Emotion Word Comprehension from 4 to 16 Years Old: A Developmental Survey

Background: Whilst previous studies have examined comprehension of the emotional lexicon at different ages in typically developing children, no survey has been conducted looking at this across different ages from childhood to adolescence. Purpose: To report how the emotion lexicon grows with age. Method: Comprehension of 336 emotion words was tested in n = 377 children and adolescents, aged 4–16 years old, divided into 6 age-bands. Parents or teachers of children under 12, or adolescents themselves, were asked to indicate which words they knew the meaning of. Results: Between 4 and 11 years old, the size of the emotional lexicon doubled every 2 years, but between 12 and 16 years old, developmental rate of growth of the emotional lexicon leveled off. This survey also allows emotion words to be ordered in terms of difficulty. Conclusions: Studies using emotion terms in English need to be developmentally sensitive, since during childhood there is considerable change. The absence of change after adolescence may be an artifact of the words included in this study. This normative developmental data-set for emotion vocabulary comprehension may be useful when testing for delays in this ability, as might arise for environmental or neurodevelopmental reasons

Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes

BACKGROUND: Identification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized as a tumor suppressor gene in B lymphocytes. The present study aimed to identify novel oncogenes involved in malignant transformation of TRAF3-deficient B cells. METHODS: We used microarray analysis to identify genes differentially expressed in TRAF3(−/−) mouse splenic B lymphomas. We employed lentiviral vector-mediated knockdown or overexpression to manipulate gene expression in human multiple myeloma (MM) cell lines. We analyzed cell apoptosis and proliferation using flow cytometry, and performed biochemical studies to investigate signaling mechanisms. To delineate protein-protein interactions, we applied affinity purification followed by mass spectrometry-based sequencing. RESULTS: We identified mutated in colorectal cancer (MCC) as a gene strikingly up-regulated in TRAF3-deficient mouse B lymphomas and human MM cell lines. Aberrant up-regulation of MCC also occurs in a variety of primary human B cell malignancies, including non-Hodgkin lymphoma (NHL) and MM. In contrast, MCC expression was not detected in normal or premalignant TRAF3(−/−) B cells even after treatment with B cell stimuli, suggesting that aberrant up-regulation of MCC is specifically associated with malignant transformation of B cells. In elucidating the functional roles of MCC in malignant B cells, we found that lentiviral shRNA vector-mediated knockdown of MCC induced apoptosis and inhibited proliferation in human MM cells. Experiments of knockdown and overexpression of MCC allowed us to identify several downstream targets of MCC in human MM cells, including phospho-ERK, c-Myc, p27, cyclin B1, Mcl-1, caspases 8 and 3. Furthermore, we identified 365 proteins (including 326 novel MCC-interactors) in the MCC interactome, among which PARP1 and PHB2 were two hubs of MCC signaling pathways in human MM cells. CONCLUSIONS: Our results indicate that in sharp contrast to its tumor suppressive role in colorectal cancer, MCC functions as an oncogene in B cells. Our findings suggest that MCC may serve as a diagnostic marker and therapeutic target in B cell malignancies, including NHL and MM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-014-0056-6) contains supplementary material, which is available to authorized users

Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (≥ 6.60 ng/mL) vs. low sHER2 concentrations (≤ 1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer

Carnegie Supernova Project-II: Extending the Near-Infrared Hubble Diagram for Type Ia Supernovae to z∼0.1z\sim0.1

The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a "Cosmology" sample of $\sim100$ Type Ia supernovae located in the smooth Hubble flow ($0.03 \lesssim z \lesssim 0.10$). Light curves were also obtained of a "Physics" sample composed of 90 nearby Type Ia supernovae at $z \leq 0.04$ selected for near-infrared spectroscopic time-series observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.Comment: 43 pages, 10 figures, accepted for publication in PAS

Enduring Mental Health Morbidity and Social Function Impairment in World Trade Center Rescue, Recovery, and Cleanup Workers: The Psychological Dimension of an Environmental Health Disaster

Background The World Trade Center (WTC) attacks exposed thousands of workers to hazardous environmental conditions and psychological trauma. In 2002, to assess the health of these workers, Congress directed the National Institute for Occupational Safety and Health to establish the WTC Medical Monitoring and Treatment Program. This program has established a large cohort of WTC rescue, recovery, and cleanup workers. We previously documented extensive pulmonary dysfunction in this cohort related to toxic environmental exposures. Objectives Our objective in this study was to describe mental health outcomes, social function impairment, and psychiatric comorbidity in the WTC worker cohort, as well as perceived symptomatology in workers’ children. Methods Ten to 61 months after the WTC attack, 10,132 WTC workers completed a self-administered mental health questionnaire. Results Of the workers who completd the questionnaire, 11.1% met criteria for probable post-traumatic stress disorder (PTSD), 8.8% met criteria for probable depression, 5.0% met criteria for probable panic disorder, and 62% met criteria for substantial stress reaction. PTSD prevalence was comparable to that seen in returning Afghanistan war veterans and was much higher than in the U.S. general population. Point prevalence declined from 13.5% to 9.7% over the 5 years of observation. Comorbidity was extensive and included extremely high risks for impairment of social function. PTSD was significantly associated with loss of family members and friends, disruption of family, work, and social life, and higher rates of behavioral symptoms in children of workers. Conclusions Working in 9/11 recovery operations is associated with chronic impairment of mental health and social functioning. Psychological distress and psychopathology in WTC workers greatly exceed population norms. Surveillance and treatment programs continue to be needed

Altered Gene Expression in Liver from a Murine Model of Hyperhomocysteinemia

Cystathionine beta-synthase (CBS) deficiency causes severe hyperhomocysteinemia and other signs of homocystinuria syndrome, in particular a premature atherosclerosis with multiple thrombosis. However, the molecular mechanisms by which homocysteine could interfere with normal cell function are poorly understood in a whole organ like the liver, which is central to the catabolism of homocysteine. We used a combination of differential display and cDNA arrays to analyze differential gene expression in association with elevated hepatic homocysteine levels in CBS-deficient mice, a murine model of hyperhomocysteinemia. Expression of several genes was found to be reproducibly abnormal in the livers of heterozygous and homozygous CBS-deficient mice. We report altered expression of genes encoding ribosomal protein S3a and methylthioadenosine phosphorylase, suggesting such cellular growth and proliferation perturbations may occur in homozygous CBS-deficient mice liver. Many up- or down-regulated genes encoded cytochromes P450, evidence of perturbations of the redox potential in heterozygous and homozygous CBS-deficient mice liver. The expression of various genes involved in severe oxidative processes was also abnormal in homozygous CBS-deficient mice liver. Among them, the expression of heme oxygenase 1 gene was increased, concomitant with overexpression of heme oxygenase 1 at the protein level. Commensurate with the difference in hepatic mRNA paraoxonase 1 abundance, the mean hepatic activity of paraoxonase 1, an enzyme that protects low density lipoprotein from oxidation, was 3-fold lower in homozygous CBS-deficient mice. Heterozygous CBS-deficient mice, when fed a hyperhomocysteinemic diet, have also reduced PON1 activity, which demonstrates the effect of hyperhomocysteinemia in the paraoxonase 1 activity

The World Trade Center Disaster and the Health of Workers: Five-Year Assessment of a Unique Medical Screening Program

BACKGROUND: Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. METHODS: To characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. RESULTS: Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. CONCLUSION: WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters

Conceptualising paranoia in ASD: A systematic review and development of a theoretical framework

Paranoia, unfounded ideation that others deliberately intend harm, has predominately been studied in schizophrenia. Increasingly, it is recognised that there is a spectrum of severity of excessive mistrust across the general population. Relatively little is known about paranoia in individuals with autism spectrum disorders (ASD), but rates could be expected to be higher given both difficulties in understanding others’ mental states and frequent experiences of negative social interactions. A systematic search of English-language peer-reviewed publications was undertaken to synthesise empirical research about paranoia in ASD. Seven studies, comprising a total of 180 ASD participants, met the inclusion criteria. All the studies were cross-sectional, thereby limiting causal interpretations. Individuals with ASD were consistently found to have higher levels of paranoia compared to non-clinical controls, and lower levels than individuals with current psychotic experiences manifesting in the context of schizophrenia. Furthermore, the initial evidence indicates that paranoia in ASD may be linked with theory of mind performance, negative affect, and jumping to conclusions, but not to attributional style. As in typically-developing populations, causal and maintaining mechanisms for paranoia in ASD, against a background of genetic and environmental risk, most likely include cognitive and affective processes interacting with social factors. We hypothesise, however, that core ASD characteristics and associated neurocognitive impairments also serve to precipitate and perpetuate paranoia. A framework to guide further investigation is outlined