Equilibrium Distribution of Mutators in the Single Fitness Peak Model

This paper develops an analytically tractable model for determining the equilibrium distribution of mismatch repair deficient strains in unicellular populations. The approach is based on the single fitness peak (SFP) model, which has been used in Eigen's quasispecies equations in order to understand various aspects of evolutionary dynamics. As with the quasispecies model, our model for mutator-nonmutator equilibrium undergoes a phase transition in the limit of infinite sequence length. This "repair catastrophe" occurs at a critical repair error probability of $\epsilon_r = L_{via}/L$, where $L_{via}$ denotes the length of the genome controlling viability, while $L$ denotes the overall length of the genome. The repair catastrophe therefore occurs when the repair error probability exceeds the fraction of deleterious mutations. Our model also gives a quantitative estimate for the equilibrium fraction of mutators in {\it Escherichia coli}.Comment: 4 pages, 2 figures (included as separate PS files

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography Organ-based Tube Current Modulation Technique

Purpose This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol

CT Automated Exposure Control Using A Generalized Detectability Index

Purpose Identifying an appropriate tube current setting can be challenging when using iterative reconstruction due to the varying relationship between spatial resolution, contrast, noise, and dose across different algorithms. This study developed and investigated the application of a generalized detectability index (d\u27gen) to determine the noise parameter to input to existing automated exposure control (AEC) systems to provide consistent image quality (IQ) across different reconstruction approaches. Methods This study proposes a task‐based automated exposure control (AEC) method using a generalized detectability index (d\u27gen). The proposed method leverages existing AEC methods that are based on a prescribed noise level. The generalized d\u27gen metric is calculated using lookup tables of task‐based modulation transfer function (MTF) and noise power spectrum (NPS). To generate the lookup tables, the American College of Radiology CT accreditation phantom was scanned on a multidetector CT scanner (Revolution CT, GE Healthcare) at 120 kV and tube current varied manually from 20 to 240 mAs. Images were reconstructed using a reference reconstruction algorithm and four levels of an in‐house iterative reconstruction algorithm with different regularization strengths (IR1–IR4). The task‐based MTF and NPS were estimated from the measured images to create lookup tables of scaling factors that convert between d\u27gen and noise standard deviation. The performance of the proposed d\u27gen‐AEC method in providing a desired IQ level over a range of iterative reconstruction algorithms was evaluated using the American College of Radiology (ACR) phantom with elliptical shell and using a human reader evaluation on anthropomorphic phantom images. Results The study of the ACR phantom with elliptical shell demonstrated reasonable agreement between the d\u27gen predicted by the lookup table and d\u27 measured in the images, with a mean absolute error of 15% across all dose levels and maximum error of 45% at the lowest dose level with the elliptical shell. For the anthropomorphic phantom study, the mean reader scores for images resulting from the d\u27gen‐AEC method were 3.3 (reference image), 3.5 (IR1), 3.6 (IR2), 3.5 (IR3), and 2.2 (IR4). When using the d\u27gen‐AEC method, the observers’ IQ scores for the reference reconstruction were statistical equivalent to the scores for IR1, IR2, and IR3 iterative reconstructions (P \u3e 0.35). The d\u27gen‐AEC method achieved this equivalent IQ at lower dose for the IR scans compared to the reference scans. Conclusions A novel AEC method, based on a generalized detectability index, was investigated. The proposed method can be used with some existing AEC systems to derive the tube current profile for iterative reconstruction algorithms. The results provide preliminary evidence that the proposed d\u27gen‐AEC can produce similar IQ across different iterative reconstruction approaches at different dose levels

Characterization of grain boundaries in silicon

Zero-bias conductance and capacitance measurements at various temperatures were used to study trapped charges and potential barrier height at the boundaries. Deep-level transient spectroscopy (DLTS) was applied to measure the density of states at the boundary. A study of photoconductivity of grain boundaries in p-type silicon demonstrated the applicability of the technique in the measurement of minority carrier recombination velocity at the grain boundary. Enhanced diffusion of phosphorus at grain boundaries in three cast polycrystalline photovoltaic materials was studied. Enhancements for the three were the same, indicating that the properties of boundaries are similar, although grown by different techniques. Grain boundaries capable of enhancing the diffusion were found always to have strong recombination activities; the phenomena could be related to dangling bonds at the boundaries. Evidence that incoherent second-order twins of (111)/(115) type are diffusion-active is presented

Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objective To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL) function in people with dementia. Design Overview of systematic reviews. Methods A systematic search in the Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE and PsycInfo in April 2015. Systematic reviews of randomised controlled trials conducted in people with Alzheimer's disease or dementia measuring the impact on ADL function were included. Methodological quality of the systematic reviews was independently assessed by two authors using the AMSTAR tool. The quality of evidence of the primary studies for each intervention was assessed using GRADE. Results A total of 23 systematic reviews were included in the overview. The quality of the reviews varied; however most (65%) scored 8/11 or more on the AMSTAR tool, indicating high quality. Interventions that were reported to be effective in minimising decline in ADL function were: exercise (6 studies, 289 participants, standardised mean difference (SMD) 0.68, 95% CI 0.08 to 1.27; GRADE: low), dyadic interventions (8 studies, 988 participants, SMD 0.37, 95% CI 0.05 to 0.69; GRADE: low) acetylcholinesterase inhibitors and memantine (12 studies, 4661 participants, donepezil 10 mg SMD 0.18, 95% CI 0.03 to 0.32; GRADE: moderate), selegiline (7 studies, 810 participants, SMD 0.27, 95% CI 0.13 to 0.41; GRADE: low), huperzine A (2 studies, 70 participants, SMD 1.48, 95% CI 0.95 to 2.02; GRADE: very low) and Ginkgo biloba (7 studies, 2530 participants, SMD 0.36, 95% CI 0.28 to 0.44; GRADE: very low). Conclusions Healthcare professionals should ensure that people with dementia are encouraged to exercise and that primary carers are trained and supported to provide safe and effective care for the person with dementia. Acetylcholinesterase inhibitors or memantine should be trialled unless contraindicated. Trial registration number CRD42015020179

A systematic review and meta-analysis comparing carer focused and dyadic multicomponent interventions for cares of people with dementia

CC BY-NCObjective: The aim of this study was to compare the efficacy of two approaches: multicomponent interventions that focus on working with the carer and dyadic interventions that work with both the carer and the person with dementia. Method: A systematic review involving a search of Medline, EMBASE, and PsycINFO in October 2015 was performed. Randomized controlled trials involving carers of people with dementia and comparing multicomponent interventions with usual care were included. Results: Pooling of all studies demonstrated that multicomponent interventions can reduce depressive symptoms, improve quality of life, reduce carer impact, and reduce behavioral and psychological symptoms of dementia as well as caregiver upset with these symptoms. We were unable to find a significant difference in the effects of dyadic interventions in comparison with carer focused interventions for these outcomes. Discussion: Although effect sizes associated with intervention are small, multicomponent interventions are relatively inexpensive to deliver, acceptable, and widely applicable

Influence of health locus of control on recovery of function in recently hospitalized frail older adults

"This is the peer reviewed version of the following article: [Milte, C. M., Luszcz, M. A., Ratcliffe, J., Masters, S. and Crotty, M. (2015), Influence of health locus of control on recovery of function in recently hospitalized frail older adults. Geriatrics & Gerontology International, 15: 341–349.], which has been published in final form at [http://dx.doi.org/10.1111/ggi.12281]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms"AIM: To investigate the influence of health locus of control on physical function, quality of life, depression and satisfaction with care transition in a sample of older adults after a hospital admission. METHODS: A total of 230 older adults referred for transition care after a hospital admission (mean length of stay 25.7 days, SD 17.2) were recruited into a randomized controlled intervention trial investigating the effect of specialized coaching compared with usual care. Older adults completed the multidimensional health locus of control (MHLC) survey at baseline. Self-rated quality of life, depression and physical function were assessed at baseline and 12 months using the EuroQol five-dimension, Geriatric Depression Scale (GDS) and Modified Barthel Index (MBI), respectively. RESULTS: Results from hierarchical multiple regression analysis in 136 participants (70 usual care and 66 specialized care) with complete data showed that higher scores on the MHLC internal subscale were related to better quality of life, and better physical function in the usual care group at 12 months, but not depression or transition process satisfaction at 3 months. No relationships between MHLC subscales and outcome measures were observed in the specialized care group, where the coaching intervention might have precluded any relationship observed. CONCLUSIONS: A stronger sense of personal control over health was associated with better maintenance of quality of life and physical function at 12 months in older adults undergoing usual care transition after acute hospitalization. Modification of control beliefs has the potential to promote resilience and impact on health outcomes in older adults during care transitions

Polarization Dependent Coupling of Whispering Gallery Modes in Microspheres

Two sets of resonances in glass microspheres attached to a standard communication-grade single-mode optical fiber have been observed. It has been found that the strength of the resonances depends strongly on the polarization of the coupled light. Furthermore, the position of the resonances in the wavelength domain depends on the polarization of light in the optical fiber with maximum magnitudes shifted by approximately 45

New results from an extensive aging test on bakelite Resistive Plate Chambers

We present recent results of an extensive aging test, performed at the CERN Gamma Irradiation Facility on two single--gap RPC prototypes, developed for the LHCb Muon System. With a method based on a model describing the behaviour of an RPC under high particle flux conditions, we have periodically measured the electrode resistance R of the two RPC prototypes over three years: we observe a large spontaneous increase of R with time, from the initial value of about 2 MOhm to more than 250 MOhm. A corresponding degradation of the RPC rate capabilities, from more than 3 kHz/cm2 to less than 0.15 kHz/cm2 is also found.Comment: 6 pages, 7 figures, presented at Siena 2002, 8th Topical Seminar on Innovative Particle and Radiation Detectors 21-24 October 2002, Siena, Ital

The Error and Repair Catastrophes: A Two-Dimensional Phase Diagram in the Quasispecies Model

This paper develops a two gene, single fitness peak model for determining the equilibrium distribution of genotypes in a unicellular population which is capable of genetic damage repair. The first gene, denoted by $\sigma_{via}$, yields a viable organism with first order growth rate constant $k > 1$ if it is equal to some target ``master'' sequence $\sigma_{via, 0}$. The second gene, denoted by $\sigma_{rep}$, yields an organism capable of genetic repair if it is equal to some target ``master'' sequence $\sigma_{rep, 0}$. This model is analytically solvable in the limit of infinite sequence length, and gives an equilibrium distribution which depends on \mu \equiv L\eps , the product of sequence length and per base pair replication error probability, and \eps_r , the probability of repair failure per base pair. The equilibrium distribution is shown to exist in one of three possible ``phases.'' In the first phase, the population is localized about the viability and repairing master sequences. As \eps_r exceeds the fraction of deleterious mutations, the population undergoes a ``repair'' catastrophe, in which the equilibrium distribution is still localized about the viability master sequence, but is spread ergodically over the sequence subspace defined by the repair gene. Below the repair catastrophe, the distribution undergoes the error catastrophe when $\mu$ exceeds \ln k/\eps_r , while above the repair catastrophe, the distribution undergoes the error catastrophe when $\mu$ exceeds $\ln k/f_{del}$, where $f_{del}$ denotes the fraction of deleterious mutations.Comment: 14 pages, 3 figures. Submitted to Physical Review