Causes of death in patients with rheumatoid arthritis over a 40-year period : with special emphasis on autopsy

Rheumatoid arthritis (RA) patients have premature mortality. Contrary to the general population, mortality in RA has not declined over time. This study aimed to evaluate determinants of mortality in RA by examining causes of death (CoDs) over time, accuracy of CoD diagnoses, and contribution of RA medication to CoDs. This study further evaluated detection rate of reactive systemic amyloid A amyloidosis, which is an important contributor to RA mortality. CoDs were examined in 960 RA patients between 1971 and 1991 (Study population A) and in 369 RA patients autopsied from 1952 to 1991, with non-RA patients serving as the reference cases (Study population B). In Study population B, CoDs by the clinician before autopsy were compared to those by the pathologist at autopsy to study accuracy of CoD diagnoses. In Study population B, autopsy tissue samples were re-examined systematically for amyloidosis (90% of patients) and clinical data for RA patients was studied from 1973. RA patients died most frequently of cardiovascular diseases (CVDs), infections, and RA. RA deaths declined over time. Coronary deaths showed no major change in Study population A, but, in Study population B, coronary deaths in RA patients increased from 1952 to 1991, while non-RA cases had a decrease in coronary deaths starting in the 1970s. Between CoD diagnoses by the clinician and those by the pathologist, RA patients had lower agreement than non-RA cases regarding cardiovascular (Kappa reliability measure: 0.31 vs. 0.51) and coronary deaths (0.33 vs. 0.46). Use of disease modifying anti-rheumatic drugs was not associated with any CoD. In RA patients, re-examination of autopsy tissue samples doubled the prevalence of amyloid compared with the original autopsy: from 18% to 30%. In the amyloid-positive RA patients, amyloidosis was diagnosed before autopsy in only 37%; and they had higher inflammatory levels and longer duration of RA than amyloid-negative RA patients. Of the RA patients with amyloid, only half had renal failure or proteinuria during lifetime. In RA, most important determinants of mortality were CVDs, RA, and infections. In RA patients, RA deaths decreased over time, but this was not true for coronary deaths. Coronary death being less accurately diagnosed in RA may indicate that coronary heart disease (CHD) often goes unrecognized during lifetime. Thus, active search for CHD and its effective treatment is important to reduce cardiovascular mortality. Reactive amyloidosis may often go undetected. In RA patients with proteinuria or renal failure, as well as with active and long-lasting RA, a systematic search for amyloid is important to enable early diagnosis and early enhancement of therapy. This is essential to prevent clinical manifestations of amyloidosis such as renal failure, which has a poor prognosis.

Why Don't Students Talk? Causes of Foreign Language Communication Apprehension in English Classes: A Comparison of High Apprehensive and Low Apprehensive Upper Secondary Students.

OBJECTIVES. Oral foreign language skills are an integral part of one's social, academic and professional competence. This can be problematic for those suffering from foreign language communication apprehension (CA), or a fear of speaking a foreign language. CA manifests itself, for example, through feelings of anxiety and tension, physical arousal and avoidance of foreign language communication situations. According to scholars, foreign language CA may impede the language learning process significantly and have detrimental effects on one's language learning, academic achievement and career prospects. Drawing on upper secondary students' subjective experiences of communication situations in English as a foreign language, this study seeks, first, to describe, analyze and interpret why upper secondary students experience English language communication apprehension in English as a foreign language (EFL) classes. Second, this study seeks to analyse what the most anxiety-arousing oral production tasks in EFL classes are, and which features of different oral production tasks arouse English language communication apprehension and why. The ultimate objectives of the present study are to raise teachers' awareness of foreign language CA and its features, manifestations and impacts in foreign language classes as well as to suggest possible ways to minimize the anxiety-arousing features in foreign language classes. METHODS. The data was collected in two phases by means of six-part Likert-type questionnaires and theme interviews, and analysed using both quantitative and qualitative methods. The questionnaire data was collected in spring 2008. The respondents were 122 first-year upper secondary students, 68 % of whom were girls and 31 % of whom were boys. The data was analysed by statistical methods using SPSS software. The theme interviews were conducted in spring 2009. The interviewees were 11 second-year upper secondary students aged 17 to 19, who were chosen by purposeful selection on the basis of their English language CA level measured in the questionnaires. Six interviewees were classified as high apprehensives and five as low apprehensives according to their score in the foreign language CA scale in the questionnaires. The interview data was coded and thematized using the technique of content analysis. The analysis and interpretation of the data drew on a comparison of the self-reports of the highly apprehensive and low apprehensive upper secondary students. RESULTS. The causes of English language CA in EFL classes as reported by the students were both internal and external in nature. The most notable causes were a low self-assessed English proficiency, a concern over errors, a concern over evaluation, and a concern over the impression made on others. Other causes related to a high English language CA were a lack of authentic oral practise in EFL classes, discouraging teachers and negative experiences of learning English, unrealistic internal demands for oral English performance, high external demands and expectations for oral English performance, the conversation partner's higher English proficiency, and the audience's large size and unfamiliarity. The most anxiety-arousing oral production tasks in EFL classes were presentations or speeches with or without notes in front of the class, acting in front of the class, pair debates with the class as audience, expressing thoughts and ideas to the class, presentations or speeches without notes while seated, group debates with the class as audience, and answering to the teacher's questions involuntarily. The main features affecting the anxiety-arousing potential of an oral production task were a high degree of attention, a large audience, a high degree of evaluation, little time for preparation, little linguistic support, and a long duration.

Studies on Causes of Multiple Sclerosis : From Genes to Transcriptome

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults, affecting more than two million people worldwide. It manifests as a chronic inflammation in the central nervous system (CNS) and causes demyelination and neurodegeneration. Depending on the location of the demyelinated plaques and axonal loss, a variety of symptoms can be observed including deficits in vision, coordination, balance and movement. With a typical age of onset at 20-40 years, the social and economic impacts of MS on lives of the patients and their families are considerable. Unfortunately the current treatments are relatively inefficient and the development of more effective treatments has been impeded by our limited understanding of the causes and pathogenesis of MS. Risk of MS is higher in biological relatives of MS patients than in the general population. Twin and adoption studies have shown that familial clustering of MS is explained by shared genetic factors rather than by shared familial environment. While the involvement of the human leukocyte antigen (HLA) genes was first discovered four decades ago, additional genetic risk factors have only recently been identified through genome-wide association studies (GWAS). Current evidence suggests that MS is a highly polygenic disease with perhaps hundreds of common variants with relatively modest effects contributing to susceptibility. Despite extensive research, the majority of these risk factors still remain to be identified. In this thesis the aim was to identify novel genes and pathways involved in MS. Using genome-wide microarray technology, gene expression levels in peripheral blood mononuclear cells (PBMC) from 12 MS patients and 15 controls were profiled and more than 600 genes with altered expression in MS were identified. Three of five selected findings, DEFA1A3, LILRA4 and TNFRSF25, were successfully replicated in an independent sample. Increased expression of DEFA1A3 in MS is a particularly interesting observation, because its elevated levels have previously been reported also in several other autoimmune diseases. A systematic review of seven microarray studies was then performed leading to identification of 229 genes, in which either decreased or increased expression in MS had been reported in at least two studies. In general there was relatively little overlap across the experiments: 11 of the 229 genes had been reported in three studies and only HSPA1A in four studies. Nevertheless, these 229 genes were associated with several immunological pathways including interleukin pathways related to type 2 and type 17 helper T cells and regulatory T cells. However, whether these pathways are involved in causing MS or related to secondary processes activated after disease onset remains to be investigated. The 229 genes were also compared with loci identified in published MS GWASs. Single nucleotide polymorphisms (SNP) in 17 of the 229 loci had been reported to be associated with MS with P-value less than 0.0001 including variants in CXCR4 and SAPS2, which were the only loci where evidence for correlation between the associated variant and gene expression was found. The CXCR4 variant was further tested for association with MS in a large case-control sample and the previously reported suggestive association was replicated (P-value is 0.0004). Finally, common genetic variants in candidate genes, which had been selected on the basis of showing association with other autoimmune diseases (MYO9B) or showing differential expression in MS in our study (DEFA1A3, LILRA4 and TNFRSF25), were tested for association with MS, but no evidence of association was found. In conclusion, through a systematic review of genome-wide expression studies in MS we have identified several promising candidate genes and pathways for future studies. In addition, we have replicated a previously suggested association of a SNP variant upstream of CXCR4 with MS. Keywords: autoimmune disease, common variant, CXCR4, DEFA1A3, HSPA1A,gene expression, genetic association, GWAS, MS, multiple sclerosis, systematic review

Bayesian Accelerated Life Testing under Competing Weibull Causes of Failure

Consider a J-component series system which is put on Accelerated Life Test (ALT) involving K stress variables. First, a general formulation of ALT is provided for log-location-scale family of distributions. A general stress translation function of location parameter of the component log-lifetime distribution is proposed which can accommodate standard ones like Arrhenius, power-rule, log-linear model, etc., as special cases. Later, the component lives are assumed to be independent Weibull random variables with a common shape parameter. A full Bayesian methodology is then developed by letting only the scale parameters of the Weibull component lives depend on the stress variables through the general stress translation function. Priors on all the parameters, namely the stress coefficients and the Weibull shape parameter, are assumed to be log-concave and independent of each other. This assumption is to facilitate Gibbs sampling from the joint posterior. The samples thus generated from the joint posterior is then used to obtain the Bayesian point and interval estimates of the system reliability at usage condition.

Bayesian Accelerated Life Testing under Competing Weibull Causes of Failure

Consider a J-component series system which is put on Accelerated Life Test (ALT) involving K stress variables. First, a general formulation of ALT is provided for log-location-scale family of distributions. A general stress translation function of location parameter of the component log-lifetime distribution is proposed which can accommodate standard ones like Arrhenius, power-rule, log-linear model, etc., as special cases. Later, the component lives are assumed to be independent Weibull random variables with a common shape parameter. A full Bayesian methodology is then developed by letting only the scale parameters of the Weibull component lives depend on the stress variables through the general stress translation function. Priors on all the parameters, namely the stress coefficients and the Weibull shape parameter, are assumed to be log-concave and independent of each other. This assumption is to facilitate Gibbs sampling from the joint posterior. The samples thus generated from the joint posterior is then used to obtain the Bayesian point and interval estimates of the system reliability at usage condition.

Maximum likelihood analysis of multi-stress accelerated life test data of series systems with competing log-normal causes of failure

This article presents frequentist inference of accelerated life test data of series systems with independent log-normal component lifetimes. The means of the component log-lifetimes are assumed to depend on the stress variables through a linear stress translation function that can accommodate the standard stress translation functions in the literature. An expectation-maximization algorithm is developed to obtain the maximum likelihood estimates of model parameters. The maximum likelihood estimates are then further refined by bootstrap, which is also used to infer about the component and system reliability metrics at usage stresses. The developed methodology is illustrated by analyzing a real as well as a simulated dataset. A simulation study is also carried out to judge the effectiveness of the bootstrap. It is found that in this model, application of bootstrap results in significant improvement over the simple maximum likelihood estimates.

Characteristics and causes of Texas marine strandings

Three major mass mortality events occurred on the upper Texas coast during 1994, from January through the second week of May. These events were distinguished by unusually large numbers of dead dolphins, sea turtles, and fishes washing ashore on Texas beaches. The beach stranding of dead animals began in January with bottlenose dolphins. By the end of March, 142 dolphins had washed ashore as compared to about 40 expected. By the latter part of April, dolphin mortalities declined but stranding of dead and comatose sea turtles increased. By the end of April, at least 127 sea turtles had stranded on the Texas coast since the beginning of the year, about double the expected number. Then, during May and June, a third mortality event began with a massive fish kill and more turtle deaths. By the middle of May, mortalities of all species as indicated by beach strandings returned to within expected levels. Nevertheless, 1994 stood out as a record year of marine mass mortalities in the northwestern Gulf of Mexico. (PDF file contains 94 pages.)

Potential causes of mortality for horseshoe crabs (Limulus polyphemus) during the biomedical bleeding process

Biomedical companies catch and bleed horseshoe crabs for the production of Limulus amebocyte lysate (LAL), a product used for protecting public health (Berkson and Shuster, 1999). LAL is a clotting agent, derived solely from horseshoe crab blood cells, which is used to detect the presence of pathogenic gramnegative bacteria in injectable drugs and implantable medical and dental devices (Mikkelsen, 1988; Novitsky, 1991). In addition, LAL is used in many diagnostic tests for such illnesses as gram-negative bacterial meningitis and typhoid fever (Ding and Ho, 2001). Because the LAL test allows one to detect femtogram levels of endotoxin (Ding and Ho, 2001), it is the most effective test for detecting endotoxin contamination, and its increasing use in medical and pharmaceutical laboratories makes it a highly valued product.

Causes of fish depletion: a factor analysis approach

A study was conducted in 54 wetlands of 13 districts of Assam, India to evaluate the causes of fish depletion. Twenty-two variables were considered for the study. Seven factors were extracted through factor analysis (Principal Component Analysis) based on Eigen Value Criteria of more than one. These seven factors together accounted for 69.3% of the total variance. Based on the characteristics of the variables, all the factors were given descriptive names. These variables can be used to measure the extent of management deficiency of the causes of fish depletion in the wetlands. The factors are management deficiency, organic load interference, catchment condition, extrinsic influence, fishermen’s ignorance, external environment and aquaculture program. Management deficiency accounted for a substantial portion of the total variance.

Identification of causes of Thai pangas mortality in ponds and their control strategies

Mass mortality of Thai pangas (Pangasius hypophthalmus) is reported to be a big threat to monoculture of the species in Bangladesh. Twenty affected and twenty control Thai pangas ponds were investigated around Mymensingh district in order to identify the causes of pangas mortality. Sixty affected and sixty unaffected fish samples were examined and compared to find the fish-level variables associated with the disease. A range of haemorrhagic signs on snout, skin and fins were recorded during examination with naked eyes. Aeromonas spp. and Edwardsiella spp. were isolated from 87% and 80% of the affected fish, respectively. Even 4% of the seemingly healthy fish carried Aeromonas spp. on their skin. Among the four water quality parameters monitored, remarkably higher total ammonia (1.5 ppm) was found in water of the affected ponds compared to that of the unaffected ones (0.4 ppm). High ammonia in affected water caused by excessive organic decomposition and poor pond management might have reduced the immunity of fish, which predisposed them for bacterial invasion and consequent disease outbreak.

Status of the shore area from Tiengiang to Camau: causes of accumulation and erosion

The paper presents some results of the research programs which had been performed during 1996-1999 (“Studying of river-sea interaction in the mouth of Tien river” and KHCN.06.08). Based on these results the morphological schemes of the shore areas from Tiengiang to Camau were compiled; causes and mechanics of accumulation and erosion were also determined. These results may be used as scientific basis for forecasting the development of the shoreline, it will contribute to the management, protection and reasonable exploitation the shore areas.

The status and causes of alien species invasion in China

Data of classification, origin, pathway and environmental impacts of invasive alien micro-organisms, invertebrates, amphibians and reptiles, fish, birds, mammals, weeds, trees, and marine organisms in terrestrial, aquatic and marine ecosystems of China, were analyzed, based on literature retrieval, field survey and consultation. Some 283 invasive alien species were recorded in China, including 19 invasive alien micro-organisms, 18 aquatic plants, 170 terrestrial plants, 25 aquatic invertebrates, 33 terrestrial invertebrates, 3 amphibians and reptiles, 10 fish, and 5 mammals. Of the invasive alien species, 55.1% originated from North and South America, 21.7% from Europe, 9.9% from Asia, 8.1% from Africa and 0.6% from Oceania. Many institutions and individuals in China lack adequate knowledge of ecological and environmental consequences caused by invasive alien species, with some ignorance of the dangerous invasion in the introduction of alien species. For instance, 50.0% of invasive alien plants were intentionally introduced as pasture, feedingstuff, ornamental plants, textile plants, medicinal plants, vegetables, or lawn plants, 25% of alien invasive animals were intentionally introduced for cultivation, ornament, or biological control, In addition, more efforts are being made in the introduction of alien species, and little attention is paid on the management of introduced alien species, which may cause their escape into natural environment and potential threats to the environment. There were also gaps in quarantine system in China. All microorganisms were unintentionally introduced, through timber, seedling, flowerpot, or soil; 76.3% of alien invasive animals invaded through commodity or transportation facility because of the failure of quarantine. Therefore, quarantine measures should be strictly implemented; and meanwhile the intentional introduction of alien species should be strictly managed and a system of risk assessment should be implemented.