The electroencephalogram in hepato-lenticular degeneration (Wilson's disease)

The literature on EEG's in hepato-lenticular degeneration has been reviewed; over half of 80 reported patients had abnormal tracings. Eight additional EEG's on seven patients are presented; two definitely abnormal, three borderline and three normal. Trends include continuous slowing of background frequency and sharp diphasic forms bicentrally and elsewhere. There is no specific EEG abnormality in this disease.Although there are many exeptions, in general the degree of EEG abnormality parallels the severity of clinical involvement. No individual clinical finding consistently relates to EEG abnormality, although there is a suggestion both from our cases and those previously reported that tremor and incoordination may show such a relationship.Some patients have EEG improvement during or after treatment; it is uncertain whether this change is cause-and-effect or coincidence. More studies of pre- and post-treatment EEG's would be of interest.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32297/1/0000364.pd

The pacing stress test: Thallium-201 myocardial imaging after atrial pacing. Diagnostic value in detecting coronary artery disease compared with exercise testing

Many patients suspected of having coronary artery disease are unable to undergo adequate exercise testing. An alternate stress, pacing tachycardia, has been shown to produce electrocardiographic changes that are as sensitive and specific as those observed during exercise testing. To compare thallium-201 imaging after atrial pacing stress with thallium imaging after exercise stress, 22 patients undergoing cardiac catheterization were studied with both standard exercise thallium imaging and pacing thallium imaging.Positive ischemic electrocardiographic changes (> 1 mm ST segment depression) were noted in 11 of 16 patients with coronary artery disease during exercise, and in 15 of the 16 patients during atrial pacing. One of six patients with normal or trivial coronary artery disease had a positive electrocardiogram with each test. Exercise thallium imaging was positive in 13 of 16 patients with coronary artery disease compared with 15 of 16 patients during atrial pacing. Three of six patients without coronary artery disease had a positive scan with exercise testing, and two of these same patients developed a positive scan with atrial pacing. Of those patients with coronary artery disease and an abnormal scan, 85% showed redistribution with exercise testing compared with 87% during atrial pacing. Segment by segment comparison of thallium imaging after either atrial pacing or exercise showed that there was a good correlation of the location and severity of the thallium defects (r = 0.83, p = 0.0001, Spearman rank correlation).It is concluded that the location and presence of both fixed and transient thallium defects after atrial pacing are closely correlated with the findings after exercise testing. Thus, atrial pacing may be used as a stress for myocardial perfusion scintigraphy in patients unable to complete a satisfactory exercise test

A Powerful Statistical Framework for Generalization Testing in GWAS, with Application to the HCHS/SOL

In GWAS, “generalization” is the replication of genotype-phenotype association in a population with different ancestry than the population in which it was first identified. The standard for reporting findings from a GWAS requires a two-stage design, in which discovered associations are replicated in an independent follow-up study. Current practices for declaring generalizations rely on testing associations while controlling the Family Wise Error Rate (FWER) in the discovery study, then separately controlling error measures in the follow-up study. While this approach limits false generalizations, we show that it does not guarantee control over the FWER or False Discovery Rate (FDR) of the generalization null hypotheses. In addition, it fails to leverage the two-stage design to increase power for detecting generalized associations. We develop a formal statistical framework for quantifying the evidence of generalization that accounts for the (in)consistency between the directions of associations in the discovery and follow-up studies. We develop the directional generalization FWER (FWERg) and FDR (FDRg) controlling r-values, which are used to declare associations as generalized. This framework extends to generalization testing when applied to a published list of SNP-trait associations. We show that our framework accommodates various SNP selection rules for generalization testing based on p-values in the discovery study, and still control FWERg or FDRg. A key finding is that it is often beneficial to use a more lenient p-value threshold then the genome-wide significance threshold. For instance, in a GWAS of Total Cholesterol (TC) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), when testing all SNPs with p-values\u3c 5 × 10−8 (15 genomic regions) for generalization in a large GWAS of whites, we generalized SNPs from 15 regions. But when testing all SNPs with p-values\u3c 6.6×10−5 (89 regions), we generalized SNPs from 27 regions

Dinâmicas comunitárias em deslocados e não deslocados residentes em áreas de exclusão social em Barranquilla (Colômbia)

El sentido de comunidad, la participación y el empoderamiento permiten comprender el proceso de desplazamiento y reasentamiento en el contexto de recepción, así como las consecuencias derivadas de ambos fenómenos. Los objetivos de la investigación son a) evaluar los tres constructos mencionados, b) analizar la sinergia que existe entre estos y c) proponer estrategias para aumentar su capacidad de influencia en los procesos de toma de decisiones. Llevamos a cabo una investigación exploratoria y transversal con población desplazada (n=30) y no desplazada (n=32) en dos localidades de bajos ingresos en Barranquilla (Colombia). Existe retroalimentación positiva entre los procesos evaluados, aunque no se observan diferencias significativas entre el grupo de desplazados y el de no desplazados. La dimensión Pertenencia (sentido de comunidad) es la que mejor explica la varianza del empoderamiento y de la participación en ambos grupos. Presentamos iniciativas para reforzar el sentido de comunidad y facilitar el acceso a los recursos socio-comunitarios en población desplazada.The sense of community, participation and empowerment enable us to understand the process of displacement and resettlement in the context of reception, as well as the consequences of both phenomena. Our objectives are a) to assess the three constructs mentioned above, b) to analyze the synergy existing among them and c) to propose strategies for increasing their capacity to influence the decision-making processes. We carried out a cross-sectional exploratory study with displaced (n=30) and non-displaced (n=32) people in two low-income districts of Barranquilla (Colombia). There is positive feedback between the processes evaluated, although no significant differences are observed between the displaced and the non-displaced groups. The dimension of belonging (sense of community) is the one that best explains the variance of empowerment and participation in both groups. Finally, we present a set of initiatives to reinforce the sense of community and to facilitate access to the community’s social resources for the displaced population.O sentido de comunidade, a participação e o empoderamento permitem compreender o processo de deslocamento e reassentamento no contexto de recepção bem como as consequências derivadas de ambos os fenômenos. Os objetivos desta pesquisa são: a) avaliar os três construtos mencionados; b) analisar a sinergia que existe entre estes e c) propor estratégias para aumentar sua capacidade de influência nos processos de tomada de decisões. Realizamos uma pesquisa exploratória e transversal com população deslocada (n=30) e não deslocada (n=32) em duas localidades de baixa renda em Barranquilla (Colômbia). Existe retroalimentação positiva entre os processos avaliados, embora não se observem diferenças significativas entre o grupo de deslocados e o de não deslocados. A dimensão Pertencimento (sentido de comunidade) é a que melhor explica a variância do empoderamento e da participação em ambos os grupos. Apresentamos iniciativas para reforçar o sentido de comunidade e facilitar o acesso aos recursos sociocomunitários em população deslocada

Phenotypic and Genotypic Characterization and Treatment of a Cohort with Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome

Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated while iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in 7 subjects; no causative mutation was found in the eighth. Biopsies from 4 subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in 1 subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the 2 subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and peri-lesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations. Overwhelming systemic inflammation has not been described previously in FTC/HHS; the response to IL-1 antagonists suggests that anti-inflammatory drugs may be useful adjuvants. In addition, this is the first description of heterotopic ossification reported in FTC/HHS, possibly mediated by the adjacent inflammation

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences