Size reconstructibility of graphs

The deck of a graph $G$ is given by the multiset of (unlabelled) subgraphs $\{G-v:v\in V(G)\}$. The subgraphs $G-v$ are referred to as the cards of $G$. Brown and Fenner recently showed that, for $n\geq29$, the number of edges of a graph $G$ can be computed from any deck missing 2 cards. We show that, for sufficiently large $n$, the number of edges can be computed from any deck missing at most $\frac1{20}\sqrt{n}$ cards.Comment: 15 page

Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability

Although correlations between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established, the mechanisms underlying these connections remain poorly understood. Here, we used a mutant version of the transcription elongation factor TFIIS (TFIISmut), aiming to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. Indeed, TFIISmut expression results in slower elongation rates, relative depletion of polymerases from the end of genes, and increased levels of stopped RNAPII; it affects mRNA splicing and termination as well. Remarkably, TFIISmut expression also dramatically increases R-loops, which may form at the anterior end of backtracked RNAPII and trigger genome instability, including DNA strand breaks. These results shed light on the relationship between transcription stress and R-loops and suggest that different classes of R-loops may exist, potentially with distinct consequences for genome stability.Cancer Research UK FC001166UK Medical Research Council FC001166Wellcome Trust FC001166European Research Council 693327, ERC2014 AdG669898Ministerio de Economía y Competitividad BFU2013-42918-P, BFU2016-75058-

Implications of Simultaneity in a Physical Damage Function

A modeler must often rely on highly simplified representations of complex physical systems when analyzing associated economic issues. Herein, we consider a management problem in which a bioeconomic system exhibits simultaneity in processes governing productivity and damage. In this case, it may benefit the producer to sacrifice productivity to reduce the costs associated with increased damage. We specify empirically a structural damage relationship that explains the biological process by which an invasive species damages a host and estimate the structural model and its reduced form with an exceptional dataset on infestation of olives by the olive fruit fly. We contrast the results of these models with the approach typically taken in the economic literature, which expresses damage as a function of pest density. The population-based approach introduces significantly greater bias into the individual grower\u27s choice of damage-control inputs than estimates based on the structural model

Mechanisms of Communicating Health Information Through Facebook: Implications for Consumer Health Information Technology Design

Background: Consumer health information technology (IT) solutions are designed to support patient health management and have the ability to facilitate patients\u27 health information communication with their social networks. However, there is a need for consumer health IT solutions to align with patients\u27 health management preferences for increased adoption of the technology. It may be possible to gain an understanding of patients\u27 needs for consumer health IT supporting their health information communication with social networks by explicating how they have adopted and adapted social networking sites, such as Facebook, for this purpose. Objective: Our aim was to characterize patients\u27 use of all communication mechanisms within Facebook for health information communication to provide insight into how consumer health IT solutions may be better designed to meet patients\u27 communication needs and preferences. Methods: This study analyzed data about Facebook communication mechanisms use from a larger, three-phase, sequential, mixed-methods study. We report here on the results of the study\u27s first phase: qualitative interviews (N=25). Participants were over 18, used Facebook, were residents or citizens of the United States, spoke English, and had a diagnosis consistent with type 2 diabetes. Participants were recruited through Facebook groups and pages. Participant interviews were conducted via Skype or telephone between July and September 2014. Data analysis was grounded in qualitative content analysis and the initial coding framework was informed by the findings of a previous study. Results: Participants\u27 rationales for the use or disuse of a particular Facebook mechanism to communicate health information reflected six broad themes: (1) characteristics and circumstances of the person, (2) characteristics and circumstances of the relationship, (3) structure and composition of the social network, (4) content of the information, (5) communication purpose, and (6) attributes of the technology. Conclusions: The results of this study showed that participants consider multiple factors when choosing a Facebook mechanism for health information communication. Factors included what information they intended to share, what they were trying to accomplish, attributes of technology, and attributes and communication practices of their social networks. There is a need for consumer health IT that allows for a range of choices to suit the intersectionality of participants\u27 rationales. Technology that better meets patients\u27 needs may lead to better self-management of health conditions, and therefore, improve overall health outcomes

Locomotor muscle fatigue is not critically regulated after prior upper body exercise

This study examined the effects of prior upper body exercise on subsequent high-intensity cycling exercise tolerance and associated changes in neuromuscular function and perceptual responses. Eight men performed three fixed work-rate (85% peak power) cycling tests: 1) to the limit of tolerance (CYC); 2) to the limit of tolerance after prior high-intensity arm-cranking exercise (ARM-CYC); and 3) without prior exercise and for an equal duration as ARM-CYC (ISOTIME). Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force during supramaximal electrical femoral nerve stimulation. Voluntary activation was assessed using twitch interpolation during maximal voluntary contractions. Cycling time during ARM-CYC and ISOTIME (4.33 ± 1.10 min) was 38% shorter than during CYC (7.46 ± 2.79 min) (P < 0.001). Twitch force decreased more after CYC (−38 ± 13%) than ARM-CYC (−26 ± 10%) (P = 0.004) and ISOTIME (−24 ± 10%) (P = 0.003). Voluntary activation was 94 ± 5% at rest and decreased after CYC (89 ± 9%, P = 0.012) and ARM-CYC (91 ± 8%, P = 0.047). Rating of perceived exertion for limb discomfort increased more quickly during cycling in ARM-CYC [1.83 ± 0.46 arbitrary units (AU)/min] than CYC (1.10 ± 0.38 AU/min, P = 0.003) and ISOTIME (1.05 ± 0.43 AU/min, P = 0.002), and this was correlated with the reduced cycling time in ARM-CYC (r = −0.72, P = 0.045). In conclusion, cycling exercise tolerance after prior upper body exercise is potentially mediated by central fatigue and intolerable levels of sensory perception rather than a critical peripheral fatigue limit

What motivates community mental and behavioral health organizations to participate in LGBTQ+ cultural competency trainings?

LGBTQ+ populations show elevated rates of poor mental health and substance use relative to their heterosexual and cisgender counterparts but often experience stigma and marginalization when seeking mental health care. Mental and behavioral health organizations and therapists recognize a need for LGBTQ+ cultural competency training opportunities and are interested in participating in these trainings. Professional organizations and state licensing bodies should consider policies that require accredited graduate programs and continuing education opportunities to include LGBTQ+ training and competencies.The constantly evolving language, understanding, and cultural context regarding the mental health of lesbian, gay, bisexual, transgender, queer, and other sexual and gender diverse individuals (LGBTQ+) require mental health providers to obtain LGBTQ+ cultural competency training to be affirmative and effective with this population. Unfortunately, many providers are not obtaining this ongoing training and mental health disparities continue to plague LGBTQ+ populations. Guided by the Consolidation Framework for Implementation Research (CFIR), we conducted eight focus groups with community mental and behavioral health organization (MBHO) administrators (e.g., directors, clinical supervisors) and therapists to explore what factors facilitated or inhibited their adoption and implementation of a multicomponent LGBTQ+ cultural competency training program that required administrator and therapist participation in multiple learning sessions over several months (i.e., workshop, clinical consultation, and organizational technical assistance). Results from template analysis supported CFIR-aligned themes, including characteristics of individuals, inner setting, outer setting, and process, and two additional codes—marketing and other/previous training opportunities—emerged from the focus group data. Findings suggest that therapists are motivated to engage in such a program because they want to feel more efficacious, and administrators see the benefits of LGBTQ+ training programs for their clientele and marketing. Barriers to adoption and implementation include cost and personnel resistance, although participants believed these barriers were surmountable. Emphasizing therapist efficacy, clientele need, and benefits for marketing mental and behavioral health services could motivate MBHOs’ and therapists’ adoption and implementation of LGBTQ+ cultural competency training.This work was supported by the University of Maryland Prevention Research Center cooperative agreement no. U48DP006382 from the Centers for Disease Control and Prevention (CDC). Any interpretations and opinions expressed herein are solely those of the authors and may not reflect those of the CDC

IGF1-Stimulated Posttraumatic Hippocampal Remodeling Is Not Dependent on mTOR

Adult hippocampal neurogenesis is stimulated acutely following traumatic brain injury (TBI). However, many hippocampal neurons born after injury develop abnormally and the number that survive long-term is debated. In experimental TBI, insulin-like growth factor-1 (IGF1) promotes hippocampal neuronal differentiation, improves immature neuron dendritic arbor morphology, increases long-term survival of neurons born after TBI, and improves cognitive function. One potential downstream mediator of the neurogenic effects of IGF1 is mammalian target of rapamycin (mTOR), which regulates proliferation as well as axonal and dendritic growth in the CNS. Excessive mTOR activation is posited to contribute to aberrant plasticity related to posttraumatic epilepsy, spurring preclinical studies of mTOR inhibitors as therapeutics for TBI. The degree to which pro-neurogenic effects of IGF1 depend upon upregulation of mTOR activity is currently unknown. Using immunostaining for phosphorylated ribosomal protein S6, a commonly used surrogate for mTOR activation, we show that controlled cortical impact TBI triggers mTOR activation in the dentate gyrus in a time-, region-, and injury severity-dependent manner. Posttraumatic mTOR activation in the granule cell layer (GCL) and dentate hilus was amplified in mice with conditional overexpression of IGF1. In contrast, delayed astrocytic activation of mTOR signaling within the dentate gyrus molecular layer, closely associated with proliferation, was not affected by IGF1 overexpression. To determine whether mTOR activation is necessary for IGF1-mediated stimulation of posttraumatic hippocampal neurogenesis, wildtype and IGF1 transgenic mice received the mTOR inhibitor rapamycin daily beginning at 3 days after TBI, following pulse labeling with bromodeoxyuridine. Compared to wildtype mice, IGF1 overexpressing mice exhibited increased posttraumatic neurogenesis, with a higher density of posttrauma-born GCL neurons at 10 days after injury. Inhibition of mTOR did not abrogate IGF1-stimulated enhancement of posttraumatic neurogenesis. Rather, rapamycin treatment in IGF1 transgenic mice, but not in WT mice, increased numbers of cells labeled with BrdU at 3 days after injury that survived to 10 days, and enhanced the proportion of posttrauma-born cells that differentiated into neurons. Because beneficial effects of IGF1 on hippocampal neurogenesis were maintained or even enhanced with delayed inhibition of mTOR, combination therapy approaches may hold promise for TBI

Concert recording 2017-11-20b

[Track 1]. Soccorrete, luci avare , op. 2 from La Travagliata [Track 2]. Spesso per entro al petto , op. 2 from La Fanciuletta semolice / Barbara Strozzi -- [Track 3]. Exultate, jubilate KV 165. I. Allegro [Track 4]. II. Andante III. Allegro / Wolfgang Amadeus Mozart -- [Track 5]. From Mörike-Lieder. Verborgenheit , op. 1 no. 11 [Track 6]. Nimmersatte, Liebe , op. 19 no. 19 [Track 7]. Er ist\u27s , op. 79 no. 23 / Hugo Wolf -- [Track 8]. Three songs. I. Insomnia & so on [Track 9]. II. You [Track 10]. III. Drifting at midday / Ching-chu Hu -- [Track 11]. Kommt ein schlanker bursch gegangen from Der Freischütz / Carl Maria von Weber -- [Track 12]. Ah! Je ris de me voir si belle en ce miroir from Faust / Charles Gounod

Validation of the Oncomine™ Focus Panel for Next Generation Sequencing of clinical tumour samples

The clinical utility of next-generation sequencing (NGS) for a diverse range of targets is expanding, increasing the need for multiplexed analysis of both DNA and RNA. However, translation into daily use requires a rigorous and comprehensive validation strategy. The aim of this clinical validation was to assess the performance of the Ion Torrent Personal Genome Machine (IonPGM™) and validate the Oncomine™ Focus DNA and RNA Fusion panels for clinical application in solid tumour testing of formalin-fixed, paraffin-embedded (FFPE) tissue. Using a mixture of routine FFPE and reference material across a variety of tissue and specimen types, we sequenced 86 and 31 samples on the Oncomine™ Focus DNA and RNA Fusion assays, respectively. This validation considered a number of parameters including the clinical robustness of the bioinformatics pipeline for variant detection and interpretation. The Oncomine™ Focus DNA assay had a sample and variant-based sensitivity of 99.1 and 97.1%, respectively, and an assay specificity of 100%. The Oncomine™ Focus Fusion panel had a good sensitivity and specificity based upon the samples assessed, however requires further validation to confirm findings due to limited sample numbers. We observed a good sequencing performance based upon amplicon, gene (hotspot variants within gene) and sample specific analysis with 92% of clinical samples obtaining an average amplicon coverage above 500X. Detection of some indels was challenging for the routine IonReporter™ workflow; however, the addition of NextGENe® software improved indel identification demonstrating the importance of both bench and bioinformatic validation. With an increasing number of clinically actionable targets requiring a variety of methodologies, NGS provides a cost-effective and time-saving methodology to assess multiple targets across different modalities. We suggest the use of multiple analysis software to ensure identification of clinically applicable variants.Publisher PDFPeer reviewe

The development and pilot testing of the Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease (SPACE for COPD)

Purpose: There is no independent standardized self-management approach available for chronic obstructive pulmonary disease (COPD). The aim of this project was to develop and test a novel self-management manual for individuals with COPD. Patients: Participants with a confirmed diagnosis of COPD were recruited from primary care. Methods: A novel self-management manual was developed with health care professionals and patients. Five focus groups were conducted with individuals with COPD (N = 24) during development to confirm and enhance the content of the prototype manual. The Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease (SPACE for COPD) manual was developed as the focus of a comprehensive self-management approach facilitated by health care professionals. Preference for delivery was initial face-to-face consultation with telephone follow-up. The SPACE for COPD manual was piloted with 37 participants in primary care. Outcome measures included the Self-Report Chronic Respiratory Questionnaire, Incremental Shuttle Walk Test, and Endurance Shuttle Walking Test (ESWT); measurements were taken at baseline and 6 weeks. Results: The pilot study observed statistically significant improvements for the dyspnea domain of the Self-Report Chronic Respiratory Questionnaire and ESWT. Dyspnea showed a mean change of 0.67 (95% confidence interval 0.23–1.11, P = 0.005). ESWT score increased by 302.25 seconds (95% confidence interval 161.47–443.03, P &lt; 0.001). Conclusion: This article describes the development and delivery of a novel self-management approach for COPD. The program, incorporating the SPACE for COPD manual, appears to provoke important changes in exercise capacity and breathlessness for individuals with COPD managed in primary care