Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model

BACKGROUND: Although many infections that are transmissible from person to person are acquired through direct contact between individuals, a minority, notably pulmonary tuberculosis (TB), measles and influenza are known to be spread by the airborne route. Airborne infections pose a particular threat to susceptible individuals whenever they are placed together with the index case in confined spaces. With this in mind, waiting areas of healthcare facilities present a particular challenge, since large numbers of people, some of whom may have underlying conditions which predispose them to infection, congregate in such spaces and can be exposed to an individual who may be shedding potentially pathogenic microorganisms. It is therefore important to understand the risks posed by infectious individuals in waiting areas, so that interventions can be developed to minimise the spread of airborne infections. METHOD: A stochastic Monte Carlo model was constructed to analyse the transmission of airborne infection in a hypothetical 132 m3 hospital waiting area in which occupancy levels, waiting times and ventilation rate can all be varied. In the model the Gammaitoni-Nucci equation was utilized to predict probability of susceptible individuals becoming infected. The model was used to assess the risk of transmission of three infectious diseases, TB, influenza and measles. In order to allow for stochasticity a random number generator was applied to the variables in the model and a total of 10000 individual simulations were undertaken. The mean quanta production rates used in the study were 12.7, 100 and 570 per hour for TB, influenza and measles, respectively. RESULTS: The results of the study revealed the mean probability of acquiring a TB infection during a 30-minute stay in the waiting area to be negligible (i.e. 0.0034), while that for influenza was an order of magnitude higher at 0.0262. By comparison the mean probability of acquiring a measles infection during the same period was 0.1349. If the duration of the stay was increased to 60 minutes then these values increased to 0.0087, 0.0662 and 0.3094, respectively. CONCLUSION: Under normal circumstances the risk of acquiring a TB infection during a visit to a hospital waiting area is minimal. Likewise the risks associated with the transmission of influenza, although an order of magnitude greater than those for TB, are relatively small. By comparison, the risks associated with measles are high. While the installation of air disinfection may be beneficial, when seeking to prevent the transmission of airborne viral infection it is important to first minimize waiting times and the number of susceptible individuals present before turning to expensive technological solutions

Intriguing Electrostatic Potential of CO: Negative Bond-ends and Positive Bond-cylindrical-surface

The strong electronegativity of O dictates that the ground state of singlet CO has positively charged C and negatively charged O, in agreement with ab initio charge analysis, but in disagreement with the dipole direction. Though this unusual phenomenon has been fairly studied, the study of electrostatic potential (EP) for noncovalent interactions of CO is essential for better understanding. Here we illustrate that both C and O atom-ends show negative EP (where the C end gives more negative EP), favoring positively charged species, whereas the cylindrical surface of the CO bond shows positive EP, favoring negatively charged ones. This is demonstrated from the interactions of CO with Na+, Cl-, H2O, CO and benzene. It can be explained by the quadrupole driven electrostatic nature of CO (like N2) with very weak dipole moment. The EP is properly described by the tripole model taking into account the electrostatic multipole moments, which has a large negative charge at a certain distance protruded from C, a large positive charge on C, and a small negative charge on O. We also discuss the EP of the first excited triplet COopen0

Anisotropic Charge Distribution and Anisotropic van der Waals Radius Leading to Intriguing Anisotropic Noncovalent Interactions

Although group (IV-VII) nonmetallic elements do not favor interacting with anionic species, there are counterexamples including the halogen bond. Such binding is known to be related to the charge deficiency because of the adjacent atom's electron withdrawing effect, which creates s/p-holes at the bond-ends. However, a completely opposite behavior is exhibited by N-2 and O-2, which have electrostatically positive/negative character around cylindrical-bond-surface/bond-ends. Inspired by this, here we elucidate the unusual features and origin of the anisotropic noncovalent interactions in the ground and excited states of the 2nd and 3rd row elements belonging to groups IV-VII. The anisotropy in charge distributions and van der Waals radii of atoms in such molecular systems are scrutinized. This provides an understanding of their unusual molecular configuration, binding and recognition modes involved in new types of molecular assembling and engineering. This work would lead to the design of intriguing molecular systems exploiting anisotropic noncovalent interactions.open

Calculating the potential for within-flight transmission of influenza A (H1N1)

Abstract Background Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. Methods We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. Results The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Conclusions Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one infectious individual, rather than causing a single outbreak of H1N1, could cause several simultaneous outbreaks. These results imply that, during a pandemic, quarantining passengers who travel in Economy on long-haul flights could potentially be an important control strategy. Notably, our results show that quarantining passengers who travel First Class would be unlikely to be an effective control strategy

Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, Myalgic encephalomyelitis unclear pathophysiology and with no diagnostic test or biomarker available. Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive. The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants. In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis. There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients. Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants. In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8+ T cells and decreased proportions of terminally differentiated effector CD8+ T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients. These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection, or may indicate future increased susceptibility to infection. Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS

Distinctive features of spatial planning nearby estuaries – an exploratory analysis of water-related rules in municipal master plans in Portugal

Land-use types and related intensities are often associated with pressures and disturbances on estuarine envi- ronmental values and ecosystem services provided by water. Although with varied legal frameworks across countries, broadly, spatial planning has been expected to contribute to the protection of environmentally sen- sitive areas, such as estuaries. Among the various planning tools are the plan’s land-use control rules. This article studies the incorporation of water-related terms in the regulations of municipal master plans to assess if land-use rules established on estuarine areas are significantly different from others, such as in upstream areas. It does so by developing a content analysis of a set of plans’ regulations located in estuarine and upstream areas of two river basins of Mainland Portugal. The results show greater incorporation of water-related terms in plans’ reg- ulations located in estuarine areas. Moreover, they show a greater diversity of water-related topics, types, and focus of rules on estuarine areas, whereas on upstream areas the regulatory approaches look poorer. Although the incorporation of water-related terms is globally higher in younger plans, and to a certain extent, in more arti- ficialized and dense territories, a clear distinctiveness of water-related concerns in land-use regulations of municipal plans on estuarine areas remains visible. Surprisingly, the results bring to the fore fragilities of land- use regulations on upstream areas worthy of attention in future studies. The methodology used for content analysis disclosed a valuable path for future research as it is easily expandable to take into consideration different land-uses or to be applied to different regions, to further refine if the distinctive features are explicitly related with estuarine areas or with other types of water problems.publishe

Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes: A Meta-Analysis of Published Studies and Recommendations

Despite discrepant results on clinical utility, several trials are already prospectively randomizing non-small cell lung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematic review and meta-analysis.Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates considered separately.23 eligible studies provided survival results in 2,726 patients. Substantial heterogeneity was observed in all meta-analyses (I(2) always >30%), partly due to variability in thresholds defining 'low' and 'high' ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC (average unadjusted HR = 1.61, 95%CI:1.23-2.1, p = 0.014), but not in NSCLC untreated with chemotherapy (average unadjusted HR = 0.82, 95%CI:0.51-1.31). Meta-analysis of adjusted estimates was limited by variable choice of adjustment factors and potential publication bias (Egger's p<0.0001). There was evidence that high ERCC1 was associated with reduced response to platinum (average RR = 0.80; 95%CI:0.64-0.99). SCLC data were inadequate to draw firm conclusions.Current evidence suggests high ERCC1 may adversely influence survival and response in platinum-treated NSCLC patients, but not in non-platinum treated, although definitive evidence of a predictive influence is lacking. International consensus is urgently required to provide consistent, validated ERCC1 assessment methodology. ERCC1 assessment for treatment selection should currently be restricted to, and evaluated within, clinical trials

Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines?

The bioreductive drug tirapazamine (TPZ, SR 4233, WIN 59075) is a lead compound in a series of potent cytotoxins that selectively kill hypoxic rodent and human solid tumour cells in vitro and in vivo. Phases II and III trials have demonstrated its efficacy in combination with both fractionated radiotherapy and some chemotherapy. We have evaluated the generality of an enzyme-directed approach to TPZ toxicity by examining the importance of the one-electron reducing enzyme NADPH:cytochrome P450 reductase (P450R) in the metabolism and toxicity of this lead prodrug in a panel of seven human non-small-cell lung cancer cell lines. We relate our findings on TPZ sensitivity in these lung lines with our previously published results on TPZ sensitivity in six human breast cancer cell lines (Patterson et al (1995) Br J Cancer 72: 1144–1150) and with the sensitivity of all these cell types to eight unrelated cancer chemotherapeutic agents with diverse modes of action. Our results demonstrate that P450R plays a significant role in the activation of TPZ in this panel of lung lines, which is consistent with previous observations in a panel of breast cancer cell lines (Patterson et al (1995) Br J Cancer 72: 1144–1150; Patterson et al (1997) Br J Cancer 76: 1338–1347). However, in the lung lines it is likely that it is the inherent ability of these cells to respond to multiple forms of DNA damage, including that arising from P450R-dependent TPZ metabolism, that underlies the ultimate expression of toxicity. © 1999 Cancer Research Campaig

Tumor Cell Marker PVRL4 (Nectin 4) Is an Epithelial Cell Receptor for Measles Virus

Vaccine and laboratory adapted strains of measles virus can use CD46 as a receptor to infect many human cell lines. However, wild type isolates of measles virus cannot use CD46, and they infect activated lymphocytes, dendritic cells, and macrophages via the receptor CD150/SLAM. Wild type virus can also infect epithelial cells of the respiratory tract through an unidentified receptor. We demonstrate that wild type measles virus infects primary airway epithelial cells grown in fetal calf serum and many adenocarcinoma cell lines of the lung, breast, and colon. Transfection of non-infectable adenocarcinoma cell lines with an expression vector encoding CD150/SLAM rendered them susceptible to measles virus, indicating that they were virus replication competent, but lacked a receptor for virus attachment and entry. Microarray analysis of susceptible versus non-susceptible cell lines was performed, and comparison of membrane protein gene transcripts produced a list of 11 candidate receptors. Of these, only the human tumor cell marker PVRL4 (Nectin 4) rendered cells amenable to measles virus infections. Flow cytometry confirmed that PVRL4 is highly expressed on the surfaces of susceptible lung, breast, and colon adenocarcinoma cell lines. Measles virus preferentially infected adenocarcinoma cell lines from the apical surface, although basolateral infection was observed with reduced kinetics. Confocal immune fluorescence microscopy and surface biotinylation experiments revealed that PVRL4 was expressed on both the apical and basolateral surfaces of these cell lines. Antibodies and siRNA directed against PVRL4 were able to block measles virus infections in MCF7 and NCI-H358 cancer cells. A virus binding assay indicated that PVRL4 was a bona fide receptor that supported virus attachment to the host cell. Several strains of measles virus were also shown to use PVRL4 as a receptor. Measles virus infection reduced PVRL4 surface expression in MCF7 cells, a property that is characteristic of receptor-associated viral infections