We propose the concept of Cognitive Debt to characterize thoughts and behaviors that increase vulnerability to symptomatic Alzheimer's disease (AD). Evidence indicates that depression, anxiety, sleep disorder, neuroticism, life stress, and post-traumatic stress disorder increase risk for AD, and we suggest they do so by increasing Cognitive Debt. Repetitive negative thinking (RNT), a behaviorally measurable process common to these factors, may drive Cognitive Debt acquisition. RNT transcends disorder-specific definition, encompasses rumination and worry, and is defined by perseverative, negative thought tendencies. Evidence of dysregulated stress responses supports the concept of Cognitive Debt, of RNT as its causal mechanism, and of an interaction with the APOE-?4 genotype to increase vulnerability to clinical AD, independent from traditional AD pathology. Defining a more specific behavioral profile of risk would enable interventions to be targeted earlier and more precisely at individuals most vulnerable to developing AD. Additionally, modulating RNT could potentially reduce risk of clinical AD. Interventions to reduce RNT are discussed, as are suggestions for future research. For these reasons we submit that the Cognitive Debt model may aid understanding of the psychological mechanisms that potentially increase predisposition to AD.
ABSTRACT Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as "strongly agree" or "somewhat agree" (68-88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82?weeks with a treatment period of 78?weeks.
This study aimed to systematically review available evidence relevant to the following issues: (1) whether psychotic major depression (PMD) in older people differs in overall severity from non-PMD, besides the presence of psychotic symptoms; (2) whether it constitutes a distinct clinical entity from non-PMD; and (3) whether it differs from PMD in younger adults.
The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.
The power law of practice holds that a power function best interrelates skill performance and amount of practice. However, the law's validity and generality are moot. Some researchers argue that it is an artifact of averaging individual exponential curves while others question whether the law generalizes to complex skills and to performance measures other than response time. The present study tested the power law's generality to development over many years of a very complex cognitive skill, chess playing, with 387 skilled participants, most of whom were grandmasters. A power or logarithmic function best fit grouped data but individuals showed much variability. An exponential function usually was the worst fit to individual data. Groups differing in chess talent were compared and a power function best fit the group curve for the more talented players while a quadratic function best fit that for the less talented. After extreme amounts of practice, a logarithmic function best fit grouped data but a quadratic function best fit most individual curves. Individual variability is great and the power law or an exponential law are not the best descriptions of individual chess skill development.
Dopamine D2/3 receptor positron emission tomography tracers have guided antipsychotic prescribing in young people with schizophrenia by establishing a 'therapeutic window' of striatal D2/3 receptor occupancy. Older people, particularly those with dementia, are highly susceptible to motor side effects and may benefit from the appropriate application of imaging techniques. The study aimed to adapt [18F]fallypride imaging for use in occupancy studies in Alzheimer's disease (AD) and to investigate whether data acquisition could be made more tolerable by piloting the protocol in a small sample.
We describe a simple route to fabricate two dimensionally well-ordered, periodic nanopatterns using the self-assembly of brush block copolymers (brush BCPs). Well-developed lamellar microdomains oriented perpendicular to the substrate are achieved, without modification of the underlying substrates, and structures with feature sizes greater than 200 nm are generated due to the reduced degree of chain entanglements of brush BCPs. A near-perfect linear scaling law was found for the period, L, as a function of backbone degree of polymerization (DP) for two series of brush BCPs. The exponent increases slightly from 0.99 to 1.03 as the side chain molecular weight increases from ?2.4 to ?4.5 kg/mol(-1) and saturated with further increase in the side chain molecular weight due to the entropic penalty associated with the packing of the side chains. Porous templates and scaffolds from brush BCP thin films are also obtained by selective etching of one component.
Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.
Despite rigorous research into the genetics of neuropsychiatric disorders, the mechanism by which polygenic risk leads to complex clinical phenotypes remains unclear. The Encyclopedia of DNA Elements (ENCODE) project gives us new insight into gene regulation, and gene-gene and gene-environment interaction. Better understanding of these key genomic mechanisms may provide the answers we have been searching for.
Assistive technology and telecare (ATT) are relatively new ways of delivering care and support to people with social care needs. It is claimed that ATT reduces the need for community care, prevents unnecessary hospital admission, and delays or prevents admission into residential or nursing care. The current economic situation in England has renewed interest in ATT instead of community care packages. However, at present, the evidence base to support claims about the impact and effectiveness of ATT is limited, despite its potential to mitigate the high financial cost of caring for people with dementia and the social and psychological cost to unpaid carers.Method/design: ATTILA (Assistive Technology and Telecare to maintain Independent Living At Home for People with Dementia) is a pragmatic, multi-centre, randomised controlled trial over 104 weeks that compares outcomes for people with dementia who receive ATT and those who receive equivalent community services but not ATT. The study hypothesis is that fewer people in the ATT group will go into institutional care over the 4-year period for which the study is funded. The study aims to recruit 500 participants, living in community settings, with dementia or significant cognitive impairment, who have recently been referred to social services.Primary outcome measures are time in days from randomisation to institutionalisation and cost effectiveness. Secondary outcomes are caregiver burden, health-related quality of life in carers, number and severity of serious adverse events, and data on acceptability, applicability and reliability of ATT intervention packages. Assessments will be undertaken in weeks 0 (baseline), 12, 24, 52 and 104 or until institutionalisation or withdrawal of the participant from the trial.
Apathy is a neurocognitive syndrome of reduced goal-directed behaviour and is an important cause of disability in neurodegenerative disorders. Frontal-subcortical dysfunction is thought to be important in apathy, but the contribution of individual brain regions to different aspects of the apathy syndrome is poorly understood. We aimed to test the hypotheses that apathy in two distinct neurodegenerative disorders would be associated with frontal lobe atrophy and that reduced initiative and emotional blunting would be associated with distinct patterns of atrophy in functionally relevant brain areas. Seventeen patients with progressive supranuclear palsy (PSP) and 17 patients with Alzheimers disease (AD) underwent structural MRI scanning at 3 T to provide data for voxel based morphometric analysis. Apathy was defined using Roberts 2009 diagnostic criteria and specific symptoms were assessed with the Apathy Inventory. Patients with and without apathy were matched for important demographic and clinical characteristics. Apathy was associated with atrophy of the ventromedial orbitofrontal cortex and left insula in both AD and PSP. Reduced initiative was specifically associated with atrophy of the anterior cingulate and ventrolateral orbitofrontal cortex whilst emotional blunting was specifically associated with atrophy of the left insula. These findings provide further support for the role of medial frontal regions and insular cortex in apathy and suggest that behavioural and emotional aspects of the apathy syndrome may have distinct neuroanatomical bases.
Summary Males predominate at the top in chess, and chess is a useful domain to investigate possible causes of gender differences in high achievement. Opportunity, interest and extent of practice can be controlled for. Organized chess has objective performance measures, extensive longitudinal population-level data and little gatekeeper influence. Previous studies of gender differences in chess performance have not controlled adequately for females on average playing fewer rated games and dropping out at higher rates. The present study did so by examining performance of international chess players at asymptote and over equal numbers of rated games. Males still were very disproportionately represented at the top. Top female players showed signs of having less natural talent for chess than top males, such as taking more rated games to gain the grandmaster title. The hypothesis that males predominate because many more males play chess was tested by comparing gender performance differences in nations with varying percentages of female players. In well-practised participants, gender performance differences stayed constant even when the average national percentage of female international players increased from 4.2% to 32.3%. In Georgia, where women are encouraged strongly to play chess and females constitute nearly 32% of international players, gender performance differences are still sizeable. Males on average may have some innate advantages in developing and exercising chess skill.
[(18)F]fallypride is a high-affinity dopamine D2/3 receptor tracer with the ability to reliably quantify D2/3 receptor sites in both striatal and corticolimbic regions. The translational potential of [(18)F]fallypride imaging is, however, limited by the lengthy scanning sessions (60-80?minutes duration over a total of 3-4?hours) required by current protocols. The aims of our study were to adapt [(18)F]fallypride imaging for use in clinical populations with neurological and neuropsychiatric disorders, by reducing the duration of individual scanning sessions; and to establish the reproducibility and reliability of our adapted protocol in healthy older people. Eight participants (five male and three female; mean age=75.87±4.39 years) were scanned twice, 4-6 weeks apart. [(18)F]fallypride binding potential was determined from image data collected during three sampling times: 0-30; 60-90; and 210-240?minutes post injection. High reproducibility and reliability (test-retest variability <8%; intraclass correlation coefficient >0.8) were observed in all but the prefrontal regions, and remained so when sampling times were reduced to 20?minutes (0-20; 70-90; 220-240?minutes). The adapted protocol is feasible for use across neuropsychiatric disorders in which dopamine has been implicated and is sufficiently sensitive to detect within-subject changes between 2.7% and 5.5% in striatal and limbic regions.
Self-assembled structures of brush block copolymers (BrBCPs) with polylactide (PLA) and polystyrene (PS) side chains were studied. The polynorbornene-backbone-based BrBCPs containing approximately equal volume fractions of each block self-assembled into highly ordered lamellae with domain spacing ranging from 20 to 240 nm by varying molecular weight of the backbone in the bulk state, as revealed by small-angle X-ray scattering (SAXS). The domain size increased approximately linearly with backbone length, which indicated an extended conformation of the backbone in the ordered state. In situ SAXS measurements suggested that the BrBCPs self-assemble with an extremely fast manner which could be attributed to a reduced number of entanglements between chains. The strong segregation theory and Monte Carlo simulation also confirmed this near-linear dependence of the domain spacing on backbone length, rationalizing experimental results.
The osteoporosis self-assessment tool (OST) is a screening instrument that uses age and weight as parameters to predict the risk of osteoporosis. This study was designed to evaluate OST in predicting osteoporosis in males. Male veterans aged 50yr and older with no prior diagnosis of osteoporosis and no prior bone densitometry (dual-energy X-ray absorptiometry [DXA]) testing were eligible for the study. Sociodemographic information, medical history, and risk factors for osteoporosis were recorded. Anthropometric measurements were taken and DXA testing performed. The OST index for each subject was calculated and predictive values and receiver operating characteristic (ROC) curves were evaluated for OST and osteoporosis. Five hundred eighteen subjects underwent DXA, 92 (17.8%) had osteoporosis, 281 (54.2%) had low bone mass, and 145 (28.0%) had normal bone mineral density. The OST index ranged from -8 to 23 with a mean of 4 (standard deviation ± 4.3). An OST index of 6 or lower predicted osteoporosis with a sensitivity of 82.6%, specificity of 33.6%, and an area under the curve for the ROC curve of 0.67. OST index performed better in non-Hispanic whites and males >65yr. OST predicts osteoporosis with moderate sensitivity and poor specificity in men.
The purpose of this study was to track creatine kinase (CK) and serum cortisol over an American college football season starting with the preseason practice. A secondary purpose was to observe changes in basic clinical chemistries. Twenty-two National Collegiate Athletic Association Division I football players (age: 20.4 ± 1.1 years, height: 188.27 ± 8.3 cm, weight: 115.8 ± 29.7 kg) volunteered to participate in this study. Each of the players had participated in the summer strength and conditioning supervised program. Resting blood samples were obtained just before the start of preseason practice (T-1), 2 weeks later (T-2), and the day after game 2 (T-3), game 4 (T-4), game 6 (T-5), and game 9 (T-6) of a 12-game season. Creatine kinase, a panel of clinical chemistries, cortisol, and testosterone were assayed at each time point. No significant changes in CK concentrations were observed over the season with peak values of each range ?1,070.0 IU·L(-1), but the largest range was observed at T-6 after game 9 (119-2,834 IU·L(-1). The analysis of covariance analysis demonstrated that the number of plays in the ninth game (T-6) explained the magnitude of the changes in CK. No changes in serum cortisol concentrations were observed yet, again large variations existed with peak values of each range ?465.0 nmol·L(-1). Clinical chemistries showed various significant changes from T-1, but none were considered clinically relevant changes for any player over the time course of the study. In conclusion, the strength and conditioning program before preseason camp or the structure of summer camp practices and the in-season strength and conditioning appeared to mute muscle damage and the stress response of cortisol. Such data demonstrate that changes in muscle damage and adrenal cortical stress over the season are minimal, yet large individual variations can be observed. Management of these variables appears to be related to optimal strength and conditioning and sports medicine programs. Thus, the greater concerns for student-athlete safety in the sport of American football are related to preventing sudden death, traumatic injury, and managing concussion syndromes.
Composite tissue defects in the head and neck region present unique challenges. Definitive head and neck reconstruction of these cases is often complicated by complex 3-dimensional defects that may require multiple flap or chimeric flap procedures. These advanced techniques can have serious repercussions should poor perfusion of the flap cause flap failure, which can be devastating.
Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.
INTRODUCTION. This study used Item-Response Theory (IRT) to model the psychometric properties of a false belief picture sequencing task. Consistent with the mental time travel hypothesis of paranoia, we anticipated that performance on this deductive theory of mind (ToM) task would not be associated with the presence of persecutory delusions but would be related to other clinical, cognitive, and demographic factors. METHOD. A large (N=237) and diverse clinical and nonclinical sample differing in levels of depression and paranoid ideation performed 2 ToM tasks: the false belief sequencing task and a ToM stories task that was used to assess the validity of the false belief sequencing task as a measure of ToM. RESULTS. A unidimensional IRT model was found to fit the data well. Latent ToM ability as measured by the false belief sequencing task was negatively related with age and positively with IQ. In contrast to the ToM stories measure, there was no association between clinical diagnosis or symptoms and false belief picture sequencing after controlling for age and IQ. CONCLUSIONS. In line with mental time travel hypothesis of paranoia (Corcoran, 2010 ), performance on this deductive nonverbal ToM task is not related to the presence of paranoid symptoms. This measure is best suited for assessing ToM functioning where participants performance falls just short of the average latent ToM ability. Furthermore, it is sensitive to the effects of increasing age and decreasing IQ.
Expertise typically develops slowly over years, and controlled experiments to study its development may be impractical. Researchers often use a correlational, retrospective recall method in which participants recall career data, sometimes over many years before. However, recall accuracy is uncertain. The present study investigated the accuracy of recalled career data for up to 38 years, in over 600 international chess players. Participants estimates of their entry year into international chess, total career games played, and number of games in a typical year were compared with the known true values. Entry year typically was recalled fairly accurately, and accuracy did not diminish systematically with time since list entry from 10 years earlier to 25 or more years earlier. On average, games-count estimates were reasonably accurate. However, some participants were very inaccurate, and some were more inaccurate in their total-games counts and entry-year estimates. The retrospective recall method yields usable data but may have some accuracy problems. Possible remedies are outlined.
Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy).
The purpose of this study was to examine the influence of a cold treatment and a dynamic warm-up on lower body power in the form of a countermovement vertical jump (CMVJ). Nine physically active men, who were either current or ex-National Collegiate Athletic Association (NCAA) Division 1 athletes, consented to participate in the study. Using a balanced, randomized presentation and a within-subject design, each subject performed 4 environmental and warm-up protocols (i.e., ambient temperature without warm-up, ambient temperature with warm-up, cold without warm-up, or cold with warm-up). Two sets of 3 maximal effort CMVJs were performed on a force plate at each testing time point. For each protocol, the subjects completed a pretest set of CMVJ (pretreatment [PRE]), were then exposed to 1 of the 2 temperature treatments, completed another set of CMVJ (initial [IT]), then either went through a 15-minute warm-up, or were asked to sit in place. Then a final set of CMVJs was completed (posttreatment [PT]). The primary finding in this study was that warm-up was effective in offsetting the negative effects of cold exposure on CMVJ power. There was a significant main effect for Time (PRE > PT > IT), and there was a significant (p ? 0.05) main effect for Trial (AMB = AMBWU > COLDWU > COLD). Because athletic competitions happen in various colder climates, it is important to make sure that a proper warm-up be completed to maximize the athletes power output. The results of this study demonstrate that when athletes are exposed to cold conditions, it is recommended that before practice or play, a dynamic warm-up be employed to optimize performance.
Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.
The fragile X syndrome (FXS) is caused by silencing of the fragile X mental retardation gene (FMR1) and the absence of its product, fragile X mental retardation protein (FMRP), resulting from CpG island methylation associated with large CGG repeat expansions (more than 200) termed full mutation (FM). We have identified a number of novel epigenetic markers for FXS using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), naming the most informative fragile X-related epigenetic element 1 (FREE1) and 2 (FREE2). Methylation of both regions was correlated with that of the FMR1 CpG island detected using Southern blot (FREE1 R = 0.97; P < 0.00001, n = 23 and FREE2 R = 0.93; P < 0.00001, n = 23) and negatively correlated with lymphocyte expression of FMRP (FREE1 R = -0.62; P = 0.01, n = 15 and FREE2 R = -0.55; P = 0.03, n = 15) in blood of partially methylated high functioning FM males. In blood of FM carrier females, methylation of both markers was inversely correlated with the FMR1 activation ratio (FREE1 R = -0.93; P < 0.0001, n = 12 and FREE2 R = -0.95; P < 0.0001, n = 9). In a sample set of 49 controls, 18 grey zone (GZ 40-54 repeats), 22 premutation (PM 55-170 repeats) and 22 (affected) FXS subjects, the FREE1 methylation pattern was consistent between blood and chorionic villi as a marker of methylated FM alleles and could be used to differentiate FXS males and females from controls, as well as from carriers of GZ/PM alleles, but not between GZ and PM alleles and controls. Considering its high-throughput and specificity for pathogenic FM alleles, low cost and minimal DNA requirements, FREE MALDI-TOF MS offers a unique tool in FXS diagnostics and newborn population screening.
Brain training, or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry, yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals and preschool children, and video-game players outperform non-players on some tests of visual attention. However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.
We report a case of globe rupture associated with the use of post cataract-surgery protective eyewear. The patient had routine cataract surgery 3 months before presentation and had adapted his post cataract-surgery glasses to use on the tennis court. He experienced a large posterior globe rupture after falling directly onto his face during a match. Spectacle torsion is the suspected biomechanical process that led to the rupture. We conclude that although the glasses given to many patients after cataract surgery are protective for most low-impact injuries, patients should be aware they are not designed for activities with a risk for significant impact. Patients should also be counseled to use protective eyewear specifically designed and approved for the sport or activity in which they participate.
A results-driven approach to optimizing patient flow, grounded on quality improvement, change management and organizational learning principles, is described. Tactics included collaborative governance, performance management, rapid process improvements and implementation toolkits. Results included an 83.1% decrease in emergent volumes waiting for greater than 24 hours and a 49.1% improvement in emergency department length of stay for admitted patients. There were no adverse outcomes on other key indicators. Sustainability remains the challenge but early results are encouraging.
A crucial role of corticostriatal dopaminergic networks in cognitive and motor processes has been well established but largely unexplored in Alzheimers disease (AD). The study investigated the relationship between striatal DA (D(2)) receptor availability and specific aspects of cognitive (sustained visual attention, spatial planning, word recognition) and motor (speed and dexterity) function in 24 people with mild to moderate AD. In vivo dopamine DA (D(2)) receptor availability was determined with [(11)C] raclopride (RAC) positron emission tomography (PET). Imaging data were analysed using both region of interest (ROI) and voxel-based approaches. Higher [(11)C] RAC binding was associated with increased motor speed and, paradoxically, poorer attentional performance. These findings are broadly consistent with previously conducted studies in healthy older adults and would suggest that the use of DA (D(2)) receptor agonists as an adjunctive treatment strategy in AD may have dissociable effects upon cognitive function.
Good practice guidelines state that a psychological intervention should usually precede pharmacotherapy, but there are no data evaluating the feasibility of psychological interventions used in this way.
To standardise the delivery of a brief group cognitive behaviour therapy intervention (CBT-G). To apply the intervention in a research setting and to estimate its effect on recurrence rates in recently depressed older adults, in preparation for a definitive study.
Delirium is a serious and common disorder especially among older people on inpatients units. Numerous modifiable or manageable delirium risk factors have been identified. As a result, there is now a widespread notion that many cases of delirium can be prevented. In this review, published data evaluating non-pharmacological interventions for delirium prevention were assessed in relation to their efficacy. Currently, most published studies are based on direct targeting of risk factors and/or introduction of educational programmes to increase staff knowledge and awareness. However, there continues to be a dearth of randomised controlled trials evaluating non-pharmacological interventions, partly because of the inherent difficulties associated with delirium research in general and with the evaluation of non-pharmacological interventions in particular. Instead, many of the available studies have been observational or non-randomised in nature. Nevertheless, the majority of these support a role for non-pharmacological interventions in delirium prevention. While more research is certainly needed, the majority of available data are based on best practice protocols, guidelines and interventions. Hence, a consistent and concerted effort is now justified to introduce non-pharmacological prevention strategies across units to help tackle the increasingly prevalent delirium among older people.
The purpose of this study was to examine markers of skeletal muscle tissue damage and circulating anabolic and catabolic hormones to gain insight into the recovery process from Friday until Monday, when a new practice week begins. Twenty-eight National Collegiate Athletic Association Division I football players gave consent to participate in the investigation in the ninth game of the season. Sixteen players started the game and played the entire game (PL), and 12 others did not play and were on the bench during the game (DNP). Each player had fasted blood samples obtained at the same time of day between 1000 and 1200 hours the day before the game (Friday; T1), 18-20 hours after the game (Sunday; T2), and then 42-44 hours after the game (Monday; T3). Blood samples were analyzed for concentrations of creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin, testosterone, and cortisol. The PL players showed significantly (p T1 and T3), myoglobin (T2 > T1 and T3), and LDH (T2 > T1). In contrast, DNP players showed significant differences in cortisol (T3 < T1 and T2) and testosterone:cortisol (T3 > T1). Few changes were observed in testosterone and cortisol changes, indicating stability of the anabolic/catabolic hormones. In conclusion, these data indicate that participation in a college football game late in the season results in some degree of tissue damage but with minimal hormonal responses, which seem to have stabilized at resting concentrations without predominance of cortisols catabolic presence. As previously noted in the literature, some type of "contact adaptation" to the season may have occurred with regard to tissue damage responses. However, by the ninth game of a season, players do carry soft tissue damage levels above resting ranges into subsequent games, indicating that recovery should be monitored, with coaches being careful with scheduling scrimmage and full-contact drills. How such data implicate overuse injuries remains unclear, considering that hormonal status in this study was highly stable, with catabolic influences minimized by the high level of athlete conditioning. These data again support that high-level conditioning can stabilize anabolic and catabolic hormonal signals and limit acute soft tissue injury, making cerebral concussion (acute and chronic) and traumatic injury the biggest threats to a student-athletes health and well-being during an American football game.
Following the discovery of an endogenous cannabinoid system and the identification of specific cannabinoid receptors in the central nervous system, much work has been done to investigate the main effects of these compounds. There is increasing evidence that the cannabinoid system may regulate neurodegenerative processes such as excessive glutamate production, oxidative stress and neuroinflammation. Neurodegeneration is a feature common to the various types of dementia and this has led to interest in whether cannabinoids may be clinically useful in the treatment of people with dementia. Recent studies have also shown that cannabinoids may have more specific effects in interrupting the pathological process in Alzheimers disease.
Paranoid delusions are a common symptom of a range of psychotic disorders. A variety of psychological mechanisms have been implicated in their cause, including a tendency to jump to conclusions, an impairment in the ability to understand the mental states of other people (theory of mind), an abnormal anticipation of threat, and an abnormal explanatory style coupled with low self-esteem.
Delirium is a very common and serious disorder with high morbidity and mortality. Despite symptomatic treatment the outcome can be poor for some especially when no underlying cause is identified. As a result, various strategies for delirium prevention have been assessed. Pharmacological agents such as antipsychotics, acetylcholinesterase inhibitors, sleep-wake cycle regulators, anti-inflammatories and others have been advocated for a potential role in delirium prevention. The aim of this paper is to review the available evidence for their use in the prevention of delirium.
Learners acquire expertise at different rates and reach different peak performance levels. Key questions arise regarding what patterns of individual differences in expertise development occur and whether innate talent affects such development. International chess is a good test domain for both issues, because it has objective performance measures, actual practice measures (number of games), longitudinal population data, and minimal gatekeeper influence. Players expertise development typically follows either a logarithmic or a power-function curve, approaching asymptote by around 750 games. A comparison of eventual top players and other eventually well-practiced players typically reveals a performance difference at domain entry, which widens progressively with practice and then stays large and constant. The data show various correlated signs of apparent greater natural talent in eventual top players: precocity (indexed by entering the domain and gaining the grandmaster title much younger on average), faster acquisition of expertise (indexed by fewer years and games needed to gain the grandmaster title from domain entry), and a higher peak performance level after extensive actual practice. A factor analysis found evidence for an underlying natural talent factor that constrains ultimate performance level.
Dysfunction within corticostriatal dopaminergic neurocircuitry has been implicated in neuropsychiatric symptoms associated with Alzheimer disease (AD). This study aimed to test the hypothesis that the symptom domains delusions and apathy would be associated with striatal dopamine (D2) receptor function in AD.
The management of Behavioural and Psychological Symptoms of Dementia (BPSD) has been the subject of considerable debate over the last few years in view of the poor evidence base for pharmacological agents and concerns about their safety.
Evidence that chess expertise rests on practice alone mostly comes from studies using a correlational retrospective recall paradigm, which confounds amount of study with number of games played and possible innate talent. Researchers also often use latest performance rating and include participants who play and study little. Study 1 partially replicated such studies with improvements such as use of peak rating and a large, skilled sample. Number of internationally-rated games played was the strongest predictor of peak rating. Total study hours was a significant but weaker predictor. Study 2 controlled for sampling confounds by including only very well-practiced players who had played at least 350 internationally-rated games. Total study hours did not predict rating at 350 games. Study 3 found that the subjective phenomenon of reaching a performance ceiling and undertaking specific practice to get beyond it does occur but does not distinguish between stronger and weaker players. Study 4 found that many players play relatively few internationally-rated games mostly because of other commitments, such as work and education. Extensive study may go along with great interest in and persistence at chess but apparently lacks a major causative role in chess performance level.
Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ?900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
The purpose of this case report is to describe a novel use of computer assistance in identifying and restoring the mechanical axis in the treatment of a periprosthetic distal femur fracture in a 76-year-old female patient with a total knee arthroplasty.
Blast exposure is a common cause of soft tissue injury within the battlefield setting, with the extremities often critically involved. The resulting injury pattern presents with massive soft tissue defects that may be further complicated by varying degrees of accompanying orthopedic and peripheral nerve damage. To address the severe soft tissue defect, various combinations of advanced reconstructive methods are typically required to achieve definitive wound coverage. Continuous external tissue expansion has been used by our institution to significantly reduce wound burden and provide for definitive wound closure in certain blast-injured patients.
Research over the past two decades supports a shared aetiology for delusions in Alzheimers disease (AD) and schizophrenia. Functional networks involved in salience attribution and belief evaluation have been implicated in the two conditions, and striatal D2/3 receptors are increased to a comparable extent. Executive/frontal deficits are common to both disorders and predict emergent symptoms. Putative risk genes for schizophrenia, which may modify the AD process, have been more strongly implicated in delusions than those directly linked with late-onset AD. Phenotypic correlates of delusions in AD may be dependent upon delusional subtype. Persecutory delusions occur early in the disease and are associated with neurochemical and neuropathological changes in frontostriatal circuits. In contrast, misidentification delusions are associated with greater global cognitive deficits and advanced limbic pathology. It is unclear whether the two subtypes are phenomenologically and biologically distinct or are part of a continuum, in which misidentification delusions manifest increasingly as the pathological process extends. This has treatment implications, particularly if they are found to have discrete chemical and/or pathological markers.
The emissions from a Garrett-AiResearch (now Honeywell) Model GTCP85-98CK auxiliary power unit (APU) were determined as part of the National Aeronautics and Space Administrations (NASAs) Alternative Aviation Fuel Experiment (AAFEX) using both JP-8 and a coal-derived Fischer Tropsch fuel (FT-2). Measurements were conducted by multiple research organizations for sulfur dioxide (SO2, total hydrocarbons (THC), carbon monoxide (CO), carbon dioxide (CO2), nitrogen oxides (NOx), speciated gas-phase emissions, particulate matter (PM) mass and number, black carbon, and speciated PM. In addition, particle size distribution (PSD), number-based geometric mean particle diameter (GMD), and smoke number were also determined from the data collected. The results of the research showed PM mass emission indices (EIs) in the range of 20 to 700 mg/kg fuel and PM number EIs ranging from 0.5 x 10(15) to 5 x 10(15) particles/kg fuel depending on engine load and fuel type. In addition, significant reductions in both the SO2 and PM EIs were observed for the use of the FT fuel. These reductions were on the order of approximately 90% for SO2 and particle mass EIs and approximately 60% for the particle number EI, with similar decreases observed for black carbon. Also, the size of the particles generated by JP-8 combustion are noticeably larger than those emitted by the APU burning the FT fuel with the geometric mean diameters ranging from 20 to 50 nm depending on engine load and fuel type. Finally, both particle-bound sulfate and organics were reduced during FT-2 combustion. The PM sulfate was reduced by nearly 100% due to lack of sulfur in the fuel, with the PM organics reduced by a factor of approximately 5 as compared with JP-8.
Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimers disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.
To review the magnitude and duration of and factors associated with effects of cognitive behavioral therapy (CBT) for anxiety disorders in older people.
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