Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

Increased Rate of CD4+ T-Cell Decline and Faster Time to Antiretroviral Therapy in HIV-1 Subtype CRF01_AE Infected Seroconverters in Singapore

It remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART).We recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models. viral load.Infecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis

A through-life costing methodology for use in product-service-systems

Availability-based contracts which provide customers with the use of assets such as machines, ships, aircraft platforms or subsystems like engines and avionics are increasingly offered as an alternative to the purchase of an asset and separate support contracts. The cost of servicing a durable product can be addressed by Through-life Costing (TLC). Providers of advanced services are now concerned with the cost of delivering outcomes that meet customer requirements using combinations of assets and activities via a Product Service System (PSS). This paper addresses the question: To what extent are the current approaches to TLC methodologically appropriate for costing the provision of advanced services, particularly availability, through a PSS? A novel methodology for TLC is outlined addressing the challenges of PSS cost assessment with regard to 'what?' (cost object), 'why/to what extent?' (scope and boundaries), and 'how?' (computations). The research provides clarity for those seeking to cost availability in a performance-orientated contractual setting and provides insight to the measures that may be associated with it. In particular, a reductionist approach that focuses on one cost object at a time is not appropriate for a PSS. Costing an advanced service delivered through a PSS is a problem of attributing the value of means to the economic activities carried out for specific ends to be achieved. Cost results from the interplay between monetary and non-monetary metrics, and uncertainties thereof. Whilst seeking to ensure generality of the findings, the application of TLC examined here is limited to a military aircraft platform and subsystems. © 2014 Elsevier B.V. All rights reserved

Clinicians' evaluations of, endorsements of, and intentions to use practice guidelines change over time: a retrospective analysis from an organized guideline program

<p>Abstract</p> <p>Purpose</p> <p>Clinical practice guidelines (CPGs) can improve clinical care but uptake and application are inconsistent. Objectives were: to examine temporal trends in clinicians' evaluations of, endorsements of, and intentions to use cancer CPGs developed by an established CPG program; and to evaluate how predictor variables (clinician characteristics, beliefs, and attitudes) are associated with these trends.</p> <p>Design and methods</p> <p>Between 1999 and 2005, 756 clinicians evaluated 84 Cancer Care Ontario CPGs, yielding 4,091 surveys that targeted four CPG quality domains (rigour, applicability, acceptability, and comparative value), clinicians' endorsement levels, and clinicians' intentions to use CPGs in practice.</p> <p>Results</p> <p>Time: In contrast to the applicability and intention to use in practice scores, there were small but statistically significant annual net gains in ratings for rigour, acceptability, comparative value, and CPG endorsement measures (p < 0.05 for all rating categories). Predictors: In 17 comparisons, ratings were significantly higher among clinicians having the most favourable beliefs and most positive attitudes and lowest for those having the least favourable beliefs and most negative attitudes (p < 0.05). Interactions Time × Predictors: Over time, differences in outcomes among clinicians decreased due to positive net gains in scores by clinicians whose beliefs and attitudes were least favorable.</p> <p>Conclusion</p> <p>Individual differences among clinicians largely explain variances in outcomes measured. Continued engagement of clinicians least receptive to CPGs may be worthwhile because they are the ones showing most significant gains in CPG quality ratings, endorsement ratings, and intentions to use in practice ratings.</p

The effects of juvenile stress on anxiety, cognitive bias and decision making in adulthood:a rat model

Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze), to investigate the effects of juvenile stress (JS) on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus (e.g. rough) was associated with a lower value reward than the other (e.g. smooth). Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model

Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers

Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, while its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs