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Mental problems are written in your face

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Reading is one of the most complex cognitive activities that most of us engage in on a regular basis. It requires a host of sensory, perceptual, and linguistic abilities, and it takes many years to fully master. Even among educated adults, there is considerable variability in reading skill (Jackson & McCelland, 1979). In an attempt to understand complex cognitive processes, psychologists have often developed models in which these processes are conceptualized in terms of their component skills (e.g., Badderly, 1986). In the case of reading, Gough and Tunmer (1986) proposed the Simple View of Reading. According to this view, reading comprehension is the product of two basic components: word recognition and linguistic comprehension. Over the last 15 years, considerable evidence has emerged in support of the Simple View of Reading (Aaron, Joshi, & Williams, 1999; Catts, Hogan, & Fey, 2003; Hoover & Gough, 1990). Although this work has documented the important roles of word recognition and linguistic comprehension in reading, little data are available on how these roles change over time. In this chapter, we present the results of a longitudinal investigation that demonstrates the developmental changes in the component processes of reading, and we discuss the implications of these changes for the identification and remediation of children with reading disabilities.

 
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The opioid system plays a crucial role in the neural modulation of anxiety. The involvement of opioid ligands and receptors in physiological and dysfunctional forms of anxiety is supported by findings from a wide range of preclinical and clinical studies, including clinical trials, experimental research, and neuroimaging, genetic, and epidemiological data. In this review we provide a summary of studies from a variety of research disciplines to elucidate the role of the opioid system in the neurobiology of anxiety. First, we report data from preclinical studies using animal models to examine the modulatory role of central opioid system on defensive responses conducive to fear and anxiety. Second, we summarize the human literature providing evidence that clinical and experimental human studies are consistent with preclinical models. The implication of these data is that activation of the opioid system leads to anxiolytic responses both in healthy subjects and in patients suffering from anxiety disorders. The role of opioids in suppressing anxiety may serve as an adaptive mechanism, collocated in the general framework of opioid neurotransmission blunting acute negative and distressing affective responses.

 
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The uneven profile of performance on standard assessments of intelligence and the highincidence of savant skills have prompted interest in the nature of intelligence in autism. Thepresent paper reports the first group study of speed of processing in children with autism (IQ 1SD below average) using an inspection time task. The children with autism showedinspection times as fast as an age-matched group of young normally developing children (IQ 1SD above average). They were also significantly faster than mentally handicappedchildren without autism of the same age, even when these groups were pairwise matched onWechsler IQ. To the extent that IT tasks tap individual differences in basic processing efficiency,children with autism in this study appear to have preserved information processing capacitydespite poor measured IQ. These findings have implications for the role of general and specificcognitive systems in knowledge and skill acquisition: far from showing that children with autismare unimpaired, we suggest that our data may demonstrate the vital role of social insight in thedevelopment of manifest “intelligence.”
 
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The present study explored the relationship between nonverbal IQ and restricted and repetitive behaviors (RRBs) in 830 children with Autism Spectrum Disorders. The role of chronological age as a moderator of this relationship was also investigated. For many behaviors, there was a significant interaction between nonverbal IQ and chronological age, such that nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children. For the majority of such behaviors (e.g. repetitive use of objects, hand and finger mannerisms), RRB prevalence was negatively associated with NVIQ. However, the prevalence of certain behaviors (e.g. circumscribed interests) showed positive relationships with NVIQ, which provides some support for the idea of different classes of RRBs. For the severity of different RRBs, there were several significant effects for age and NVIQ, but few interactions.

 
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Restricted and repetitive behaviors (RRBs) on the Autism Diagnostic Interview– Revised (ADI-R: Lord, Rutter, & Le Couteur (1994) were examined in 165 children with Autism Spectrum Disorders (ASD), 49 children with non-spectrum developmental disorders (DD), and 65 children with typical development (TD) at approximately 2 years of age. A factor analysis found evidence for a repetitive sensorimotor (RSM) factor and an insistence on sameness (IS) factor. Behaviors that loaded on the RSM factor were prevalent in children with ASD and significantly more common and severe than in children with DD or TD. On average, children with ASD had more RSM behaviors. Behaviors that loaded on the IS factor were relatively uncommon and did not differ in prevalence or severity across groups.
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Background​

Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures.

Methods​

We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM).

Results​

Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes.

Conclusion​

Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism.
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We argue that there will be no single (genetic or cognitive) cause for the diverse symptoms defining autism. We present recent evidence of behavioral fractionation of social impairment, communication difficulties and rigid and repetitive behaviors. Twin data suggest largely nonoverlapping genes acting on each of these traits. At the cognitive level, too, attempts at a single explanation for the symptoms of autism have failed. Implications for research and treatment are discussed.
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While the cause of autism remains unknown, the high concordance between monozygotic twins supports a strong genetic component. The importance of genetic factors in autism encourages the development of mutant mouse models, to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (i) face validity (resemblance to the human symptoms) (ii) construct validity (similarity to the underlying causes of the disease) and (iii) predictive validity (expected responses to treatments that are effective in the human disease). There is a growing need for mouse behavioral tasks with all three types of validity, to define robust phenotypes in mouse models of autism. Ideal mouse models will incorporate analogies to the three diagnostic symptoms of autism: abnormal social interactions, deficits in communication and high levels of repetitive behaviors. Social approach is tested in an automated three chambered apparatus that offers the subject a choice between spending time with another mouse, with a novel object, or remaining in an empty familiar environment. Reciprocal social interaction is scored from videotapes of interactions between pairs of unfamiliar mice. Communication is evaluated by measuring emission and responses to vocalizations and olfactory cues. Repetitive behaviors are scored for measures of grooming, jumping, or stereotyped sniffing of one location or object. Insistence on sameness is modeled by scoring a change in habit, for example, reversal of the spatial location of a reinforcer in the Morris water maze or T-maze. Associated features of autism, for example, mouse phenotypes relevant to anxiety, seizures, sleep disturbances and sensory hypersensitivity, may be useful to include in a mouse model that meets some of the core diagnostic criteria. Applications of these assays include (i) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism; (ii) characterization of inbred strains of mice; (iii) evaluation of environmental toxins; (iv) comparison of behavioral phenotypes with genetic factors, such as unusual expression patterns of genes or unusual single nucleotide polymorphisms; and (v) evaluation of proposed therapeutics for the treatment of autism.
 
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In this study we compared 33 IQ and age matched pairs of individuals with Aspergers Disorder (ASP) and high functioning autism (HFA) on measures of repetitive behavior. On the Repetitive Behavior Scale-Revised (RBS-R), the ASP and HFA groups showed no differences in RBS-R Intensity score (severity) score or Frequency score (number of problems present). This suggests that the two groups are similar with respect to␣the intensity or severity of repetitive behaviors and the presence of repetitive behaviors. At the item level there were no differences on scales typically associated with autism (Stereotyped Behavior) and ASP (Restricted Interests). Similarly, there were no differences between the groups on the Aberrant Behavior Checklist Stereotypy scale. These findings add to the body of literature showing that HFA and ASP fail to differ with respect to repetitive behaviors. The implications of the findings for neurobiologic and genetic studies are discussed.
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Children with Autism Spectrum Disorders (ASD) and children with Obsessive Compulsive Disorder (OCD) were compared on a range of repetitive behaviours. Parents reported similar levels of sameness behaviour and repetitive movements in the clinical groups, although children with OCD engaged in more repetitive behaviour focussed around routines and rituals. Children with OCD reported more compulsions and obsessions than children with ASD; both groups reported more compulsions and obsessions than a typically developing comparison group. Types of compulsions and obsessions tended to be less sophisticated in children with ASD than those with OCD. Sameness behaviour was more prevalent in younger children with OCD, but for children with ASD, age was not significantly related to sameness behaviour, repetitive movements, compulsions, or obsessions.

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Autistic spectrum disorders (ASD) can be difficult to diagnose in toddlers. This study compared diagnostic measures (ADOS-G, ADI-R, CARS, and clinical judgment using DSM-IV criteria) applied to toddlers. Results indicated that the ADOS-G, CARS, and clinical judgment agreed with each other but not with the ADI-R. Many of the children classified with ASD by the other measures were not classified with autism by the ADI-R because they did not display enough repetitive behaviors and stereotyped interests. These results indicate that young children with ASD may not display repetitive behaviors and stereotyped interests, and for toddlers, the ADI-R would have a higher sensitivity if revised to include a diagnosis of PDD-NOS, for which the requirement of repetitive behaviors is less stringent.
 
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Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder. Large genetically informative cohorts of individuals with ASD have led to the identification of a limited number of common genome-wide significant (GWS) risk loci to date. However, many more common genetic variants are expected to contribute to ASD risk given the high heritability. Here, we performed a genome-wide association study (GWAS) on 6222 case-pseudocontrol pairs from the Simons Foundation Powering Autism Research for Knowledge (SPARK) dataset to identify additional common genetic risk factors and molecular mechanisms underlying risk for ASD. We identified one novel GWS locus from the SPARK GWAS and four significant loci, including an additional novel locus from meta-analysis with a previous GWAS. We replicated the previous observation of significant enrichment of ASD heritability within regulatory regions of the developing cortex, indicating that disruption of gene regulation during neurodevelopment is critical for ASD risk. We further employed a massively parallel reporter assay (MPRA) and identified a putative causal variant at the novel locus from SPARK GWAS with strong impacts on gene regulation (rs7001340). Expression quantitative trait loci data demonstrated an association between the risk allele and decreased expression of DDHD2 (DDHD domain containing 2) in both adult and prenatal brains. In conclusion, by integrating genetic association data with multi-omic gene regulatory annotations and experimental validation, we fine-mapped a causal risk variant and demonstrated that DDHD2 is a novel gene associated with ASD risk.


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The hypersystemizing theory of autism suggests that autistic individuals, on average, have superior attention to detail, and a stronger drive to systemize. Systemizing involves identifying input-operation-output relationships. Here, we report the results of genome-wide association studies (GWAS) of systemizing measured using the Systemizing Quotient - Revised in n = 51,564 individuals. We identify three genome-wide significant loci: Two of these were significant in the non-stratified GWAS: rs4146336 on chromosome 3 (P = 2.58×10−8) and rs1559586 on chromosome 18 (P = 4.78×10−8). In addition, we also identified a significant locus in the males-only GWAS (rs8005092 on chromosome 14, P = 3.74×10−8). We find that 12%± 1.2 of the variance in systemizing is captured by SNPs (P=1.2×10−20). We identify a positive genetic correlation between autism and systemizing (rg = 0.26±0.06; P = 3.35×10−5), which is independent of genetic contribution to educational attainment. We further demonstrate that genetic risk for autism from systemizing is genetically distinct from genetic risk emerging from social autistic traits, suggesting distinct shared genetics between autism and social and non-social traits. Our results highlight the importance of considering both social and non-social autistic traits in elucidating the genetic architecture of autism.

 
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Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles.

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Oxytocin (OT) effects on brain function and behavior are mediated by the oxytocin receptor (OXTR). The distribution of OXTR in the brain can profoundly influence social behavior. Emerging evidence suggests that DNA methylation of OXTR influences OXTR expression. Previously, we conducted a pharmaco-functional Magnetic Resonance Imaging (fMRI) study in which healthy subjects were randomized to 24 IU intranasal OT or placebo and imaged with fMRI while playing a dyadic social interaction task known as the iterated Prisoner's Dilemma (PD) game with same-sex partners. Here, we investigate whether DNA methylation of OXTR modulates the effect of intranasal OT on the neural response to positive and negative social interactions in the PD game. OXTR methylation did not modulate OT effects within brain regions where we previously reported OT effects in response to reciprocated (caudate nucleus) and unreciprocated cooperation (amygdala and anterior insula). However, OXTR methylation did modulate OT effects on the response to both reciprocated and unreciprocated cooperation in other brain regions such as the precuneus and visual cortex. Further restricting the analysis to OXTR rs53576 GG individuals revealed that OXTR methylation modulated OT effects on the precuneus response to reciprocated cooperation in men, the lateral septum response to reciprocated cooperation in women, and the visual cortex response to unreciprocated cooperation in men. These results suggest that OXTR methylation status may influence OT effects on mentalizing, attention and reward processing during social interactions. OXTR methylation may be important to consider if exogenous OT is used to treat social behavioral disorders in the future.

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Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.

 
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This chapter lays the foundation for an understanding of what reading comprehension is and how it is conceptualised in the literature. It develops the notion that reading comprehension is a flexible and ongoing cognitive and constructive process. It is asserted that there are both conceptually driven (top-down) and data-driven processes (bottom-up) that contribute to the construction of a situation (mental) model of text ideas. It is a two-way process that integrates information from the text-based model with information from prior knowledge using inferential processing. The chapter will examine how readers construct mental or situation models of text to enable reading comprehension.The second part of the chapter examines a number of factors that impede children’s reading comprehension. By nature reading comprehension difficulties are complex and reader difficulties may be related to a combination of factors such as: biological, cognitive, or behavioural issues. What is important is the realisation that reading comprehension outcomes are influenced by a combination of factors that may be situated within or outside of the learner.

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Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related death. Despite therapeutic advances, the overall survival of patients with HCC has not significantly improved in the last two decades. In the majority of the cases there is underlying cirrhosis, so the prognosis of HCC depends on not only tumor stage but also liver function. There is not a widely accepted HCC staging system. In our group we have developed a new staging classification that stratifies HCC patients into four major categories and simultaneously links staging with treatment. Patients at an early stage are those who present with an asymptomatic single HCC with a maximum diameter of 5 cm or up to three nodules each less than 3 cm. They will benefit from curative therapies, including resection, liver transplantation (LT), and percutaneous ablation. Patients exceeding these limits, but who are free of cancer-related symptoms and vascular invasion or extrahepatic spread fit into the intermediate stage and may benefit from palliation with chemoembolization. The patients with mild cancer-related symptoms and/or vascular invasion or extrahepatic spread are included in the advanced stage. In this stage there is not effective therapy, and these patients may profit from new therapies in the setting of randomized controlled trials (RCTs). Finally, the patients with severe cancer-related symptoms or great tumor burden belong to the terminal stage and only benefit from symptomatic treatment.


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VIQ–PIQ differences have been studied in children with autism and Asperger syndrome but have not been studied in a separate group of children with PDD-NO, although, PDD-NOS has a much higher prevalence rate than autism and deficits in communication and social interaction are severe. The Wechsler Intelligence Scale for Children-Revised (WISC-R) was administered to 100 children, aged 6–12 years, with PDD-NOS (n = 76), autism (n = 13), and Asperger syndrome (n = 11). PDD-NOS was diagnosed using explicit research criteria. No overall differences between VIQ and PIQ were found in PDD-NOS and autism. Peaks in the subtest scores on Information, Similarities, Picture Arrangement, and Mazes, and troughs in the subtest scores on Comprehension, Digit Span, and Coding were demonstrated in children with PDD-NOS. Their score on the Freedom from Distractibility factor was lower than the scores on the Verbal Comprehension factor and the Perceptual Organization factor. Children with PDD-NOS seemed to have a similar VIQ–PIQ profile as children with autism, and on the subtest level children with PDD-NOS showed some similarities to children with Asperger syndrome or autism. It was not possible to distinguish PDD-NOS from autism or Asperger syndrome by using IQ scores.
 
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Autists are persecuted by normies and psychopaths
 
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The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR variants included in association studies render it unclear whether OXTR is truly associated with ASD, and, if so, which OXTR single-nucleotide polymorphisms (SNPs) are associated. Thus, a meta-analytic review of extant studies is needed to determine whether OXTR shows association with ASD, and to elucidate which specific SNPs have a significant effect on ASD. The current meta-analysis of 16 OXTR SNPs included 3941 individuals with ASD from 11 independent samples, although analyses of each individual SNP included a subset of this total. We found significant associations between ASD and the SNPs rs7632287, rs237887, rs2268491 and rs2254298. OXTR was also significantly associated with ASD in a gene-based test. The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.
 
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Observed impairment in reciprocal social interaction is a diagnostic hallmark of autism spectrum disorders. There is no effective medical treatment for these problems. Psychological treatments remain costly, time intensive, and developmentally sensitive for efficacy. In this review, we explore the potential of oxytocin-based therapies for social impairments in autism. Evidence shows that acute oxytocin administration improves numerous markers critical to the social circuitry underlying social deficits in autism. Oxytocin may optimize these circuits and enhance reward, motivation, and learning to improve therapeutic outcomes. Despite this, the current evidence of therapeutic benefit from extended oxytocin treatment remains very limited. We highlight complexity in crossing from the laboratory to the autism clinical setting in evaluation of this therapeutic. We discuss a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation. For the autism field, the therapeutic challenges will be resolved by a range of treatment strategies, including greater focus on specific interventions, such as oxytocin, that have a strong basis in the fundamental neurobiology of social behavior. More sophisticated and targeted clinical trials utilizing such approaches are now required, placing oxytocin into the autism context.
 
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Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.

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This article presents our discovery that intranasal administration of oxytocin enhances activity in the brain for socially meaningful stimuli and attenuates its response to nonsocially meaningful stimuli in children with autism spectrum disorder (ASD) as measured via functional MRI. We also identified a relationship between changes in salivary oxytocin following administration and enhancements in brain function. These discoveries are particularly important given the urgent need for treatments that target the core social dysfunction in ASD. The functional neural attunement we demonstrated might facilitate social learning, thus potentially bringing about long-term change in neural systems and subsequent behavioral improvements. Our results illustrate the power of a translational neuroscience approach to facilitate the development of pharmacological interventions for neurodevelopmental disorders like ASD.
 
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Obsessive-compulsive symptoms in schizophrenia are often initially unrecognized or missed
entirely in the diagnostic process. Sexual obsession is common in patients with schizophre-
nia. Therefore, identifying sexual obsession early in treatment has significant implications for
appropriate multidisciplinary management and prognosis. We report the case of a Hispanic
male in his 20s who presented with self-injurious behavior and worsening psychotic symp-
toms in the context of a recent diagnosis of schizophrenia and without a past diagnosis or
historical symptoms of obsessive-compulsive disorder (OCD). This report elucidates the
importance of identifying the underlying cause of self-injurious behavior, which in this young
man was due to new onset OCD presenting as sexual obsession comorbid with schizophre-
nia. Olanzapine, paroxetine, and cognitive behavioral therapy (CBT) were administered with
good therapeutic response.
 
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Autism spectrum disorders (ASDs) are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression, and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.




Introduction​


Several neurodevelopmental disorders have complex genetic and epigenetic features that lead to their phenotype and for some there is no single genetic marker for the diagnosis; therefore, the diagnosis is made phenotypically as in schizophrenia, ADHD, and autism spectrum disorder (ASD). While phenotypic characterization of neurodevelopmental disorders is an integral part of advances in clinical practice and research, a given phenotype may arise from a diverse set of biochemical processes (especially when the disorder is caused by numerous genetic and epigenetic factors). Therefore, the treatment of a “phenotypic diagnosis” with a specific drug or intervention might be extremely effective for one “phenotypically characterized” individual with a given set of genetic and/or epigenetic biomarkers, but completely ineffective for another with a different pattern of biomarkers. An important goal of ongoing research in ASD, therefore, is to more precisely identify the many different abnormal genetic and epigenetic processes that underlie the phenotype of the disorder. This might allow individuals with ASD to be characterized into subsets with certain biomarker profiles that would respond more favorably to specific treatments. It also has the potential to elucidate the abnormal physiology that leads to autism, which could improve the understanding of the disorder and lead to earlier diagnosis and more targeted treatments.

A significant challenge in identifying biomarkers in ASD is that biomarkers may reflect genetic and neurobiological changes or epigenetic (broadly defined, see below) processes that may be active only during particular periods of time and do not define the disorder, only the process that led to it. In addition, treatment research should ideally include biomarkers that are believed to predict improvements in clinical symptoms from clinical interventions (1) to know if an intervention is altering or targeting an active biomedical process that relates to response in the subject at that time. Indeed, the National Institute of Mental Health (NIMH) has changed how they fund clinical trials so that “trial proposals will need to identify a target or mediator; a positive result will require not only that an intervention ameliorated a symptom but also that it had a demonstrable effect on a target, such as a neural pathway implicated in the disorder or a key cognitive operation”(2).

Traditionally, research in psychiatry has been guided by DSM symptom based diagnoses and selection criteria for clinical trials were based on these symptom clusters. Biomarkers have not been reliable or valid markers of response to treatment in past trials, and this may be due to the wide variety of genetic and epigenetic processes that underlie the DSM-based diagnosis. Recently, progress in biomarker research has led to the commitment to the Research Domain Criteria project (RDoC) as a basis for future NIMH funding for biomarker based research (3, 4). The RDoC goal is to define basic dimensions of functioning to be studied across multiple units of analysis, from genes to neural circuits to behaviors, cutting across disorders as traditionally defined. The intent is to translate rapid progress in basic neurobiological and behavioral research to an improved integrative understanding of psychopathology and the development of new and/or optimally matched treatments for mental disorders (5).

In this article, we review the literature on biomarkers for ASD including genetic, epigenetic, brain based, and body metabolism biomarkers. This is a huge area and this review is not intended to be comprehensive. New potential biomarkers for ASD are being identified every day so the list needs to be updated frequently. We do extensively review the literature at the time of this writing, report on methodologically sounds studies, offer summary tables, and summarize what we know.

Genetic Biomarkers​


The literature supports a hereditary component in the susceptibility to ASDs, there are much higher concordance rates of ASDs in monozygotic twins (92%) than dizygotic twins (10%), and a recent estimate of the sibling recurrence risk ratio (λs) is 22 for autism. Despite being highly heritable, ASDs show heterogeneous clinical symptoms and genetic architecture, which have hindered the identification of common genetic susceptibility factors. Although previous linkage studies, candidate gene association studies, and cytogenetic studies have implicated several chromosomal regions for the presence of autism susceptibility loci, they have not consistently identified and replicated common genetic variants that increase the risk of ASDs other than some clearly genetic disorders such as fragile X, tuberous sclerosis, and RASopathies whose phenotypes meet the ASD category description (5). As autism is not a single clinical entity, it can be viewed as a behavioral manifestation of tens or perhaps hundreds of genetic and genomic disorders (6). It has been estimated that there are over 500 distinct genetic loci that may be related to ASD (7) (Figure 1).



FIGURE 1


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BACKGROUND:
Pediatricians, neurologists, and geneticists are important sources for autism surveillance, screening, and referrals, but practical time constraints limit the clinical utility of behavioral observations. We analyzed behaviors under favorable conditions (ie, video of autism evaluations reviewed by experts) to determine what is optimally observable within 10-minute samples, asked for referral impressions, and compared these to formal screening and developmental testing results.
METHODS:
Participants (n = 42, aged 15 to 33 months) were typically developing controls and children who screened positive during universal autism screening within a large community pediatric practice. Diagnostic evaluations were performed after screening to determine group status (autism, language delay, or typical). Licensed psychologists with toddler and autism expertise, unaware of diagnostic status, analyzed two 10-minute video samples of participants’ autism evaluations, measuring 5 behaviors: Responding, Initiating, Vocalizing, Play, and Response to Name. Raters were asked for autism referral impressions based solely on individual 10-minute observations.
RESULTS:
Children who had autism showed more typical behavior (89% of the time) than atypical behavior (11%) overall. Expert raters missed 39% of cases in the autism group as needing autism referrals based on brief but highly focused observations. Significant differences in cognitive and adaptive development existed among groups, with receptive language skills differentiating the 3 groups.
CONCLUSIONS:
Brief clinical observations may not provide enough information about atypical behaviors to reliably detect autism risk. High prevalence of typical behaviors in brief samples may distort clinical impressions of atypical behaviors. Formal screening tools and general developmental testing provide critical data for accurate referrals.


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Importance The economic effect of autism spectrum disorders (ASDs) on individuals with the disorder, their families, and society as a whole is poorly understood and has not been updated in light of recent findings.

Objective To update estimates of age-specific, direct, indirect, and lifetime societal economic costs, including new findings on indirect costs, such as individual and parental productivity costs, associated with ASDs.

Design, Setting, and Participants A literature review was conducted of US and UK studies on individuals with ASDs and their families in October 2013 using the following keywords: age, autism spectrum disorder, prevalence, accommodation, special education, productivity loss, employment, costs, and economics. Current data on prevalence, level of functioning, and place of residence were combined with mean annual costs of services and support, opportunity costs, and productivity losses of individuals with ASDs with or without intellectual disability.

Exposure Presence of ASDs.

Main Outcomes and Measures Mean annual medical, nonmedical, and indirect economic costs and lifetime costs were measured for individuals with ASDs separately for individuals with and without intellectual disability in the United States and the United Kingdom.

Results The cost of supporting an individual with an ASD and intellectual disability during his or her lifespan was $2.4 million in the United States and £1.5 million (US $2.2 million) in the United Kingdom. The cost of supporting an individual with an ASD without intellectual disability was $1.4 million in the United States and £0.92 million (US $1.4 million) in the United Kingdom. The largest cost components for children were special education services and parental productivity loss. During adulthood, residential care or supportive living accommodation and individual productivity loss contributed the highest costs. Medical costs were much higher for adults than for children.

Conclusions and Relevance The substantial direct and indirect economic effect of ASDs emphasizes the need to continue to search for effective interventions that make best use of scarce societal resources. The distribution of economic effect across many different service systems raises questions about coordination of services and sectors. The enormous effect on families also warrants policy attention.




Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social ability, especially communication, and restricted, repetitive patterns of behavior, interests, or activities. Autism spectrum disorder can be associated with significant functional impairments and long-term health, social, and financial costs for individuals with ASDs, their families, and society as a whole.1 The increase in the number of individuals diagnosed as having ASDs2-4 and ensuing discussions regarding personal, family, and societal responsibilities emphasize the urgent need for accurate estimates of the economic effect of ASDs.


Most previous studies of costs associated with ASDs provide estimates within particular domains, primarily health care, but the overall economic effect of ASDs is not well established. The most recent comprehensive estimates of costs associated with ASDs were published in 2006 for the United States5 and 2009 for the United Kingdom6; both studies needed to rely on many assumptions about prevalence and costs for which no published data existed. Since then, studies have provided more accurate estimates of costs in various domains, such as individual and parental productivity loss.7,8 We therefore provide new estimates of the costs of ASDs for the United States and the United Kingdom. Our study differs from previous research in 3 ways: we provide more comprehensive estimates of costs associated with ASDs, we offer estimates for 2 countries, and we separate individuals with and without intellectual disability (ID), an important distinction given that cognitive impairments, separate from impairments associated with ASDs, may significantly influence costs.


Methods

New estimates of prevalence and some costs were obtained through a literature review conducted in 2013 concentrating on UK and US studies using age, autism spectrum disorder, prevalence, accommodation, special education, and productivity loss as keywords. Availability of relevant data differs across countries, particularly because of differences in how education, health care, and other systems are organized and financed. In the absence of nationally representative samples with complete cost-related data for individuals with ASDs and their families in either country, we used a bottom-up approach, drawing on previous studies, updating and supplementing them as needed, and structuring our estimates around the 7 questions listed below. A number of sources were used to estimate the costs of type of accommodation,6,9-12 medical and nonmedical services,7,13-17 special education,6,18-21 employment support,22 and productivity loss.6,8,15,23-27 Further details of our country-specific assumptions are given in Table 1.


How Many People Have ASDs?

We used accepted prevalence estimates from each country. For each country, we relied on the most accepted prevalence estimates from the most reliable sources. For the United States, this source was the Centers for Disease Control and Prevention,28 and for the United Kingdom, we relied on 3 relatively consistent prevalence studies.10,29,30 For the United Kingdom, on the basis of population-based studies, we assumed 10% of children aged 0 to 3 years with ASDs have their condition diagnosed and receive some type of service in response (0.1% of all children in this age group), and 1.1% of children of all other ages.7,13 For the United States, we assumed 1.1% of children and adults had ASDs and were treated.8,28 In both cases, people in prison and defense establishments were excluded.


What Are the Characteristics and Needs of People With ASDs That Have Potential Economic Cost Implications?

Individuals with ASDs can differ greatly in their clinical and functional presentation, resulting in potentially substantial differences in costs of treatment, care, and support. The presence of ID in individuals with ASDs can greatly affect these costs. Studies10,13,29,30 report that 40% to 60% of people with ASDs also have ID.


Costs also may vary by age. We distinguished age groups that matched administrative distinctions and data sets in each country. For the United Kingdom, we distinguished toddlers (0-1 year of age), preschool children (2-3 years of age), primary school children (4-11 years of age), secondary school children (12-17 years of age), and adults (≥18 years of age).6 For the United States, we distinguished preschool children (0-5 years of age), school-age children (6-17 years of age), and adults (≥18 years of age).


How Does Care Differ for Individuals Based on Age and the Presence of ID?

We sought data on services and interventions for each age group, distinguishing people with and without ID. As far as possible, we included only utilization attributable to ASDs. The most recent figures on service costs of very young children were used.31


In What Domains Do Individuals With ASD, Their Families, and Various Service Systems Accrue Cost?

We sought data on accommodation, medical services, nonmedical services, and out-of-pocket payments by families. Cost categories sometimes referred to slightly different services in the 2 countries because of different health care, education, and other systems. For example, in the United States, accommodation refers to residential care (intermediate care facility) costs only, whereas in the United Kingdom it includes all housing (private, supported living, residential, and hospital stay). If no data were available for a particular category in one country, we applied the most relevant cost from the other country.


How Do We Estimate the Costs of These Different Types of Care?

Medical service costs include inpatient, outpatient, emergency, physician, other health care professional, home health care, pharmacy, and out-of-pocket costs. As far as possible, only service use attributable to ASDs was included. Medical costs for other family members were not included because of lack of data.


Nonmedical service costs include special education, treatment for ASD-related needs (in the United Kingdom), child care, special programs, after-school care, day care, weekend programs, summer school, overnight and other respite, travel to medical appointments, home care modifications, and damage replacement. Family out-of-pocket expenses were estimated by pooling evidence from previous studies,6,8 in which further details are given.


Place of accommodation can be an important cost driver in the United Kingdom. Accommodation settings in the United Kingdom were categorized into 4 types based on previous research on people with IDs10 (Box). Nonaccommodation service data for the United Kingdom came from previous studies of people with IDs.6 Unit costs were attached to service use attributable to ASDs and largely taken from the Personal Social Services Research Unit compendium32 adjusted to 2010-2011 prices using the Health and Community Health Services index. Figures for England were assumed to apply proportionately to Scotland, Wales, and Northern Ireland.

 
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Re: LMAO YOU CAN LITERALLY GET A LINK TO EBOLA
AnonyAnonymous
noFilter

Join Date: 2013-06-23
Post Count: 6332
#158402458Sunday, March 22, 2015 3:09 AM CDT
There's genomes for nearly every known pathogen on various online databases.
Re: shut up about ebola
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#147494222Tuesday, October 07, 2014 6:24 AM CDT
Well, the HIV pathogen has been around for plenty of years and still continues to spread and cause potentially fatal illnesses.
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Re: I decided to research HIV in biology
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#148053543Thursday, October 16, 2014 1:01 PM CDT
Ah yes, the "Human Immunodeficiency Virus" is a very unique and interesting pathogen to research.
Re: ebola isn't real,
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#148245653Sunday, October 19, 2014 1:25 PM CDT
"EbolaVirus" is certainly a lethal pathogen, although, I wouldn't suggest panicking over it as it will only lead to unnecessary problems.
Re: How Diseases And Vaccines Work
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#148439250Wednesday, October 22, 2014 7:57 PM CDT
Antibodies are proteins developed by certain cell groups to disable and identify pathogens.Also, it should be noted that antibodies have very limited effectiveness against different strains of the same pathogen depending on how it mutates and it's frequency.
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Re: Whelp, I got pink eye...
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#151088328Thursday, December 04, 2014 4:03 PM CST
Which pathogen did you become infected with?
Re: [ Content Deleted ]
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#151089648Thursday, December 04, 2014 4:20 PM CST
The "EbolaVirus" pathogen doesn't discriminate against people of specific racial origin.
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This study examines the impact of popular cultural tropes and contemporary ideologies on U.S. collegiate women’s constructions of romantic love and marriage. Although research shows that shifts in the public sphere intimately affect the private realm, little is known regarding how young women negotiate concurrent romantic ideals and capitalist notions of romance. Based on interviews with 30 collegiate women, we argue that women’s negotiations of romantic love and marriage can be understood through conceptualizations of time, including investment of time, timelessness, and envisioning the future despite impermanence. Our findings suggest a love paradox, in that participants define love as controllable, reflecting late capitalistic terms of love as work and individuals’ responsibilities, and uncontrollable, as love is also deemed magical and timeless. Ambiguities thus arise from perceptions of instability, with women desiring idealized, everlasting love yet remaining doubtful that it can come to fruition in a rationalized, unstable time.
 
MillerSoRock
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Post Count: 4888
#141037604Monday, July 21, 2014 2:44 AM CDT
Like the code to use if I wanted to make a function for it
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#141037733Monday, July 21, 2014 2:46 AM CDT
It's detected as a normal key.
AnonyAnonymous
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Join Date: 2013-06-23
Post Count: 6332
#141037846Monday, July 21, 2014 2:48 AM CDT
Actually, just use something such as,Mouse = game.Players.LocalPlayer:GetMouse()Mouse.KeyDown:connect(function(Key)if Key == " " thenprint(Key)endend)
MillerSoRock
noFilter

Join Date: 2010-02-27
Post Count: 4888
#141037999Monday, July 21, 2014 2:50 AM CDT
Thanks, all I needed was elseif k == " " thenIt's for a crouch script.


View: https://youtu.be/hfuEhG3iRBk?t=179
 
Claiming to have a diagnosis is not equivalent to actually having it. Observing someone else and teaching someone to feign symptoms for your own comfort is useless when people have recordings of you.
Oh My God Omg GIF
 
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Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes.

A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR) = 1.54; 95% CI 1.16–2.04], emotional abuse [OR = 3.06; 95% CI 2.43–3.85], and neglect [OR = 2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR = 1.92; 95% CI 1.67–2.20], emotional abuse [OR = 1.41; 95% CI 1.11–1.79], and neglect [OR = 1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR = 3.40; 95% CI 2.17–5.32], emotional abuse [OR = 3.37; 95% CI 2.44–4.67], and neglect [OR = 1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR = 1.78; 95% CI 1.50–2.10], emotional abuse [OR = 1.75; 95% CI 1.49–2.04], and neglect [OR = 1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships.

Child maltreatment—the abuse and neglect of children—is a global problem. There are four types of child maltreatment—sexual abuse (the involvement of a child in sexual activity that he or she does not understand, is unable to give consent to, or is not developmentally prepared for), physical abuse (the use of physical force that harms the child's health, survival, development, or dignity), emotional abuse (the failure to provide a supportive environment by, for example, verbally threatening the child), and neglect (the failure to provide for all aspects of the child's well-being). Most child maltreatment is perpetrated by parents or parental guardians, many of whom were maltreated themselves as children. Other risk factors for parents abusing their children include poverty, mental health problems, and alcohol and drug misuse. Although there is considerable uncertainty about the frequency and severity of child maltreatment, according to the World Health Organization (WHO) about 20% of women and 5%–10% of men report being sexually abused as children, and the prevalence of physical abuse in childhood may be 25%–50%.


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Information Systems Security Management (ISSM)
Success Factor: Retrospection From the Scholars
Azah Anir Norman and Norizan Mohd Yasin
University of Malaya, Kuala Lumpur, Malaysia
[email protected]
[email protected]
Abstract: Information System Security Management (ISSM) studies today have presented remarkable solutions
in addressing security management (SM) problems. Many companies have designed SM procedures to protect
their businesses from threats. Often, ISSM implemented by these businesses are based largely on common
practices, current understanding and business requirements which seldom reach optimum levels. This presents
risks as such practices often lead to resource wastage and security abuse. This paper attempts to review
previous studies on ISSM implementation. This retrospection study aims to determine the most influential factors
for successful ISSM implementation in a business. The study reviewed selected journal articles and conference
papers in the field of information systems security. The three main classes of success factors in ISSM comprise
technology characteristics, organizational structure and environmental influences. The success factors were
collated from the ISSM success theoretical model which is based on selected IS theories. Fundamentally,
technology, process and human elements that form the management mechanism were found to be vital for
successful ISSM implementation. Retrospection of various scholars’ practical-theoretical-experimental
researches and views enables better understanding and the subsequent assimilation of success factors that
influence successful ISSM implementation in a business context.
Keywords: information system security management, success factor, security management, information systems
security
1. Introduction
The use of Information Systems (IS) is no longer bound to the company but has spread externally to
customers and suppliers. Businesses today have developed and adopted many types of information
systems to manage and fulfill customers’ requests. Through information systems, business processes
were improved thus increasing business productivity. Similarly, the explosive advent of Internet
technology has seen a dramatic increase in the use of information systems.
The potential benefit of global marketing has become the most profitable advantage the Internet offers
(Kaynak et al., 2005). However, despite being highly advantageous, free Internet access has invited
various unethical activities over the past 20 years. Systems were breached and different types of
losses were incurred during this time. As of December 2011, CyberSecurity Malaysia reported
approximately 15218 cases involving Internet related threats as compared to 8090 reported cases in
2010 (MyCERT, 2012). A recent survey by (Kaspersky Lab, 2011) indicated that 46% of respondents
identified cyber threats as potential business risks of the future. Almost half of the businesses in this
survey agreed that cyber threats are the top three emerging risks.
The latest security survey by PWC, (2012) revealed that 33% respondents had not reported any
security incidents, but there was an increase in reported incidents from 3% in 2010 to 8% in 2011.
Alarmingly, the report also shows a decrease from 76% in 2010 to 72% in 2011, in the IT personnel’s
confidence regarding the readiness of their business to confront critical information threats. The
decrease in confidence befitted the report, as only 40% of respondents are shown to be practicing
effective SM while the remaining businesses are still trying to determine the best SM for their
business.
The report also highlighted issues which are holding back SM in a business, emphasising the
importance of SM success factors in guaranteeing effective SM. Adoption of security tools and
techniques is worthless if businesses fail to understand the essence of ISSM success. This paper
seeks to distinguish the success factors of ISSM through the scholars’ lenses. Retrospection of
previous studies leads to the identification of the possible success factors for successful ISSM
implementation in a business


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The increasing need to share information in dynamic environments has created a requirement for risk-aware access control systems. In this paper, we present a metamodel for risk-aware authorization that captures the key aspects of a system in relation to risk mitigation. In particular, we develop various risk-aware models as instances of the metamodel that broadly differ in the form of risk mitigation that is used (system obligations and user obligations respectively), and study how those obligations are applied to reduce and account for the risk incurred by granting access. Unlike system obligations, an access control system cannot guarantee that user obligations are fulfilled. We propose two approaches to defining risk-aware authorization semantics that takes unfulfilled obligations into account: one is to restrict users' future access because of prior failure to fulfill obligations, and the other is to “reward” users who have been diligent in fulfilling their obligations by permitting risky access requests.

 
Brief Recap:

incels.is/threads/mental-problems-are-written-in-your-face.3996/page-3
 
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To a mathematician, cryptography means public-key encryption using a one-way
trapdoor function. We often teach it as an elegant application of results in number
theory, such as the Euler–Fermat Theorem, the basis of the RSA cryptosystem,
or the discrete logarithm problem using either a primitive root of a large prime or
an element of an elliptic curve over a prime field, the basis of the ElGamal and
Diffie–Hellman cryptosystems.
But to an engineer, public-key encryption is only a mi-
nor part of cryptography. He or she is concerned with
the efficient encryption, transmission and decryption
in real time of vast amounts of data in the form
of strings of binary digits. The favoured procedure,
symmetric-key encryption, is for the sender, popularly
known as Alice, to encrypt the plaintext by bitwise
addition of a secret pseudorandom key of the same
length as the plaintext, and for the receiver, Bob, to
add the same key to the ciphertext to recover the
plaintext. But how can Alice and Bob both have
access to a secret key? The answer is that they
don’t: they generate it dynamically during the process
of encryption or decryption. The idea is that Alice
encrypts a short seed, say 128 bits for normal security
or 256 for top secret security, by public-key encryption
and transmits it to Bob who recovers the seed. The first 128-bit block of plaintext
is encrypted by Alice and decrypted by Bob using the seed. Then Alice uses a
public algorithm such as AES (Advanced Encryption Standard) to permute each
ciphertext block as it is produced and then encrypts the next plaintext block using
this permutation. Bob of course does the same to decrypt the ciphertext. The
point is that symmetric-key cryptography is fast and reliable, while public-key
cryptography is far too slow to use on mobile phone communications, financial
transactions or pay TV signals.
But there is much more to cryptography than encryption and decryption. Bob
needs to know that the message he received really did come from Alice, requiring
a digital signature; that it was really the message she sent, requiring a message
authentication code; and that it is the message she most recently sent, requiring
a timestamp. Alice, in turn, may need to know that the recipient of her message
really is Bob. Cryptography is also needed for secure storage of passphrases, as
well as identification codes and corresponding PINs for smart cards. This is where
232 Book Reviews
hash functions are part of the arsenal of the cryptographer. In fact, a major part
of practical cryptography is concerned with ensuring data integrity and secure key
management. It seems that most of the hacking of email storage and mobile phones
that have made the news recently is the result of the failure not of cryptographic
security, but of humans to observe the appropriate protocols.
I come now to the book Everyday Cryptography. The author, Keith M. Martin,
is truly on the engineering side of cryptography. He is Professor of Information
Security at Royal Holloway, University of London, and this book is an introduc-
tion to the subject aimed at beginning Communications Engineers. As such, it
is light on theory and heavy on implementation. Mathematics gets short shrift;
for example, modular arithmetic, the Fermat–Euler Theorem and the discrete
logarithm problem are relegated to a few pages in the appendix and students are
several times comforted that they don’t really have to master this material. Many
pages are devoted to explanations of engineering standards for symmetric-key en-
cryption as well as message authentication codes, timestamps and digital signature
protocols. There are detailed explanations of applications to information security
on the Internet, wireless local area networks, mobile phone communications, pay
TV broadcasts and financial transactions.
This is not a text suitable for mathematics students; but if you want to know how
secure your credit card and PIN are, you will find it all here.


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This paper introduces a technical, social and ethical organization freely sharing cyber attack vectors in the spirit of global co-operation crossing geo-political borders by deploying active monitoring. More importantly it introduces a radically new and better suited workforce to identify past, present and future cyber threats by better “big data” analytics. Current tools and techniques lag behind the cyber attacks and cannot be automated as the attackers are humans and can circumvent controls. The problem is that security tasks are difficult and complex. We lose focus and don't see the patterns that we should and few, if any, current staff like this manual work. securITism delivers a globally unique solution to this problem by using local high-functioning autistic (Asperger's Syndrome) graduates to actively monitor networks and flows. They are selected for the fact that they have strong 3D visualization; pattern recognition; long term memory; sense of logic; and thinking outside the box. The vision for this solution came from research, design, development and deployment of electronics, operating systems and resilient network security technologies spanning almost three decades. Armed with the knowledge down to component/kernel levels and having to think like a hacker, it is completely feasible that a single person can potentially cause catastrophic failure to virtually any critical infrastructure.

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This study examined the social impact of being a typical peer model as part of a social skills intervention for children with autism spectrum disorder (ASD). Participants were drawn from a randomized-controlled-treatment trial that examined the effects of targeted interventions on the social networks of 60 elementary-aged children with ASD. Results demonstrated that typical peer models had higher social network centrality, received friendships, friendship quality, and less loneliness than non-peer models. Peer models were also more likely to be connected with children with ASD than non-peer models at baseline and exit. These results suggest that typical peers can be socially connected to children with ASD, as well as other classmates, and maintain a strong and positive role within the classroom.

 
self improvement is a bunch of bullshit
Self improvement is just a way to gaslight people into taking responsibility for things they don't have any control over.
 
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A clinical study of 50 Vietnam veterans hospitalized in the Palo Alto Veterans Administration Hospital's psychiatric wards demonstrated a high rate of psychosis (31 pateints), often masked by apparent character and behavioral disorders. Nineteen of these patients were seriously disabled in Vietnam, as suggested by clinical evidence, yet only seven were treated as psychotic while there. Seven were diagnosed as psychotic within 1 month after their return to the United States, and the remaining patients manifested their illness much later. Psychiatric sequelae, secondary to military activities, and the return to civilian life, relatively unique to Vietnam veterans, were recognized, in addition to classical war neuroses. Many of the patients had significant drug abuse problems, including alcohol and heroin addiction. Some of the methods and problems of military psychiatry and of the Veterans Administration were discussed.


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View: https://youtu.be/8kpWM292c1Q?t=2

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The present study investigated the influence of Vyvanse (lisdexamfetamine), a psychomotor stimulant, on spatial working memory, body weight, and adiposity in rats. Control and experimental rats were placed in individual cages equipped with a running wheel, and food and water were provided ad-libitum. The study was divided into three periods: 1) habituation, 2) experimental, and 3) withdrawal. Control rats received a placebo in periods 1, 2 and 3, while experimental rats received a placebo in periods 1 and 3. Experimental rats received a treatment of Vyvanse in place of the placebo during period 2. Spatial working memory was examined by utilizing the methodology of the Morris Water Maze. Rats were evaluated by performance in the maze each day during the experimental and withdrawal periods. Each assessment consisted of two trials. The first was a sample trial in which an escape platform was discovered by trial and error. The second was a test trial in which the platform location was recalled using working memory. Platform placement and start location of the rats were changed every session. It was hypothesized that Vyvanse would effectively enhance spatial working memory, and significantly decrease body weight and adiposity without side effects on activity level and anxiety in rats. Results supported the hypothesis. Compared to control rats, Vyvanse treated rats had significant improvement in working memory and significantly lowered body weight, as well as significantly decreased mesenteric, renal, and epididymal adiposity. No significant effects on activity level and task specific anxiety were noted in experimental animals. When compared to placebo treatment, Vyvanse treatment produced no significant influence on food and water intake. It was concluded that Vyvanse treatment in rats can enhance spatial working memory, and decrease adiposity without suppressing normal appetite.
 
We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

 
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Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population

Abstract​

Background Musical abilities such as recognising music and singing performance serve as means for communication and are instruments in sexual selection. Specific regions of the brain have been found to be activated by musical stimuli, but these have rarely been extended to the discovery of genes and molecules associated with musical ability.
Methods A total of 1008 individuals from 73 families were enrolled and a pitch-production accuracy test was applied to determine musical ability. To identify genetic loci and variants that contribute to musical ability, we conducted family-based linkage and association analyses, and incorporated the results with data from exome sequencing and array comparative genomic hybridisation analyses.
Results We found significant evidence of linkage at 4q23 with the nearest marker D4S2986 (LOD=3.1), whose supporting interval overlaps a previous study in Finnish families, and identified an intergenic single nucleotide polymorphism (SNP) (rs1251078, p=8.4×10−17) near UGT8, a gene highly expressed in the central nervous system and known to act in brain organisation. In addition, a non-synonymous SNP in UGT8 was revealed to be highly associated with musical ability (rs4148254, p=8.0×10−17), and a 6.2 kb copy number loss near UGT8 showed a plausible association with musical ability (p=2.9×10−6).
Conclusions This study provides new insight into the genetics of musical ability, exemplifying a methodology to assign functional significance to synonymous and non-coding alleles by integrating multiple experimental methods.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode

 
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This article draws on constructs in second-language acquisition, literacy, cultural, and media studies as theoretical bases for examining how networked technologies and fan culture provide a young English language learner (ELL) with a site for developing her English language and writing skills. During this process, she also develops an online identity as a popular, multiliterate writer. To understand how this happens, the notion of identity is explored as a fluid construct that shifts over time with this ELL's long-term participation in a fan community. Popular and fan culture are also examined as points of affiliation and as dialogic resources that she appropriates, both in her writing and in her interactions with other fans. In so doing, the article demonstrates how popular culture and technology converge to provide a context in which this adolescent ELL is able to develop a powerful, transcultural identity, discursively constructed through the different cultural perspectives and literacies that she and other fans from across the globe bring to this space.

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Online fanfiction communities provide adolescent English-language learners (ELLs) with a forum for engaging in an array of sophisticated literacy practices. This article draws on constructs from literacy studies and second-language acquisition as conceptual bases for exploring the writing, reviewing, and social practices in an online fanfiction community. Analyses focus on how the networked structure of such sites facilitates English-language learning and promotes writing by providing ELLs with access to a broad audience of readers and multiple community writing resources. By highlighting the social and interactive nature of writing in this space, connections among language, literacy, and identity are emphasized. In conclusion, the author explores some of the possibilities that networked computer environments offer for developing authentic, interactive writing activities in the classroom.

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This article provides a brief overview of the nature of online fan fiction communities. In doing so, it demonstrates the range of writing practices (and other media practices) that fans negotiate together to role-play scenes of engagement with canonical texts. Members involved in a 400 participant fan fiction world (Middle Earth Insanity) were studied to determine their general literacy practices within forums, chatting, role-playing and the discussions strands of the community. The interactivity of some particular members of the study who volunteered to engage in interviews and posts about their discursive and social experiences within their community allowed a clear understanding of these practices to emerge, and provided the opportunity to interrogate and critically analyse the context in which these practices occurred. The ways in which the young girls responded to both their texts and their role-playing experiences offered them the opportunity to also engage in self-reflexive critical practice about their reading, their choices, and their identities in their different forms. The article concludes by bringing the various experiences together and offering what was and could be learned through fan fiction online communities.

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Nancy Drew is widely recognized as an influential American cultural icon. In this paper I make a detailed examination of Nancy's initial characterization as girl sleuth in the first ten books of the Nancy Drew Mystery Stories, published in the 1930s. I spend another chapter examining the initial volumes of later Nancy Drew series books, specifically the 1960s rewritten texts, the 1980s-90s Nancy Drew Files series, and the contemporary Girl Detective series. My penultimate chapter discusses Nancy Drew as realized in fanfiction, or stories written by readers and fans. My emphasis is on explaining Nancy's appeal as a cultural icon and the ways fanfiction authors reinvent and appropriate that icon for their own purposes in stories. To this end I cite fanfic writers and readers' response to why they read and write Nancy Drew fanfiction, and I analyze the content and function of a sample of stories written by Nancy Drew fans. I conclude that Nancy's appeal and the basis of her status as cultural icon is due to her unique nature as a figure frozen in transition between adolescence and adulthood, along with her more conventionally admirable traits. Her Everygirl appearance when removed from that unique matrix makes her extremely adaptable to readers for their own purposes, both within the context of fanfiction and without.

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There is an often unacknowledged symbiotic relationship between creators and owners of
mass media works and the fan communities inspired by their work. The nature of
participatory fan communities makes it possible for both authors and fans to be active
agents in collectively determining the validity of the “official” storyline. The interaction
between creators and fans illustrates John Fiske's idea of a “semiotic democracy,” the
power of media in enabling audiences to become involved in the creative process of
constructing cultural symbols rather than serving merely as passive consumers.1
This paper will explore the concepts of pop culture canon and “fanon.” “Canon,” from a
pop culture standpoint is defined as the official storylines and back stories invented by
the creators of television shows, movies and books. Relatedly, “fanon,” is described as
the ideas and concepts that fan communities have collectively decided are part of an
accepted storyline or character interpretation. We propose the idea that the concept of
fanon is best illustrated as an example of folksonomy, a user-generated classification
used in Internet social communities; or as a "tag:" an aggregation of content emerging
through bottom-up consensus by the public/fan communities. We will also discuss the
impact of fanon folksonomy on the future of participatory fandom and popular culture.
In his book Textual Poachers, Henry Jenkins uses The Velveteen Rabbit -– with toys
becoming real only when they are part of a child’s imagination – as a metaphor for the
participatory nature of fan culture, explaining that meaning is only derived from items
through their use, not through their “intrinsic merits or economic value.”2 This metaphor
is expanded by Jonathan Lethem in a recent article in Harper’s Magazine on creativity
(January 2007), where
“The Rabbit is fearful, recognizing that consumer goods don't become “real”
without being actively reworked [but] “It doesn't happen all at once … You
become. It takes a long time … Generally, by the time you are Real, most of your
hair has been loved off, and your eyes drop out and you get loose in the joints and
very shabby.” Seen from the perspective of the toymaker, the Velveteen Rabbit's
loose joints and missing eyes represent vandalism, signs of misuse and rough
treatment; for others, these are marks of its loving use.”3
1 John Fiske, Television Culture, 236, 239 (1997)
2 Henry Jenkins, Textual Poachers 50-51 (1992).
3 Note here
2
The gradual process of debating and establishing canon and creating fanon is the
equivalent of the Velveteen Rabbit for pop culture fans, giving life to a static, fictional
world and making it “real.”
But what are the limits of authority that owners and creators of mass media set when they
are faced with fans that push back, creating their own limits of “realness” that directly or
indirectly challenge the work’s ownership or authenticity? According to legal scholar
Susan Scafidi in her book, Who Owns Culture?,
“Reverse cultural appropriation [the use of cultural items by the public] is treated
as potential infringement by laws that seldom recognize the contribution of the
public to ... iconic intellectual properties.”4
For example, Scafidi states that
“Although the public is invited to purchase and consume Star Trek and other
commercial creations to internalize or identify with them and become fans, and
even join together in social groups that share a common bond of appreciation for a
television show, sports team, or entertainer, this use is typically expected to be
passive and not active or transformative.”5
Why is this important?
Ten years ago, Janet Murray in Hamlet on the Holodeck stated that “Contemporary
stories, in high and low culture, keep ... inviting us to second guess the choices [the
storyteller] has made [and] can be experienced as an invitation to join in the creative
process.”6 She posits that media creators invite fans to play with canon in non-canon
settings, “assum[ing] a sophistication on the part of the audience, an eagerness to
transpose and reassemble the separate elements of a story and an ability to keep in mind
multiple alternative versions of the same fictional world.”7 According to Will Brooker,
the “wealth of fan-based material, rich in detail and imagination, is left to fill in the gaps
of these official plots, to suggest new directions, flesh out secondary characters and build
on or knock down the framework imposed from 'above'”8
In the past ten years, the evolution of online social communities has transformed the way
that mass media fans interact with each other and the creators of the media works they
consume. Websites, blogs, and online message boards deliver entertainment news and
industry at a rapid pace and allow for a previously unseen level of media transparency.
4 Susan Scafidi, Who Owns Culture? 134 (2005)
5 Susan Scafidi, Who Owns Culture? 128 (2005)
6 Janet Murray, Hamlet on the Holodeck 38 (1997)
7 Janet Murray, Hamlet on the Holodeck 40 (1997)
8 Will Brooker, Internet Fandom and the Continuing Narratives of Star Wars, Blade Runner, and Alien, in
Alien Zone II 50, 50 (1999)
3
At the same time, the collaborative nature of online communities creates a social
environment in which media content may be labeled and classified by users to be better
understood and used by all.
This ongoing direct interaction between media producers and fans moves beyond the
previously discussed ways of understanding media as presented by Fiske – the semiotic
resistant readings of texts can become the majority opinion and can even influence
owners and creators. We believe this interaction represents a sea change in how the
United States most lucrative and influential commodities – entertainment media – is
consumed and used worldwide. Observing the converging process and social
environments by which media producers, owners, and fans interact will lend a greater
insight into how U.S. pop culture will be produced and marketed in the future.
I. Definitions of Pop Culture Canon and Fanon
A. Origins of Pop Culture Canon
In many fan communities, it is common to hear the phrase “canon” used by fans in
reference to a TV show, movie franchise, or book series (“That plot development does
not follow canon,” This character's parentage does not work with canon, etc.”) But rather
than a discussion about pop culture's place in literature or high art, the “canon” that many
fan communities refer to is connected to storyline and character consistency. As fans of
popular media become more invested in particular characters, fictional worlds and
storylines, many of them do seek a certain level of consistency and fluidity within the
story. “Pop culture canon” is usually defined as a body of work that establishes its own
internal storylines and/or character history, deemed to be “official” by either the creator
or publisher.
This concept of a pop culture canon is derived from literary canon, where particular
works are chosen – usually by a small group of experts – to be representative of a
particular genre. Literary canon is constantly argued, updated and changed by this
contained community; the focus is not on the internal content of the works themselves,
but if the work as a whole has outstanding, lasting merit and relevance as a work of art.
The list itself is largely subjective – and by nature, created by communality.
The creation of both literary and pop culture canon rests upon the input of a large, yet
specialized community. However, pop culture canon differs from literary canon in a
number of ways: one in that the “canon” in question deals with the internal content of the
work. Additionally, a small group of people (or many times, one individual author)
establishes, creates and contradicts the canon – Consumers of the work can argue the
validity of the canon, but cannot individually adapt or change it. Or can they?
We suggest a framework to understand how alternative forms of pop culture canon,
specifically regarding character traits and plotlines, are often created and sustained by the
fans that support it. Specifically, we refer to the concept of a fan-established pop culture
canon, commonly known as “fanon.”
4
"Canon [is] the events presented in the media source that provide the universe,
setting, and characters, and fanon [is] the events created by the fan community in
a particular fandom and repeated pervasively throughout the fantext. Fanon often
creates particular details or character readings even though canon does not fully
support it–or at times, outright contradicts it.” 9
Fanon is commonly described in fan communities as an alternate universe where – either
through inference in the original text, or wishful thinking on the part of the fans –
elements of the story are pulled into the “official story."10
We illustrate this process by using a new method of applying taxonomic structure to the
layman: folksonomy. Folksomies, such as tagging and metadata for the web, are open-
ended forms of user classification, allowing the public to collectively and
collaboratively create meaning through a “many-to-many” model of understanding and
organizing information, through labeling. Information architect Thomas Vander Wal
created the term "folksonomy" by to describe the bottom-up process of determining
meaning through collective intelligence.11
It is important to note that we are using the “folksnomy” concept as a metaphor, using the
tangible process of tagging to describe the largely abstract process used by fans to
classify and organize media texts. Fans do not literally “tag” media texts with descriptive
data as “canon” as they would tag a photograph in Flickr with “empire state building”
or “summer 2006.” Instead they make decisions, both collaboratively and individually
about the content of the media texts (including event timelines, character back stories,
etc.) and then share these determinations with others, more commonly online, but
sometimes through other fan social environments, such as 'zines or fan conventions.
More often than not, the medium by which this fandom folksonomy takes place is
through fan fiction. The shared conventions of character traits, physical descriptions
 
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This essay is a study in why erotic - and homoerotic fanfiction especially - has for long been denied the status of "literature" by critics. The topics dealt with are whether the status of slash fiction depends more on the gender and class of the writers than the quality of the works, how writers of slash are taking an active part in the art of creating rather than simply copying the works of others and, how J.R.R. Tolkien himself led on to homoerotic tensions in his works.

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https://www.fanfiction.net/s/2454432/1/Pan-The-Virgin
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https://www.fanfiction.net/s/2369836/1/We-Are-One

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Word reading and math computation scores were predicted from Wechsler Abbreviated Scale of Intelligence Full Scale IQ, 10 neuropsychological tests, and parent attention deficit hyperactivity disorder (ADHD) ratings in 214 general population elementary school children. IQ was the best single predictor of achievement. In addition, Digit Span contributed significantly to reading prediction, and the Developmental Test of Visual-Motor Integration (VMI) and Coding contributed to math prediction. The remaining neuropsychological test scores did not significantly improve achievement prediction. Exploratory factor analysis yielded a general ability factor (comprising the four IQ subtests, Digit Span, VMI, reading, and math), five factors made up solely of subtests from single measures (Wisconsin Card Sorting Test, Stroop Color and Word Test, Gordon Diagnostic System, California Verbal Learning Test, and ADHD ratings), a factor consisting of Grooved Pegboard Test and Coding, and a factor consisting of Symbol Search and Animal Naming Test.

 

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