Thin films of Ruthenium Phthalocyanine complexes

Four new ruthenium phthalocyanine complexes bearing axial ligands with thioacetate groups that facilitate thin film formation on gold surfaces are presented. Scanning tunnelling microscopy (STM) images and surface coverage data obtained by solution inductively coupled plasma mass spectrometry (ICP-MS) experiments show that peripheral and axial ligand substituents on the complexes have a significant effect on their surface coverage. A laser ablation ICP-MS technique that provides information about thin films across macro-sized areas is described here for the first time. Using the technique, the maximum surface coverage of a ruthenium phthalocyanine complex was found to occur within one minute of gold substrate immersion in the complexcontaining solution

When does perceptual organization happen?

Reflectional (mirror) symmetry is an important visual cue for perceptual organization. The brain processes symmetry rapidly and efficiently. Previous work suggests that symmetry activates the extrastriate cortex and generates an event related potential (ERP) called the Sustained Posterior Negativity (SPN). It has been claimed that no tasks completely block symmetry processing and abolish the SPN. We tested the limits of this claim with a series of eight new Electroencephalography (EEG) experiments (344 participants in total). All experiments used the same symmetrical or asymmetrical dot patterns. When participants attended to regularity in Experiment 1, there was a substantial SPN (Mean amplitude = -2.423 μV). The SPN was reduced, but not abolished, when participants discriminated dot luminance in Experiments 2 and 3 (-.835 and -1.410 μV) or the aspect ratio of a superimposed cross in Experiments 4 and 5 (-.722 and -.601 μV). The SPN also survived when the background pattern was potentially disruptive to the primary task in Experiment 6 (-1.358 μV) and when participants classified negative superimposed words in Experiment 7 (-.510 μV). Finally, the SPN remained when participants attended to the orientation of a diagonal line in Experiment 8 (-.589 μV). While task manipulations can turn down the extrastriate symmetry activation, they cannot render the system completely unresponsive. Permanent readiness to detect reflectional symmetry at the centre of the visual field could be an evolved adaptation

Improving quality indicator report cards through Bayesian modeling

<p>Abstract</p> <p>Background</p> <p>The National Database for Nursing Quality Indicators^®(NDNQI^®) was established in 1998 to assist hospitals in monitoring indicators of nursing quality (eg, falls and pressure ulcers). Hospitals participating in NDNQI transmit data from nursing units to an NDNQI data repository. Data are summarized and published in reports that allow participating facilities to compare the results for their units with those from other units across the nation. A disadvantage of this reporting scheme is that the sampling variability is not explicit. For example, suppose a small nursing unit that has 2 out of 10 (rate of 20%) patients with pressure ulcers. Should the nursing unit immediately undertake a quality improvement plan because of the rate difference from the national average (7%)?</p> <p>Methods</p> <p>In this paper, we propose approximating 95% credible intervals (CrIs) for unit-level data using statistical models that account for the variability in unit rates for report cards.</p> <p>Results</p> <p>Bayesian CrIs communicate the level of uncertainty of estimates more clearly to decision makers than other significance tests.</p> <p>Conclusion</p> <p>A benefit of this approach is that nursing units would be better able to distinguish problematic or beneficial trends from fluctuations likely due to chance.</p

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process

The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity

The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5(+) malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5(+)-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Patients in cohort 4 received increased intensity pre-conditioning (cyclophosphamide and fludarabine), systemic IL2 support and CAR T cells. No objective clinical responses were observed. CAR T cell engraftment in patients within cohort 4 was significantly higher. However, engraftment was short-lived with a rapid decline of systemic CAR T cells within 14 days. Patients in cohort 4 had transient, acute respiratory toxicity which, in combination with lack of prolonged CAR T cell persistence, resulted in the premature closure of the trial. Elevated levels of systemic IFNγ and IL-6 implied that the CEACAM5-specific T cells had undergone immune activation in vivo but only in patients receiving high-intensity pre-conditioning. Expression of CEACAM5 on lung epithelium may have resulted in this transient toxicity. Raised levels of serum cytokines including IL-6 in these patients implicate cytokine release as one of several potential factors exacerbating the observed respiratory toxicity. Whilst improved CAR designs and T cell production methods could improve the systemic persistence and activity, methods to control CAR T 'on-target, off-tissue' toxicity are required to enable a clinical impact of this approach in solid malignancies

Overexpression of antibiotic resistance genes in hospital effluents over time

$\textbf{Objectives}$: Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. $\textbf{Methods}$: Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. $\textbf{Results}$: We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital (ρ=0.9, two-tailed $\textit{P}$<0.0001) and farm (ρ=0.5, two-tailed $\textit{P}$<0.0001) effluents and that two β-lactam resistance genes ($\textit{bla}$GES and $\textit{bla}$OXA) were overexpressed in all hospital effluent samples. High β-lactam resistance gene transcript abundance was related to hospital antibiotic usage over time and hospital effluents contained antibiotic residues. $\textbf{Conclusions}$: We conclude that effluents contribute high levels of antibiotic resistance genes to the aquatic environment; these genes are expressed at significant levels and are possibly related to the level of antibiotic usage at the effluent source.This research was funded by the Biotechnology and Biological Sciences Research Council, GlaxoSmithKline and the Centre for Environment, Fisheries and Aquaculture Science

How does healthcare worker hand hygiene behaviour impact upon the transmission of MRSA between patients?: an analysis using a Monte Carlo model

BACKGROUND: Good hand hygiene has for many years been considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, there is evidence that the law of diminishing returns applies to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance. While this raises intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI, analysis of this subject has been hampered by a lack of quantifiable data relating to the risk of transmission between patients on wards. METHODS: In order to gain a greater understanding of the transmission of infection between patients via the hands of healthcare workers (HCWs), we constructed a stochastic Monte Carlo model to simulate the spread of methicillin-resistant Staphylococcus aureus (MRSA) between patients. We used the model to calculate the risk of transmission occurring, firstly between two patients in adjacent beds, and then between patients in a four-bedded bay. The aim of the study was to quantify the probability of transmission under a variety of conditions and thus to gain an understanding of the contribution made by the various factors which influence transmission. RESULTS: The study revealed that on a four-bedded bay, the average probability of transmitting an infection by the handborne route is generally low (i.e. in the region 0.002 - 0.013 depending on the hand hygiene behaviour of HCWs and other factors). However, because transmission is strongly influenced by stochastic events, it is the frequency with which 'high-risk events' occur, rather than average probability, that governs whether or not transmission will take place. The study revealed that increased hand hygiene compliance has a dramatic impact on the frequency with which 'high-risk events' occur. As compliance increases, so the rate at which 'high-risk events' occur, rapidly decreases, until a point is reached, beyond which, further hand hygiene is unlikely to yield any greater benefit. CONCLUSION: The findings of the study confirm those of other researchers and suggest that the greatest benefits derived from hand hygiene occur as a result of the first tranche of compliance, with higher levels (>50%) of hand hygiene events yielding only marginal benefits. This suggests that in most situations relatively little benefit is accrued from seeking to achieve very high levels of hand hygiene compliance

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases