Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity

Bifurcation Boundary Conditions for Switching DC-DC Converters Under Constant On-Time Control

Sampled-data analysis and harmonic balance analysis are applied to analyze switching DC-DC converters under constant on-time control. Design-oriented boundary conditions for the period-doubling bifurcation and the saddle-node bifurcation are derived. The required ramp slope to avoid the bifurcations and the assigned pole locations associated with the ramp are also derived. The derived boundary conditions are more general and accurate than those recently obtained. Those recently obtained boundary conditions become special cases under the general modeling approach presented in this paper. Different analyses give different perspectives on the system dynamics and complement each other. Under the sampled-data analysis, the boundary conditions are expressed in terms of signal slopes and the ramp slope. Under the harmonic balance analysis, the boundary conditions are expressed in terms of signal harmonics. The derived boundary conditions are useful for a designer to design a converter to avoid the occurrence of the period-doubling bifurcation and the saddle-node bifurcation.Comment: Submitted to International Journal of Circuit Theory and Applications on August 10, 2011; Manuscript ID: CTA-11-016

Dynamics of dental evolution in ornithopod dinosaurs.

Ornithopods were key herbivorous dinosaurs in Mesozoic terrestrial ecosystems, with a variety of tooth morphologies. Several clades, especially the 'duck-billed' hadrosaurids, became hugely diverse and abundant almost worldwide. Yet their evolutionary dynamics have been disputed, particularly whether they diversified in response to events in plant evolution. Here we focus on their remarkable dietary adaptations, using tooth and jaw characters to examine changes in dental disparity and evolutionary rate. Ornithopods explored different areas of dental morphospace throughout their evolution, showing a long-term expansion. There were four major evolutionary rate increases, the first among basal iguanodontians in the Middle-Late Jurassic, and the three others among the Hadrosauridae, above and below the split of their two major clades, in the middle of the Late Cretaceous. These evolutionary bursts do not correspond to times of plant diversification, including the radiation of the flowering plants, and suggest that dental innovation rather than coevolution with major plant clades was a major driver in ornithopod evolution

Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic

Developing a utility index for the Aberrant Behavior Checklist (ABC-C) for fragile X syndrome

Purpose This study aimed to develop a utility index (the ABC-UI) from the Aberrant Behavior Checklist-Community (ABC-C), for use in quantifying the benefit of emerging treatments for fragile X syndrome (FXS). Methods The ABC-C is a proxy-completed assessment of behaviour and is a widely used measure in FXS. A subset of ABC-C items across seven dimensions was identified to include in health state descriptions. This item reduction process was based on item performance, factor analysis and Rasch analysis performed on an observational study dataset, and consultation with five clinical experts and a methodological expert. Dimensions were combined into health states using an orthogonal design and valued using time trade-off (TTO), with lead-time TTO methods used where TTO indicated a state valued as worse than dead. Preference weights were estimated using mean, individual level, ordinary least squares and random-effects maximum likelihood estimation [RE (MLE)] regression models. Results A representative sample of the UK general public (n = 349; mean age 35.8 years, 58.2 % female) each valued 12 health states. Mean observed values ranged from 0.92 to 0.16 for best to worst health states. The RE (MLE) model performed best based on number of significant coefficients and mean absolute error of 0.018. Mean utilities predicted by the model covered a similar range to that observed. Conclusions The ABC-UI estimates a wide range of utilities from patient-level FXS ABC-C data, allowing estimation of FXS health-related quality of life impact for economic evaluation from an established FXS clinical trial instrument

Measurements of daily energy intake and total energy expenditure in people with dementia in care homes: the use of wearable technology.

Objectives: To estimate daily total energy expenditure (TEE) using a physical activity monitor, combined with dietary assessment of energy intake to assess the relationship between daily energy expenditure and patterns of activity with energy intake in people with dementia living in care homes. Design and setting: A cross-sectional study in care homes in the UK. Participants: Twenty residents with confirmed dementia diagnosis were recruited from two care homes that specialised in dementia care. Measurements: A physical activity monitor (Sensewear TM Armband , Body Media, Pittsburgh, PA) was employed to objectively determine total energy expenditure, sleep duration and physical activity. The armband was placed around the left upper triceps for up to 7 days. Energy intake was determined by weighing all food and drink items over 4 days (3 weekdays and 1 weekend day) including measurements of food wastage. Results: The mean age was 78.7 (SD ± 11.8) years, Body Mass Index (BMI) 23.0 (SD ± 4.2) kg/m2 ; 50% were women. Energy intake (mean 7.4; SD ± 2.6) MJ/d) was correlated with TEE (mean 7.6; SD ± 1.8 MJ/d; r=0.49, p<0.05). Duration of sleeping ranged from 0.4-12.5 (mean 6.1) hrs/d and time spent lying down was 1.3-16.0 (8.3) hrs/d. On average residents spent 17.9 (6.3-23.4) hrs/d undertaking sedentary activity. TEE was correlated with BMI (r=0.52, p<0.05) and body weight (r=0.81, p<0.001) but inversely related to sleep duration (r=-0.59, p<0.01) and time lying down (r=-0.62, p<0.01). Multiple linear regression analysis revealed that after taking BMI, sleep duration and time spent lying down into account, TEE was no longer correlated with energy intake. Conclusions: The results show the extent to which body mass, variable activity and sleep patterns may be contributing to TEE and together with reduced energy intake, energy requirements were not satisfied. Thus wearable technology has the potential to offer real-time monitoring to provide appropriate nutrition management that is more person-centred to prevent weight loss in dementi

A systematic review of prostate cancer heterogeneity: understanding the clonal ancestry of multifocal disease

Context Studies characterising genomic changes in prostate cancer (PCa) during natural progression have greatly increased our understanding of the disease. A better understanding of the evolutionary history of PCa would allow advances in diagnostics, prognostication, and novel therapies that together will improve patient outcomes. Objective To review the molecular heterogeneity of PCa and assess recent efforts to profile intratumoural heterogeneity and clonal evolution. Evidence acquisition We screened a total of 1313 abstracts from PubMed published between 2009 and 2020, of which we reviewed 84 full-text articles. We excluded 49, resulting in 35 studies for qualitative analysis. Evidence synthesis In studies of primary disease (16 studies, 4793 specimens), there is a lack of consensus regarding the monoclonal or polyclonal origin of primary PCa. There is no consistent mutation giving rise to primary PCa. Detailed clonal analysis of primary PCa has been limited by current techniques. By contrast, clonal relationships between PCa metastases and a potentiating clone have been consistently identified (19 studies, 732 specimens). Metastatic specimens demonstrate consistent truncal genomic aberrations that suggest monoclonal metastatic progenitors. Conclusions The relationship between the clonal dynamics of PCa and clinical outcomes needs further investigation. It is likely that this will provide a biological rationale for whether radical treatment of the primary tumour benefits patients with oligometastatic PCa. Future studies on the mutational burden in primary disease at single-cell resolution should permit the identification of clonal patterns underpinning the origin of lethal PCa. Patient summary Prostate cancers arise in different parts of the prostate because of DNA mutations that occur by chance at different times. These cancer cells and their origin can be tracked by DNA mapping. In this review we summarise the state of the art and outline what further science is needed to provide the missing answers

Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities

Purpose of Review: The article discusses the two most significant modifiable risk factors for dementia, namely, physical inactivity and lack of stimulating cognitive activity, and their effects on developing cognitive reserve. Recent Findings: Both of these leisure-time activities were associated with significant reductions in the risk of dementia in longitudinal studies. In addition, physical activity, particularly aerobic exercise, is associated with less age-related gray and white matter loss and with less neurotoxic factors. On the other hand, cognitive training studies suggest that training for executive functions (e.g., working memory) improves prefrontal network efficiency, which provides support to brain functioning in the face of cognitive decline. Summary: While physical activity preserves neuronal structural integrity and brain volume (hardware), cognitive activity strengthens the functioning and plasticity of neural circuits (software), thus supporting cognitive reserve in different ways. Future research should examine whether lifestyle interventions incorporating these two domains can reduce incident dementia

Understanding the implementation and effectiveness of a group-based early parenting intervention : a process evaluation protocol

BACKGROUND: Group-based early parenting interventions delivered through community-based services may be a potentially effective means of promoting infant and family health and wellbeing. Process evaluations of these complex interventions provide vital information on how they work, as well as the conditions which shape and influence outcomes. This information is critical to decision makers and service providers who wish to embed prevention and early interventions in usual care settings. In this paper, a process evaluation protocol for an early years parenting intervention, the Parent and Infant (PIN) program, is described. This program combines a range of developmentally-appropriate supports, delivered in a single intervention process, for parents and infants (0–2 years) and aimed at enhancing parental competence, strengthening parent-infant relationships and improving infant wellbeing and adjustment. METHODS: The process evaluation is embedded within a controlled trial and accompanying cost-effectiveness evaluation. Building from extant frameworks and evaluation methods, this paper presents a systematic approach to the process evaluation of the PIN program and its underlying change principles, the implementation of the program, the context of implementation and the change mechanisms which influence and shape parent and infant outcomes. We will use a multi-method strategy, including semi-structured interviews and group discussions with key stakeholders, documentary analysis and survey methodology. DISCUSSION: The integration of innovations into existing early years systems and services is a challenging multifaceted undertaking. This process evaluation will make an important contribution to knowledge about the implementation of such programs, while also providing an example of how theory-based research can be embedded within the evaluation of community-based interventions. We discuss the strengths of the research, such as the adoption of a collaborative approach to data collection, while we also identify potential challenges, including capturing and assessing complex aspects of the intervention. TRIAL REGISTRATION: ISRCTN17488830 (Date of registration: 27/11/15). This trial was retrospectively registered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-016-1737-3) contains supplementary material, which is available to authorized users

Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature.

BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages