Experimental Evidence of an Eco-evolutionary Feedback during Adaptive Divergence

Differences in how organisms modify their environment can evolve rapidly and might influence adaptive population divergence [1, 2]. In a common garden experiment in aquatic mesocosms, we found that adult stickleback from a recently diverged pair of lake and stream populations had contrasting effects on ecosystem metrics. These modifications were caused by both genetic and plastic differences between populations and were sometimes comparable in magnitude to those caused by the presence/ absence of stickleback. Lake and streamfish differentially affected the biomass of zooplankton and phytoplankton, the concentration of phosphorus, and the abundance of several prey (e.g., copepods) and non-prey (e.g., cyanobacteria) species. The adult mediated effects on mesocosm ecosystems influenced the survival and growth of a subsequent generation of juvenile stickleback reared in the same mesocosms. The prior presence of adults decreased the overall growth rate of juveniles, and the prior presence of stream adults lowered overall juvenile survival. Among the survivors, lake juveniles grew faster than co-occurring stream juveniles, except in mesocosm ecosystems previously modified by adult lake fish that were reared on plankton. Overall, our results provide evidence for reciprocal interactions between ecosystem dynamics and evolutionary change (i.e., eco-evolutionary feedbacks) in the early stages of adaptive population divergence.

Cutaneous Collagenous Vasculopathy: A Rare Form of Microangiopathy Successfully Treated with a Combination of Multiplex Laser and Optimized Pulsed Light with a Review of the Literature.

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy of the cutaneous vasculature characterized histologically by the presence of dilated small blood vessels with flat endothelial cells and thickened walls containing hyaline material in the upper dermis. We report an elderly patient presenting with an extensive form of CCV involving the trunk, upper and lower limbs. She was treated with Multiplex PDL 595-nm/Nd:YAG 1,064-nm laser and optimized pulsed light. This approach, which has never been reported for CCV so far, resulted in a striking and almost complete clearance of the widespread lesions. We here review our knowledge about CCV and therapeutic options available with a survey of the literature.

Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.

BACKGROUND Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. METHODS Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. RESULTS Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. CONCLUSIONS Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

Context Aware e-Learning Objects and their Types from the Perspective of the Object-Oriented Paradigm

The contribution of this article demonstrates how to identify context-aware types of e-Learning objects (eLOs) derived from the subject domains. This perspective is taken from an engineering point of view and is applied during requirements elicitation and analysis relating to present work in constructing an object-oriented (OO), dynamic, and adaptive model to build and deliver packaged e-Learning courses. Consequently, three preliminary subject domains are presented and, as a result, three primitive types of eLOs are posited. These types educed from the subject domains are of structural, conceptual, and granular nature. Structural objects are responsible for the course itself, conceptual objects incorporate adaptive and logical interoperability, while granular objects congregate granular assets. Their differences, interrelationships, and responsibilities are discussed. A major design challenge relates to adaptive behaviour. Future research addresses refinement on the subject domains and adaptive hypermedia systems.

Elucidating underlying processes of psychometric intelligence: A comparison of behavioral response latency and P3 latency in a modified Hick reaction time paradigm

The mental speed approach explains individual differences in intelligence by faster information processing in individuals with higher compared to lower intelligence - especially in elementary cognitive tasks (ECTs). One of the most examined ECTs is the Hick paradigm. The present study aimed to contrast reaction time (RT) and P3 latency in a Hick task as predictors of intelligence. Although both, RT and P3 latency, are commonly used as indicators of mental speed, it is also known that they measure different aspects of information processing. Participants were 113 female students. RT and P3 latency were measured while participants completed the Hick task with four levels of complexity. Intelligence was assessed with Cattell's Culture Fair Test. A RT factor and a P3 factor were extracted by employing a PCA across complexity levels. There was no significant correlation between the factors. Commonality analysis was used to determine the proportions of unique and shared variance in intelligence explained by the RT and P3 latency factors. RT and P3 latency explained 5.5% and 5% of unique variance in intelligence. However, the two speed factors did not explain a significant portion of shared variance. This result suggests that RT and P3 latency in the Hick paradigm are measuring different aspects of information processing that explain different parts of variance in intelligence.

Impact of Software Settings on Multiple-Breath Washout Outcomes

BACKGROUND AND OBJECTIVES Multiple-breath washout (MBW) is an attractive test to assess ventilation inhomogeneity, a marker of peripheral lung disease. Standardization of MBW is hampered as little data exists on possible measurement bias. We aimed to identify potential sources of measurement bias based on MBW software settings. METHODS We used unprocessed data from nitrogen (N2) MBW (Exhalyzer D, Eco Medics AG) applied in 30 children aged 5-18 years: 10 with CF, 10 formerly preterm, and 10 healthy controls. This setup calculates the tracer gas N2 mainly from measured O2 and CO2concentrations. The following software settings for MBW signal processing were changed by at least 5 units or >10% in both directions or completely switched off: (i) environmental conditions, (ii) apparatus dead space, (iii) O2 and CO2 signal correction, and (iv) signal alignment (delay time). Primary outcome was the change in lung clearance index (LCI) compared to LCI calculated with the settings as recommended. A change in LCI exceeding 10% was considered relevant. RESULTS Changes in both environmental and dead space settings resulted in uniform but modest LCI changes and exceeded >10% in only two measurements. Changes in signal alignment and O2 signal correction had the most relevant impact on LCI. Decrease of O2 delay time by 40 ms (7%) lead to a mean LCI increase of 12%, with >10% LCI change in 60% of the children. Increase of O2 delay time by 40 ms resulted in mean LCI decrease of 9% with LCI changing >10% in 43% of the children. CONCLUSIONS Accurate LCI results depend crucially on signal processing settings in MBW software. Especially correct signal delay times are possible sources of incorrect LCI measurements. Algorithms of signal processing and signal alignment should thus be optimized to avoid susceptibility of MBW measurements to this significant measurement bias.

No Routine Postoperative Head CT following Elective Craniotomy - A Paradigm Shift?

INTRODUCTION Patient management following elective cranial surgery often includes routine postoperative computed tomography (CT). We analyzed whether a regime of early extubation and close neurological monitoring without routine CT is safe, and compared the rate of postoperative emergency neurosurgical intervention with published data. METHODS Four hundred ninety-two patients were prospectively analyzed; 360 had supra- and 132 had infratentorial lesions. Extubation within one hour after skin closure was aimed for in all cases. CT was performed within 48 hours only in cases of unexpected neurological findings. RESULTS Four-hundred sixty-nine of the 492 patients (95.3%) were extubated within one hour, 20 (4.1%) within 3 hours, and three (0.6%) within 3 to 10 hours. Emergency CT within 48 hours was performed for 43/492 (8.7%) cases. Rate of recraniotomy within 48 hours for patients with postoperative hemorrhage was 0.8% (n = 4), and 0.8% (n = 4) required placement of an external ventricular drain (EVD). Of 469 patients extubated within one hour, 3 required recraniotomy and 2 required EVD placements. Of 23 patients with delayed extubation, 1 recraniotomy and 2 EVDs were required. Failure to extubate within one hour was associated with a significantly higher risk of surgical intervention within 48 hours (rate 13.0%, p = 0.004, odds ratio 13.9, 95% confidence interval [3.11-62.37]). DISCUSSION Early extubation combined with close neurological monitoring is safe and omits the need for routine postoperative CT. Patients not extubated within one hour do need early CT, since they had a significantly increased risk of requiring emergency neurosurgical intervention. TRIAL REGISTRATION ClinicalTrials.gov NCT01987648.

Optimized on-line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.

Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.