63 research outputs found

    Carol Anne Bond v the United States of America: How a woman scorned threatened the Chemical Weapons Convention

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    The case of Carol Anne Bond v the United States of America stemmed from a domestic dispute when Ms. Bond attempted to retaliate against her best friend by attacking her with chemical agents. What has emerged is a much greater issue--a test of standing on whether a private citizen can challenge the Tenth Amendment. Instead of being prosecuted in state court for assault, Ms. Bond was charged and tried in district court under a federal criminal statute passed as part of implementation of the Chemical Weapons Convention (CWC). Ms. Bond\u27s argument rests on the claim that the statute exceeded the federal government\u27s enumerated powers in criminalizing her behavior and violated the Constitution, while the government contends legislation implementing treaty obligations is well within its purview. This question remains unanswered because there is dispute among the lower courts as to whether Ms. Bond, as a citizen, even has the right to challenge an amendment guaranteeing states rights when a state is not a party to the action. The Supreme Court heard the case on February 22, 2011, and, if it decides to grant Ms. Bond standing to challenge her conviction, the case will be returned to the lower courts. Should the court decide Ms. Bond has the standing to challenge her conviction and further questions the constitutionality of the law, it would be a significant blow to implementation of the CWC in the U.S. and the effort of the federal government to ensure we are meeting our international obligations

    Aspergillus nodules; another presentation of Chronic Pulmonary Aspergillosis

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    BACKGROUND: There are a number of different manifestations of pulmonary aspergillosis. This study aims to review the radiology, presentation, and histological features of lung nodules caused by Aspergillus spp. METHODS: Patients were identified from a cohort attending our specialist Chronic Pulmonary Aspergillosis clinic. Patients with cavitating lung lesions, with or without fibrosis and those with aspergillomas or a diagnosis of invasive aspergillosis were excluded. Demographic, laboratory, and clinical data and radiologic findings were recorded. RESULTS: Thirty-three patients with pulmonary nodules and diagnostic features of aspergillosis (histology and/or laboratory findings) were identified. Eighteen (54.5 %) were male, mean age 58 years (range 27–80 years). 19 (57.6 %) were former or current smokers. The median Charleston co-morbidity index was 3 (range 0–7). All complained of a least one of; dyspnoea, cough, haemoptysis, or weight loss. None reported fever. Ten patients (31 %) did not have an elevated Aspergillus IgG, and only 4 patients had elevated Aspergillus precipitins. Twelve patients (36 %) had a single nodule, six patients (18 %) had between 2 and 5 nodules, 2 (6 %) between 6 and 10 nodules and 13 (39 %) had more than 10 nodules. The mean size of the nodules was 21 mm, with a maximum size ranging between 5–50 mm. No nodules had cavitation radiographically. The upper lobes were most commonly involved. Histology was available for 18 patients and showed evidence of granulation tissue, fibrosis, and visualisation of fungal hyphae. CONCLUSION: Pulmonary nodules are a less common manifestation of aspergillosis in immunocompetent patients. Distinguishing these nodules from other lung pathology may be difficult on CT findings alone

    Trait positive and negative emotionality differentially associate withdiurnal cortisol activity

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    Inter-individual variability in metrics of hypothalamic-pituitary-adrenocortical (HPA) activity, such asthe slope of the diurnal decline in cortisol, cortisol awakening response (CAR), and total cortisol out-put, have been found to associate inversely with trait ratings of extraversion and positive affect (E/PA)and positively with neuroticism and negative affect (N/NA) in some, but not all, investigations. Theseinconsistencies may partly reflect varied intensity of cortisol sampling among studies and reliance onself-rated traits, which are subject to reporting biases and limitations of introspection. Here, we furtherexamined dispositional correlates of HPA activity in 490 healthy, employed midlife volunteers (M age = 43years; 54% Female; 86% white). Trait ratings were requested from participants and 2 participant-electedinformants using the Positive and Negative Affect Schedule (PANAS) and Extraversion and Neuroticismdimensions of NEO personality inventories. CAR was assessed as percent increase in cortisol levels fromawakening to 30 min after awakening; and the diurnal slope and total output of cortisol [Area Underthe Curve (AUC)] were determined from cortisol measurements taken at awakening, +4 and +9 h later,and bedtime, across 3 workdays. Structural equation modeling was used to estimate multi-informantE/PA and N/NA factors. We used 3 days of measurement as indicators to model each of the three latentcortisol factors (slope, CAR, and AUC). With the two latent emotionality and three latent cortisol indicesincluded there was good fit to the data ( 2(200)= 278.38, p = 0.0002; RMSEA = 0.028, 90% CI = 0.02–0.04;CFI/TLI = 0.97/0.96; SRMR = 0.04). After controlling for covariates (age, sex, race), results showed higherlatent E/PA associated with a steeper diurnal slope (Standardized ˇ = −0.19, p = 0.02) and smaller CAR(Standardized ˇ = −0.26, p = 0.004), whereas N/NA did not associate with any cortisol metric (Standard-ized ˇ’s = −0.12 to 0.13, p’s = 0.10 to 0.53). These findings suggest that positive emotionality may be moreclosely associated with indices of diurnal cortisol release than negative emotionality

    Trait positive and negative emotionality differentially associate withdiurnal cortisol activity

    Get PDF
    Inter-individual variability in metrics of hypothalamic-pituitary-adrenocortical (HPA) activity, such asthe slope of the diurnal decline in cortisol, cortisol awakening response (CAR), and total cortisol out-put, have been found to associate inversely with trait ratings of extraversion and positive affect (E/PA)and positively with neuroticism and negative affect (N/NA) in some, but not all, investigations. Theseinconsistencies may partly reflect varied intensity of cortisol sampling among studies and reliance onself-rated traits, which are subject to reporting biases and limitations of introspection. Here, we furtherexamined dispositional correlates of HPA activity in 490 healthy, employed midlife volunteers (M age = 43years; 54% Female; 86% white). Trait ratings were requested from participants and 2 participant-electedinformants using the Positive and Negative Affect Schedule (PANAS) and Extraversion and Neuroticismdimensions of NEO personality inventories. CAR was assessed as percent increase in cortisol levels fromawakening to 30 min after awakening; and the diurnal slope and total output of cortisol [Area Underthe Curve (AUC)] were determined from cortisol measurements taken at awakening, +4 and +9 h later,and bedtime, across 3 workdays. Structural equation modeling was used to estimate multi-informantE/PA and N/NA factors. We used 3 days of measurement as indicators to model each of the three latentcortisol factors (slope, CAR, and AUC). With the two latent emotionality and three latent cortisol indicesincluded there was good fit to the data ( 2(200)= 278.38, p = 0.0002; RMSEA = 0.028, 90% CI = 0.02–0.04;CFI/TLI = 0.97/0.96; SRMR = 0.04). After controlling for covariates (age, sex, race), results showed higherlatent E/PA associated with a steeper diurnal slope (Standardized ˇ = −0.19, p = 0.02) and smaller CAR(Standardized ˇ = −0.26, p = 0.004), whereas N/NA did not associate with any cortisol metric (Standard-ized ˇ’s = −0.12 to 0.13, p’s = 0.10 to 0.53). These findings suggest that positive emotionality may be moreclosely associated with indices of diurnal cortisol release than negative emotionality

    Quality of life and satisfaction with life in SLE patients—the importance of clinical manifestations

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    To assess the correlation between quality of life (QoL) and satisfaction with life (SL) in SLE patients and correlate both with clinical symptoms of the disease. The study was performed in 83 patients. QoL was assessed by Short Form 36, and SL was assessed by the Satisfaction with Life Scale. Clinical manifestations presented at the time of examination were taken into consideration. SLE patients assessed their QoL and SL as rather low. Those with photosensitivity as well as neurological symptoms presented lower QoL in particular domains, while those with renal manifestation of SLE assessed their QoL as higher. Similar observations were made for SL only in relation to neurological symptoms. Moreover, our findings show that although SL is a part of QoL, both these parameters should be distinguished in order to fully assess the state of the patient

    Multivalent helix mimetics for PPI-inhibition.

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    The exploitation of multivalent ligands for the inhibition of protein-protein interactions has not yet been explored as a supramolecular design strategy. This is despite the fact that protein-protein interactions typically occur within the context of multi-protein complexes and frequently exploit avidity effects or co-operative binding interactions to achieve high affinity interactions. In this paper we describe preliminary studies on the use of a multivalent N-alkylated aromatic oligoamide helix mimetic for inhibition of p53/hDM2 and establish that protein dimerisation is promoted, rather than enhanced binding resulting from a higher effective concentration of the ligand. This journal i

    In vitro models of medulloblastoma: choosing the right tool for the job

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    The recently-defined four molecular subgroups of medulloblastoma have required updating of our understanding of in vitro models to include molecular classification and risk stratification features from clinical practice. This review seeks to build a more comprehensive picture of the in vitro systems available for modelling medulloblastoma. The subtype classification and molecular characterisation for over 40 medulloblastoma cell-lines has been compiled, making it possible to identify the strengths and weaknesses in current model systems. Less than half (18/44) of established medulloblastoma cell-lines have been subgrouped. The majority of the subgrouped cell-lines (11/18) are Group 3 with MYC-amplification. SHH cell-lines are the next most common (4/18), half of which exhibit TP53 mutation. WNT and Group 4 subgroups, accounting for 50% of patients, remain underrepresented with 1 and 2 cell-lines respectively. In vitro modelling relies not only on incorporating appropriate tumour cells, but also on using systems with the relevant tissue architecture and phenotype as well as normal tissues. Novel ways of improving the clinical relevance of in vitro models are reviewed, focusing on 3D cell culture, extracellular matrix, co-cultures with normal cells and organotypic slices. This paper champions the establishment of a collaborative online-database and linked cell-bank to catalyse preclinical medulloblastoma research
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