5,064 research outputs found
Rule 58\u27s Dirty Little Secret: The Problematic Lack of Uniform Enforcement of Federal Rule of Civil Procedure 58 Within the Federal Court System
Is the Size Distribution of Income in Canada a Random Walk?
Several recent studies have investigated whether the size distribution of income in the United States follows a random walk meaning that it has a unit root, with mixed results. In this paper, we investigate the same issue using Canadian national and provincial income inequality data. The investigation is conducted using three different unit root tests. The results suggest modeling the Gini coefficients for Canada and for most provinces as an I(1) is quite reasonable.
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Next-generation sequencing of prostate cancer: genomic and pathway alterations, potential actionability patterns, and relative rate of use of clinical-grade testing.
Despite being one of the most common cancers, treatment options for prostate cancer are limited. Novel approaches for advanced disease are needed. We evaluated the relative rate of use of clinical-grade next generation sequencing (NGS) in prostate cancer, as well as genomic alterations identified and their potential actionability. Of 4864 patients from multiple institutions for whom NGS was ordered by physicians, only 67 (1.4%) had prostate cancer, representing 1/10 the ordering rate for lung cancer. Prostate cancers harbored 148 unique alterations affecting 63 distinct genes. No two patients had an identical molecular portfolio. The median number of characterized genomic alterations per patient was 3 (range, 1 to 9). Fifty-six of 67 patients (84%) had ≥ 1 potentially actionable alteration. TMPRSS2 fusions affected 28.4% of patients. Genomic aberrations were most frequently detected in TP53 (55.2% of patients), PTEN (29.9%), MYC (17.9%), PIK3CA (13.4%), APC (9.0%), BRCA2 (9.0%), CCND1 (9.0%), and RB1 genes (9.0%). The PI3K (52.2% of patients), WNT (13.5%), DNA repair (17.9%), cell cycle (19.4%), and MAPK (14.9%) machinery were commonly impacted. A minority of patients harbored BRAF, NTRK, ERBB2, or mismatch repair gene abnormalities, which are highly druggable in some cancers. Only ~ 10% of prostate cancer trials (clinicaltrials.gov, year 2017) applied a (non-hormone) biomarker before intervention. In conclusion, though use of clinical-grade NGS is relatively low and only a minority of trials deploy DNA-based biomarkers, many prostate cancer-associated molecular alterations may be pharmacologically tractable with genomcially targeted therapy or, in the case of mismatch repair anomalies, with checkpoint inhibitor immunotherapy
Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania.
A follow-up study was conducted to determine the magnitude of and factors related to adherence to artemether/lumefantrine (ALu) treatment in rural settings in Tanzania. Children in five villages of Kilosa District treated at health facilities were followed-up at their homes on Day 7 after the first dose of ALu. For those found to be positive using a rapid diagnostic test for malaria and treated with ALu, their caretakers were interviewed on drug administration habits. In addition, capillary blood samples were collected on Day 7 to determine lumefantrine concentrations. The majority of children (392/444; 88.3%) were reported to have received all doses, in time. Non-adherence was due to untimeliness rather than missing doses and was highest for the last two doses. No significant difference was found between blood lumefantrine concentrations among adherent (median 286 nmol/l) and non-adherent [median 261 nmol/l; range 25 nmol/l (limit of quantification) to 9318 nmol/l]. Children from less poor households were more likely to adhere to therapy than the poor [odds ratio (OR)=2.45, 95% CI 1.35-4.45; adjusted OR=2.23, 95% CI 1.20-4.13]. The high reported rate of adherence to ALu in rural areas is encouraging and needs to be preserved to reduce the risk of emergence of resistant strains. The age-based dosage schedule and lack of adherence to ALu treatment guidelines by health facility staff may explain both the huge variability in observed lumefantrine concentrations and the lack of difference in concentrations between the two groups
Exploring the Relationship Between Daily Steps, Body Mass Index and Physical Self-Esteem in Female Australian Adolescents
Current research suggests that a decline in physical activity occurs some time during the adolescent years, but at what specific age is unknown. Determination of the age at which physical activity levels decline and possible contributors to this phenomenon, are needed to increase Australian healthcare knowledge. The participants involved in the study were female adolescents (n = 297) aged 13-15 years from a high school in Southeast Queensland, Australia. The purpose of this study was to: (a) determine mean steps per day, using pedometers, for grade 8 through 10 girls, (b) determine body mass index (BMI) by measuring height (cm) and weight (kg), and (c), using the Children and Youth Physical Self-Perception Profile (CY-PSPP) questionnaire, identify determinants of physical self-worth in Australian female adolescents and their relationship to activity level and BMI. The study revealed that a significant drop-off in pedometer-determined mean daily steps occurred at grade ten, or approximately 15 years of age. A significant inverse relationship between mean daily steps and BMI was found (r = ¯.251, p<.0001). The study also revealed negative correlations between BMI and all self-perceptions (p<.05), except strength, which showed a positive correlation (p<0.05). A positive correlation was found between level of physical activity and all self-perceptions, except Global Self-Worth, which showed no significant difference
Genomic landscape of salivary gland tumors.
Effective treatment options for advanced salivary gland tumors are lacking. To better understand these tumors, we report their genomic landscape. We studied the molecular aberrations in 117 patients with salivary gland tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One, Inc. (Lexington, MA). There were 354 total aberrations, with 240 distinct aberrations identified in this patient population. Only 10 individuals (8.5%) had a molecular portfolio that was identical to any other patient (with four different portfolios amongst the ten patients). The most common abnormalities involved the TP53 gene (36/117 [30.8% of patients]), cyclin pathway (CCND1, CDK4/6 or CDKN2A/B) (31/117 [26.5%]) and PI3K pathway (PIK3CA, PIK3R1, PTEN or AKT1/3) (28/117 [23.9%]). In multivariate analysis, statistically significant co-existing aberrations were observed as follows: TP53 and ERBB2 (p = 0.01), cyclin pathway and MDM2 (p = 0.03), and PI3K pathway and HRAS (p = 0.0001). We were able to identify possible cognate targeted therapies in most of the patients (107/117 [91.5%]), including FDA-approved drugs in 80/117 [68.4%]. In conclusion, salivary gland tumors were characterized by multiple distinct aberrations that mostly differed from patient to patient. Significant associations between aberrations in TP53 and ERBB2, the cyclin pathway and MDM2, and HRAS and the PI3K pathway were identified. Most patients had actionable alterations. These results provide a framework for tailored combinations of matched therapies
The effect of rural-to-urban migration on renal function in an Indian population: cross-sectional data from the Hyderabad arm of the Indian Migration Study.
BACKGROUND: Urban migration is associated with an increased risk of hypertension, obesity and diabetes in Indian migrants. This study assessed the relationship between internal migration and renal function in the Hyderabad arm of the Indian Migration Study. METHODS: We assessed 841 subjects; urban non-migrants (n = 158), urban migrants (n = 424) and rural non-migrants (n = 259). Muscle mass was ascertained from DXA scanning. We derived urban life years for urban migrants and rural non-migrants. Multivariable linear regression was used to examine the association between tertiles of urban life years and 4-variable MDRD eGFR using Stata 11. RESULTS: Mean eGFR was lower in urban non-migrants and urban migrants compared to rural non-migrants. The prevalence of CKD 3-5 was higher in the rural non-migrant population (5.0%) than in the urban non-migrant populations (2.5%) due to a negatively skewed distribution of eGFR in rural non-migrants. As urban life years increased, eGFR declined (p = 0.008) though there was no obvious dose response effect. After adjustment for muscle mass, the association was attenuated and the trend was consistent with chance (p = 0.08). Further adjustment for vascular risk factors weakened the association to a small degree (p = 0.11). CONCLUSIONS: The high prevalence of reduced eGFR in rural areas requires further research. Urbanization was associated with reduced eGFR. This association appears mostly to be due to higher muscle mass with a small contribution from adverse vascular disease risk factors
Long-term follow-up after comprehensive rehabilitation of persons with epilepsy, with emphasis on participation in employment or education
The objective of this study was to describe the current situation of patients with epilepsy after rehabilitation with emphasis on employment and education and to investigate if clinical factors at admission were associated with increase in employment or education. All patients that participated in a comprehensive rehabilitation were eligible. Data were collected from medical records at admission, during rehabilitation, at discharge and from a structured telephone interview at follow-up 1-17 years after admission. In total, 124 patients participated in the follow-up. Participation in employment or education improved from admission to follow-up in 38 patients. In univariable analysis, active epilepsy with tonic-clonic seizures at admission was significantly associated with increased participation in employment or education at follow-up, so was decreased frequency of tonic-clonic seizures from admission to follow-up. The significance of the associations disappeared in adjusted multivariable analysis. Participation in employment or education was improved for many patients at follow-up.AFA InsuranceAccepte
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