The Chelsea Critical Care Physical Assessment Tool (CPAx): validation of an innovative new tool to measure physical morbidity in the general adult critical care population; an observational proof-of-concept pilot study.

Objective To develop a scoring system to measure physical morbidity in critical care – the Chelsea Critical Care Physical Assessment Tool (CPAx). Method The development process was iterative involving content validity indices (CVI), a focus group and an observational study of 33 patients to test construct validity against the Medical Research Council score for muscle strength, peak cough flow, Australian Therapy Outcome Measures score, Glasgow Coma Scale score, Bloomsbury sedation score, Sequential Organ Failure Assessment score, Short Form 36 (SF-36) score, days of mechanical ventilation and inter-rater reliability. Participants Trauma and general critical care patients from two London teaching hospitals. Results Users of the CPAx felt that it possessed content validity, giving a final CVI of 1.00 (P < 0.05). Construct validation data showed moderate to strong significant correlations between the CPAx score and all secondary measures, apart from the mental component of the SF-36 which demonstrated weak correlation with the CPAx score (r = 0.024, P = 0.720). Reliability testing showed internal consistency of α = 0.798 and inter-rater reliability of κ = 0.988 (95% confidence interval 0.791 to 1.000) between five raters. Conclusion This pilot work supports proof of concept of the CPAx as a measure of physical morbidity in the critical care population, and is a cogent argument for further investigation of the scoring system

Case study in six sigma methadology : manufacturing quality improvement and guidence for managers

This article discusses the successful implementation of Six Sigma methodology in a high precision and critical process in the manufacture of automotive products. The Six Sigma define–measure–analyse–improve–control approach resulted in a reduction of tolerance-related problems and improved the first pass yield from 85% to 99.4%. Data were collected on all possible causes and regression analysis, hypothesis testing, Taguchi methods, classification and regression tree, etc. were used to analyse the data and draw conclusions. Implementation of Six Sigma methodology had a significant financial impact on the profitability of the company. An approximate saving of US$70,000 per annum was reported, which is in addition to the customer-facing benefits of improved quality on returns and sales. The project also had the benefit of allowing the company to learn useful messages that will guide future Six Sigma activities

Rising Population Cost for Treating People Living with HIV in the UK, 1997-2013

Background The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997–2006 and projected them 2007–2013. Methods Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997–2006 and projected 2007–2013. Results Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013. Conclusions Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources

Overlap in signaling between Smoothened and the α subunit of the heterotrimeric G protein G₁₃

The Hedgehog family of morphogens has long been known to utilize, through the 7-transmembrane protein Smoothened (Smo), the heterotrimeric G protein Gi in both canonical and noncanonical forms of signaling. Other G proteins, while not specifically utilized by Smo, may nonetheless provide access to some of the events controlled by it. We reported several years ago that the G protein G₁₃ activates one or more forms of the Gli family of transcription factors. While the Gli transcription factors are well known targets for Smo, the uncertain mechanism of activation by G₁₃ and the identity of the targeted Gli(s) limited predictions as to the extent to which G₁₃ might mimic Smo’s actions. We evaluate here the potential for overlap in G₁₃ and Smo signaling using C3H10T1/2 and 3T3-L1 cells as models of osteogenesis and adipogenesis, respectively. We find in C3H10T1/2 cells that a constitutively active form of Gα₁₃ (Gα₁₃QL) increases Gli1 mRNA, as does a constitutively active form of Smo (SmoA1). We find as well that Gα₁₃QL induces alkaline phosphatase activity, a marker of osteogenesis, albeit the induction is far less substantial than that achieved by SmoA1. In 3T3-L1 cells both Gα₁₃QL and SmoA1 markedly suppress adipogenic differentiation as determined by triglyceride accumulation. RNA sequencing reveals that Gα₁₃QL and SmoA1 regulate many of the same genes but that quantitative and qualitative differences exist. Differences also exist, we find, between SmoA1 and purmorphamine, an agonist for Smo. Therefore, while comparisons of constitutively active proteins are informative, extrapolations to the setting of agonists require care

Sociodemographic Trends in National Ambulatory Care Visits for Hepatitis C Virus Infection

Poor and non-white patients are disproportionately infected with the hepatitis C virus (HCV). The objective of this research is to determine sociodemographic patterns of HCV-related ambulatory care visits over time. Data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey-Outpatient (NHAMCS-OPD) for the years 1997–2005 were analyzed in 3-year intervals. Demographic and other variables were compared for each period, and multivariable logistic regression was performed to examine whether the likelihood of a visit being HCV-related (versus non-HCV) was independently associated with (1) race and/or (2) Medicaid status over time. The total number of HCV-related ambulatory visits more than doubled from 3,583,585 during the years 1997–1999 to 8,027,166 during 2003–2005. During this time, the proportion of non-whites and Medicaid recipients presenting for HCV-related visits approximately doubled (non-whites: 16% vs. 33%, P = 0.04; Medicaid recipients: 10% vs. 25%, P = 0.07). In 2003–2005, HCV-related visits were more than twice as likely to occur among non-white patients vs. white patients (OR = 2.49; 95% CI: 1.60–3.86) and patients on Medicaid vs. non-Medicaid (3.49; 1.79–6.80). Our results show that HCV-associated ambulatory care visits are increasing, with a greater proportion of visits occurring among non-white patients and Medicaid recipients

The local economic development processes in low-income countries: the case of the metropolis of Chegutu in Zimbabwe

Local authorities are widely regarded as catalysts accelerating localised processes of economic development in industrialised countries but in low-income countries they are perceived as dysfunctional, inefficient and ineffective in meeting and addressing societal demands. This abstract view is however, not grounded in empirical research. As such, utilising the case of the metropolis of Chegutu a survey was designed to empirically explicate the economic processes militating its economic development. The findings are useful to policy-makers, local government authorities and management scholars. The study's unique contribution lies in its examination of the processes of local economic development in a low-income country

MAESTRI Toolkit for Industrial Symbiosis: overview, lessons learnt and implications

This paper presents a structured approach to support the development of self-organized industrial symbiosis, the Toolkit for Industrial Symbiosis. Developed within MAESTRI project, it provides a set of tools and methods to help companies gain value from wasted resources and contributes to MAESTRI goal of advancing the sustainability of European manufacturing and process industry. A participatory approach was taken for its development. The ultimate objective of this work is to encourage companies to change their attitude and consider waste as a resource and potential source for value creation

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

Till death (or an intruder) do us part: intrasexual-competition in a monogamous Primate

Polygynous animals are often highly dimorphic, and show large sex-differences in the degree of intra-sexual competition and aggression, which is associated with biased operational sex ratios (OSR). For socially monogamous, sexually monomorphic species, this relationship is less clear. Among mammals, pair-living has sometimes been assumed to imply equal OSR and low frequency, low intensity intra-sexual competition; even when high rates of intra-sexual competition and selection, in both sexes, have been theoretically predicted and described for various taxa. Owl monkeys are one of a few socially monogamous primates. Using long-term demographic and morphological data from 18 groups, we show that male and female owl monkeys experience intense intra-sexual competition and aggression from solitary floaters. Pair-mates are regularly replaced by intruding floaters (27 female and 23 male replacements in 149 group-years), with negative effects on the reproductive success of both partners. Individuals with only one partner during their life produced 25% more offspring per decade of tenure than those with two or more partners. The termination of the pair-bond is initiated by the floater, and sometimes has fatal consequences for the expelled adult. The existence of floaters and the sporadic, but intense aggression between them and residents suggest that it can be misleading to assume an equal OSR in socially monogamous species based solely on group composition. Instead, we suggest that sexual selection models must assume not equal, but flexible, context-specific, OSR in monogamous species.Wenner-Gren Foundation, L.S.B. Leakey Foundation, the National Geographic Society, National Science Foundation (BCS- 0621020), the University of Pennsylvania Research Foundation and the Zoological Society of San Diego, German Science Foundation (HU 1746-2/1