Too early initiation of renal replacement therapy may be harmful

In an observational multicenter study, Elseviers and colleagues report that renal replacement therapy (RRT) in acutely ill patients treated for acute kidney injury is an independent risk factor for death. This result may question the benefit of the current practice of early RRT initiation

Differential effects of dopaminergic therapies on dorsal and ventral striatum in Parkinson\u27s disease: implications for cognitive function.

Cognitive abnormalities are a feature of Parkinson\u27s disease (PD). Unlike motor symptoms that are clearly improved by dopaminergic therapy, the effect of dopamine replacement on cognition seems paradoxical. Some cognitive functions are improved whereas others are unaltered or even hindered. Our aim was to understand the effect of dopamine replacement therapy on various aspects of cognition. Whereas dorsal striatum receives dopamine input from the substantia nigra (SN), ventral striatum is innervated by dopamine-producing cells in the ventral tegmental area (VTA). In PD, degeneration of SN is substantially greater than cell loss in VTA and hence dopamine-deficiency is significantly greater in dorsal compared to ventral striatum. We suggest that dopamine supplementation improves functions mediated by dorsal striatum and impairs, or heightens to a pathological degree, operations ascribed to ventral striatum. We consider the extant literature in light of this principle. We also survey the effect of dopamine replacement on functional neuroimaging in PD relating the findings to this framework. This paper highlights the fact that currently, titration of therapy in PD is geared to optimizing dorsal striatum-mediated motor symptoms, at the expense of ventral striatum operations. Increased awareness of contrasting effects of dopamine replacement on dorsal versus ventral striatum functions will lead clinicians to survey a broader range of symptoms in determining optimal therapy, taking into account both those aspects of cognition that will be helped versus those that will be hindered by dopaminergic treatment

Implementing Dynamic Coarse & Fine Grained Taint Analysis for Rhino JavaScript

Web application systems today are at great risk from attackers. They use methods like cross-site scripting, SQL injection, and format string attacks to exploit vulnerabilities in an application. Standard techniques like static analysis, code audits seem to be inadequate in successfully combating attacks like these. Both the techniques point out the vulnerabilities before an application is run. However, static analysis may result in a higher rate of false positives, and code audits are time-consuming and costly. Hence, there is a need for reliable detection mechanisms. Dynamic taint analysis offers an alternate solution — it marks the incoming data from the untrusted source as ‘tainted.’’ The flow of tainted data is tracked during the program execution. Whenever tainted data is used in a security-sensitive context, a proper action is taken. The execution may also be suspended depending upon the severity of the operation. This project implements dynamic taint analysis in Rhino JavaScript. The focus is on adding support for coarse-grained and fine-grained string tainting. Coarse-grained tainting works at the granularity level of a string while fine-grained tainting works at the granularity level of a character in a string. Both approaches are discussed in further detail in the paper. I have also written a SQL library to leverage my implementation of taint analysis in Rhino and conducted performance tests to contrast the overhead of coarse & fine grained taint analysis. My test results show that fine-grained taint analysis in general incurs more overhead than coarse-grained taint analysis

Age Affects How Task Difficulty and Complexity Modulate Perceptual Decision-Making

Decisions differ in difficulty and rely on perceptual information that varies in richness (complexity); aging affects cognitive function including decision-making, and yet, the interaction between difficulty and perceptual complexity have rarely been addressed in aging. Using a parametric fMRI modulation analysis and psychophysics, we address how task difficulty affects decision-making when controlling for the complexity of the perceptual context in which decisions are made. Perceptual complexity was varied in a factorial design while participants made perceptual judgments on the spatial frequency of two patches that either shared the same orientation (simple condition) or were orthogonal in orientation (complex condition). Psychophysical thresholds were measured for each participant in each condition and served to set individualized levels of difficulty during scanning. Findings indicate that discriminability interacts with complexity, to influence decisional difficulty. Modulation as a function of difficulty is maintained with age, as indicated by coupling between increased activation in fronto-parietal regions and suppression in the lateral hubs, however, age has a specific effect in the ventral anterior cingulate cortex (ACC), driven by performance at near-threshold (difficult) levels for the simpler stimulus combination condition, but not the more complex one. Taken together, our findings suggest that the context of difficulty, or what is perceived as important, changes with age, and that decisions that would seem neutral to younger participants, may carry more emphasis with age

Are Verbal Fluency and Nonliteral Language Comprehension Deficits Related to Depressive Symptoms in Parkinson's Disease?

Depression in Parkinson's disease (PD) is frequently associated with executive deficits, which can influence nonliteral comprehension and lexical access. This study explores whether depressive symptoms in PD modulate verbal fluency and nonliteral language comprehension. Twelve individuals with PD without depressive symptoms, 13 with PD and depressive symptoms (PDDSs), and 13 healthy controls completed a semantic and phonemic verbal fluency task and an indirect speech acts comprehension task. All groups had the same performance in the phonemic fluency task while the PDDS group was impaired in the semantic task. For the indirect speech act comprehension task, no difference was observed between the groups. However, the PDDS group had difficulty answering direct speech act questions. As some language impairments in PD become apparent when depressive symptoms are associated with the disease, it would appear to be important to take the presence of depressive symptoms into account when evaluating language abilities in PD

Repetitive Transcranial Magnetic Stimulation of Dorsolateral Prefrontal Cortex Affects Performance of the Wisconsin Card Sorting Task during Provision of Feedback

Early functional neuroimaging studies of tasks evaluating executive processes, such as the Wisconsin card sorting task (WCST), only assessed trials in blocks that may contain a large amount of different cognitive processes. More recently, we showed using event-related fMRI that the dorsolateral prefrontal cortex (DL-PFC) significantly increased activity during feedback but not matching periods of the WCST, consistent with its proposed role in the monitoring of information in working memory. Repetitive transcranial magnetic stimulation (rTMS) is a method that allows to disrupt processing within a given cortical region and to affect task performance for which this region is significantly solicited. Here we applied rTMS to test the hypothesis that the DL-PFC stimulation influences monitoring of working memory without interfering with other executive functions. We applied rTMS to the right DL-PFC and the vertex (control site) in different time points of the WCST. When rTMS was applied to the DL-PFC specifically during the period when subjects were receiving feedback regarding their previous response, WCST performance deteriorated, while rTMS did not affect performance during matching either when maintaining set or during set-shifting. This selective impairment of the DL-PFC is consistent with its proposed role in monitoring of events in working memory

Structural Neuroimaging Markers of Cognitive Decline in Parkinson’s Disease

Cognitive impairment in patients with Parkinson’s disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson’s disease and to take into consideration the near-future possibilities of their implementation into clinical practice

High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]

INTRODUCTION: To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted. METHODS: Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up. RESULTS: The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22–2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43–3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI. CONCLUSION: No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI