Issues of methods and interpretation in the National Cancer Institute formaldehyde cohort study

In 2004, the International Agency for Research on Cancer (IARC) reclassified formaldehyde (FA) from a probable (Group 2A) to a known human carcinogen (Group 1) citing results for nasopharyngeal cancer (NPC) mortality from the follow-up through 1994 of the National Cancer Institute formaldehyde cohort study. To the contrary, in 2012, the Committee for Risk Assessment of the European Chemicals Agency disagreed with the proposal to classify FA as a known human carcinogen (Carc. 1A), proposing a lower but still protective category, namely as a substance which is presumed to have carcinogenic potential for humans (Carc. 1B). Thus, U.S. and European regulatory agencies currently disagree about the potential human carcinogenicity of FA. In 2013, the National Cancer Institute reported results from their follow-up through 2004 of the formaldehyde cohort and concluded that the results continue to suggest a link between FA exposure and NPC. We discuss in this commentary why we believe that this interpretation is neither consistent with the available data from the most recent update of the National Cancer Institute cohort study nor with other research findings from that cohort, other large cohort studies and the series of publications by some of the current authors, including an independent study of one of the National Cancer Institute's study plants. Another serious concern relates to the incorrectness of the data from the follow-up through 1994 of the National Cancer Institute study stemming from incomplete mortality ascertainment. While these data were corrected by the National Cancer Institute in subsequent supplemental publications, incorrect data from the original publications have been cited extensively in recent causal evaluations of FA, including IARC. We conclude that the NCI publications that contain incorrect data from the incomplete 1994 mortality follow-up should be retracted entirely or corrected via published errata in the corresponding journals, and efforts should be made to re-analyze data from the 2004 follow-up of the NCI cohort study. © 2014 Marsh et al.; licensee BioMed Central Ltd

How willing are you to accept sexual requests from slightly unattractive to exceptionally attractive imagined requestors?

This is the post print version of the article. The official published version can be accessed from the link below.In their classic study of differences in mating strategies (Clark & Hatfield, 1989), men and women demonstrated a striking difference in interest in casual sex. The current study examined the role of requestor physical attractiveness (slightly unattractive, moderately attractive and exceptionally attractive) on men's and women's willingness to accept three different requests (go out, come to apartment, go to bed) in a questionnaire study. We tested two hypotheses, using a sample of 427 men and 443 women from three countries. Hypothesis 1 states that men, relative to women, will demonstrate a greater willingness to accept the “come to apartment” and “go to bed” requests but not the “go out” request for all three levels of requestor attractiveness. This hypothesis reflects Clark and Hatfield's (1989) main findings. Hypothesis 2 states that the physical attractiveness of a potential partner will have a greater effect on women's than on men's willingness to accept all three requests, and particularly for the explicit request for casual sex. The results partially supported Hypothesis 1 and fully supported Hypothesis 2. The discussion highlights limitations of the current research and presents directions for future research

Female economic dependence and the morality of promiscuity

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ The Author(s) 2014.In environments in which female economic dependence on a male mate is higher, male parental investment is more essential. In such environments, therefore, both sexes should value paternity certainty more and thus object more to promiscuity (because promiscuity undermines paternity certainty). We tested this theory of anti-promiscuity morality in two studies (N = 656 and N = 4,626) using U.S. samples. In both, we examined whether opposition to promiscuity was higher among people who perceived greater female economic dependence in their social network. In Study 2, we also tested whether economic indicators of female economic dependence (e.g., female income, welfare availability) predicted anti-promiscuity morality at the state level. Results from both studies supported the proposed theory. At the individual level, perceived female economic dependence explained significant variance in anti-promiscuity morality, even after controlling for variance explained by age, sex, religiosity, political conservatism, and the anti-promiscuity views of geographical neighbors. At the state level, median female income was strongly negatively related to anti-promiscuity morality and this relationship was fully mediated by perceived female economic dependence. These results were consistent with the view that anti-promiscuity beliefs may function to promote paternity certainty in circumstances where male parental investment is particularly important

Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal

OBJECTIVE: To examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is safe and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram, can increase HIV transcription in people with HIV (PWH) on antiretroviral therapy (ART). Together these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated (CA) unspliced (US) RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA and plasma concentrations of ART, vorinostat and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4- and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8-37 (peak 81 copies/mL) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSIONS: The combination of prolonged high dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal

Divided attention selectively impairs memory for self-relevant information

Information that is relevant to oneself tends to be remembered more than information that relates to other people, but the role of attention in eliciting this "self-reference effect" is unclear. In the present study, we assessed the importance of attention in self-referential encoding using an ownership paradigm, which required participants to encode items under conditions of imagined ownership by themselves or by another person. Previous work has established that this paradigm elicits a robust self-reference effect, with more "self-owned" items being remembered than "other-owned" items. Access to attentional resources was manipulated using divided-attention tasks at encoding. A significant self-reference effect emerged under full-attention conditions and was related to an increase in episodic recollection for self-owned items, but dividing attention eliminated this memory advantage. These findings are discussed in relation to the nature of self-referential cognition and the importance of attentional resources at encoding in the manifestation of the self-reference effect in memory

Maladaptive behaviors are linked with inefficient sleep in individuals with developmental disabilities

The purpose of the current study was to assess the relations between nightly sleep patterns and the frequency of daily maladaptive behavior. Antecedent and consequential relations between sleep patterns and behavior were evaluated with time series analysis. Sleep efficiency and maladaptive behavior were determined for 20 female residents of an institutional care facility for adults with developmental disabilities. Daily maladaptive behavioral data and nightly sleep/awake logs were collected for 4 months for each participant. Efficient sleep patterns were significantly associated with lower frequencies of maladaptive behaviors. All lagged cross-correlations 8 days before and 8 days after an evening of sleep were significant. These findings suggested that inefficient sleep was associated with increased maladaptive behaviors and that the lagged associations reflected a chronic but not an acute linkage between sleep and behavior

Combined T2 and diffusion-weighted MR Imaging with template prostate biopsies in men suspected with prostate cancer but negative transrectal ultrasound-guided biopsies

PURPOSE: Transperineal template prostate (TPB) biopsy has been shown to improve prostate cancer detection in men with rising PSA and previous negative TRUS biopsies. Diagnostic performance of this approach especially MR imaging and using reliable reference standard remains scantly reported. MATERIALS AND METHODS: A total of 200 patients, who were previously TRUS biopsy negative, were recruited in this study. All the participants had at least 28-core TPB under general anesthetic within 8 weeks of previous negative TRUS biopsies. In 15 men undergoing laparoscopic radical prostatectomy, prostate specimens were sectioned using custom-made molds and analyzed by experienced pathologist as a feasibility study. RESULTS: In total, 120 of 200 patients (60 %) had positive TPB biopsy results. All of these men had at least one negative biopsy from transrectal route. T2 diffusion-weighted MR imaging showed no lesion in almost one-third of these men (61/200; 30.5 %). Out of these, 33 (33/61; 54 %) showed malignancy on TPB including high-grade tumors (>Gleason 7). Out of 15 patients underwent surgery with a total of 52 lesions (mean 3.5) on radical prostatectomy histology analyses, TPB detected 36 (70 %) lesions only. Some of these lesions were Gleason 7 and more mostly located in the posterior basal area of prostate. CONCLUSIONS: Transperineal template biopsy technique is associated with significantly high prostate cancer detection rate in men with previous negative TRUS biopsies, however compared to radical prostatectomy histology map, a significant number of lesions can still be missed in the posterior and basal area of prostate

Transmission Dynamics of Methicillin-Resistant Staphylococcus aureus in a Medical Intensive Care Unit in India

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a global pathogen and an important but seldom investigated cause of morbidity and mortality in lower and middle-income countries where it can place a major burden on limited resources. Quantifying nosocomial transmission in resource-poor settings is difficult because molecular typing methods are prohibitively expensive. Mechanistic statistical models can overcome this problem with minimal cost. We analyse the transmission dynamics of MRSA in a hospital in south India using one such approach and provide conservative estimates of the organism's economic burden. Methods and Findings: Fifty months of MRSA infection data were collected retrospectively from a Medical Intensive Care Unit (MICU) in a tertiary hospital in Vellore, south India. Data were analysed using a previously described structured hidden Markov model. Seventy-two patients developed MRSA infections and, of these, 49 (68%) died in the MICU. We estimated that 4.2% (95%CI 1.0, 19.0) of patients were MRSA-positive when admitted, that there were 0.39 MRSA infections per colonized patient month (0.06, 0.73), and that the ward-level reproduction number for MRSA was 0.42 (0.08, 2.04). Anti-MRSA antibiotic treatment costs alone averaged $124/patient, over three times the monthly income of more than 40% of the Indian population. Conclusions: Our analysis of routine data provides the first estimate of the nosocomial transmission potential of MRSA in India. The high levels of transmission estimated underline the need for cost-effective interventions to reduce MRSA transmission in hospital settings in low and middle income countries. © 2011 Christopher et al

Enhancement of Vaccinia Virus Based Oncolysis with Histone Deacetylase Inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004