Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi – a systematic review and economic evaluation

Background: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. Objectives: To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE® (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest™ (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-offlight mass spectrometry). Data sources: Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. Review methods: A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. Results: For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. Limitations: Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. Conclusions: The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required.

A Rare Loss-of-Function Variant in Scavenger Receptor Class B Type I (SCARB1) Raises HDL Cholesterol and Increases Risk of Coronary Disease

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL)
cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a
lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI
knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased
atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains
unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328
individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function
variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene
encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and
abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells
derived from induced pluripotent stem cells from the homozygous subject, and in mice.
Large population-based studies revealed that subjects who are heterozygous carriers of
the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have
a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is
statistically significant).

New Organizational Leadership: Nonstate Actors in Global Economic Governance

States and international organizations have found irresistible cause in a globalizing world to coopt nonstate actors (NGOs, private standard setters and so forth) to manage the manifold problems arising under their stretched mandates and resources. The pooling of capacities in the pursuit of common goals seems perfectly sensible. Yet although the strategy of cooptation has become a policy of choice, policy makers often lack full knowledge of its implications. As Philip Selznick first showed, cooptation can have unintended consequences, shifting leadership from one organization to another. We place this fertile insight in a better specified analytical framework. That is, one capable of explaining when and how leadership shifts occur and where the status quo leaders will remain at the helm. Using original interview data and structured focused comparisons to test the framework, we reveal dramatic variation in leadership changes following the cooptation of outside actors in global financial and environmental governance.

British economic growth 1270-1870

This is a definitive new account of Britain's economic evolution from a backwater of Europe in 1270 to the hub of the global economy in 1870. For the first time Britain's national accounts are reconstructed right back into the thirteenth century to show what really happened quantitatively during the centuries leading up to the Industrial Revolution. Contrary to traditional views of the earlier period as one of Malthusian stagnation, they reveal how the transition to modern economic growth built on the earlier foundations of a persistent upward trend in GDP per capita which doubled between 1270 and 1700. Featuring comprehensive estimates of population, land use, agricultural production, industrial and service-sector production and GDP per capita, as well as analysis of their implications, this is an essential reference work for those interest in British economic history and the origins of modern economic growth more generally.

National incomes and economic growth in pre-industrial Europe: insights from recent research

Pessimistic Malthusian verdicts on the capacity of pre-industrial European economies to sustain a degree of real economic growth under conditions of population growth are challenged using current reconstructions of urbanisation ratios, the real wage rates of building and agricultural labourers, and GDP per capita estimated by a range of methods. Economic growth is shown to have outpaced population growth and raised GDP per capita to in excess of $1,500 (1990 $ international at PPP) in Italy during its twelfth- and thirteenth-century commercial revolution, Holland during its fifteenth- and sixteenth-century golden age, and England during the seventeenth- and eighteenth-century runup to its industrial revolution. During each of these Smithian growth episodes expanding trade and commerce sustained significant output and employment growth in the manufacturing and service sectors. These positive developments were not necessarily reflected by trends in real wage rates for the latter were powerfully influenced by associated changes in relative factor prices and the per capita supply of labour as workers varied the length of the working year in order to consume either more leisure or more goods. The scale of the divergence between trends in real wage rates and GDP per capita nevertheless varied a great deal between countries for reasons which have yet to be adequately explained.

Testing the psychometric properties of Kidscreen-27 with Irish children of low socio-economic status

Background

Kidscreen-27 was developed as part of a cross-cultural European Union-funded project to standardise the measurement of children’s health-related quality of life. Yet, research has reported mixed evidence for the hypothesised 5-factor model, and no confirmatory factor analysis (CFA) has been conducted on the instrument with children of low socio-economic status (SES) across Ireland (Northern and Republic).

Method

The data for this study were collected as part of a clustered randomised controlled trial. A total of 663 (347 male, 315 female) 8–9-year-old children (M = 8.74, SD = .50) of low SES took part. A 5- and modified 7-factor CFA models were specified using the maximum likelihood estimation. A nested Chi-square difference test was conducted to compare the fit of the models. Internal consistency and floor and ceiling effects were also examined.

Results

CFA found that the hypothesised 5-factor model was an unacceptable fit. However, the modified 7-factor model was supported. A nested Chi-square difference test confirmed that the fit of the 7-factor model was significantly better than that of the 5-factor model. Internal consistency was unacceptable for just one scale. Ceiling effects were present in all but one of the factors.

Conclusions

Future research should apply the 7-factor model with children of low socio-economic status. Such efforts would help monitor the health status of the population.

Biodiversity offsetting and restoration under the European Union Habitats Directive: balancing between no net loss and deathbed conservation?

Biodiversity offsets have emerged as one of the most prominent policy approaches to align economic development with nature protection across many jurisdictions, including the European Union. Given the increased level of scrutiny that needs to be applied when authorizing economic developments near protected Natura 2000 sites, the incorporation of onsite biodiversity offsets in project design has grown increasingly popular in some member states, such as the Netherlands and Belgium. Under this approach, the negative effects of developments are outbalanced by restoration programs that are functionally linked to the infrastructure projects. However, although taking into consideration that the positive effects of onsite restoration measures leads to more leeway for harmful project development, the EU Court of Justice has recently dismissed the latter approaches for going against the preventative underpinnings of the EU Habitats Directive. Also, the expected beneficial outcomes of the restoration efforts are uncertain and thus cannot be relied upon in an ecological assessment under Article 6(3) of the Habitats Directive. Although biodiversity offsets can still be relied upon whenever application is being made of the derogation clause under Article 6(4) of the Habitats Directive, they cannot be used as mitigation under the generic decision-making process for plans and programs liable to adversely affect Natura 2000 sites. We outline the main arguments pro and contra the stance of the EU Court of Justice with regards to the exact delineation between mitigation and compensation. The analysis is also framed in the ongoing debate on the effectiveness of the EU nature directives. Although ostensibly rigid, it is argued that the recent case-law developments are in line with the main principles underpinning biodiversity offsetting. Opening the door for biodiversity offsetting under the Habitats Directive will certainly not reverse the predicament of the EU’s biodiversity. A reinforcement of the preventative approach is instrumental to avert a further biodiversity loss within the European Union, even if it will lead to additional permit refusals for unsustainable project developments.

Socio-economic aspects of the fisheries of Nabugabo lakes and implications for management

Fisheries are very important to Uganda's economy. The sector provides a vital source of food, recreation, trade and socioeconomic well being for the people and community globally. The fisheries of small lakes are important for producing fish for local populations who are not near the large lakes. These satellite lakes support important fisheries and other economic activities like fishing, water for domestic purposes and tourism, besides socio-cultural values. A number-of fish;- species, some of which were found only in Lake Victoria have been depleted through over-exploitation, introduction of exotics especiaily Nile perch and environmental degradation. Some of these fishes have been observed to survive in satellite lakes in the Victoria and Kyoga Lake basins. The Nabugabo satellite lakes (Manywa, Kayugi and Kayanja) contain endemic Cichlid fish species acting as reservoirs and therefore very important for conservation of fish biodiversity. Despite the socio-economic importance and uniqueness of these satellite lakes little research on socio-economic studies has been carried out. The sustainability of the lake is being threatened by increasing human activities. The fish stocks and species diversity are declining and this poses a threat to the livelihood of the people who depend on fish for food and income. Arising from this need a study was carried out to establish the socio-economic aspects of Nabugabo fisheries and implications for management, on which basis resource users would be made aware of the impacts of their activities. It was hoped that this would go further to ensure wise use and management of the resources by the users. The specific objectives were identifying activities around the lake, establishing socioeconomic values attached to the lake, identifying problems of the lake and resource users and examining existing local based management institutions. Results show that the activities taking place around the lakes include fishing, farming, watering of animals, deforestation and charcoal burning, brick making, resort beach development and food and refreshment. The major problem facing the lake was found to be encroachment of Hippo grass (Vossia) on the lake, which is decreasing the size of the lake, and limiting open waters for fishing (this only applied to Lake Nabugabo). Other important problems include use of illegal fishing methods, declining fish stocks and loss of cultural identity. The resource users are most pressed by the low incomes resulting from poor fish catches, theft of gears and lack of market. On examining the resource base for the lakes, it was only Lake Nabugabo that had a Landing Management Committee. The other three lakes did not have leadership institutions in place except the local councils for the respective villages. This was probably due to observed limited fisheries activities. Majority of the respondents agreed that Government and other service providers should work jointly to supplement local beach management committees in the management of the lakes resources. This is a good gesture because with increase in fishing effort and rampant use of illegal fishing methods, there is need to strengthen management institutions present on the lake. This would require Government, local community and other service providers to work together in a participatory way to control environment-degrading activities and stop the use of illegal fishing methods. Burning of vegetation on the lake should be stopped since it enhances growth of this grass. Finally, traditional taboos; which are present on some of the Nabugabo lakes, should be enhanced, as away of preserving them.

Interest rate (in)sensitivity of emerging market corporate debt : economic analysis based on 2002-2015 empirical evidence

Interest rate sensitivity assessment framework based on fixed income yield indexes is developed and applied to two types of emerging market corporate debt: investment grade and high yield exposures. Our research advances beyond the correlation analyses focused on co- movements in yields and/or spreads of risky and risk-free assets. We show that correlation- based analyses of interest rate sensitivity could appear rather inconclusive and, hence, we investigate the bottom line profit and loss of a hypothetical model portfolio of corporates. We consider historical data covering the period 2002 – 2015, which enable us to assess interest rate sensitivity of assets during the development, the apogee, and the aftermath of the global financial crisis. Based on empirical evidence, both for investment and speculative grades securities, we find that the emerging market corporates exhibit two different regimes of sensitivity to interest rate changes. We observe switching from a positive sensitivity under the normal market conditions to a negative one during distressed phases of business cycles. This research sheds light on how financial institutions may approach interest rate risk management, evidencing that even plain vanilla portfolios of emerging market corporates, which on average could appear rather insensitive to the interest rate risk in fact present a binary behavior of their interest rate sensitivities. Our findings allow banks and financial institutions for optimizing economic capital under Basel III regulatory capital rules.

Estimated crop loss due to coconut mite and financial analysis of controlling the pest using the acaricide abamectin.

Reducing the losses caused by Aceria guerreronis Keifer has been an arduous task for farmers. However, there are no detailed studies on losses that simultaneously analyse correlated parameters, and very few studies that address the economic viability of chemical control, the main strategy for managing this pest. In this study the objectives were (1) to estimate the crop loss due to coconut mite and (2) to perform a financial analysis of acaricide application to control the pest. For this, the following parameters were evaluated: number and weight of fruits, liquid albumen volume, and market destination of plants with and without monthly abamectin spraying (three harvests). The costs involved in the chemical control of A. guerreronis were also quantified. Higher A. guerreronis incidence on plants resulted in a 60 % decrease in the mean number of fruits harvested per bunch and a 28 % decrease in liquid albumen volume. Mean fruit weight remained unaffected. The market destination of the harvested fruit was also affected by higher A. guerreronis incidence. Untreated plants, with higher A. guerreronis infestation intensity, produced a lower proportion of fruit intended for fresh market and higher proportions of non-marketable fruit and fruit intended for industrial processing. Despite the costs involved in controlling A. guerreronis, the difference between the profit from the treated site and the untreated site was 18,123.50 Brazilian Real; this value represents 69.1 % higher profit at the treated site. Keywords