Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Air pollution and the microvasculature: A cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA)

10.1371/journal.pmed.1000372PLoS Medicine711

Mother and Adolescent Reports of Associations Between Child Behavior Problems and Mother-Child Relationship Qualities: Separating Shared Variance from Individual Variance

This study contrasts results from different correlational methods for examining links between mother and child (N = 72 dyads) reports of early adolescent (M = 11.5 years) behavior problems and relationship negativity and support. Simple (Pearson) correlations revealed a consistent pattern of statistically significant associations, regardless of whether scores came from the same reporter or from different reporters. When correlations between behavior problems and relationship quality differed, within-reporter correlations were always greater in magnitude than between-reporter correlations. Dyadic (common fate) analyses designed for interdependent data decomposed within-reporter correlations into variance shared across reporters (dyadic correlations) and variance unique to specific reporters (individual correlations). Dyadic correlations were responsible for most associations between adolescent behavior problems and relationship negativity; after partitioning variance shared across reporters, no individual correlations emerged as statistically significant. In contrast, adolescent behavior problems were linked to relationship support via both shared variance and variance unique to maternal perceptions. Dyadic analyses provide a parsimonious alternative to multiple contrasts in instances when identical measures have been collected from multiple reporters. Findings from these analyses indicate that same-reporter variance bias should not be assumed in the absence of dyadic statistical analyses

Treatment course and outcomes following drug and alcohol-related traumatic injuries

Both authors are with the NeuroTexas Institute at St. David's HealthCare, St. David's Medical Center, 1015 East 32nd Street, Suite 404, Austin, Texas 78705, USA -- Matthew C. Cowperthwaite is with the Center for Systems and Synthetic Biology, The University of Texas at Austin, 1 University Station, A4800, Austin, Texas 78712, USABackground: Alcohol and drug use is known to be a major factor affecting the incidence of traumatic injury. However, the ways in which immediate pre-injury substance use affects patients' clinical care and outcomes remains unclear. The goal of the present study is to determine the associations between pre-injury use of alcohol or drugs and patient injury severity, hospital course, and clinical outcome. Materials and methods: This study used more than 200,000 records from the National Trauma Data Bank (NTDB), which is the largest trauma registry in the United States. Incidents in the NTDB were placed into one of four classes: alcohol related, drug related, alcohol-and-drug related, and substance negative. Logistic regression models were used to determine comorbid conditions or treatment complications that were significantly associated with pre-injury substance use. Hospital charges were associated with the presence or absence of drugs and alcohol, and patient outcomes were assessed using discharge disposition as delimited by the NTDB. Results: The rates of complications arising during treatment were 8.3, 10.9, 9.9 and 8.6 per one hundred incidents in the alcohol related, drug related, alcohol-and-drug related, and substance-negative classes, respectively. Regression models suggested that pre-injury alcohol use is associated with a 15% higher risk of infection, whereas pre-injury drug use is associated with a 30% higher risk of infection. Pre-injury substance use did not appear to significantly impact clinical outcomes following treatment for traumatic injury, however. Conclusion: This study suggests that pre-injury drug use is associated with a significantly higher complication rate. In particular, infection during hospitalization is a significant risk for both alcohol and drug related trauma visits, and drug-related trauma incidents are associated with increased risk for additional circulatory complications. Although drug and alcohol related trauma incidents are not associated with appreciably worse clinical outcomes, patients experiencing such complications are associated with significantly greater length of stay and higher hospitalization costs. Therefore significant benefits to trauma patients could be gained with enhanced surveillance for pre-injury substance use upon admission to the ED, and closer monitoring for infection or circulatory complications during their period of hospitalization.Center for Systems and Synthetic [email protected]

Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n-back working memory paradigm

{Purpose} Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with 99mTc-HMPAO using low irradiation dose. {Materials and methods} A two-scans protocol was applied to 12 healthy young volunteers using 270 MBq of 99mTc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal {n}-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. {Results} Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and 15O-PET studies. {Conclusion} The results support the use of 99mTc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical populations

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

BACKGROUND: Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. METHODS: The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP), the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. RESULTS: The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate), cellulose sulfate, carrageenan, CAP (in soluble form) and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold) diminished in the presence of SP (33.3%). Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. CONCLUSION: The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP) or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors

The synthetic bacterial lipopeptide Pam3CSK4 modulates respiratory syncytial virus infection independent of TLR activation

Respiratory syncytial virus (RSV) is an important cause of acute respiratory disease in infants, immunocompromised subjects and the elderly. However, it is unclear why most primary RSV infections are associated with relatively mild symptoms, whereas some result in severe lower respiratory tract infections and bronchiolitis. Since RSV hospitalization has been associated with respiratory bacterial co-infections, we have tested if bacterial Toll-like receptor (TLR) agonists influence RSVA2- GFP infection in human primary cells or cell lines. The synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary epithelial, myeloid and lymphoid cells. Surprisingly, enhancement was optimal when lipopeptides and virus were added simultaneously, whereas addition of Pam3CSK4 immediately after infection had no effect. We have identified two structurally related lipopeptides without TLR-signaling capacity that also modulate RSV infection, whereas Pam3CSK4-reminiscent TLR1/2 agonists did not, and conclude that modulation of infection is independent of TLR activation. A similar TLR-independent enhancement of infection could also be demonstrated for wild-type RSV strains, and for HIV-1, measles virus and human metapneumovirus. We show that the effect of Pam3CSK4 is primarily mediated by enhanced binding of RSV to its target cells. The Npalmitoylated cystein