Impact of Fat-Free Adipose Tissue on the Prevalence of Low Muscle Mass Estimated Using Calf Circumference in Middle-Aged and Older Adults.

Previous studies proposed calf circumference cutoff values for predicting dual-energy X-ray absorptiometry (DXA)-derived low muscle mass. However, DXA-derived appendicular lean mass (aLM) includes non-skeletal muscle components such as the appendicular fat-free component of adipose tissue fat cells (aFFAT). The purpose of this study was to compare the calf circumference method of classification before (Model #1) and after (Model #2) eliminating the influence of FFAT in healthy Japanese adults (50 to 79 years; mean age 70 (SD 7) years). Model 1, and Model 2 for classifying low muscle mass had a sensitivity of 78% and 64%, specificity of 76% and 75%, positive predictive value of 31% and 28%, and negative predictive value of 96% and 93%, respectively. Appendicular fat-free component of adipose tissue has the potential to influence the ability of calf circumference to accurately classify individuals with low muscle mass. Consideration should be made when using this as a screening tool for low muscle mass.

Integrated genomic profiling identifies two distinct molecular subtypes with divergent outcome in neuroblastoma with loss of chromosome 11q.

Imbalances in chromosome 11q occur in approximately 30% of primary neuroblastoma and are associated with poor outcome. It has been suggested that 11q loss constitutes a distinct clinico-genetic neuroblastoma subgroup by affecting expression levels of corresponding genes. This study analysed the relationship of 11q loss, clinical phenotype and global transcriptomic profiles in four clinico-genetic subgroups (11q alteration/favourable outcome, n=7; 11q alteration/unfavourable outcome, n=14; no 11q alteration/favourable outcome, n=81; no 11q alteration/unfavourable outcome, n=8; tumours with MYCN amplification and/or 1p loss were excluded). Unsupervised and supervised comparisons of gene expression profiles consistently showed significantly different mRNA patterns between favourable and unfavourable neuroblastomas, both in the subgroups with and without 11q loss. In contrast, favourable tumours with and without 11q loss showed highly similar transcriptomic profiles. Disproportionate downregulation of 11q genes was observed only in unfavourable tumours with 11q loss. The diverging molecular profiles were neither caused by considerable differences in the size of the deleted regions nor by differential methylation patterns of 11q genes. Together, this study shows that neuroblastoma with 11q loss comprises two biological subgroups that differ both in their clinical phenotype and gene expression patterns, indicating that 11q loss is not a primary determinant of neuroblastoma tumour behaviour.

International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee.

Neuroblastoma serves as a paradigm for utilising tumour genomic data for determining patient prognosis and treatment allocation. However, before the establishment of the International Neuroblastoma Risk Group (INRG) Task Force in 2004, international consensus on markers, methodology, and data interpretation did not exist, compromising the reliability of decisive genetic markers and inhibiting translational research efforts. The objectives of the INRG Biology Committee were to identify highly prognostic genetic aberrations to be included in the new INRG risk classification schema and to develop precise definitions, decisive biomarkers, and technique standardisation. The review of the INRG database (n=8800 patients) by the INRG Task Force finally enabled the identification of the most significant neuroblastoma biomarkers. In addition, the Biology Committee compared the standard operating procedures of different cooperative groups to arrive at international consensus for methodology, nomenclature, and future directions. Consensus was reached to include MYCN status, 11q23 allelic status, and ploidy in the INRG classification system on the basis of an evidence-based review of the INRG database. Standardised operating procedures for analysing these genetic factors were adopted, and criteria for proper nomenclature were developed. Neuroblastoma treatment planning is highly dependant on tumour cell genomic features, and it is likely that a comprehensive panel of DNA-based biomarkers will be used in future risk assignment algorithms applying genome-wide techniques. Consensus on methodology and interpretation is essential for uniform INRG classification and will greatly facilitate international and cooperative clinical and translational research studies.

Risk estimation of neuroblastoma patients using molecular markers.

The pediatric tumor neuroblastoma is a heterogeneous disease: Patients' clinical courses can range from spontaneous regression to fatal progression of the disease. Accordingly, treatment protocols vary from "wait and see" approaches to intensive multimodal therapies. Accurate risk estimation of the patients is therefore mandatory to choose the most adequate therapy. Current trials stratify by a limited number of clinical variables, such as stage of the disease and age of the patient at diagnosis, as well as molecular markers, such as amplification of the oncogene MYCN and loss of the short arm of chromosome 1. However, misclassifications of patients still occur, and thus, a precise prediction of the clinical courses remains a challenge of neuroblastoma research. In recent years, genomic alterations and gene expression profiles of this neoplasm have been characterized thoroughly. It has been shown that the diverse clinical phenotypes are reflected by both specific cytogenetic aberrations and distinct gene expression patterns. Moreover, a variety of DNA copy number changes and gene expression-based classifiers have been described that could predict the outcome of neuroblastoma patients more precisely than established prognostic variables. In this review, the recent advances in the detection and evaluation of molecular prognostic markers for neuroblastoma patients are summarized, and their current and potential contribution to risk stratification systems is discussed.

Genotype-environment correlations for language-related abilities: implications for typical and atypical learners.

Recent behavioral genetic research has shown that genetic propensities are associated with individual differences in experiences, and thus, what may appear to be environmental effects can reflect genetic influence. This study examines passive genotype-environment correlations (GECs) for language-related abilities by comparing environment-child language associations in adoptive and nonadoptive families. The results provide evidence for the genetic mediation of the association between home environmental variables, such as the provision of toys and games, maternal involvement, and degree of intellectual/cultural orientation with children's language-related abilities. Developmental changes in passive GECs are considered, and the implications for typical and atypical learners are discussed.

Serum cholesterol concentrations and mood states in violent psychiatric patients: an experience sampling study.

The well-documented negative association between serum cholesterol and aggressive behavior has led Kaplan to propose a cholesterol-serotonin hypothesis of aggression. According to this hypothesis, low dietary cholesterol intake leads to depressed central serotonergic activity, which itself has been reported in numerous studies of violent individuals. In the present study, 25 violent psychiatric patients participated in a microbehavioral experience sampling procedure to examine differences in self-reports of affective and cognitive experiences as a function of serum cholesterol concentrations. For 7 days, they wore signaling devices that emitted an average of seven signals a day. Following each signal, patients filled out a mood questionnaire. Total serum cholesterol (TSC) concentration was positively associated with measures of affect, cognitive efficiency, activation, and sociability, suggesting a link between low TSC and dysphoria. These findings are consistent with the cholesterol-serotonin hypothesis and with the substantive literature linking both aggression and depression to depressed central serotonergic activity.

Medication adherence failure in schizophrenia: a forensic review of rates, reasons, treatments, and prospects.

Forensic patients with schizophrenia who fail to adhere to prescribed antipsychotic medication risk recidivism, which continues to be a serious concern. It affects all stages of trial proceedings and impacts on the treaters' liability. Although much remains unchanged since the authors reviewed the subject in 1986, significant advances have occurred. A patient's insight can be assessed with greater precision. Risks posed by past noncompliance, substance abuse, and a dysphoric response to medication are more clearly documented. Clinical and laboratory methods for assessing compliance have improved. Major advances in the effective amelioration of adverse effects can be applied to promote adherence. New augmentation strategies enable adequate treatment at lower doses. The development of atypical antipsychotic agents makes compliance easier to achieve and maintain. Other advances apply to the containment of relapse when it does occur. This review organizes the literature documenting these trends for use in both treatment and consultation.

The home inventory of dangers and safety precautions-2: addressing critical needs for prescriptive assessment devices in child maltreatment and in healthcare.

OBJECTIVE: This paper describes the development and preliminary validation of a prescriptive home danger and safety precaution instrument containing 14 epidemiological categories to be used in the design and evaluation of family-tailored injury prevention and safety interventions. METHOD: The HIDSP-2 evolved from application and revision of the previous home danger and safety precaution recognition and observation instruments. As part of this process, the suitability of the HIDSP-2 for use in a broad-based trial was evaluated with 29 low income parents exhibiting individual learning needs. Inter-rater reliability and stability of scores were examined. Internal consistency was examined for total dangers and precautions and for those categories in which there were sufficient items to do so. RESULTS: Administrative time was reduced while continuing usefulness in the identification and remediation of dangers and implementation of precautions was demonstrated. Stability of observation was high. Alphas as a measure of internal consistency was satisfactory for total danger and precautions separately; however, those for most individual categories were low. There was significant reduction in the number of dangers identified initially and significant improvement in the safety precautions implemented. CONCLUSIONS: The HIDSP-2 can assist healthcare, education, disability, and child protective service workers in the development of home safety plans for remediating home dangers and implementing precautions. While we see this instrument as eminently suitable for use in broad-based interventions and in epidemiological studies, further research must continue to examine the psychometric characteristics of the individual danger and precaution categories.

Creatine kinase elevations and aggressive behavior in hospitalized forensic patients.

The relationship between creatine kinase (CK) and aggressive behavior was tested in 195 males consecutively admitted to a forensic hospital. Among patients receiving antipsychotic medication, the most violent patients had higher CK levels than less violent patients. This was not the case in patients who did not receive antipsychotic medication. CK levels were not influenced by age, ethnicity, or clinical diagnosis. CK levels were however influenced by prior assaultiveness and restraints. When these two factors were controlled for, CK levels remained strongly associated with subsequent violence. CK appears to be a potential predictor of violent behavior. It has the advantage of easy availability in comparison to other biological markers of aggression (e.g., 5-HIAA). Prospective studies are needed to confirm the validity of this biobehavioral association.

Look who's talking: a prospective study of familial transmission of language impairments.

Language impairments have been hypothesized to have a genetic component. Previous studies of the familial aggregation of language impairments have relied on a retrospective approach based on parental/self-reported history of language development. This study examined familial aggregation prospectively, by investigating language acquisition and cognitive development in the younger siblings and offspring of individuals with well-defined language impairments. It was predicted that children with a positive family history for language impairments would be more likely to show delays in language acquisition than would age- and gender-matched controls. Similar delays were not expected in nonlinguistic domains, such as conceptual, gestural, or general cognitive development. Ten children with a positive family history and 10 age- and gender-matched controls were tested. Analyses of linguistic and cognitive assessments at 16 to 26 months confirmed the predictions. Children with a family history of language impairments had lower receptive and expressive language scores than controls, with 50% of them scoring at least 1.5 SD below the mean for their age. At the same time, performance on a number of tasks that did not rely on language abilities did not differ as a function of family history. These results indicate that children with a positive family history for language impairments are at risk for language delay; the results also support a familial component to language impairments.

Ethnicity, aggression and serum creatine kinase in hospitalized male forensic patients.

OBJECTIVE: This study examined the relationship of serum creatine kinase (CK) levels with aggressive behavior as a function of psychosis and ethnicity in a sample of violent forensic patients. DESIGN: CK levels were determined on admission in a sample of 195 males consecutively admitted to a forensic hospital. The patients' aggressive behavior during their hospital stay was monitored using the Overt Aggression Scale (OAS). All data for this study was archival and gathered from hospital records. METHODS: Multivariate analysis of variance was used to examine whether African-American and Caucasian patients differed in serum CK levels and severity, frequency, and type (verbal vs physical) of aggression. T-tests were performed to compare ethnic groups in terms of age, weight, height, systolic and diastolic blood pressure. All patients who had been in restraints, had been administered intramuscular medications, had a history of drug or alcohol abuse, and were classified as schizophrenic were compared using chi-square analysis. For each of these variables further comparisons were made of CK levels between African-American and Caucasian patients. RESULTS: Mean serum CK in African-American patients was 64% higher than in Caucasians. African Americans displayed significantly greater physical aggression than Caucasian patients. In addition, African-American patients with a diagnosis of schizophrenia had significantly higher CK levels than African Americans with other diagnoses, with no significant differences related to schizophrenia noted within the Caucasian group. No significant differences in aggressive behavior related to schizophrenia were found in African-American patients. CONCLUSIONS: This study confirms the findings of previous reports which observed higher CK levels in African Americans than in Caucasians. It is also proposed that a confluence of physiologic and psychosocial factors may affect biological marker presentation, particularly as manifest in CK differences between ethnic groups.

Characteristics and cost of staff injuries in a forensic hospital.

At a maximum-security forensic hospital over a three-year period, 79 patients (35 percent of all patients) were involved in 157 staff injuries. Staff members' average postinjury absence from work was 85 days, at a cost equivalent to about 2 percent of the hospital's budget. Nursing staff, particularly psychiatric technicians, had the highest injury rate. Male staff were about twice as likely to be injured as female staff. More injuries occurred on the second shift. Patients who injured staff were younger than those who did not. Florid psychotic behavior, nonpsychotic agitation, and the recent use of restraints were the most common prodromal signs.

Serum cholesterol and aggression in hospitalized male forensic patients.

Human studies of the link between serum cholesterol and aggression have yielded equivocal results. Depending on the type of aggression studied (e.g., criminal violence or Type A hostility), investigators have found either a negative or a positive association between cholesterol and aggressive behavior. We conducted a retrospective analysis of aggressive incidents in a sample of hospitalized male forensic patients. The whole sample had lower cholesterol levels than the general population. Patients with low cholesterol levels (< 200 mg/dl) engaged in more frequent aggressive behavior but showed no difference in severity of aggression. They also showed no difference in verbal vs physical aggression. The relationship between cholesterol and frequency of aggression was curvilinear, with the most frequent acts of aggression committed by patients with moderately low cholesterol levels. Current research findings regarding the cholesterol-aggression association suggest the need for further clarification of the behavioral parameters under investigation.

Serum cholesterol levels and frequency of aggression.

Analysis of serum cholesterol levels of 106 male forensic patients showed significant differences in frequency of aggression, with low cholesterol levels predominant among those more frequently violent.

Hematological changes and severity of aggression in black and white forensic patients.

Analysis of hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration, and red blood-cell count for a group of 46 black and 59 white male forensic patients showed significant hematological differences between the groups, with white patients demonstrating higher mean values for all four measures.

Infant use of relative motion as information for form: evidence for spatiotemporal integration of complex motion displays.

Previous studies of infants' ability to integrate and to utilize relative motion as information for form in the absence of structural cues have primarily involved motions that are uniform in rate, direction, and path within the form to be constructed. In the present study, we examined infants' ability to integrate relative motion information from motions that are nonuniform along these dimensions, and from this integrative process to construct a coherently rotating two-dimensional form. Infants' ability to integrate nonuniform motion was measured with regard to their ability to discriminate the rotating form from a noncoherent control display containing the same absolute motions. The results showed that discrimination of the coherent and incoherent displays was not demonstrated until 7 months of age. Two additional experiments were conducted to rule out the possibility that this discrimination was based on the detection of local regions of coherence, rather than the perception of the global rotating form. In both experiments, the results did not support discrimination based exclusively on local cues alone. From the combined results of all three experiments, we conclude that infants demonstrate the capacity to integrate the information contained within nonuniform trajectories into a coherent structure by 7 months of age.

The hearing-impaired infant: patterns of identification and habilitation revisited.

This study is a follow-up of an 1980-1982 study that examined the occurrence of risk factors and the patterns of identification and habilitation in a group of hearing-impaired infants from an urban setting. Current findings covering the period 1983-1988, indicate that only one out of three hearing-impaired infants can be expected to be identified through audiological screening programs in Neonatal Intense Care Units (NICUs) and although the age at diagnosis for NICU graduates is significantly earlier than for Well Baby Nursery (WBN) graduates, age at enrollment in a parent-infant program for both NICU and WBN infants is around 20 months. Over the 8 year period covered by our two studies, the age hearing-impaired infants are enrolled in habilitation has remained a year or more later than the 6 month ideal recommended in 1982 by the Joint Committee on Infant Hearing.