Solving kk-means on High-dimensional Big Data

In recent years, there have been major efforts to develop data stream algorithms that process inputs in one pass over the data with little memory requirement. For the $k$-means problem, this has led to the development of several $(1+\varepsilon)$-approximations (under the assumption that $k$ is a constant), but also to the design of algorithms that are extremely fast in practice and compute solutions of high accuracy. However, when not only the length of the stream is high but also the dimensionality of the input points, then current methods reach their limits. We propose two algorithms, piecy and piecy-mr that are based on the recently developed data stream algorithm BICO that can process high dimensional data in one pass and output a solution of high quality. While piecy is suited for high dimensional data with a medium number of points, piecy-mr is meant for high dimensional data that comes in a very long stream. We provide an extensive experimental study to evaluate piecy and piecy-mr that shows the strength of the new algorithms.Comment: 23 pages, 9 figures, published at the 14th International Symposium on Experimental Algorithms - SEA 201

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology

Delinquent Behavior of Dutch Rural Adolescents

This article compares Dutch rural and non-rural adolescents’ delinquent behavior and examines two social correlates of rural delinquency: communal social control and traditional rural culture. The analyses are based on cross-sectional data, containing 3,797 participants aged 13–18 (48.7% females). The analyses show that rural adolescents are only slightly less likely to engage in delinquent behavior. Furthermore, while rural adolescents are exposed more often to communal social control, this does not substantially reduce the likelihood that they engage in delinquent behavior. Concerning rural culture, marked differences appeared between rural and non-rural adolescents. First, alcohol use and the frequency of visiting pubs were more related to rural adolescents’ engagement in delinquent behavior. Second, the gender gap in delinquency is larger among rural adolescents: whereas rural boys did not differ significantly from non-rural boys, rural girls were significantly less likely to engage in delinquent behavior than non-rural girls. However, the magnitude of the effects of most indicators was rather low. To better account for the variety of rural spaces and cultures, it is recommended that future research into antisocial and criminal behavior of rural adolescents should adopt alternative measurements of rurality, instead of using an indicator of population density only

Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model

Using a computer simulation based on US data, R. Scott Braithwaite and colleagues calculate the benefits of value-based insurance design, in which patients pay less for highly cost-effective services

Cell Cycle- and Cancer-Associated Gene Networks Activated by Dsg2: Evidence of Cystatin A Deregulation and a Potential Role in Cell-Cell Adhesion

This work was supported by grants from the National Institutes of Health (Mahoney, R01AR056067; Riobo, RO1 GM088256). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Hepatitis B Virus infection in HIV-positive population in Brazil: results of a survey in the state of Mato Grosso and a comparative analysis with other regions of Brazil

BACKGROUND: End-stage liver disease is currently a major concern among HIV-positive individuals due to co-infection with hepatotropic virus. Hepatitis C has been pointed out as a remarkable factor for that. More recently, hepatitis B virus (HBV) infection has also been found to play a role on liver disease in this population. HIV-HBV co-infection prevalence remains largely unknown in vast areas of Brazil. The objective of the present study was to estimate the prevalence of HBV and HDV infection in HIV-infected subjects living in the state of Mato Grosso, in the Central region of Brazil, and compare it to other Brazilian studies. We also assess epidemiologic data regarding risk factors and vaccinal status. METHODS: HIV-positive individuals followed at the Central Laboratory of the Department of Public Health of Mato Grosso in the city of Cuiabá composed the sample. Participants answered a specific questionnaire and had a blood sample taken and tested for serologic markers. RESULTS: A thousand individuals were interviewed and tested for HBsAg, anti-HBc, anti-HBs and anti-HDV if positive for HBsAg. Measurements of CD4 and viral load for HIV-1 were also performed. Overall prevalence of HBV exposure (anti-HBc +ve) was 40.0%, and 3.7% for HBsAg. This prevalence data was similar or slightly lower than for other Brazilian regions, which ranged from 40% and 3% to 71% and 24%, respectively. Testing for anti-HDV in the 37 HBsAg positive patients was positive in only one subject. Factors that showed independent association with HBV exposure, after adjustment, were: male gender, older age groups, tattooing, and reporting more than ten sexual partners throughout life (p < 0.01). Eighty-one (27.5%) out of 291 HBV-unexposed individuals who reported vaccination were anti-HBs positive. Anti-HBs prevalence was higher among those who had higher levels of CD4 by multivariate analysis. CONCLUSION: Our data showed HBV infection prevalence similar or slightly lower than that reported in other regions of Brazil. In addition, our data revealed a less important role for drug injection in the spread of HIV and HBV in Mato Grosso compared to other regions of the country. The high rate of non-vaccinated subjects among this HBV-unexposed, HIV-infected population is a matter of considerable health concern in this region. The relationship between CD4 levels and HBV vaccine response found in the present study reinforces the need of keeping health care workers alert to this issue

Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis

Mitochondrial dysfunction is one of the pathogenic mechanisms that lead to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). Astrocytes expressing the ALS-linked SOD1G93A mutation display a decreased mitochondrial respiratory capacity associated to phenotypic changes that cause them to induce motor neuron death. Astrocyte-mediated toxicity can be prevented by mitochondria-targeted antioxidants, indicating a critical role of mitochondria in the neurotoxic phenotype. However, it is presently unknown whether drugs currently used to stimulate mitochondrial metabolism can also modulate ALS progression. Here, we tested the disease-modifying effect of dichloroacetate (DCA), an orphan drug that improves the functional status of mitochondria through the stimulation of the pyruvate dehydrogenase complex activity (PDH). Applied to astrocyte cultures isolated from rats expressing the SOD1G93A mutation, DCA reduced phosphorylation of PDH and improved mitochondrial coupling as expressed by the respiratory control ratio (RCR). Notably, DCA completely prevented the toxicity of SOD1G93A astrocytes to motor neurons in coculture conditions. Chronic administration of DCA (500 mg/L) in the drinking water of mice expressing the SOD1G93A mutation increased survival by 2 weeks compared to untreated mice. Systemic DCA also normalized the reduced RCR value measured in lumbar spinal cord tissue of diseased SOD1G93A mice. A remarkable effect of DCA was the improvement of grip strength performance at the end stage of the disease, which correlated with a recovery of the neuromuscular junction area in extensor digitorum longus muscles. Systemic DCA also decreased astrocyte reactivity and prevented motor neuron loss in SOD1G93A mice. Taken together, our results indicate that improvement of the mitochondrial redox status by DCA leads to a disease-modifying effect, further supporting the therapeutic potential of mitochondria-targeted drugs in ALS

Prevention of fall incidents in patients with a high risk of falling: design of a randomised controlled trial with an economic evaluation of the effect of multidisciplinary transmural care

Background. Annually, about 30% of the persons of 65 years and older falls at least once and 15% falls at least twice. Falls often result in serious injuries, such as fractures. Therefore, the prevention of accidental falls is necessary. The aim is to describe the design of a study that evaluates the efficacy and cost-effectiveness of a multidisciplinary assessment and treatment of multiple fall risk factors in independently living older persons with a high risk of falling. Methods/Design. The study is designed as a randomised controlled trial (RCT) with an economic evaluation. Independently living persons of 65 years and older who recently experienced a fall are interviewed in their homes and screened for risk of recurrent falling using a validated fall risk profile. Persons at low risk of recurrent falling are excluded from the RCT. Persons who have a high risk of recurrent falling are blindly randomised into an intervention (n = 100) or usual care (n = 100) group. The intervention consists of a multidisciplinary assessment and treatment of multifactorial fall risk factors. The transmural multidisciplinary appraoch entails close cooperation between geriatrician, primary care phys