Uncertainty in phylogenetic tree estimates

Estimating phylogenetic trees is an important problem in evolutionary biology, environmental policy and medicine. Although trees are estimated, their uncertainties are discarded by mathematicians working in tree space. Here we explicitly model the multivariate uncertainty of tree estimates. We consider both the cases where uncertainty information arises extrinsically (through covariate information) and intrinsically (through the tree estimates themselves). The importance of accounting for tree uncertainty in tree space is demonstrated in two case studies. In the first instance, differences between gene trees are small relative to their uncertainties, while in the second, the differences are relatively large. Our main goal is visualization of tree uncertainty, and we demonstrate advantages of our method with respect to reproducibility, speed and preservation of topological differences compared to visualization based on multidimensional scaling. The proposal highlights that phylogenetic trees are estimated in an extremely high-dimensional space, resulting in uncertainty information that cannot be discarded. Most importantly, it is a method that allows biologists to diagnose whether differences between gene trees are biologically meaningful, or due to uncertainty in estimation.Comment: Final version accepted to Journal of Computational and Graphical Statistic

The response of the mitochondrial proteome and ROS production to ageing and dietary restriction

PhD ThesisThe free radical theory of ageing proposes ageing is the result of macromolecules, damaged by free radicals, accumulating in cells over time. Mitochondria are critical to this theory as they are the primary source of the free radical superoxide. This thesis aims to understand the effect of age and dietary restriction (DR) with regard to mitochondrial protein abundance and superoxide generation. Superoxide production and protein composition was studied from multiple ages in isolated mitochondria from both ad libitum (AL) and DR mice. Superoxide production was assessed by measuring hydrogen peroxide release from multiple electron transport chain (ETC) sites. Mass spectrometry was used to determine the mitochondrial protein composition from mouse liver tissue. Older mice have increased hydrogen peroxide release from ETC complexes I and III. DR has decreased complex I hydrogen peroxide release in brain, skeletal muscle and liver mitochondria analysed at 15 and 24 months old. DR doesn’t prevent but delays the age associated hydrogen peroxide release. Hydrogen peroxide release at the same survival point is not significantly different between AL and DR mice. The liver mitochondrial proteome is affected by age and DR. Fatty acid metabolism protein abundance increases with age whereas amino acid metabolism protein abundance decreased. Superoxide clearance protein abundance is increased in older and DR liver mitochondria. Catalase had increased abundance in DR mitochondria at 15 and 24 months than at 3 or 36 months old. In conclusion hydrogen peroxide release, superoxide clearance protein abundance and fatty acid metabolism protein abundance are increased with ageing. The age associated increase in hydrogen peroxide release is delayed in DR mitochondria possibly due to increased abundance of catalase

Secondary amenorrhea

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of secondary amenorrhea

Evaluating social skills in long term cochlear implant recipients

A longitudinal study observing cochlear implant recipients\u27 social skills using ratings from their parents and the students themselves over time. The study looked at how adolescents using cochlear implants rate their own social skills compared to an age matched normative group of hearing students, and compared these ratings with social skills ratings obtained from their parents. The study also compared social ratings in adolescence to previous ratings of the same children obtained in elementary school

Fibrocystic changes of the breast

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of fibrocystic changes of the breast

NUTRITIONAL INFLUENCES ON NET ACID EXCRETION

Net acid excretion (NAE) is implicated in bone loss, as increased calcium loss is seen with high NAE. Protein is the main source of dietary acid load and fruit and vegetables provide potassium salts which counteract this effect. Two studies investigated how dietary factors affect NAE and markers of bone loss. The purpose of Study 1 was to determine if pH paper strip measurement of first morning urine reflected NAE and to investigate dietary effects on NAE and markers of bone loss in free-living individuals. Twenty-three subjects recorded 24-hour food records and collected 24-hour urine, as day (-7 a.m. to 11 p.m.) and overnight (-11 p.m. to 7 a.m.), and fasting second morning urine collections. NAE was measured as titratable acidity minus HCO3 (TA) plus NH4±. pH paper strip measurement of first morning urine was significantly correlated with 24-hour TA (r = -0.466, p < 0.025), but not with 24-hour NAE. The expected relationship between NAE and dietary protein or potassium intake was not evident, instead there was an association between protein and potassium intake (r = 0.679, p < 0.005). Nor was the ratio of protein to potassium associated with NAE. A positive association was found between urinary sodium (reflecting dietary sodium) and fasting urinary calcium excretion (indirect measure of bone loss). A surprising significant negative correlation was found between NAE and urinary cross-linked N-telopeptides (NTx), suggesting that NAE may not be a significant factor in bone turnover. The log transformation of urinary sodium versus NTx indicates a possible effect of sodium on bone turnover (r = 0.407, p = 0.084). Although pH paper strips are a good estimate of NAE, they measure a factor that appears less important than sodium intake. The purpose of Study 2 was to determine if fruit intake (a source of alkalinity) would lower NAE and thereby urinary calcium loss. A crossover, acute load study was designed to investigate if processed fruit was as effective as fresh fruit in reducing NAE and protein induced hypercalciuria. Fifteen volunteers completed 3 dietary treatments on 3 different days. A fasting urine sample was collected before consuming one of the following 3 isocaloric high protein treatments: control (C), sugar and protein; fresh (F), apples, sugar and protein; and processed (P), applesauce and protein. Fruit treatments were designed to each provide 9 mmol of potassium, according to published food labels. Urine was collected at 1.5 hour, 3 hour, and 4.5 hour. The mean NAE at 3 hour was (mmol/mmol Cr): C, 366 ± 2.18; F, 2.05 ± 2.05; and P, 1.63 ± 2.56, (p = 0.082), indicating a trend for lower NAE with fruit. The change in calcium excretion at 3 hour was (mmol): C, 0.239 ± 0.20; F, 0.126 ± 0.11; and P, 0.079 ± 0.21, (p = 0.048). Post hoc LSD test did not show a significant difference between treatments. Therefore, fruit intake is able to reduce protein induced hypercalciuria, and processed fruit appears to be as effective as fresh fruit, although a larger serving had to be consumed. While protein has received much attention for its role in increasing NAE and urinary calcium, these studies support other current literature which indicate that protein may not be harmful to bone when the diet is adequate in fruits and vegetables. Therefore, a diet generous in fruits and vegetables, adequate in protein, and low in sodium appears to be a dietary pattern which would promote bone health

Beetle II: an adaptable tutorial dialogue system

We present BEETLE II, a tutorial dialogue system which accepts unrestricted language input and supports experimentation with different dialogue strategies. Our first system evaluation compared two dialogue policies. The resulting corpus was used to study the impact of different tutoring and error recovery strategies on user satisfaction and student interaction style. It can also be used in the future to study a wide range of research issues in dialogue systems.

What test is the best for diagnosing infectious mononucleosis?

Tests for antibodies to Epstein-Barr viral capsid antigen (EBVCA) or Epstein-Barr nuclear antigen (EBNA) are the most sensitive, are highly specific, and are also the most expensive for diagnosing infectious mononucleosis (strength of recommendation [SOR]: C, based on validating cohort study). Heterophile antibody tests have similar specificity and are cheaper, but are less sensitive in children or in adults during the early days of the illness (SOR: C, based on validating cohort study)

AN EVALUATION OF COLLEGE PREPAREDNESS ON NATURAL SELECTION PRINCIPLES FOLLOWING THE COMPLETION OF AN ENTRY-LEVEL BIOLOGY COURSE

Abstract Evolution education in secondary education has long been a topic of research. The level of knowledge and acceptance of students upon entering college has been studied using various methods; however, no study had provided the perception of preparedness from the student perspective nor had analyzed the individual Natural Selection principles. This study analyzed college freshmen (n=162) in an entry-level BIO 101 course. Participants were given the Conceptual Inventory of Natural Selection Instrument (CINSI) and perception survey questions upon completion of the course. The CINSI data was then analyzed for each of the four Natural Selection principles as well as overall evolution concept and analyzed against the level of preparation students perceived they had received in high school biology for those areas. The study had five research questions; four regarding each Natural Selection principles, then a fifth regarding evolution as an overall concept. Of the five hypotheses, four were accepted with statistical significance, using Wilcoxon sign-ranked test. The only rejected hypotheses was regarding reproductive success principle of Natural Selection. This study concluded that students do not perceive themselves to be well-prepared in high school biology and that, while they averaged a failing grade on each principle and overall concept of the CINSI, there are certain principles they do perform better on than others. Recommendations and limitations are also discussed