AbstractThe iCAP is a tool for blood-based diagnostics that addresses the low signal-to-noise ratio of blood biomarkers by using cells as biosensors. The assay exposes small volumes of patient serum to standardized cells in culture and classifies disease by AI analysis of gene-expression readouts from the cells. It simplifies the complexity of blood into a concise readout in a scalable cell-based assay. We developed the LC-iCAP as a rule-out test for nodule management in CT-based lung cancer screening. The assay achieved an AUC of 0.63 (95% CI 0.50-0.75) in retrospective-blind-temporal validation. When integrated with CT data after validation, it demonstrated potential to reduce unnecessary follow-up procedures by significantly outperforming the Mayo Clinic model with 90% sensitivity, 67% specificity and 95% NPV using an estimated 25% prevalence. Analytical validation established LC-iCAP reproducibility and identified unwanted variation from long-term serum storage suggesting a prospective study design could enhance performance.
The human papilloma virus (HPV) vaccine is the world's first proven and effective vaccine to prevent cancers in males and females when administered pre-exposure. Like most of the US, barely half of Vermont teens are up-to-date with the vaccination, with comparable deficits in New Hampshire and Maine. The rates for HPV vaccine initiation and completion are as low as 33% in rural New England. Consequently, there is a compelling responsibility to communicate its importance to unvaccinated teenagers before their risk for infection increases. Messaging in rural areas promoting HPV vaccination is compromised by community-based characteristics that include access to appropriate medical care, poor media coverage, parental and peer influence, and skepticism of science and medicine. Current strategies are predominantly passive access to literature and Internet-based information. Evidence indicates that performance-based messaging can clarify the importance of HPV vaccination to teenagers and their parents in rural areas. Increased HPV vaccination will significantly contribute to the prevention of a broadening spectrum of cancers. Reducing rurality-based inequities is a public health priority. Development of a performance-based peer-communication intervention can capture a window of opportunity to provide increasingly effective and sustained HPV protection. An effective approach can be partnering rural schools and regional health teams with a program that is nimble and scalable to respond to public health policies and practices compliant with COVID-19 pandemic-related modifications on physical distancing and interacting in the foreseeable future.
IN 1896, Mary Mapes Dodge published a novel about a young Dutch boy's struggle to win a pair of silver ice skates. Hans Brinker: or, the Silver Skates; a Story of Life in Holland contains a chapter that has become a classic American tale of ingenuity, grit, and fortitude.1Dodge MM Hans Brinker: Or, the silver skates; a story of life in Holland. Scribner, New York, NY1896Google Scholar This hero of Haarlem who, despite frequent misattributions, is never actually given a name, is known by many school-age children as the boy who put his finger in the dam. Although universally familiar, the poignant image of a small child standing alone throughout a cold winter night holding back the inevitable flood of a broken dike loses the plot in the imagery. In fact, the story is thematically designed to juxtapose that simple solution against the vast complexity and grandeur of the dam's sluice gates and the precise demands of their operation to keep the village from flooding. I would argue that this story puts forward a timeless and topical illustration of the way in which our most impressive technologic systems continue to demand simple, effective, and timely solutions in the face of failure. This concept was well-illustrated by Liu et al.2Liu X Kimmelstiel C Couper GS Brovman EY Echocardiographic assessment of left ventricular assist device outflow velocity during percutaneous decommissioning.J Cardiothorac Vasc Anesth. 2021; 35: 1534-1538Abstract Full Text Full Text PDF Scopus (1) Google Scholar in their recent E-Challenge in the Journal of Cardiothoracic and Vascular Anesthesia, which describes an ingenious and simple solution to the problem of left ventricular overcirculation after left ventricular assist device (LVAD) decommissioning. The minimally invasive surgical technique left both the inflow cannula and outflow graft patent, creating a low-resistance circuit that resulted in left ventricular volume overload and systemic hypoperfusion. In this rare but meaningful case of ventricular recovery after LVAD implantation as a bridge to transplantation,3Gosev I Kiernan MS Eckman P et al.Long-term survival in patients receiving a continuous-flow left ventricular assist device.Ann Thorac Surg. 2018; 105: 696-701Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar,4Soon JL Tan JL Lim CP et al.Percutaneous decommissioning of left ventricular assist device.Heart Lung Circ. 2018; 27: 853-855Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar the authors used a metaphoric finger in the dike by deploying a percutaneous vascular plug into the aortic outflow graft to close the accessory circuit. This elegant solution allowed for the avoidance of invasive and highly morbid open surgical techniques in a population at particularly high periprocedural risk.5Adamson RM Dembitsky WP Baradarian S et al.Aortic valve closure associated with HeartMate left ventricular device support: Technical considerations and long-term results.J Heart Lung Transplant. 2011; 30: 576-582Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar The contrapositive case here is equally interesting—Is there a role for the application of similar principles in the treatment of severe aortic insufficiency (AI) in LVAD patients? The incidence of severe AI after durable ventricular assist device (VAD) placement has increased with the adoption of continuous-flow devices and is associated with significantly increased morbidity and mortality.6Kalathiya RJ Grinstein J Uriel N et al.Percutaneous transcatheter therapies for the management of left ventricular assist device complications.J Invasive Cardiol. 2017; 29: 151-162PubMed Google Scholar, 7Truby LK Garan AR Givens RC et al.Aortic insufficiency during contemporary left ventricular assist device support: Analysis of the INTERMACS Registry.JACC Heart Fail. 2018; 6: 951-960Crossref PubMed Scopus (56) Google Scholar, 8Rajagopal K Daneshmand MA Patel CB et al.Natural history and clinical effect of aortic valve regurgitation after left ventricular assist device implantation.J Thorac Cardiovasc Surg. 2013; 145: 1373-1379Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar This progressive regurgitation leads to device recirculation, left ventricular distention, loss of pulsatility, systemic hypoperfusion, and early device failure.9Cowger J Pagani FD Haft JW et al.The development of aortic insufficiency in left ventricular assist device-supported patients.Circ Heart Fail. 2010; 3: 668-674Crossref PubMed Scopus (250) Google Scholar Although patients with significant preexisting AI typically undergo surgical intervention at the time of VAD placement,10Feldman D Pamboukian SV Teuteberg JJ et al.The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: Executive summary.J Heart Lung Transplant. 2013; 32: 157-187Abstract Full Text Full Text PDF PubMed Scopus (925) Google Scholar those in whom AI develops de novo present a special case. These individuals are at particularly high risk of surgical complications in the case of redo sternotomy for surgical aortic valve replacement. It is at this intersection of medical necessity and fragility within a complex system that the simplest solution becomes the most appealing. Both transcatheter aortic valve replacement (TAVR) and percutaneous aortic valve closure via the Amplatzer Cribriform (a multifenestrated septal occluder by Abbott Medical, Abbott Park, IL) are minimally invasive approaches that have been posited as solutions to the problem of comorbid AI in patients with durable assist devices.11Parikh KS Mehrotra AK Russo MJ et al.Percutaneous transcatheter aortic valve closure successfully treats left ventricular assist device-associated aortic insufficiency and improves cardiac hemodynamics.JACC Cardiovasc Interv. 2013; 6: 84-89Crossref PubMed Scopus (51) Google Scholar,12D'Ancona G Pasic M Buz S et al.TAVI for pure aortic valve insufficiency in a patient with a left ventricular assist device.Ann Thorac Surg. 2012; 93: e89-e91Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar A recent review and meta-analysis of 15 studies comprising 29 patients found no statistical difference in outcomes between the two approaches.13Phan K Haswell JM Xu J et al.Percutaneous transcatheter interventions for aortic insufficiency in continuous-flow left ventricular assist device patients: A systematic review and meta-analysis.ASAIO J. 2017; 63: 117-122Crossref PubMed Scopus (31) Google Scholar Theoretical device-related concerns regarding the use of TAVR in this case include the risk of device embolization in a native valve, with a low calcium burden and the risk of stuck leaflets, or device thrombosis in low-output states.6Kalathiya RJ Grinstein J Uriel N et al.Percutaneous transcatheter therapies for the management of left ventricular assist device complications.J Invasive Cardiol. 2017; 29: 151-162PubMed Google Scholar,14Yehya A Rajagopal V Meduri C et al.Short-term results with transcatheter aortic valve replacement for treatment of left ventricular assist device patients with symptomatic aortic insufficiency.J Heart Lung Transplant. 2019; 38: 920-926Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar TAVR devices also are significantly more expensive than septal occluder devices.15Goldsweig AM Tak HJ Chen LW et al.Relative costs of surgical and transcatheter aortic valve replacement and medical therapy.Circ Cardiovasc Interv. 2020; 13e008681Crossref PubMed Scopus (11) Google Scholar Transcatheter valve replacement may be a feasible solution but, in this case, represents a solution that is simultaneous minimally invasive but technologically complex. Treatment of LVAD-associated AI via a transcatheter septal occluder device then could be conceptualized as the ideal minimally invasive and low-tech solution. Even though an off-label use, the Cribriform device most frequently has been described in the literature.11Parikh KS Mehrotra AK Russo MJ et al.Percutaneous transcatheter aortic valve closure successfully treats left ventricular assist device-associated aortic insufficiency and improves cardiac hemodynamics.JACC Cardiovasc Interv. 2013; 6: 84-89Crossref PubMed Scopus (51) Google Scholar,13Phan K Haswell JM Xu J et al.Percutaneous transcatheter interventions for aortic insufficiency in continuous-flow left ventricular assist device patients: A systematic review and meta-analysis.ASAIO J. 2017; 63: 117-122Crossref PubMed Scopus (31) Google Scholar It was designed for deployment across thin, potentially mobile tissue flaps, not unlike the aortic valve leaflets. The device also has a low profile on both sides of the waist, which minimizes risk of aortomitral continuity impingement on the left ventricular outflow tract side and coronary ostial occlusion on the aortic side.16Russo MJ Freed BH Jeevanandam V et al.Percutaneous transcatheter closure of the aortic valve to treat cardiogenic shock in a left ventricular assist device patient with severe aortic insufficiency.Ann Thorac Surg. 2012; 94: 985-988Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar When deployed in the case of LVAD-mediated AI, it reliably and irreversibly closes the aortic valve to regurgitant flow. While the Cribriform also may be prone to displacement from the aortic valve position, it is designed to easily be retrieved even after full deployment in the case of device migration. A small, but robust case series, prospectively has shown improved hemodynamic parameters, including pulmonary capillary wedge pressure and left ventricular end-diastolic pressure, after percutaneous aortic valve occlusion.11Parikh KS Mehrotra AK Russo MJ et al.Percutaneous transcatheter aortic valve closure successfully treats left ventricular assist device-associated aortic insufficiency and improves cardiac hemodynamics.JACC Cardiovasc Interv. 2013; 6: 84-89Crossref PubMed Scopus (51) Google Scholar,17Stevenson LW Tillisch JH Hamilton M et al.Importance of hemodynamic response to therapy in predicting survival with ejection fraction ≤20% secondary to ischemic or nonischemic dilated cardiomyopathy.Am J Cardiol. 1990; 66: 1348-1354Abstract Full Text PDF PubMed Scopus (290) Google Scholar There are reasons to be wary of this approach. Of note is a trend toward increased mortality in the review by Phan et al., which did not reach statistical significance.13Phan K Haswell JM Xu J et al.Percutaneous transcatheter interventions for aortic insufficiency in continuous-flow left ventricular assist device patients: A systematic review and meta-analysis.ASAIO J. 2017; 63: 117-122Crossref PubMed Scopus (31) Google Scholar This likely is explained by selection bias; individuals believed to have had the strongest chance of recovery may have been chosen for TAVR rather than permanent aortic valve occlusion. The following two circumstances, in particular, may give one pause: the case of sudden LVAD mechanical failure and the case of unexpected ventricular recovery. In the case of acute, unexpected pump failure, which accounts for only 13% of device malfunction events,18Kormos RL McCall M Althouse A et al.Left ventricular assist device malfunctions: It is more than just the pump.Circulation. 2017; 136: 1714-1725Crossref PubMed Scopus (40) Google Scholar there is no opportunity for native ejection through the occluded aortic valve, and this event becomes uniformly fatal. In the case of unexpected ventricular recovery (1% of all destination or bridge-to-transplantation VADs),8Rajagopal K Daneshmand MA Patel CB et al.Natural history and clinical effect of aortic valve regurgitation after left ventricular assist device implantation.J Thorac Cardiovasc Surg. 2013; 145: 1373-1379Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar,19Kagawa H Aranda-Michel E Kormos RL et al.Aortic insufficiency after left ventricular assist device implantation: Predictors and outcomes.Ann Thorac Surg. 2020; 110: 836-843Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar the device cannot be decommissioned without invasive surgical intervention to restore the left ventricular outflow tract. It may not be worthwhile, however, to wring our hands over potential future challenges while making decisions regarding the acute care of the critically ill patient in front of us. As the use of transcatheter vascular occlusion devices becomes more practiced and the devices more refined, we are likely to see them put to increasingly novel and innovative use. Indeed, it is hard to imagine a group more well-suited to the varied and frequent application of minimally invasive solutions than patients requiring durable VAD support. Whether in the circumstance of system failure via acquired AI (as many as 38% of those who develop moderate AI may go on to develop symptomatic heart failure)20Jorde UP Uriel N Nahumi N et al.Prevalence, significance, and management of aortic insufficiency in continuous flow left ventricular assist device recipients.Circ Heart Fail. 2014; 7: 310-319Crossref PubMed Scopus (121) Google Scholar or unexpected ventricular recovery, sometimes the simplest answer is the best. Indeed, it may well be that all we need is a finger in the dike. The author has no conflicts of interest to disclose. Echocardiographic Assessment of Left Ventricular Assist Device Outflow Velocity During Percutaneous DecommissioningJournal of Cardiothoracic and Vascular AnesthesiaVol. 35Issue 5PreviewLeft ventricular assist devices (LVADs) have been used as an effective therapeutic option in patients with advanced heart failure, either as a bridge to transplantation or, in some patients, as a bridge to recovery. LVAD withdrawal with ventricular recovery represents the optimal outcome for patients previously implanted with an LVAD. In this E-Challenge, the authors present a case of percutaneous decommissioning of an LVAD, in which TEE provided critical, real-time perioperative evaluation. The authors also review the current perspectives on LVAD decommissioning in terms of patient selection and surgical techniques. Full-Text PDF
Despite advances in cardiac surgery and anesthesia, the rates of brain injury remain high in aortic arch surgery requiring circulatory arrest. The mechanisms of brain injury, including permanent and temporary neurologic dysfunction, are multifactorial, but intraoperative brain ischemia is likely a major contributor. Maintaining optimal cerebral perfusion during cardiopulmonary bypass and circulatory arrest is the key component of intraoperative management for aortic arch surgery. Various brain monitoring modalities provide different information to improve cerebral protection. Electroencephalography gives crucial data to ensure minimal cerebral metabolism during deep hypothermic circulatory arrest, transcranial Doppler directly measures cerebral arterial blood flow, and near-infrared spectroscopy monitors regional cerebral oxygen saturation. Various brain protection techniques, including hypothermia, cerebral perfusion, pharmacologic protection, and blood gas management, have been used during interruption of systemic circulation, but the optimal strategy remains elusive. Although deep hypothermic circulatory arrest and retrograde cerebral perfusion have their merits, there have been increasing reports about the use of antegrade cerebral perfusion, obviating the need for deep hypothermia. With controversy and variability of surgical practices, moderate hypothermia, when combined with unilateral antegrade cerebral perfusion, is considered safe for brain protection in aortic arch surgery performed with circulatory arrest. The neurologic outcomes of brain protection in aortic arch surgery largely depend on the following three major components: cerebral temperature, circulatory arrest time, and cerebral perfusion during circulatory arrest. The optimal brain protection strategy should be individualized based on comprehensive monitoring and stems from well-executed techniques that balance the major components contributing to brain injury.
Energy efficiency (EE) program administrators and policy makers have long encouraged the adoption of efficient technologies and conservation practices across all energy users and sectors. Energy users who haven’t yet participated in efficiency and conservation programs despite ongoing outreach are often referred to as “Hard-to-Reach” (HTR). These individuals or organizations can include, for instance, low income or rural audiences on the residential side and small businesses or building operators on the commercial side. More effectively engaging underserved and HTR audiences is key to ensuring everyone benefits equitably from efficiency and conservation interventions. In June 2019, energy efficiency, behavior change and HTR researchers, practitioners, and policy makers from five countries embarked on a 3-year project in partnership with the UserCentred Energy Systems Technology Collaboration Programme (Users TCP) by the International Energy Agency (IEA). The purpose of this effort is to characterize the diverse audience segments commonly referred to as HTR and to uncover the barriers and behavioral opportunities to more effectively engage them. This paper describes the first of these efforts. We have synthesized data from a global survey (N=110) and stakeholder interviews with 40+ energy efficiency experts striving to better understand and engage HTR in their respective countries. This paper provides initial insights from this data into how HTR energy users are defined across the world and which segments have been prioritized globally for focused outreach. The overarching goal is to use a standardized research process to inform and improve how energy efficiency, behavior change, and demand response programs targeting specific HTR audiences are designed, implemented and evaluated.
Increased lung clearance index scores and abnormal exercise ventilatory parameters consistent with small-airway disease show promise as noninvasive diagnostic markers that may help identify symptomatic deployers with deployment-related distal lung disease.
Two children with autism were assessed for preference between intersession distribution of mastered and unknown instructional trials on a computerized matching-to-sample task consisting of 12 total learning opportunities. Choice responses yielded presentation of either massed-trial sequencing (six unknown/six mastered stimuli relations or vice-versa) or alternating-trial sequencing delivery (alternation of unknown and mastered stimuli relations) followed by reinforcement for correct responses. An extinction condition served as an experimental control. Both children demonstrated a preference for the alternating-trial sequencing condition, and implications for instructional programming and possible effects to delays to higher rates of reinforcement are discussed.
Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, but it does not incorporate network inference and underperforms in eukaryotes. We present an Integrated Deduced REgulation And Metabolism (IDREAM) method that combines statistically inferred Environment and Gene Regulatory Influence Network (EGRIN) models with the PROM framework to create enhanced metabolic-regulatory network models. We used IDREAM to predict phenotypes and genetic interactions between transcription factors and genes encoding metabolic activities in the eukaryote, Saccharomyces cerevisiae. IDREAM models contain many fewer interactions than PROM and yet produce significantly more accurate growth predictions. IDREAM consistently outperformed PROM using any of three popular yeast metabolic models and across three experimental growth conditions. Importantly, IDREAM’s enhanced accuracy makes it possible to identify subtle synthetic growth defects. With experimental validation, these novel genetic interactions involving the pyruvate dehydrogenase complex suggested a new role for fatty acid-responsive factor Oaf1 in regulating acetyl-CoA production in glucose grown cells. Author Summary The integration of gene regulatory and metabolic network models is an important goal in computational biology, in order to develop methods that can identify the underlying mechanistic links in biological networks and advance metabolic engineering techniques. In this paper, we develop a framework called Integrated Deduced REgulation And Metabolism (IDREAM) that can improve our ability to predict phenotypes of microorganisms, and particularly it can address the challenges in evaluating phenotypic consequence of perturbing transcriptional regulation of metabolism in a eukaryotic cell. We compare the predictive performance of an IDREAM S. cerevisiae model with a PROM model using a TRN available from the YEASTRACT database. IDREAM outperforms PROM using any of three popular yeast metabolic models and across three experimental growth conditions, making it possible to identify subtle synthetic growth defects, and a new role for Oaf1 in the regulation of acetyl-CoA biosynthesis.
This is the second of the paired volumes which derive from the conference ‘MMECL 2011: Middle and Modern English Corpus Linguistics’ held in Osaka on 26-9 August 2011. While the first volume edited by Yoko Iyeiri and Jennifer Smith (Studies in Middle and Modern English: Historical Change, 2014, Osaka: Osaka Books Ltd.) is more concerned with historical change in Middle and Modern English, the present volume includes papers whose interests are more focused on historical (or synchronic) variation of the English language, though naturally with an eye to historical change as well. In the present volume, the six papers discuss variation in language use in the historical record, demonstrating the fact that corpus-based studies, when combined with minute reading or philological approach, can offerinsightful findingsin the analysis of both synchronicand diachronic variation in English. The volume is ordered thematically from morphology via syntax to pragmatics and stylistics.
In recent years the biosynthesis of auxin has been clarified with the aid of mutations in auxin biosynthesis genes. However, we know little about the effects of these mutations on the seed-filling stage of seed development. Here we investigate a key auxin biosynthesis mutation of the garden pea, which results in auxin deficiency in developing seeds. We exploit the large seed size of this model species, which facilitates the measurement of compounds in individual seeds. The mutation results in small seeds with reduced starch content and a wrinkled phenotype at the dry stage. The phenotypic effects of the mutation were fully reversed by introduction of the wild-type gene as a transgene, and partially reversed by auxin application. The results indicate that auxin is required for normal seed size and starch accumulation in pea, an important grain legume crop.
Adaptive prediction is a capability of diverse organisms, including microbes, to sense a cue and prepare in advance to deal with a future environmental challenge. Here, we investigated the time frame over which adaptive prediction emerges when an organism encounters an environment with novel structure. We subjected yeast to laboratory evolution in a novel environment with repetitive, coupled exposures to a neutral chemical cue (caffeine), followed by a sublethal dose of a toxin (5-FOA), with an interspersed requirement for uracil prototrophy to counter-select mutants that gained constitutive 5-FOA resistance. We demonstrate the remarkable ability of yeast to internalize a novel environmental pattern within 50-150 generations by adaptively predicting 5-FOA stress upon sensing caffeine. We also demonstrate how novel environmental structure can be internalized by coupling two unrelated response networks, such as the response to caffeine and signaling-mediated conditional peroxisomal localization of proteins.
Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAY extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.
We have established proof of principle for the Indicator Cell Assay Platform™ (iCAP™), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients’ blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, cost-effective disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% accuracy (p-Value=3.81E-6) and correctly identified samples from a murine Huntington’s disease model as non-carriers of ALS. In a preliminary human disease assay, the iCAP detected early stage Alzheimer’s disease with 72% cross-validated accuracy (p-Value=3.10E-3). For both assays, iCAP features were enriched for disease-related genes, supporting the assay’s relevance for disease research.
OBJECTIVES:To evaluate a new prenatal education program evaluation tool, the UpStart Parent Survey - Prenatal, in terms of: (a) reliability and validity; (b) sensitivity to change over time; (c) whether results differed for mothers versus fathers; and (d) whether results differed when using an electronic tablet-computer versus a paper survey.DESIGN AND SAMPLE:Psychometric study. Participants were 277 expectant mothers (n = 161) and fathers (n = 106) enrolled in Childbirth Essentials, a 6-week prenatal education program.MEASURES:The UpStart Parent Survey - Prenatal is a retrospective pretest/posttest survey with three scales: Parenting Knowledge, Parenting Experience, and Program Satisfaction, and three open-ended questions.RESULTS:The UpStart Parent Survey - Prenatal is sensitive to change and demonstrated significant positive differences in parenting knowledge and parenting experience. There was no difference in results whether the survey was completed by mothers or fathers. Results were similar whether paper or electronic formats were used. The survey was easy to complete.CONCLUSION:The UpStart Parent Survey - Prenatal holds promise as a reliable and valid evaluation tool to capture outcomes of brief prenatal education programs that target the general population of expectant parents.
ABSTRACT Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAY extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.
BACKGROUND:Biclustering is a popular method for identifying under which experimental conditions biological signatures are co-expressed. However, the general biclustering problem is NP-hard, offering room to focus algorithms on specific biological tasks. We hypothesize that conditional co-regulation of genes is a key factor in determining cell phenotype and that accurately segregating conditions in biclusters will improve such predictions. Thus, we developed a bicluster sampled coherence metric (BSCM) for determining which conditions and signals should be included in a bicluster.RESULTS:Our BSCM calculates condition and cluster size specific p-values, and we incorporated these into the popular integrated biclustering algorithm cMonkey. We demonstrate that incorporation of our new algorithm significantly improves bicluster co-regulation scores (p-value = 0.009) and GO annotation scores (p-value = 0.004). Additionally, we used a bicluster based signal to predict whether a given experimental condition will result in yeast peroxisome induction. Using the new algorithm, the classifier accuracy improves from 41.9% to 76.1% correct.CONCLUSIONS:We demonstrate that the proposed BSCM helps determine which signals ought to be co-clustered, resulting in more accurately assigned bicluster membership. Furthermore, we show that BSCM can be extended to more accurately detect under which experimental conditions the genes are co-clustered. Features derived from this more accurate analysis of conditional regulation results in a dramatic improvement in the ability to predict a cellular phenotype in yeast. The latest cMonkey is available for download at https://github.com/baliga-lab/cmonkey2. The experimental data and source code featured in this paper is available http://AitchisonLab.com/BSCM. BSCM has been incorporated in the official cMonkey release.