Physical rehabilitation for critical illness myopathy and neuropathy (Protocol)

Protocol for a review - no abstract

A Method to Identify and Analyze Biological Programs through Automated Reasoning.

Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function

LMDA Review, volume 12, issue 2

Contents include: Relevance, Residency & Playwriting, The Dramaturgy Residency Project Overview, Residency Project One: Kristen Gandrow at Voice & Vision, Interview with the Dramaturg Kristen Gandrow, Residency Project Two: Brad Rothbart at INTAR Hispanic American Arts Center, Interview with the Dramaturg Brad Rothbart, Residency Project Three: Maxine Kern at New Dramatists, Interview with the Artistic Director Todd London, Interview with the Dramaturg Maxine Kern, Michele Volansky President-Elect of LMDA, LMDA at the Crossroads, Conference 2002 Vancouver, British Columbia, Conference Overview (tentative), LMDA Canada Report, The Musical Structure of Playwriting: A Planel Discussion, and Announcing our new Administrator Cynthia Croot. Issue editor: Gretchen Haleyhttps://soundideas.pugetsound.edu/lmdareview/1025/thumbnail.jp

A Method to Identify and Analyze Biological Programs through Automated Reasoning.

Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function.G.M. holds a career development award from the Armenise Harvard foundation, and a Telethon-DTI career award. A.G.S. is a Medical Research Council Professor

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Physical rehabilitation for critical illness myopathy and neuropathy

Background: intensive care unit (ICU) acquired or generalised weakness due to critical illness myopathy (CIM) and polyneuropathy (CIP) are major causes of chronically impaired motor function that can affect activities of daily living and quality of life. Physical rehabilitation of those affected might help to improve activities of daily living.Objectives: our primary objective was to assess the effects of physical rehabilitation therapies and interventions for people with CIP and CIM in improving activities of daily living such as walking, bathing, dressing and eating. Secondary objectives were to assess effects on muscle strength and quality of life, and to assess adverse effects of physical rehabilitation.Search methods: on 16 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register and on 14 July 2014 we searched CENTRAL, MEDLINE, EMBASE and CINAHL Plus. In July 2014, we searched the Physiotherapy Evidence Database (PEDro, http://www.pedro.org.au/) and three trials registries for ongoing trials and further data about included studies. There were no language restrictions. We also handsearched relevant conference proceedings and screened reference lists to identify further trials.Selection criteria: we planned to include randomised controlled trials (RCTs), quasi-RCTs and randomised controlled cross-over trials of any rehabilitation intervention in people with acquired weakness syndrome due to CIP/CIM.Data collection and analysis: we would have extracted data, assessed the risk of bias and classified the quality of evidence for outcomes in duplicate, according to the standard procedures of The Cochrane Collaboration. Outcome data collection would have been for activities of daily living (for example, mobility, walking, transfers and self care). Secondary outcomes included muscle strength, quality of life and adverse events.Main results: the search strategy retrieved 3587 references. After examination of titles and abstracts, we retrieved the full text of 24 potentially relevant studies. None of these studies met the inclusion criteria of our review. No data were suitable to be included in a meta-analysis.Authors' conclusions: there are no published RCTs or quasi-RCTs that examine whether physical rehabilitation interventions improve activities of daily living for people with CIP and CIM. Large RCTs, which are feasible, need to be conducted to explore the role of physical rehabilitation interventions for people with CIP and CIM

“Don’t Care ” Modeling: A Logical Framework for Developing Predictive System Models ⋆

Abstract. Analysis of biological data often requires an understanding of components of pathways and/or networks and their mutual dependency relationships. Such systems are often analyzed and understood from datasets made up of the states of the relevant components and a set of discrete outcomes or results. The analysis of these systems can be assisted by models that are consistent with the available data while being maximally predictive for untested conditions. Here, we present a method to construct such models for these types of systems. To maximize predictive capability, we introduce a set of “don’t care ” (dc) Boolean variables that must be assigned values in order to obtain a concrete model. When a dc variable is set to 1, this indicates that the information from the corresponding component does not contribute to the observed result. Intuitively, more dc variables that are set to 1 maximizes both the potential predictive capability as well as the possibility of obtaining an inconsistent model. We thus formulate our problem as maximizing the number of dc variables that are set to 1, while retaining a model solution that is consistent and can explain all the given known data. This amounts to solving a quantified Boolean formula (QBF) with three levels of quantifier alternations, with a maximization goal for the dc variables. We have developed a prototype implementation to support our new modeling approach and are applying our method to part of a classical system in developmental biology describing fate specification of vulval precursor cells in the C. elegans nematode. Our work indicates that biological instances can serve as challenging and complex benchmarks for the formal-methods research community.