76 research outputs found
Increased EEG gamma band activity in Alzheimerâs disease and mild cognitive impairment
High frequency (30â70Â Hz) gamma band oscillations in the human electro-encephalogram (EEG) are thought to reflect perceptual and cognitive processes. It is therefore interesting to study these measures in cognitive impairment and dementia. To evaluate gamma band oscillations as a diagnostic biomarker in Alzheimerâs disease (AD) and mild cognitive impairment (MCI), 15 psychoactive drug naĂŻve AD patients, 20 MCI patients and 20 healthy controls participated in this study. Gamma band power (GBP) was measured in four conditions viz. resting state, music listening, story listening and visual stimulation. To evaluate testâretest reliability (TRR), subjects underwent a similar assessment one week after the first. The overall TRR was high. Elevated GBP was observed in AD when compared to MCI and control subjects in all conditions. The results suggest that elevated GBP is a reproducible and sensitive measure for cognitive dysfunction in AD in comparison with MCI and controls
The Timing of the Cognitive Cycle
We propose that human cognition consists of cascading cycles of recurring brain
events. Each cognitive cycle senses the current situation, interprets it with
reference to ongoing goals, and then selects an internal or external action in
response. While most aspects of the cognitive cycle are unconscious, each cycle
also yields a momentary âignitionâ of conscious broadcasting.
Neuroscientists have independently proposed ideas similar to the cognitive
cycle, the fundamental hypothesis of the LIDA model of cognition. High-level
cognition, such as deliberation, planning, etc., is typically enabled by
multiple cognitive cycles. In this paper we describe a timing model LIDA's
cognitive cycle. Based on empirical and simulation data we propose that an
initial phase of perception (stimulus recognition) occurs 80â100 ms from
stimulus onset under optimal conditions. It is followed by a conscious episode
(broadcast) 200â280 ms after stimulus onset, and an action selection phase
60â110 ms from the start of the conscious phase. One cognitive cycle would
therefore take 260â390 ms. The LIDA timing model is consistent with brain
evidence indicating a fundamental role for a theta-gamma wave, spreading forward
from sensory cortices to rostral corticothalamic regions. This posteriofrontal
theta-gamma wave may be experienced as a conscious perceptual event starting at
200â280 ms post stimulus. The action selection component of the cycle is
proposed to involve frontal, striatal and cerebellar regions. Thus the cycle is
inherently recurrent, as the anatomy of the thalamocortical system suggests. The
LIDA model fits a large body of cognitive and neuroscientific evidence. Finally,
we describe two LIDA-based software agents: the LIDA Reaction Time agent that
simulates human performance in a simple reaction time task, and the LIDA Allport
agent which models phenomenal simultaneity within timeframes comparable to human
subjects. While there are many models of reaction time performance, these
results fall naturally out of a biologically and computationally plausible
cognitive architecture
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodiumâglucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with reninâangiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodiumâglucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with reninâangiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Sublingual immunotherapy for asthma.
BACKGROUND: Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. However, it is not clear whether the sublingual delivery route is safe and effective in asthma. OBJECTIVES: To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma. SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/) and reference lists of all primary studies and review articles. The search is up to date as of 25 March 2015. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), irrespective of blinding or duration, that evaluated sublingual immunotherapy versus placebo or as an add-on to standard asthma management. We included both adults and children with asthma of any severity and with any allergen-sensitisation pattern. We included studies that recruited participants with asthma, rhinitis, or both, providing at least 80% of trial participants had a diagnosis of asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results for included trials, extracted numerical data and assessed risk of bias, all of which were cross-checked for accuracy. We resolved disagreements by discussion.We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs) or standardised mean differences (SMDs) using random-effects models. We rated all outcomes using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) and presented results in the 'Summary of findings' table. MAIN RESULTS: Fifty-two studies met our inclusion criteria, randomly assigning 5077 participants to comparisons of interest. Most studies were double-blind and placebo-controlled, but studies varied in duration from one day to three years. Most participants had mild or intermittent asthma, often with co-morbid allergic rhinitis. Eighteen studies recruited only adults, 25 recruited only children and several recruited both or did not specify (n = 9).With the exception of adverse events, reporting of outcomes of interest to this review was infrequent, and selective reporting may have had a serious effect on the completeness of the evidence. Allocation procedures generally were not well described, about a quarter of the studies were at high risk of bias for performance or detection bias or both and participant attrition was high or unknown in around half of the studies.One short study reported exacerbations requiring a hospital visit and observed no adverse events. Five studies reported quality of life, but the data were not suitable for meta-analysis. Serious adverse events were infrequent, and analysis using risk differences suggests that no more than 1 in 100 are likely to suffer a serious adverse event as a result of treatment with SLIT (RD 0.0012, 95% confidence interval (CI) -0.0077 to 0.0102; participants = 2560; studies = 22; moderate-quality evidence).Within secondary outcomes, wide but varied reporting of largely unvalidated asthma symptom and medication scores precluded meaningful meta-analysis; a general trend suggested SLIT benefit over placebo, but variation in scales meant that results were difficult to interpret.Changes in inhaled corticosteroid use in micrograms per day (MD 35.10 mcg/d, 95% CI -50.21 to 120.42; low-quality evidence), exacerbations requiring oral steroids (studies = 2; no events) and bronchial provocation (SMD 0.69, 95% CI -0.04 to 1.43; very low-quality evidence) were not often reported. This led to many imprecise estimates with wide confidence intervals that included the possibility of both benefit and harm from SLIT.More people taking SLIT had adverse events of any kind compared with control (OR 1.70, 95% CI 1.21 to 2.38; low-quality evidence; participants = 1755; studies = 19), but events were usually reported to be transient and mild.Lack of data prevented most of the planned subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS: Lack of data for important outcomes such as exacerbations and quality of life and use of different unvalidated symptom and medication scores have limited our ability to draw a clinically useful conclusion. Further research using validated scales and important outcomes for patients and decision makers is needed so that SLIT can be properly assessed as clinical treatment for asthma. Very few serious adverse events have been reported, but most studies have included patients with intermittent or mild asthma, so we cannot comment on the safety of SLIT for those with moderate or severe asthma. SLIT is associated with increased risk of all adverse events
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Simultaneous qualitation and quantification of four phytoecdysones in Radix Achyranthis Bidentatae by high-performance liquid chromatography with diode array detection
Toxicity toTradescantia of technogenic radionuclides and their mixture with heavy metals
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