Acute kidney injury and adverse outcomes of critical illness: correlation or causation?

Critically ill patients who develop acute kidney injury (AKI) are more than twice as likely to die in hospital. However, it is not clear to what extent AKI is the cause of excess mortality, or merely a correlate of illness severity. The Bradford Hill criteria for causality (plausibility, temporality, magnitude, specificity, analogy, experiment & coherence, biological gradient and consistency) were applied to assess the extent to which AKI may be causative in adverse short-term outcomes of critical illness. Plausible mechanisms exist to explain increased risk of death after AKI, both from direct pathophysiological effects of renal dysfunction and mechanisms of organ cross-talk in multiple-organ failure. The temporal relationship between increased mortality following AKI is consistent with its pathophysiology. AKI is associated with substantially increased mortality, an association that persists after accounting for known confounders. A biological gradient exists between increasing severity of AKI and increasing short-term mortality. This graded association shares similar features to the increased mortality observed in ARDS; an analogous condition with a multifactorial aetiology. Evidence for the outcomes of AKI from retrospective cohort studies and experimental animal models is coherent however both of these forms of evidence have intrinsic biases and shortcomings. The relationship between AKI and risk of death is maintained across a range of patient ages, comorbidities and underlying diagnoses. In conclusion many features of the relationship between AKI and short-term mortality suggest causality. Prevention and mitigation of AKI and its complications are valid targets for studies seeking to improve short-term survival in critical care

Family-based Genome-wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus

Purpose To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = −0.57, 95% confidence interval [CI]: −0.78 to −0.36; P = 1.7 × 10−7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = −3.94, 95% CI: −5.23 to −2.66; P = 1.7 × 10−9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits

The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration

A quantitative risk assessment of waterborne infectious disease in the inundation area of a tropical monsoon region

Flooding and inundation are annual events that occur during the rainy season in Cambodia, and inundation has a strong relationship with human health. This study simulated the coliform bacteria distribution using a hydraulic model and estimated the impact of inundation on public health using a dose–response model. The model parameters were calibrated using field survey data from Cambodia and obtained good agreement with the coliform group count distribution. The results suggest that the impact of inundation on human health is most noticeable in residential areas. The annual average risk of infection during medium-sized flood events is 0.21. The risk due to groundwater use ranges from 0.12 to 0.17 in inundation areas and reaches as high as 0.23 outside the inundation areas. The risk attributed to groundwater use is therefore higher than that for surface water use (0.02–0.06), except in densely populated areas at the city center. There is a high risk for infection with waterborne disease in residential areas, and the annual average risk during small flood events is 0.94. An assessment of possible countermeasures to reduce the risk shows that the control of inundation may bring more risk to public health in Cambodia. Shallower inundation water (<0.3 m) leads to a higher risk of infection, but if the depth is greater than 2 m, the risk is low in residential areas.The simulated results explain the spatial distributions of infection risk, which are vitally important for determining the highest priority places with relatively high risk and will be helpful for decision makers when considering the implementation of countermeasures

Tailored education for older patients to facilitate engagement in falls prevention strategies after hospital discharge—A pilot randomized controlled trial

Background The aims of the study were to evaluate the effect of providing tailored falls prevention education in hospital on: i) engagement in targeted falls prevention behaviors in the month after discharge: ii) patients’ self-perceived risk and knowledge about falls and falls prevention strategies after receiving the education. Methods A pilot randomized controlled trial (n = 50): baseline and outcome assessments conducted by blinded researchers. Participants: hospital inpatients 60 years or older, discharged to the community. Participants were randomized into two groups. The intervention was a tailored education package consisting of multimedia falls prevention information with trained health professional follow-up, delivered in addition to usual care. Outcome measures were engagement in falls prevention behaviors in the month after discharge measured at one month after discharge with a structured survey, and participants’ knowledge, confidence and motivation levels before and after receiving the education. The feasibility of providing the intervention was examined and falls outcomes (falls, fall-related injuries) were also collected. Results Forty-eight patients (98%) provided follow-up data. The complete package was provided to 21 (84%) intervention group participants. Participants in the intervention group were significantly more likely to plan how to safely restart functional activities [Adjusted odds ratio 3.80, 95% CI (1.07, 13.52), p = 0.04] and more likely to complete other targeted behaviors such as completing their own home exercise program [Adjusted odds ratio 2.76, 95% CI (0.72, 10.50), p = 0.14] than the control group. The intervention group was significantly more knowledgeable, confident and motivated to engage in falls prevention strategies after receiving the education than the control group. There were 23 falls (n = 5 intervention; n = 18 control) and falls rates were 5.4/1000 patient days (intervention); 18.7/1000 patient days (control). Conclusion This tailored education was received positively by older people, resulted in increased engagement in falls prevention strategies after discharge and is feasible to deliver to older hospital patients. Trial registration The study was registered with the Australian New Zealand Clinical Trials Registry; ACTRN12611000963921 on 8th November 2011

Dysregulated expression of MIG/CXCL9, IP-10/CXCL10 and CXCL16 and their receptors in systemic sclerosis

Abstract Introduction Systemic sclerosis (SSc) is characterized by fibrosis and microvascular abnormalities including dysregulated angiogenesis. Chemokines, in addition to their chemoattractant properties, have the ability to modulate angiogenesis. Chemokines lacking the enzyme-linked receptor (ELR) motif, such as monokine induced by interferon-γ (IFN-γ) (MIG/CXCL9) and IFN-inducible protein 10 (IP-10/CXCL10), inhibit angiogenesis by binding CXCR3. In addition, CXCL16 promotes angiogenesis by binding its unique receptor CXCR6. In this study, we determined the expression of these chemokines and receptors in SSc skin and serum. Methods Immunohistology and enzyme-linked immunosorbent assays (ELISAs) were used to determine chemokine and chemokine receptor expression in the skin and serum, respectively, of SSc and normal patients. Endothelial cells (ECs) were isolated from SSc skin biopsies and chemokine and chemokine receptor expression was determined by quantitative PCR and immunofluorescence staining. Results Antiangiogenic IP-10/CXCL10 and MIG/CXCL9 were elevated in SSc serum and highly expressed in SSc skin. However, CXCR3, the receptor for these chemokines, was decreased on ECs in SSc vs. normal skin. CXCL16 was elevated in SSc serum and increased in SSc patients with early disease, pulmonary arterial hypertension, and those that died during the 36 months of the study. In addition, its receptor CXCR6 was overexpressed on ECs in SSc skin. At the mRNA and protein levels, CXCR3 was decreased while CXCR6 was increased on SSc ECs vs. human microvascular endothelial cells (HMVECs). Conclusions These results show that while the expression of MIG/CXCL9 and IP-10/CXCL10 are elevated in SSc serum, the expression of CXCR3 is downregulated on SSc dermal ECs. In contrast, CXCL16 and CXCR6 are elevated in SSc serum and on SSc dermal ECs, respectively. In all, these findings suggest angiogenic chemokine receptor expression is likely regulated in an effort to promote angiogenesis in SSc skin.http://deepblue.lib.umich.edu/bitstream/2027.42/112894/1/13075_2010_Article_3001.pd

Evaluating Health Workers' Potential Resistance to New Interventions: A Role for Discrete Choice Experiments

BACKGROUND: The currently recommended approach for preventing malaria in pregnancy (MiP), intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT), has been questioned due to the spread of resistance to SP. Whilst trials are underway to test the efficacy of future alternative approaches, it is important to start exploring the feasibility of their implementation. METHODS AND FINDINGS: This study uses a discrete choice experiment (DCE) method to assess the potential resistance of health workers to changing strategies for control of MiP. In Ashanti region in Ghana, 133 antenatal clinic health workers were presented with 16 choice sets of two alternative policy options, each consisting of a bundle of six attributes representing certain clinical guidelines for controlling MiP (type of approach and drug used), possible associated maternal and neo-natal outcomes, workload and financial incentives. The data were analysed using a random effects logit model. Overall, staff showed a preference for a curative approach with pregnant women tested for malaria parasites and treated only if positive, compared to a preventive approach (OR 1.6; p = 0.001). Increasing the incidence of low birth weight or severe anaemia by 1% would reduce the odds of preferring an approach by 18% and 10% respectively. Midwives were more resistant to potential changes to current guidelines than lower-level cadres. CONCLUSIONS: In Ashanti Region, resistance to change by antenatal clinic workers from a policy of SP-IPT to IST would generally be low, and it would disappear amongst midwives if health outcomes for the mother and baby were improved by the new strategy. DCEs are a promising approach to identifying factors that will increase the likelihood of effective implementation of new interventions immediately after their efficacy has been proven

Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study

Mikolajczyk RT, Stanford JB, Ecochard R. Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study. Reproductive Biology and Endocrinology. 2008;6(1): 61.Background: To assess the amount of variability in ovarian follicular growth rate and maximum follicular diameter related to different centers, women and cycles of the same women in a multicenter observational study of follicular growth. Methods: Secondary analysis of a prospective cohort study from eight centers in Europe. There were 533 ultrasound examinations in 282 cycles of 107 women with normal fertility. A random effects model with center, woman and cycle as hierarchical units of variation was used to analyze mean follicular diameter on days preceding ovulation. Results: Follicular growth did not differ by center. There was homogenous growth across women and cycles, and the maximum follicular diameter before ovulation varied substantially across cycles but not across women. Many (about 40%) women had small maximum follicular diameter on the day before ovulation (<19 mm). Pre-ovulatory cycle length was not related to maximum follicular diameter. Conclusion: In normal fecundity, there is a substantial variation in maximum follicular diameter from cycle to cycle based on variation in the duration of follicular development, but the variation could not be explained by different characteristics of different women. Explanation of variation in follicular growth has to be found on the cycle level

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives