Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD): dispelling myths

BACKGROUND: Attention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie? RESULTS: We have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered. CONCLUSION: The genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment

On the Impact of Link Layer Retransmissions on TCP for Aeronautical Communications

In this article, we evaluate the impact of link layer retransmissions on the performance of TCP in the context of aeronautical communications.We present the architecture of aeronautical networks, which is manly driven by an important channel access delay, and the various retransmission strategies that can be implemented at both link and transport layers. We consider a worst case scenario to illustrate the benefits provided by the ARQ scheme at the link layer in terms of transmission delay.We evaluate the trade-off between allowing a fast data transmission and a low usage of satellite capacity by adjusting link layer parameters

Preliminary investigation of plasma levels of sex hormones and human growth factor(s), and P300 latency as correlates to cognitive decline as a function of gender

<p>Abstract</p> <p>Background</p> <p>Aging is marked by declines in levels of many sex hormones and growth factors, as well as in cognitive function. The P300 event-related potential has been established as a predictor of cognitive decline. We decided to determine if this measure, as well as 2 standard tests of memory and attention, may be correlated with serum levels of sex hormones and growth factors, and if there are any generalizations that could be made based on these parameters and the aging process.</p> <p>Findings</p> <p>In this large clinically based preliminary study several sex-stratified associations between hormone levels and cognition were observed, including (1) for males aged 30 to 49, both IGF-1 and IGFBP-3 significantly associated negatively with prolonged P300 latency; (2) for males aged 30 to 49, the spearman correlation between prolonged P300 latency and low free testosterone was significant; (3) for males aged 60 to 69, there was a significant negative correlation between P300 latency and DHEA levels; (4) for females aged 50 to 59 IGFBP-3 significantly associated negatively with prolonged P300 latency; (5) for females at all age periods, estrogen and progesterone were uncorrelated with P300 latency; and (6) for females aged 40 to 69, there was significant negative correlation between DHEA levels and P300 latency. Moreover there were no statistically significant correlations between any hormone and Wechsler Memory Scale-III (WMS-111). However, in females, there was a significant positive correlation between estrogen levels and the number of Attention Deficit Disorder (ADD) complaints.</p> <p>Conclusion</p> <p>Given certain caveats including confounding factors involving psychiatric and other chronic diseases as well as medications, the results may still have important value. If these results could be confirmed in a more rigorously controlled investigation, it may have important value in the diagnosis, prevention and treatment of cognitive impairments and decline.</p

Creatures Great and SMAL: Recovering the Shape and Motion of Animals from Video

We present a system to recover the 3D shape and motion of a wide variety of quadrupeds from video. The system comprises a machine learning front-end which predicts candidate 2D joint positions, a discrete optimization which finds kinematically plausible joint correspondences, and an energy minimization stage which fits a detailed 3D model to the image. In order to overcome the limited availability of motion capture training data from animals, and the difficulty of generating realistic synthetic training images, the system is designed to work on silhouette data. The joint candidate predictor is trained on synthetically generated silhouette images, and at test time, deep learning methods or standard video segmentation tools are used to extract silhouettes from real data. The system is tested on animal videos from several species, and shows accurate reconstructions of 3D shape and pose.GlaxoSmithKlin

Test of variables of attention (TOVA) as a predictor of early attention complaints, an antecedent to dementia

The goal of this study was to determine if impairments detected by the test of variables of attention (TOVA) may be used to predict early attention complaints and memory impairments accurately in a clinical setting. We performed a statistical analysis of outcomes in a patient population screened for attention deficit hyperactivity disorder or attention complaints, processing errors as measured by TOVA and the Wechsler Memory Scale (WMS-III) results. Attention deficit disorder (ADD) checklists, constructed using the Diagnostic and Statistical Manual of Mental Disorders 4th Edition criteria, which were completed by patients at PATH Medical, revealed that 72.8% of the patients had more than one attention complaint out of a total of 16 complaints, and 41.5% had more than five complaints. For the 128 males with a significant number of ADD complaints, individuals whose scores were significantly deviant or borderline (SDB) on TOVA, had a significantly greater number of attention complaints compared with normals for omissions (P < 0.02), response time (P < 0.015), and variability (P < 0.005), but not commissions (P > 0.50). For males, the mean scores for auditory, visual, immediate, and working memory scores as measured by the WMS-III were significantly greater for normals versus SDBs on the TOVA subtest, ie, omission (P < 0.01) and response time (P < 0.05), but not variability or commissions. The means for auditory, visual, and immediate memory scores were significantly greater for normals versus SDBs for variability (P < 0.045) only. In females, the mean scores for visual and working memory scores were significantly greater for normals versus SDBs for omissions (P < 0.025). The number of SDB TOVA quarters was a significant predictor for “impaired” or “normal” group membership for visual memory (P < 0.015), but not for the other three WMS-III components. For males, the partial correlation between the number of attention complaints and the number of SDB TOVA quarters was also significant (r = 0.251, P < 0.005). For the 152 females with a significant number of attention complaints, no significant differences between SDBs and normals were observed (P > 0.15). This is the first report, to our knowledge, which provides evidence that TOVA is an accurate predictor of early attention complaints and memory impairments in a clinical setting. This finding is more robust for males than for females between the ages of 40 and 90 years

Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation

Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.

Predictions from Heavy New Physics Interpretation of the Top Forward-Backward Asymmetry

We derive generic predictions at hadron colliders from the large forward-backward asymmetry observed at the Tevatron, assuming the latter arises from heavy new physics beyond the Standard Model. We use an effective field theory approach to characterize the associated unknown dynamics. By fitting the Tevatron t \bar t data we derive constraints on the form of the new physics. Furthermore, we show that heavy new physics explaining the Tevatron data generically enhances at high invariant masses both the top pair production cross section and the charge asymmetry at the LHC. This enhancement can be within the sensitivity of the 8 TeV run, such that the 2012 LHC data should be able to exclude a large class of models of heavy new physics or provide hints for its presence. The same new physics implies a contribution to the forward-backward asymmetry in bottom pair production at low invariant masses of order a permil at most.Comment: 11 pages, 6 figures. v2: added remarks on EFT validity range, dijet bounds and UV completions; matches published versio

Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary

BACKGROUND AND HYPOTHESIS. Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. PROPOSAL AND CONCLUSION. The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.LifeGen, Inc.; Electronic Waveform Lab; Huntington Beach and Path Research Foundatio

How a turn to critical race theory can contribute to our understanding of 'race', racism and anti-racism in sport

As long as racism has been associated with sport there have been consistent, if not coordinated or coherent, struggles to confront its various forms. Critical race theory (CRT) is a framework established to challenge these racialized inequalities and racism in society and has some utility for anti-racism in sport. CRT's focus on social justice and transformation are two areas of convergence between critical race theorists and anti-racists. Of the many nuanced and pernicious forms of racism, one of the most obvious and commonly reported forms of racism in sport, racial abuse, has been described as a kind of dehumanizing process by Gardiner (2003), as those who are its target are simultaneously (re)constructed and objectified according to everyday myth and fantasy. However, this is one of the many forms of everyday racist experiences. Various forms of racism can be experienced in boardrooms, on television, in print, in the stands, on the sidelines and on the pitch. Many times racism is trivialized and put down as part of the game (Long et al., 2000), yet its impact is rarely the source of further exploration. This article will explore the conceptualization of 'race' and racism for a more effective anti-racism. Critical race theory will also be used to explore the ideas that underpin considerations of the severity of racist behaviour and the implications for anti-racism. © The Author(s) 2010