Miracle-dz/UniFAR-FTUs huggingface dataset:
The Agenda for Familial Hypercholesterolemia: A Scientific Statement From the American Heart Association.

Familial hypercholesterolemia (FH) is an autosomal-dominant genetic disease present in all racial and ethnic groups and has long been recognized as a cause of premature atherosclerotic coronary heart disease.1–3 Heterozygous FH has the highest prevalence of genetic defects that cause significant premature mortality (≈1:200 to 1:500 or higher in founder populations). The genetic basis of the disorder, impaired functioning of the low-density lipoprotein (LDL) receptor, was first recognized by Goldstein and Brown4 in their Nobel Prize–winning work. Studies of LDL receptor function have identified additional mechanisms for the pathogenesis of FH (defects in apolipoprotein [apo] B impairing binding with the LDL receptor and gain-of-function mutations in proprotein convertase subtulisin/kexin type 9 [PCSK9] that enhance LDL receptor degradation). FH leads to elevated LDL concentrations, with levels in heterozygous FH generally in untreated adults >190 mg/dL LDL cholesterol (LDL-C) and in untreated children or adolescents >160 mg/dL LDL-C. Long-term exposure to elevated plasma concentrations of LDL-C begins in utero, leading in heterozygotes to premature ischemic heart disease in mid adulthood and in homozygotes to ischemic heart disease in childhood or early adulthood. In those who meet clinical definitions of FH based on LDL-C levels and family history, genetic testing identifies mutations in most children and a large percentage of adults.5,6 Complementing these cell biology discoveries has been drug discovery that has linked enhancement of LDL receptor function to LDL-C lowering and successful prevention of ischemic heart disease, first with statins and now with newer drugs that affect LDL receptor function in other ways, including those that impair PCSK9 regulation of LDL receptor recycling.7 The natural history of FH, the natural history of genetic disorders that lead to lifelong low LDL-C, and the dramatic improvement in life expectancy created by effective cholesterol lowering provide the …
Making the Most of What You've Got? Resources, Values and Inequalities in Young Women's Transitions to Adulthood

Based on an analysis of longitudinal, qualitative data from three biographical interviews carried out over a three-year period with approximately 100 young people, and informed by relevant theoretical approaches around notions of social capital, we examine the relationship between the resources young people have available to them and their resourcefulness in drawing upon these to forge their futures. To analyse the relationship between individual resources and the wider social context we use three case studies of young women from the most socially deprived or excluded of five research sites, at the transition from compulsory schooling. We suggest that 'success' and its costs are mediated through forms of lived femininity that have currency within local economies of value. We consider how our insights might contribute to debates on social capital, and draw some tentative conclusions about wider policy discussions that are centred on uncritical understandings of 'success'.
Virus-Host Coevolution: Common Patterns of Nucleotide Motif Usage in Flaviviridae and Their Hosts

Virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. Flaviviridae family is composed of fast evolving RNA viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. These host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. Flaviviridae viruses which infect a single host lineage would be subjected to specific host-induced pressures and, therefore, selected by them. In this work we compare the genomic evolutionary patterns of Flaviviridae viruses and their hosts in an attempt to uncover coevolutionary processes inducing common features in such disparate groups. Especially, we have analyzed dinucleotide and codon usage patterns in the coding regions of vertebrate and invertebrate organisms as well as in Flaviviridae viruses which specifically infect one or both host types. The two host groups possess very distinctive dinucleotide and codon usage patterns. A pronounced CpG under-representation was found in the vertebrate group, possibly induced by the methylation-deamination process, as well as a prominent TpA decrease. The invertebrate group displayed only a TpA frequency reduction bias. Flaviviridae viruses mimicked host nucleotide motif usage in a host-specific manner. Vertebrate-infecting viruses possessed under-representation of CpG and TpA, and insect-only viruses displayed only a TpA under-representation bias. Single-host Flaviviridae members which persistently infect mammals or insect hosts (Hepacivirus and insect-only Flavivirus, respectively) were found to posses a codon usage profile more similar to that of their hosts than to related Flaviviridae. We demonstrated that vertebrates and mosquitoes genomes are under very distinct lineage-specific constraints, and Flaviviridae viruses which specifically infect these lineages appear to be subject to the same evolutionary pressures that shaped their host coding regions, evidencing the lineage-specific coevolutionary processes between the viral and host groups.
Epistasis Increases the Rate of Conditionally Neutral Substitution in an Adapting Population

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations—i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations—substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations.
Determinants of the Performance of Business Associations in Rural Settlements in the United Kingdom: An Analysis of Members' Satisfaction and Willingness-to-Pay for Association Survival

Research into business associations indicates that many associations suffer from very high levels of inactive members and fail to deliver significant benefits to members. In order to improve provision, the objective of this paper is to understand the determinants that drive or limit performance of rural business associations. Previous research has focused on the ratio of perceived costs to benefits as informing the decision to remain a member. However, in small associations, membership may be more influenced by social norms than the logic of rational choice. Using measures of satisfaction and willingness to pay for association survival as in-group measures of performance this paper finds that (1) for small associations, group size is critical, (2) associations are valued higher in communities where trust is lower, (3) funding by public bodies may be counterproductive to long-term development aims, and (4) the degree of rurality is insignificant in explaining association performance.
Auditory Perceptual Learning for Speech Perception Can be Enhanced by Audiovisual Training

Speech perception under audiovisual (AV) conditions is well known to confer benefits to perception such as increased speed and accuracy. Here, we investigated how AV training might benefit or impede auditory perceptual learning of speech degraded by vocoding. In Experiments 1 and 3, participants learned paired associations between vocoded spoken nonsense words and nonsense pictures. In Experiment 1, paired-associates (PA) AV training of one group of participants was compared with audio-only (AO) training of another group. When tested under AO conditions, the AV-trained group was significantly more accurate than the AO-trained group. In addition, pre- and post-training AO forced-choice consonant identification with untrained nonsense words showed that AV-trained participants had learned significantly more than AO participants. The pattern of results pointed to their having learned at the level of the auditory phonetic features of the vocoded stimuli. Experiment 2, a no-training control with testing and re-testing on the AO consonant identification, showed that the controls were as accurate as the AO-trained participants in Experiment 1 but less accurate than the AV-trained participants. In Experiment 3, PA training alternated AV and AO conditions on a list-by-list basis within participants, and training was to criterion (92% correct). PA training with AO stimuli was reliably more effective than training with AV stimuli. We explain these discrepant results in terms of the so-called “reverse hierarchy theory” of perceptual learning and in terms of the diverse multisensory and unisensory processing resources available to speech perception. We propose that early AV speech integration can potentially impede auditory perceptual learning; but visual top-down access to relevant auditory features can promote auditory perceptual learning.
Complex spikes in Purkinje cells of the paravermal part of the anterior lobe of the cat cerebellum during locomotion.

1. The temporal pattern of the discharge of complex spikes by Purkinje cells in the paravermal cortex of the cerebellar lobule V b/c has been examined during locomotion in awake cats. 2. The peripheral receptive fields of 138 Purkinje cells were examined using light tactile stimulation. In 91% of these cells, complex spikes were evoked by stimuli applied to the ipsilateral forelimb and of eighty‐eight cells examined in most detail, 76% had receptive fields including the paw or wrist. Sixty‐six per cent had receptive fields restricted to the paw and/or wrist. 3. Complex spikes were not discharged at rigidly fixed times during the step cycle in any of sixty‐nine Purkinje cells which were recorded during locomotion on a moving belt. 4. When the discharges were averaged over many steps the probability of occurrence of complex spikes showed small fluctuations during the course of the step cycle, but these fluctuations were shown not to be statistically significantly different from those which could arise by chance. 5. These findings are inconsistent with previous suggestions (e.g. Armstrong, 1974; Rushmer, Roberts & Augter, 1976) that, during locomotion, the climbing fibres act to signal the occurrence of specific peripheral events, such as foot touch‐down or lift‐off.
Asthma control and quality of life in patients with moderate or severe asthma.

OBJECTIVE To evaluate the association between degree of asthma control and health-related quality of life in patients with moderate or severe asthma. METHODS This was a descriptive observational study involving 59 outpatients with moderate or severe asthma under treatment at the Asthma Outpatient Clinic of the Federal University of Ceará Walter Cantídio University Hospital, in the city of Fortaleza, Brazil. The patients were evaluated regarding sociodemographic and clinical characteristics, as well as spirometric parameters. The asthma control status was assessed using the asthma control test (ACT), and quality of life was assessed using the Saint George's Respiratory Questionnaire (SGRQ). RESULTS The mean age of the patients was 55.0 ± 12.4 years, and 76.3% were female. The ACT score showed statistically significant negative correlations with all SGRQ scores: total (r = -0.72); symptoms (r = -0.78); activity (r = -0.67); and impact (r = -0.68). Multiple regression analysis showed that the most robust predictive variables for SGRQ total score were ACT score (coefficient = -3.18; 95% CI: -4.14 to -2.23) and duration of disease (coefficient = -0.29; 95% CI: -0.54 to -0.03). The ACT score also explained the linear variation of the SGRQ domains: symptoms (coefficient = -3.41; 95% CI: -4.45 to -2.37); activity (coefficient = -3.07; 95% CI: -4.57 to -1.57); and impact (coefficient = -2.68; 95% CI: -3.71 to -1.65). CONCLUSIONS The degree of asthma control appears to have a significant impact on health-related quality of life.
DNA Extraction from Formalin‐fixed, Paraffin‐embedded Tissues: Protein Digestion as a Limiting Step for Retrieval of High‐quality DNA

Several DNA extraction methods have been used for formalinfixed, paraffin-embedded tissues, with variable results being reported regarding the suitability of DNA obtained from such sources to serve as template in polymerase chain reaction (PCR)-based genetic analyses. We present a method routinely used for archival material in our laboratory that reliably yields DNA of sufficient quality for PCR studies. This method is based on extended proteinase K digestion (250 μg/ml in an EDTA-free calcium-containing buffer supplemented with mussel glycogen) followed by phenol-chloroform extraction. Agarose gel electrophoresis of both digestion buffer aliquots and PCR amplification of the β-globin gene tested the suitability of the retrieved DNA for PCR amplification.
Three-Dimensional MRI Analysis of Individual Volume of Lacunes in CADASIL

Background and Purpose— Three-dimensional MRI segmentation may be useful to better understand the physiopathology of lacunar infarctions. Using this technique, the distribution of lacunar infarctions volumes has been recently reported in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Whether the volume of each lacune (individual lacunar volume [ILV]) is associated with the patients' other MRI lesions or vascular risk factors has never been investigated. The purpose of this study was to study the impact of age, vascular risk factors, and MRI markers on the ILV in a large cohort of patients with CADASIL. Methods— Of 113 patients with CADASIL, 1568 lacunes were detected and ILV was estimated after automatic segmentation on 3-dimensional T1-weighted imaging. Relationships between ILV and age, blood pressure, cholesterol, diabetes, white matter hyperintensities load, number of cerebral microbleeds, apparent diffusion coefficient, brain parenchymal fraction, and mean and median of distribution of lacunes volumes at the patient level were investigated. We used random effect models to take into account intraindividual correlations. Results— The ILV varied from 4.28 to 1619 mm3. ILV was not significantly correlated with age, vascular risk factors, or different MRI markers (white matter hyperintensity volume, cerebral microbleed number, mean apparent diffusion coefficient or brain parenchymal fraction). In contrast, ILV was positively correlated with the patients' mean and median of lacunar volume distribution (P=0.0001). Conclusions— These results suggest that the ILV is not related to the associated cerebral lesions or to vascular risk factors in CADASIL, but that an individual predisposition may explain predominating small or predominating large lacunes among patients. Local anatomic factors or genetic factors may be involved in these variations.
Attitudes towards seeking psychological help among a sample of Turkish university students: the roles of rumination and internal working models

The current study investigates how attitudes towards seeking psychological help relate to internal working models of attachment (self-model and other-model) and ruminative tendencies. The study includes 589 Turkish university students (278 females, 308 males and 3 unknown) by implementing a convenient sampling procedure. The average age of the participants was 22.4 years (SD = 2.2). Participants were administered the Attitudes toward Seeking Psychological Help-Short, the Relationship Questionnaire and the Rumination Scale. The results of the study indicate that the other-model and rumination have a relationship to women's help-seeking attitudes whereas the self-model has a relationship to men's help-seeking attitudes. The results are discussed in light of the related literature.
Voluntary Male Homemakers and Female Providers: Reported Experiences and Perceived Social Reactions

I n 1975, 221,000 men in the United States reported that they were not in the labor force because they were “keeping house” ( U S . Department of Labor, 1989); by 1988, that number had almost doubled to 438,000. In 1987, of 29 million two-income couples, five million reported that the women earned more than their husbands (U.S. Bureau of the Census, 1989). In 1991, over two million married-couple families reported that only the wife was in the labor force (U.S. Department of Commerce, 1992). Couples in which the man is the homemaker and the woman is the primary wage earner are challenging the traditional expectations that all men must work for pay outside the home (O’Neil, 1981; Pleck, 1981) and that the wife’s income is supplemental to the husband’s, an arrangement that maintains for the male the place of financial head-of-the-household. Whereas some men and their female partners make a deliberate choice to enter into a nontraditional gender role arrangement, many men may stay at home because of disability or unemployment. Furthermore, studies of role reversal arrangements have typically used samples of men who were not full-time homemakers. For example, Davis and Chavez (1985) studied Hispanic “househusbands,” but only one man in the sample had become a househusband voluntarily; further, the female partners of these men retained responsibility for most household chores (e.g., laundering, cooking, billpaying, and childcare). In Beer’s (1983) sample, nearly 70% of the husbands did less than 50% of the housework, and over 70% were employed in professional, technical, or managerial jobs outside the home. Likewise, the
Preliminary Results of the iSTEP Program on Integrated Search for Taiwan Earthquake Precursors

The predictability of earthquakes has been a hotly debated question in earthquake science for some time. The answer to which begs another question, “Are there credible earthquake precursors? ” Intrigued by these questions and encouraged by instrumental observations of conspicuous ionospheric and geomagnetic disturbances before the disastrous 1999 Chi-Chi earthquake, we decided to undertake an integrated Search for Taiwan Earthquake Precursors, called the iSTEP program. The multidisciplinary program includes five major components aimed at identifying potential seismological, geomagnetic, geodetic and ionospheric precursors, and statistical testing of any identified precursors. Since the program’s inception in April 2002, some encouraging preliminary results have been obtained. These includes precursory P wave travel-time changes six years before the Chi-Chi earthquake, identifiable geomagnetic changes two years before M 6 earthquakes, consistent ionospheric anomalies three days before M 5 earthquakes. We have also developed high-resolution radar interferometric methods for monitoring crustal deformation. A method for forecasting aftershock distribution on the basis of stress transfer has also been successfully tested on the Chi-Chi earthquake sequence. Aided by the newly installed geomagnetic and ionospheric networks we are hopeful about identifying more earthquake precursors and developing relevant physical mechanisms in the remaining two years of the iSTEP program.
Review of donepezil, rivastigmine, galantamine and memantine for the treatment of dementia in Alzheimer's disease in adults with Down syndrome: implications for the intellectual disability population

The management of dementia in Alzheimer's disease has dramatically changed since the development of anti‐dementia drugs. However, there is limited information available regarding the bio‐medical aspects of the differing drugs; particularly relating to adults with intellectual disability. Indeed the information available for the intellectual disabled population is limited to adults with Down syndrome. This review highlights the important pharmacological and clinical aspects of donepezil, rivastigmine, galantamine and memantine and supports the view that such drugs play an important part in the management of dementia in adults with intellectual disability. Future clinical and research issues are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Severe exacerbations predict excess lung function decline in asthma

Severe asthma exacerbations are periods of intense airway inflammation that have been hypothesised to contribute to structural changes in the airways. If so, accelerated lung function decline over time should be more prevalent in adult patients with asthma who have frequent exacerbations than those without, but to date this has not been demonstrated. A cohort study was performed in order to investigate the effect of severe exacerbations on the progression of airway obstruction in 93 nonsmoking asthmatics with moderate-to-severe disease prior to treatment with inhaled corticosteroids. Subjects were followed for ≥5 yrs (median follow-up 11 yrs). In total, 56 (60.2%) subjects experienced at least one severe exacerbation (median rate 0.10·yr−1). Oral corticosteroid use and more severe airway obstruction at baseline were associated with a higher exacerbation rate. Independent of these variables, asthma patients with frequent exacerbations had a significantly larger annual decline in forced expiratory volume in one second (FEV1; median difference (95% confidence interval) 16.9 (1.5–32.2) mL·yr−1). Exacerbation rate significantly predicted an excess decline in FEV1, such that one severe exacerbation per year was associated with a 30.2 mL greater annual decline in FEV1. These data support the hypothesis that exacerbations, indicating intermittent periods of worsening airway inflammation, are associated with excess lung function decline in asthma.
Racist Discourse in New Zealand and Australia: Reviewing the Last 20 Years

The discursive study of racism has developed considerably over the last 20 years, and the body of work that has emerged from Australia and New Zealand is reviewed. The historical significance and importance of studying racism is discussed. The increasingly subtle face of racism argues for methods that are sensitive to these changes. Critical, discursive approaches are introduced following which the colonial history of both countries is outlined. Race talk in New Zealand and Australia is reviewed with several key summary points being identified. The review concludes with the suggestion that this work has gone some way toward living up to the disciplinary responsibilities we have as social psychologists in seeking a better understanding of the production of racism.