Scaling violation in hadron-nucleus interaction

The scaling violation within the pionization region in the energy range of 0.2 to 2.0 TeV is shown on the basis of the analysis of angular characteristics in the interactions of the cosmic radiation hadrons with the nuclei of various substances (CH2, Al, Cu, Pb)

Assembly of the Murine Leukemia Virus Is Directed towards Sites of Cell–Cell Contact

Applying 4D imaging, this study investigates the mechanism by which cell-cell contact enhances retrovirus spreading and demonstrates that viral budding is highly polarized towards sites of cell-cell contact

Disorders of Consciousness due to Traumatic Brain Injury: Functional Status Ten Years Post-Injury

Few studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state). The study sample included 110 individuals with TBI who were unable to follow commands prior to inpatient rehabilitation and for whom follow-up data were available at 1, 2, 5, and 10 years post-injury. The sample was subdivided into those who demonstrated command-following early (before 28 days post-injury) versus late (≥ 28 days post-injury or never). Functional Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to measure functional outcomes. Measureable functional recovery occurred throughout the 10-year period, with more than two thirds of the sample achieving independence in mobility and self-care, and about one quarter achieving independent cognitive function by 10 years. Following commands prior to 28 days was associated with greater functional independence at all outcome time-points. Multi-trajectory modeling of recovery of three FIM subscales (self-care, mobility, cognition) revealed four distinct prognostic groups with different temporal patterns of change on these subscales. More than half the sample achieved near-maximal recovery by 1 year post-injury, while the later command-following subgroups recovered over longer periods of time. Significant late functional decline was not observed in this cohort. Among a cohort of patients unable to follow commands at the time of inpatient rehabilitation, a substantial proportion achieved functional independence in self-care, mobility, and cognition. The proportion of participants achieving functional independence increased between 5 and 10 years post-injury. These findings suggest that individuals with disorders of consciousness may benefit from ongoing functional monitoring and updated care plans for at least the first decade after TBI

Amantadine Did Not Positively Impact Cognition in Chronic Traumatic Brain Injury: A Multi-Site, Randomized, Controlled Trial

Despite limited evidence to support the use of amantadine to enhance cognitive function after traumatic brain injury (TBI), the clinical use for this purpose is highly prevalent and is often based on inferred belief systems. The aim of this study was to assess effect of amantadine on cognition among individuals with a history of TBI and behavioral disturbance using a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine 100 mg twice-daily versus placebo for 60 days. Included in the study were 119 individuals with two or more neuropsychological measures greater than 1 standard deviation below normative means from a larger study of 168 individuals with chronic TBI (>6 months post-injury) and irritability. Cognitive function was measured at treatment days 0, 28, and 60 with a battery of neuropsychological tests. Composite indices were generated: General Cognitive Index (included all measures), a Learning Memory Index (learning/memory measures), and Attention/Processing Speed Index (attention and executive function measures). Repeated-measures analysis of variance revealed statistically significant between-group differences favoring the placebo group at day 28 for General Cognitive Index (p = 0.002) and Learning Memory Index (p = 0.001), but not Attention/Processing Speed Index (p = 0.25), whereas no statistically significant between-group differences were found at day 60. There were no statistically significant between-group differences on adverse events. Cognitive function in individuals with chronic TBI is not improved by amantadine 100 mg twice-daily. In the first 28 days of use, amantadine may impede cognitive processing. However, the effect size was small and mean scores for both groups were generally within expectations for persons with history of complicated mild-to-severe TBI, suggesting that changes observed across assessments may not have functional significance. The use of amantadine to enhance cognitive function is not supported by these findings

Potential Impact of Amantadine on Aggression in Chronic Traumatic Brain Injury

Objective: To assess the effects of amantadine on anger and aggression among individuals with a chronic traumatic brain injury (TBI). Methods: A cohort of 118 persons with chronic TBI (>6 months postinjury) and moderate-severe aggression selected from a larger cohort of 168 participants enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine 100 mg twice daily (n = 82) versus placebo (n = 86) for treatment of irritability were studied. Anger and aggression were measured at treatment days 0, 28, and 60 using observer-rated and participant-rated State-Trait Anger Expression Inventory-2 (STAXI-2) and Neuropsychiatric Inventory-Agitation/Aggression domain (NPI-A) Most Problematic and Distress scores. Results: Participant-rated day 60 NPI-A Most Problematic (adjusted P = .0118) and NPI-A Distress (adjusted P = .0118) were statistically significant between the 2 groups, but STAXI-2 differences were not significant after adjustment for multiple comparisons. Substantial improvements were noted in both amantadine and placebo groups (70% vs 56% improving at least 3 points on day 60 Observer NPI-A; P = .11). Conclusion: Amantadine 100 mg twice daily in this population with chronic TBI appears to be beneficial in decreasing aggression from the perspective of the individual with TBI. No beneficial impact on anger was found

Association Between Frailty and Atrial Fibrillation in Older Adults: The Framingham Heart Study Offspring Cohort

Background: Frailty is associated bidirectionally with cardiovascular disease. However, the relations between frailty and atrial fibrillation (AF) have not been fully elucidated. Methods and Results: Using the FHS (Framingham Heart Study) Offspring cohort, we sought to examine both the association between frailty (2005-2008) and incident AF through 2016 and the association between prevalent AF and frailty status (2011-2014). Frailty was defined using the Fried phenotype. Models adjusted for age, sex, and smoking. Cox proportional hazards models, adjusted for competing risk of death, assessed the association between prevalent frailty and incident AF. Logistic regression models assessed the association between prevalent AF and new-onset frailty. For the incident AF analysis, we included 2053 participants (56% women; mean age, 69.7+/-6.9 years). By Fried criteria, 1018 (50%) were robust, 903 (44%) were prefrail, and 132 (6%) were frail. In total, 306 incident cases of AF occurred during an average 9.2 (SD, 3.1) follow-up years. After adjustment, there was no statistically significant association between prevalent frailty status and incident AF (prefrail versus robust: hazard ratio [HR], 1.22 [95% CI, 0.95-1.55]; frail versus robust: HR, 0.92 [95% CI, 0.57-1.47]). At follow-up, there were 111 new cases of frailty. After adjustment, there was no statistically significant association between prevalent AF and new-onset frailty (odds ratio, 0.48 [95% CI, 0.17-1.36]). Conclusions: Although a bidirectional association between frailty and cardiovascular disease has been suggested, we did not find evidence of an association between frailty and AF. Our findings may be limited by sample size and should be further explored in other populations

Machine learning for comprehensive forecasting of Alzheimer's Disease progression

Most approaches to machine learning from electronic health data can only predict a single endpoint. The ability to simultaneously simulate dozens of patient characteristics is a crucial step towards personalized medicine for Alzheimer’s Disease. Here, we use an unsupervised machine learning model called a Conditional Restricted Boltzmann Machine (CRBM) to simulate detailed patient trajectories. We use data comprising 18-month trajectories of 44 clinical variables from 1909 patients with Mild Cognitive Impairment or Alzheimer’s Disease to train a model for personalized forecasting of disease progression. We simulate synthetic patient data including the evolution of each sub-component of cognitive exams, laboratory tests, and their associations with baseline clinical characteristics. Synthetic patient data generated by the CRBM accurately reflect the means, standard deviations, and correlations of each variable over time to the extent that synthetic data cannot be distinguished from actual data by a logistic regression. Moreover, our unsupervised model predicts changes in total ADAS-Cog scores with the same accuracy as specifically trained supervised models, additionally capturing the correlation structure in the components of ADAS-Cog, and identifies sub-components associated with word recall as predictive of progression

Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.</p> <p>Results</p> <p>We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.</p> <p>Conclusion</p> <p>Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.</p

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary

Determinants of physicians' purchase intention for innovative services: Integrating professional characteristics with technology acceptance model and theory of planned behaviour

© 2015 Imperial College Press. This paper seeks to explore the factors that influence physicians' purchase intention for supplementary professional services that have been recently introduced to the market. For that reason, a model has been developed and empirically tested using data collected from 100 physicians regarding an innovative e-detailing service. Results show that physicians' purchase intention is significantly influenced by five factors. Three of them derive from the integration of Technology Acceptance Model (TAM) with the Theory of Planned Behaviour (TPB), i.e., perceived usefulness, perceived ease of use and professional image. The rest, namely work experience, working status and innovativeness, refer to physicians' professional characteristics. Work experience and innovativeness were found to have a significant effect on physicians' perceptions of the innovative service, whereas, physicians' current working status was not found to have significant influence on either their perceptions of the innovative service or their purchase intention