Looked after children in prison as adults: life adversity and neurodisability

This is the author accepted manuscript. The final version is available from Emerald via the DOI in this recordData availability statement: Due to ethical concerns, the research data supporting this publication are not publicly available.Purpose Looked after children (LAC) are criminalised at five times the rate of children in the general population. Children in contact with both child welfare and child justice systems have higher rates of neurodisability and substance use problems, and LAC in general have high rates of school exclusion, homelessness and unemployment. This study aims to understand whether these factors persist in LAC who are in prison as adults. Design/methodology/approach Administrative data collected by the Do-IT profiler screening tool in a prison in Wales, UK, were analysed to compare sentenced prisoners who were LAC (n = 631) to sentenced prisoners who were not LAC (n = 2,201). The sample comprised all prisoners who were screened on entry to prison in a two-year period. Findings Prisoners who were LAC scored more poorly on a functional screener for neurodisability (effect size = 0.24), and on four self-report measures capturing traits of dyslexia (0.22), attention-deficit hyperactivity disorder (0.40), autism spectrum disorders (0.34) and developmental co-ordination disorder (0.33). Prisoners who were LAC were more likely to have been to a pupil referral unit (0.24), have substance use problems (0.16), be homeless or marginally housed (0.18) and be unemployed or unable to work due to disability (0.13). Originality/value This study uniquely contributes to our understanding of prisoners who were LAC as a target group for intervention and support with re-integration into the community upon release. LAC in prison as adults may require additional interventions to help with employment, housing and substance use. Education programmes in prison should screen for neurodisability, to develop strategies to support engagement.Economic and Social Research Council (ESRC)HMP/YOI Par

Classical and quantum: a conflict of interest

We highlight three conflicts between quantum theory and classical general relativity, which make it implausible that a quantum theory of gravity can be arrived at by quantising classical gravity. These conflicts are: quantum nonlocality and space-time structure; the problem of time in quantum theory; and the quantum measurement problem. We explain how these three aspects bear on each other, and how they point towards an underlying noncommutative geometry of space-time.Comment: 15 pages. Published in `Gravity and the quantum' [Essays in honour of Thanu Padmanabhan on the occasion of his sixtieth birthday] Eds. Jasjeet Singh Bagla and Sunu Engineer (Springer, 2017

Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Use of conventional and alternative treatment strategies for a case of low back pain in a F/A-18 aviator

BACKGROUND: Low back pain can diminish jet pilot concentration and function during flight and be severe enough to ground pilots or cause decreased flying time. The objective of this case report is to present an example of the integration of chiropractic care with conventional treatments for the management of low back pain in a F/A-18 aviator. CASE PRESENTATION: The patient had insidious severe low back pain without radiation or neurological deficit, resulting in 24 hours of hospitalization. Spinal degeneration was discovered upon imaging. Four months later, it still took up to 10 minutes for him to get out of bed and several minutes to exit the jet due to stiffness and pain. He had discontinued his regular Marine Corps fitness training due to pain avoidance. Pain severity ranged from 1.5–7.1 cm on a visual analog scale. His Roland Morris Disability Questionnaire score was 5 out of 24. The pilot's pain was managed with the coordinated efforts of the flight surgeon, physiatrist, physical therapist, and doctor of chiropractic. Following this regimen he had no pain and no functional disability; he was able to fly multiple training missions per week and exercise to Marine Corps standards. CONCLUSION: A course of care integrating flight medicine, chiropractic, physical therapy, and physiatry appeared to alleviate pain and restore function to this F/A-18 aviator with low back pain

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Assessment of clusters of transcription factor binding sites in relationship to human promoter, CpG islands and gene expression

BACKGROUND: Gene expression is regulated mainly by transcription factors (TFs) that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS) using position weight matrices (PWMs) that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. RESULTS: We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI) against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster), we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. CONCLUSION: Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1) those that show TFBS clustered in promoters associated with CGI, and (2) those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in regulatory regions

Evidence for an increase in cosmogenic 10Be during a geomagnetic reversal

Reversals in the geomagnetic field, which occur every few hundred thousand years, represent a dramatic change in the Earth's environment. Although there is no satisfactory theory for such reversals, it is generally accepted that the dipole field intensity decreases to <20% of its 'normal' value for a few thousand years during the change in direction. Because the galactic and solar cosmic rays which impinge on the Earth's atmosphere are charged, a significant fraction (about half) of them are deflected by the geomagnetic field. At the time of a reversal, this magnetic shielding is greatly reduced, and it has been suggested that the increased flux of high-energy particles could have effects on evolutionary or climatic processes. For example, the statistically significant coincidence in levels of some marine faunal extinctions and reversal boundaries in ocean sediments could be caused, directly or indirectly, by the decreased geomagnetic intensity during the reversal. We report here evidence in marine sediments for an increase in cosmogenic 10Be production in the Earth's atmosphere during the Brunhes-Matuyama reversal 730,000 yr ago. In addition to confirming an increase in cosmogenic isotope production, the results provide information on the magnitude and duration of the geomagnetic intensity decrease during such an event, and the depth at which remanent magnetism is acquired in marine sediments

Modeling the Evolution of Regulatory Elements by Simultaneous Detection and Alignment with Phylogenetic Pair HMMs

The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation. Attempts to utilize cross-species conservation for this task have been hampered both by evolutionary changes of functional sites and poor performance of general-purpose alignment programs when applied to non-coding sequence. We describe a new and flexible framework for modeling binding site evolution in multiple related genomes, based on phylogenetic pair hidden Markov models which explicitly model the gain and loss of binding sites along a phylogeny. We demonstrate the value of this framework for both the alignment of regulatory regions and the inference of precise binding-site locations within those regions. As the underlying formalism is a stochastic, generative model, it can also be used to simulate the evolution of regulatory elements. Our implementation is scalable in terms of numbers of species and sequence lengths and can produce alignments and binding-site predictions with accuracy rivaling or exceeding current systems that specialize in only alignment or only binding-site prediction. We demonstrate the validity and power of various model components on extensive simulations of realistic sequence data and apply a specific model to study Drosophila enhancers in as many as ten related genomes and in the presence of gain and loss of binding sites. Different models and modeling assumptions can be easily specified, thus providing an invaluable tool for the exploration of biological hypotheses that can drive improvements in our understanding of the mechanisms and evolution of gene regulation

The value of position-specific priors in motif discovery using MEME

<p>Abstract</p> <p>Background</p> <p>Position-specific priors have been shown to be a flexible and elegant way to extend the power of Gibbs sampler-based motif discovery algorithms. Information of many types–including sequence conservation, nucleosome positioning, and negative examples–can be converted into a prior over the location of motif sites, which then guides the sequence motif discovery algorithm. This approach has been shown to confer many of the benefits of conservation-based and discriminative motif discovery approaches on Gibbs sampler-based motif discovery methods, but has not previously been studied with methods based on expectation maximization (EM).</p> <p>Results</p> <p>We extend the popular EM-based MEME algorithm to utilize position-specific priors and demonstrate their effectiveness for discovering transcription factor (TF) motifs in yeast and mouse DNA sequences. Utilizing a discriminative, conservation-based prior dramatically improves MEME's ability to discover motifs in 156 yeast TF ChIP-chip datasets, more than doubling the number of datasets where it finds the correct motif. On these datasets, MEME using the prior has a higher success rate than eight other conservation-based motif discovery approaches. We also show that the same type of prior improves the accuracy of motifs discovered by MEME in mouse TF ChIP-seq data, and that the motifs tend to be of slightly higher quality those found by a Gibbs sampling algorithm using the same prior.</p> <p>Conclusions</p> <p>We conclude that using position-specific priors can substantially increase the power of EM-based motif discovery algorithms such as MEME algorithm.</p