
96
Background and Study Purpose Obesity is increasing in prevalence worldwide and is known to be associated with morbidity and mortality in relation to cardiovascular disease. The etiology of obesity is complex and is not completely understood. A large portion of epidemiologic research put emphasis on individual-level risk factors. However, group-level or macro-level variables, so-called contextual factors, also play an important role through interaction with individual factors. There are also limited studies taking both familial aggregation and contextual factors of obesity into accounts. Therefore, the aim of the present study is to explore the association between obesity and familial aggregation and risk factors at individual-level and area-level by conducting a community-based study with multi-level model analysis. Materials and methods A total of 74,833 subjects with aged 20-69 years old are identified from Keelung community-based integrated screening program (KCIS) between 1999 and 2005. By dint of KCIS study, the study design is based on a case-control proband family sampling. A total of 4,499 cases and 16,932 controls were identified. Data of household registration, demographics including education and marital status, lifestyle, and diet were collected. Anthropometric measurements were taking and the criteria of obesity was defined as body mass index≧27 kg/m2. Area-level contextual factors including high educational rate, divorce or widowed rate, and population density separated with tertile were collected from seven administrative districts of Keelung City. We applied nonlinear mixed model and Bayesian analysis for multi-level analysis to investigate the odds ratios and 95% confidence interval of familial aggregation and different level factors for obesity. Results The prevalence rate of overweight and obesity were higher in aged, male, low educated, divorced or widowed subjects, the least tertile of high education rate, and the most tertile of population density among areas. The relative risk of familial aggregation in association with obesity among relatives in case proband families compared with control proband families was 1.29 (95% CI: 1.29-1.30). The relative risk of familial aggregation with obesity in the least tertile of high education rate, the most tertile of divorce rate, and the most tertile of population density were 1.39 (95% CI: 1.36-1.41), 1.36 (95%CI: 1.35-1.38), and 1.34 (95% CI: 1.32-1.35), respectively. The risk for obesity among relatives in case versus control proband families was 2.31 (95%CI: 1.67-3.20) after controlling for significant environmental factors, and it was modified by individual marital status and high education rate of area. The odds ratio was 1.52 (95%CI:1.10-2.11) in married subjects, 1.44 (95%CI:1.04-2.00) in divorced or widowed subjects, and 2.68 (95%CI:1.94-3.71) in the least tertile of high education rate, respectively. When Bayesian analysis for multi-level model is applied, the random effects considering unexplained heterogeneity among different families, different areas, and different area effect on familial aggregation are taken into account with better goodness of fit than others. Conclusion The present study confirmed a strong tendency to familial aggregation for obesity by using the case-control proband family study with a multi-level model approach. The risk of obesity was heterogeneous among families and areas by using multi-level analysis, and familial aggregation of obesity was also affected by contextual factors. The selection of more contextual factors from different levels and the selection of the appropriate contextual factors are needed in the future.
23
Lin, Hui-Min, and 林蕙敏. "Familial aggregation studies with matched case-control proband sampling." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/95886326164728245036.
Full textAbstract:
碩士淡江大學
統計學系碩士班
95
In this paper, some methods are proposed for the analysis of matched case-control proband data arising from familial aggregation studies. When there is no covariate information, we generalized the rank-sum test for clustered data (Datta & Satten, 2005) to detect familial aggregation. If there are some cavariate informations, we apply the generalized method of Liang & Pulver (1996) to analyze the cause of familial aggregation : genetic or environmental factors. We apply the proposed methods to obstructive sleep apnea pseudodata. Some simulation studies with finite sample demonstrate the usefulness of our approach.
24
XU, FANG-YUAN, and 許芳源. "Familial aggregation and multifactorial inheritance analysis of nasopharyngeal carcinoma." Thesis, 1992. http://ndltd.ncl.edu.tw/handle/05894432206923767243.
Full text
25
Xu, Fang-Yuan, and 許芳源. "Familial aggregation and multifactorial inheritance analysis of nasopharyngeal carcinoma." Thesis, 1992. http://ndltd.ncl.edu.tw/handle/55680474345169331300.
Full text
26
Huang, Kai Lin, and 黃凱琳. "Familial aggregation study of liver cancer in the penghu islets." Thesis, 1994. http://ndltd.ncl.edu.tw/handle/20921755746805883194.
Full text
27
Tibazarwa, Kemilembe B. "Peripartum cardiomyopathy: risk factor profile, familial aggregation, prognostic indicators and treatment." Thesis, 2014. http://hdl.handle.net/10539/15429.
Full textAbstract:
Introduction: Peripartum cardiomyopathy (PPCM) is a form of unexplained heart failure associated with pregnancy that leads to considerable morbidity and mortality. Most patients present with acute postpartum heart failure that otherwise resembles dilated cardiomyopathy (DCM). Little is understood about the aetiopathogenesis of PPCM, including the genetic contribution; or its treatment. I hereby report on a comprehensive collection of studies that begins with a study of familial DCM in PPCM, which incorporated genetic screening for mutations in the Lamin-A gene (LMNA), known for their virulence in familial DCM, to assess their role in the development of PPCM. I then proceeded to identify risk factors and prognostic indicators for PPCM, including those identifiable through the electrocardiogram (ECG). Finally, given the shortage of evidence for a treatment modality specific to PPCM, a trial of the use of Bromocriptine in the treatment of PPCM was conducted.
Methods: Consenting prevalent and incident PPCM patients seen at two tertiary hospitals across South Africa, were recruited, and systematic analyses done of their full clinical profiles. A small subset of patients recruited immediately post-partum underwent a trial of Bromocriptine therapy. Another subset of PPCM patients had their respective first degree relatives undergo full clinical screening for DCM.
Results and Conclusion: Our findings support the notion that over a third of PPCM cases may form part of the spectrum of familial DCM. Routine family screening may be as much merited in PPCM as it is in DCM. The ECG appears to be a useful adjunctive tool in both screening and prognostication in resource-poor settings. Further assessment of the prognostication of PPCM suggests that increased LVESD, lower BMI and lower serum cholesterol at baseline may be independent predictors of poor outcome in patients with PPCM, while older age and smaller LVESD at baseline appear to be independently associated with a higher chance of LV recovery. In the trial reported herein, the addition of Bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM.
28
Hsun, Ya-Ching, and 許雅卿. "Detecting familial aggregation of a quantitative trait with matched proband sampling." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/56164208907824045719.
Full textAbstract:
碩士淡江大學
統計學系碩士班
99
The preliminary work in genetic epidemiology is to determine whether a given disease shows familial aggregation. A typical design used for determination of familial aggregation should be the case-control family design which a case or a control proband is ascertained first, with subsequent recruitment of other members in the family. When some major confounders are difficult to measure, the matched case-control family is adopted. Although methods for analyzing familial data with a binary trait or unmatched design are well discussed, methods proposed for analysis of a quantitative trait with matched case-control family design get less attention. In this study, we apply the generalized estimating equation method (Liang & Pulver, 1996) and the weighted quantile regression analysis for clustered data (Wang & Zhao, 2008) to detect familial aggregation. We also apply the within-cluster resampling method of Hoffman et al., (2001) to fit linear regression model or quantile regression model to assess the familial aggregation. We assess the performance of the proposed methods through simulation studies and analysis of one dataset.
29
Ding, Yu Hao, and 丁宇壕. "Familial aggregation of type 2 diabetes and relative genetic and environmental contributions." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/57d63j.
Full text
30
Lin, Wen-Yuan, and 林文元. "A Population-based Case-control Proband Study on Familial Aggregation of Metabolic Syndrome." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/03661707214270182055.
Full textAbstract:
碩士國立臺灣大學
預防醫學研究所
91
Background Since components of metabolic syndrome (MS) like diabetes, hypertension, and hyperlipidemia usually involve the complexity of genetic and environmental factors, the separation of genetic factors from environmental factors is important for prevention of MS. Objectives The aims of this study are to use a community-based screening project (1) To estimate prevalence of MS; (2) To conduct a case-control proband study to elucidate familial aggregation of MS; (3) To assess the interaction between familial aggregation and environmental factors associated with MS; and (4) To identify independent environmental factors after making allowance for familial aggregation. Materials and Methods Target population consists of 390,000 residents living in Keelung, Taiwan. The 43,158 subjects in 32,553 households recruited from a community-based integrated screening formed a source population. We conducted a case-control proband study nested from 43,158 participants in the KCIS program. The total of 1,417 case probands were randomly selected from 3,225 MS. The corresponding 2,458 controls selected by matched with sex, age±3 years and area according to 1:2 ratios. For each proband in the case and control group, we selected the relatives who also participated in the KCIS program, including 1,716 relatives in the case proband and 2,974 in the control proband. Information on demographic variable, life-style factors, dietary factors, family history of disease, menstrual and reproductive factors and anthropometric factors was collected. Generalized Estimation Equation (GEE) model was used to estimate the magnitude of family aggregation and environmental factors in terms of odds ratios and their 95% confidence interval. Likelihood ratio test (LRT) was used to test interaction between family aggregation and environmental factors. Results The prevalence of MS using modified NCEP ATPIII criteria was 16.93%, with 18.52% for male and 15.96% for female, respectively. The morbidity rates of MS were 18.91% in case proband and 11.67% in control proband. The tendency of familial aggregation of MS after adjusting for age of relatives using GEE model was 1.71(95% C.I.= 1.42~2.05). The corresponding odds ratios were 1.75(95% C.I.= 1.45~2.10) for singleton and 2.43(95% C.I.=0.93-6.53) for multiple MS. The highest odds ratio was noted for mother followed by father, husband, and wife compared with other. The interaction assessment between environmental factor and familial aggregation, found only education, age at menopause, and alcohol drinking were significant effect modifiers. After selecting parsimonious multiple regression model, variables retained in the model included family aggregation (OR= 1.63, 95% C.I.=1.34~1.97), level of education (low/high: OR=1.94, 95% C.I.=1.30~2.88); (middle/high: OR=1.54, 95% C.I.=1.05~2.24), intake of vegetable (usually/infrequent: OR=0.79, 95% C.I.=0.65~0.96), betel quid (current+quit/never: OR=1.86, 95% C.I.=1.30~2.67), intake of coffee (usually/infrequent: OR= 1.40, 95% C.I.=1.13~1.73) and exercise (usually/infrequent: OR=0.77, 95% C.I.=0.63~0.93). Conclusion Using a population-based screened cohort, 16% prevalence of MS was estimated. Such a high prevalence was not only due to the tendency of familial aggregation but also due to environmental factors including betel quid chewing and coffee drinking as an independent risk factor and frequent exercise or intake of vegetable as independent preventive factors.
31
Abdullahi, Hassan. "Studies of an unusual transthyretin protein (TTR GLU51_SER52DUP) associated with familial amyloidosis." Thesis, 2017. https://hdl.handle.net/2144/23758.
Full textAbstract:
Transthyretin-related amyloidosis (ATTR) is a disease involving the formation of a misfolded transthyretin (TTR) protein and resulting insoluble aggregates that deposit in extracellular regions of various tissues and organs. There are hereditary forms of the disease, referred to as ATTRm, and more than 100 TTR amyloid-forming mutants have been reported.
The major goal of this work was to analyze the biochemical and biophysical properties of a unique and recently identified TTR mutant protein, TTR Glu51_Ser52dup, found in a patient with ATTRm. Unlike other single nucleotide replacements that have been described as amyloidogenic, the gene abnormality in the present case is the first identification of a TTR duplication mutation. The patient with TTR Glu51_Ser52dup exhibited an extremely aggressive form of ATTRm; clinical symptoms included peripheral neuropathy at baseline evaluation and rapid disease progression to early death from pneumonia and congestive heart failure. We hypothesized that the TTR Glu51_Ser52dup variant would be less stable than the wild-type protein and similar in stability to another highly amyloidogenic mutant, TTR L55P; moreover, the highly unstable nature of this TTR variant would provide a basis for understanding the extremely aggressive clinical phenotype observed in this case.
Using Escherichia coli (E. coli) as an expression system and an appropriately modified expression vector, we produced histidine-tagged recombinant human TTR Glu51_Ser52dup protein in high yield and purified to homogeneity. Structural and stability studies were performed by circular dichroism (CD) spectroscopy and SDS-PAGE analysis. We demonstrated that TTR Glu51_Ser52dup was less stable than the wild-type or L55P proteins when measured under different types of denaturing conditions, including thermal and chemical stress. The presence of diflunisal, a drug that stabilizes tetrameric TTR and is currently approved for treatment of ATTRm, was also investigated; our results indicated that diflunisal stabilized the TTR Glu51_Ser52dup protein.
Collectively, the data obtained from these studies suggest that Glu51_Ser52dup is one of the least stable and most amyloidogenic TTR variant described to date. Future investigations are necessary to determine which specific structural elements of the protein destabilize the TTR tetramer, and precisely characterize the binding of small molecules, including diflunisal, to the protein.
32
"Familial Aggregation and Biomarkers in REM Sleep Behavior Disorder: A Case-Control Family Study." 2016. http://repository.lib.cuhk.edu.hk/en/item/cuhk-1292491.
Full text
33
Hiebert, Brett. "Familial aggregation of childhood health and the socioeconomic gradient of disease: a longitudinal population-based sibling analysis." 2011. http://hdl.handle.net/1993/4884.
Full textAbstract:
This study explores the relationships that emerge between socioeconomic status (SES) and the prevalence of several health outcomes in children of different ages utilizing administrative data housed at The Manitoba Centre for Health Policy (MCHP). This research also determines the effect that family has on a child developing (or not developing) a specific health outcome. Finally, the relationship between prevalence and familial aggregation are examined.
The Johns Hopkins ACG(r) Case-Mix System grouped various physician and hospital diagnosis codes into 32 Aggregated Diagnostic Groups (ADGs). Eight of these ADGs were assessed at four age groups (0-3, 4-8, 9-13 & 14-18) for each member of the final study population. Each member was assigned to one of six SES groups, five income quintile groups and one social assistance group.
Familial aggregation was determined for eight selected ADGs using an intraclass correlation coefficient (ICC). Statistical contrasts were made for SA vs. Q1-Q5 and an overall linear trend (SA – lowest; Q5 – highest) to establish the SES differences for the prevalence and familial aggregation of a particular condition. Many of the conditions across SES had statistically significant (p<0.05) linear and SA vs. Q1-Q5 contrasts for
3
both ICCs and prevalence at all age groups. Of the eight ADGs that familial aggregation was calculated, chronic conditions related to the eye had the highest ICCs at all age groups. Injury ADGs had consistently lower ICCs for all age groups.
Factors that affected the results of ICC estimation for binary outcomes include the number of bootstrap selections, the width of the age group and the event rate for the outcome of interest. Suggested future research includes a validity review of ICC
estimates for binary outcomes, exploring the variables that may reduce or eliminate the SES gradient for ICCs and exploring the aggregation for different study samples within Manitoba.
34
Sun, Fang-Ju, and 孫芳如. "Efficacy of atropine treatment on progression of myopia and familial aggregation of NPC by GEE." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/07113564703741162040.
Full textAbstract:
碩士國立台北護理學院
醫護管理研究所
93
Graduate School: Department of Health Care Management, National Taipei College of Nursing Advisor: Chien-Jen Chen, Kung-Yee Liang, and Su-Chiu Chen Author: Fang-Ju Sun Title (Part 1): Efficacy of atropine treatment on progression of myopia by GEE Topics of myopia are important public health issues. For pupils who under -3.0 diopter, atropine (cycloplegics) is usually used to treat or prevent progression of myopia. This thesis is to study efficacy of atropine treatment on progression of myopia. This research follows the trail throughout eighteen months, tracking 188 myopia pupils of 6 to 14 years old at Department of Ophthalmology in National Taiwan University Hospital to have measurements four times every six months by a three-group randomized design. Data were for longitudinal repeated measuring or clustering, so the generalized estimating equation (GEE) was applied to analyze the particular risk and covariates for efficacy of atropine treatment on progression of myopia based on longitudinal repeated data on left and right eye. The results for efficacy of atropine treatment on progression of myopia were pupils who used both multi-focal lenses and atropine every day, and who used multi-focal lenses, compared to regular lenses ones, diopter was controlled as time increasing. Pupils who used multi-focal lenses and atropine every day, compared to multi-focal lenses ones, diopter was also controlled better (statistically significant, p<0.0001). The results can offer the reference for the relevant competent authority, making the prevention and health care policy for achieving purpose of preventive medicine to prevent and treat in early stages and to save the hospitalization cost even more finally. Title (Part 2): Familial aggregation of NPC by GEE The etiology of nasopharyngeal carcinoma (NPC) suggests the interaction of genetic and environmental factors. But past research had not analyzed odds ratio (OR) for relatives who had NPC within a family, considering correlated data. However, relatives who had NPC had higher OR, the main factor may be genetic. The purpose is to study familial aggregation of NPC. NPC patients from six hospitals in Taiwan were recruited and linked to Taiwan Cancer Registry between 1994 and 1999. The criteria for inclusion as a proband were a subject with pathological diagnosed NPC. The data were obtained from personal interviews using structured questionnaires, consisting of smoking, eating salted fish and fermented food. A total of 928 NPC families were interviewed, consisting of 9799 relatives of parents, siblings, children and spouses. Because research data are correlated data such as longitudinal repeated or clustered measurements, so the generalized estimating equation (GEE) was applied to analyze familial aggregation of NPC. Statistical models were considered smoking, eating salted fish and fermented food by adjusting for age and sex. Research results for familial aggregation of NPC were OR about 3~4 (p<0.05) for siblings’ pairs within a family who had NPC and about 10 (p=0.0032) for parents-children pairs within a family who had NPC. Relatives within a family who had NPC had higher OR, the relevant competent authority, can put more resources in the future, collect more patients’ families, set up the database of country, and educate and check the high risk NPC families to prevent from NPC.
35
"Familial aggregation of insomnia in Hong Kong Chinese: case-control study in a prospective cohort." Thesis, 2010. http://library.cuhk.edu.hk/record=b6075048.
Full textAbstract:
Backgrounds and aims. Insomnia is a common sleep problem with significant health burden to individuals, families and society. Several risk factors contributed to the development of insomnia with significant familial aggregation phenomenon. According to this prospective study, we aimed to (1) explore the longitudinal course and outcomes of insomnia in both children and their parents; (2) confirm the familial aggregation and heritability of insomnia by detailed clinical interviews; (3) explore the potential biological markers of insomnia in terms of heart rate variability, 24-hour urinary cortisol and serial salivary cortisol.Conclusions. Insomnia is commonly found in both adolescents and adults with moderate persistence rate after 5 years in Hong Kong Chinese. Our findings of increased risk of chronic medical burdens and various upper airway inflammatory diseases in both adolescent and adult subjects with insomnia suggested that insomnia requires comprehensive medical attention. Insomnia is a highly heritable disorder with robust familial aggregations, with a heritability of 0.67 for lifetime insomnia. We found gene-environment interaction on the pathogenesis of insomnia. Our findings strongly suggested the necessity of further molecular genetic analysis on insomnia. Daytime HRV, 24-hour urinary cortisol and serial salivary cortisol might not be the reliable biological markers for insomnia. (Abstract shortened by UMI.)
Results. Phase 1. The prevalences of insomnia were 4.5%, 10.8% and 13.9% at baseline and 6.6%, 8.1% and 11.6% at follow-up for children, fathers and mothers respectively. Similar incidence rate of insomnia was found across adolescents, fathers and mothers (6.2%, 5.4% and 6.8% respectively, p>0.05), while highest persistence rate of insomnia was found in mothers (43.8%), followed by fathers (26.9%) and adolescents (14.9%) (mothers vs adolescents OR(95%CI)=4.43(2.22--8.86); mothers vs fathers OR(95%CI) = 2.11(1.31--3.42); fathers vs adolescents OR(95%CI) = 2.17(0.98--4.52)). Insomnia at baseline was significantly associated with frequent episodes of allergic rhinitis, asthma, and laryngopharyngitis and chronic use of medicine at follow-up in adolescents (p<0.05). Insomnia at baseline was also significantly associated with poor medical outcomes in adults, including frequent allergic rhinitis, otitis media, hypertension, arthritis, psychiatric disorders, chronic pain and gastroesophageal reflux disease at follow-up in middle-aged adults (p<0.05). Phase 2 study . The first degree relatives' recurrent rate was higher in those adolescents with insomnia than those adolescents without insomnia (43.9% vs 22.9% for current insomnia and 51.1% vs 28.0% for lifetime insomnia, respectively p<0.001). Genetic analysis showed that the heritabilities were 0.57 +/- 0.19 for current insomnia and 0.67 +/- 0.13 for lifetime insomnia after adjusted for age and gender. There was significant synergistic interaction between parental history of insomnia and life stress on the development of insomnia of offsprings (p=0.002). Insomnia disorder and its severity were also found to correlate with neuroticism personality, psychological distress and poor quality of life. The phenotypic correlations of insomnia with these factors could be mainly explained by genetic component in bivariate genetic analysis. Phase 3 study. (1) Subjective sleep quantity and quality was consistently and negatively correlated with 24-hour urinary cortisol and salivary cortisol levels in adolescents. However, there was no such association in adults. (2) Adolescents with insomnia diagnosis had lower salivary cortisol at 0 minute after waking up (T1) but less decrease in AUCi3 than non-insomniac adolescents. Although there was no difference in serial salivary cortisol between insomniacs and non-insomniacs in adult, insomnia diagnosis interacted with gender on the effects of AC1Ji and salivary cortisol level at 10:00 pm. (3) There was no difference in 24-hour urinary cortisol between insomniacs and non-insomniacs. (4) There were some inconsistent associations of salivary cortisol with objective and subjective sleep parameters between continuous and dichotomized approaches. Fox example, there was no correlation between salivary cortisol and objective sleep measures in adults when using continuous variables, but, short sleepers as defined by objective TIB≤400 minutes had higher cortisol levels at T1 (13.5+/-7.9 nmol/L vs 11.2+/-5.0 nmol/L) and T2 (14.0+/-6.0 vs 11.5+/-6.2 nmol/L) than their counterparts (TIB>400 minutes). In brief, cortisol (both salivary and urinary samples) level was more likely to be correlated with subjective measures of sleep than objective measures or insomnia diagnosis. In particular, the association predominantly occurred in adolescent group.
Zhang, Jihui.
Adviser: Yun-bwote Wing.
Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 245-249).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
36
Lai, Yin-chieh, and 賴穎婕. "The Clinical Features, Symptom Presentation and Familial Aggregation in the Major Depressive and Bipolar Disorders in the Southern Taiwan." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/80937704066216680673.
Full textAbstract:
碩士國立成功大學
公共衛生研究所
97
Background: Affective disorders, mainly depressive (MDD) and bipolar disorders (BPD, including BP I and BP II) are common in the general population. However, little is known about their clinical characteristics, symptoms presentation, and familial aggregation. Objects: To investigate the demographic features and the distribution of symptoms for MDD, BP I, and BP II families in the Southern Taiwan using a family study design, and to evaluate the familial aggregation on social relation in the three diagnoses. Materials and method: There were 689 participants, including 290 probands and 399 relatives ascertained from three regional hospitals or clinics in the Southern Taiwan from 2008 to 2009. Participants were interviewed by well-trained interviewers using Composite International Diagnostic Interview (CIDI) to collect data on demographic and clinical features. Information on proband‘s symptoms endorsement was also obtained from family members. Familial aggregation on social relationship was evaluated by mixed models and intraclass correlation coefficient (ICC). The symptoms endorsement provided by proband and family members was examined using measurement models. Results: The males to females ratio in MDD was twice as many females as males, and was equally prevalent in BPD. MDD patients had higher proportion as married than BPD. About ninety percent of mood disorder patients had low socioeconomic status. BPD had early onset age and more depressive/manic episode frequency than MDD. Probands with severer impairments tended to have fewer contact with friends. There exhibited familial aggregation in social dependence (p<0.0001, ICC=0.14). Similar numbers of depressive symptoms were reported by MDD proband and their family members. The most frequently cited symptoms by first-degree relatives and spouse in MDD were weight change and indecisive. BPD‘s family members provided more manic symptoms than those reported from proband. First-degree relatives and spouse provided more information than proband in all manic symptoms, except for mental overactivity. Conclusions: MDD and BPD are serious diseases with familial aggregation on social relation in Taiwan. Family members provided extra information in understanding symptoms presentation of depressive and manic episodes, especially in BPD.
37
I-NingTsai and 蔡依凝. "Familial aggregation and prediction models of patients with early-onset and adult-onset schizophrenia and their nonpsychotic relatives using neurodevelopmental markers." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/ams36x.
Full textAbstract:
碩士國立成功大學
臨床醫學研究所
103
Background The neurodevelopmental hypothesis proposes that schizophrenia is originated from abnormal brain development. Minor physical anomalies (MPAs) and neurological soft signs (NSSs) are suggested as biomarkers associated with disruptions of fetal development. Schizophrenia patients have been reported to have more deficits in neurodevelopmental markers than healthy controls, but family studies have produced different results. Moreover, the onset age of schizophrenia is related to the severity of the subsequent symptoms, and thus it may be possible to estimate the predictive abilities of neurodevelopmental markers from early-onset and adult-onset schizophrenia. We aimed to examine the familial aggregation of neurodevelopmental markers in early-onset and adult-onset schizophrenia families. Methods We developed a modified physical measurement scale composed of both qualitative and quantitative items, and used the Neurological Evaluation Scale (NES) to assess NSSs. Participants included 182 schizophrenia patients, 147 unaffected first-degree relatives of schizophrenia patients, and 241 healthy controls. First, we estimated the predictive abilities of neurodevelopmental markers between early-onset schizophrenia (EOS) (onset age 〈 20) and adult-onset schizophrenia (AOS) (onset age ≥ 20) using two data mining algorithms (artificial neural networks and decision trees), and a commonly used statistical method (logistic regression), we also used a 10-fold cross-validation method to measure the unbiased estimate of the prediction models. Second, we assessed the magnitude of familial aggregation for neurodevelopmental markers for EOS and AOS families using the relative recurrence-risk ratio. Results The results of artificial neural networks were significantly more accurate than the other two methods. Therefore, we only showed the accuracy of artificial neural networks. For the measurement of qualitative MPAs, the accuracies for EOS and AOS were 78% and 73%, respectively. For qualitatively and quantitative measurements of MPAs (combined MPAs), the accuracies for EOS and AOS were 91% and 81%, respectively. The recurrence risk ratio for the total score of qualitative MPAs (Cut-Off Score MPAs ≥ 10) in EOS families was 4.16 (95%CI: 2.05-8.43), and in AOS families was 2.56 (95%CI: 1.06-6.19). The combined MPAs (Cut-Off Score MPAs ≥ 19) had a higher recurrence risk ratio than qualitative MPAs. The recurrence risk ratio was 9.27 (95%CI: 3.88-22.16) in EOS families, and 2.47 (95%CI: 0.61-9.97) in AOS families. For the measurement of NSSs, the accuracies of EOS and AOS were 85% and 78%, respectively. For sensory integration and motor coordination subscale, the recurrence risk of EOS families was greater than that of AOS families in all NSS cut-off scores. For example, for the cut-off point of ≥ 1 in the Sensory Integration subscale, the results showed that risk ratios were 2.63 (95%CI: 1.36-5.09) in EOS families, and 2.15 (95%CI: 1.19-3.89) in AOS families. For the cut-off point of ≥ 1 in the motor coordination subscale, the results showed that risk ratios were 24.54 (95%CI: 7.81-77.05) in EOS families, and 19.91 (95%CI: 6.49-61.10) in AOS families. However, no significant differences were found between EOS and AOS families for the sequencing of complex motor acts subscale and the others subscale. Conclusion To our knowledge, this study was the first to examine the association between familial aggregation and the age of onset among schizophrenia patients and their relatives in terms of neurodevelopmental markers. These findings provide support for the potential of neurodevelopmental markers as a vulnerability indicator to schizophrenia. Both MPAs and NSSs had higher predictive abilities for EOS than for AOS. Therefore, neurodevelopmental markers may have more accuracy in distinguishing EOS patients from healthy controls. Furthermore, evidence suggests that EOS families might have higher familial aggregation than AOS families in terms of MPAs and NSS. Hence, the findings of this study support the neurodevelopmental hypothesis that EOS might have greater familial and genetic risks.
38
Mente, Andrew. "High urinary calcium excretion and familial aggregation of hypertension, kidney stone disease, obesity, excessive weight gain and type 2 diabetes in patients with calcareous stones." 2007. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=478967&T=F.
Full text
39
Mulligan, Vikram. "Probing the Molecular Mechanisms Underlying Familial Amyotrophic Lateral Sclerosis: New Insight into Unfolding and Misfolding Mechanisms of the Cu, Zn Superoxide Dismutase." Thesis, 2012. http://hdl.handle.net/1807/34815.
Full textAbstract:
While great strides have been made in treating many classes of human disease, the late-onset neurodegenerative diseases continue to elude modern medicine. These diseases, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), the transmissible spongiform encephalopathies (TSEs), and amyotrophic lateral sclerosis (ALS), involve accumulation of insoluble aggregates of one or more causative proteins, leading to progressive loss of central nervous system neurons, progressively worsening neurological symptoms, and eventual patient death. All of these diseases are currently incurable and fatal.
In the case of ALS, progressive death of upper and lower motor neurons leads to full-body paralysis, respiratory difficulty, and patient death. Of the subset of ALS cases showing familial inheritance, approximately 20% are caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). These mutations do not have the common property of impairing SOD1's normal function as a free radical scavenger. Instead, they are thought to increase the protein's likelihood of misfolding and aggregating via a poorly-understood aggregation cascade. It is believed that species populated along the misfolding and aggregation pathway may prove to be good targets for therapies designed to block accumulation of downstream toxic species, or to prevent aberrant protein-protein interactions responsible for neurotoxicity.
In this thesis, several new techniques are developed to enable detailed elucidation of the SOD1 unfolding and misfolding pathways. Time-resolved measurements collected during SOD1 unfolding or misfolding of release of bound Cu and Zn, of changes in intrinsic fluorescence, of exposure of hydrophobic surface area, and of alterations in the chemical environment of histidine residues, are presented. A new mathematical analysis technique named the Analytical Laplace Inversion Algorithm is developed for rapid extraction of mechanistic information from these time-resolved signals. These tools are applied to the construction of the most detailed models to date of the unfolding and misfolding mechanisms of WT and ALS-causing mutant SOD1. The models presented identify several well-populated unfolding and misfolding intermediates that could serve as good targets for therapies designed to address the fundamental molecular mechanisms underlying SOD1-associated ALS, and to treat what is currently a devastating and incurable disease.
40
He, Qin. "Genetic contribution to the aggregation of schizophrenia and bipolar disorder in multiplex consanguineous Pakistani pedigrees." Thèse, 2019. http://hdl.handle.net/1866/21840.
Full text
41
Thyssen, Stella. "Einfluss des Proteinaggregationshemmstoffs anle138b auf Beginn und Verlauf der Amyotrophen Lateralsklerose im transgenen hSOD1-Mausmodell." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0022-5EA3-0.
Full text