Extracting Information from Adaptive Control Experiments

Optical control of chemical reactivity is achieved through the use of photonic reagents, that is, “shaped” ultrafast optical pulses created using a pulse shaper. It has been demonstrated in a number of molecular systems that these pulses can effectively guide the system into a desired final state. Effective pulses are often found through an experimental search involving thousands of individual measurements. An examination of the pulses tested in these experiments can reveal the pulse features responsible for control and also the underlying molecular dynamics. In this article we review attempts to extract information from optical control experiments using adaptive learning algorithms to search the available parameter space, and we discuss how these kinds of experiments can be used to achieve and understand multiphoton optical control.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91361/1/397_ftp.pd

Photoactivatable genetically encoded calcium indicators for targeted neuronal imaging.

Circuit mapping requires knowledge of both structural and functional connectivity between cells. Although optical tools have been made to assess either the morphology and projections of neurons or their activity and functional connections, few probes integrate this information. We have generated a family of photoactivatable genetically encoded Ca(2+) indicators that combines attributes of high-contrast photolabeling with high-sensitivity Ca(2+) detection in a single-color protein sensor. We demonstrated in cultured neurons and in fruit fly and zebrafish larvae how single cells could be selected out of dense populations for visualization of morphology and high signal-to-noise measurements of activity, synaptic transmission and connectivity. Our design strategy is transferrable to other sensors based on circularly permutated GFP (cpGFP)

Microscopic modulation and analysis of islets of Langerhans in living zebrafish larvae

Microscopic analysis of molecules and physiology in living cells and systems is a powerful tool in life sciences. While in vivo subcellular microscopic analysis of healthy and diseased human organs remains impossible, zebrafish larvae allow studying pathophysiology of many organs using in vivo microscopy. Here, we review the potential of the larval zebrafish pancreas in the context of islets of Langerhans and Type 1 diabetes. We highlight the match of zebrafish larvae with the expanding toolbox of fluorescent probes that monitor cell identity, fate and/or physiology in real time. Moreover, fast and efficient modulation and localization of fluorescence at a subcellular level, through fluorescence microscopy, including confocal and light sheet (single plane illumination) microscopes tailored to in vivo larval research, is addressed. These developments make the zebrafish larvae an extremely powerful research tool for translational research. We foresee that living larval zebrafish models will replace many cell line-based studies in understanding the contribution of molecules, organelles and cells to organ pathophysiology in whole organisms.ImPhys/Microscopy Instrumentation & Technique

Evaluating Loss to Follow-Up in Newborn Hearing Screening in a Southern State

Objective: The aim of this study was to examine loss to follow-up on the usage of diagnostic or intervention services for South Carolina infants screened or diagnosed with hearing loss and the risk factors associated with loss to follow up. Design: A cross sectional analysis of data from South Carolina was used to examine loss to follow-up on the use of audiologic evaluation services after initial newborn hearing screening and receipt of intervention services after confirmation of hearing loss. Results: Three percent (3.1%) of all children screened in the state of South Carolina did not pass their newborn hearing screening test in 2013 with less than half (49.1%) of those children not reported to have used audiologic diagnostic services within one month of their initial screening test. Factors significant with receipt of services include birth weight, mother’s education, insurance type, and rurality. The degree of hearing loss was a significant determinant of receiving intervention at some point in time. Conclusions: The highest risk children are “lost follow-up” for both the initial diagnostic services and follow-up intervention services in South Carolina. Interventions targeted at specific groups are needed to improve the delivery of hearing services and prevent a public health shortfall

Data visualization for truth maintenance in clinical decision support systems

Background and objectives The goal is to inform proactive initiatives to expand the knowledge base of clinical decision support systems. Design and setting We describe an initiative in which research informationists and health services researchers employ visualization tools to map logic models for clinical decision support within an electronic health record. Materials and methods We mapped relationships using software for social network analysis: NodeXL and CMAP. We defined relationships by shared observations, such as two Arden rules within medical logic modules that consider the same clinical observation, or by the presence of common keywords that were used to label rules according to standardized vocabularies. Results We studied the Child Health Improvement through Computer Automation (CHICA) system, an electronic medical record that contains 170 unique variables representing discrete clinical observations. These variables were used in 300 medical logic modules (MLM's) that prompted health care providers to deliver preventive counseling or otherwise served as clinical decision support. Using data visualization tools, we generated maps that illustrate connections, or lack thereof, between clinical topics within CHICA's MLMs. Conclusions The development of such maps may allow multiple disciplines commonly interacting over EMR platforms, and various perspectives (clinicians, programmers, informationists) to work more effectively as teams to refine the EMR by programming logic routines to address co-morbidities or other instances where domains of medical knowledge should be connected

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

What implementation interventions increase cancer screening rates? a systematic review

<p>Abstract</p> <p>Background</p> <p>Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC) screening. The interventions considered were: client reminders, client incentives, mass media, small media, group education, one-on-one education, reduction in structural barriers, reduction in out-of-pocket costs, provider assessment and feedback interventions, and provider incentives. Our primary outcome, screening completion, was calculated as the overall median post-intervention absolute percentage point (PP) change in completed screening tests.</p> <p>Methods</p> <p>Our first step was to conduct an iterative scoping review in the research area. This yielded three relevant high-quality systematic reviews. Serving as our evidentiary foundation, we conducted a formal update. Randomized controlled trials and cluster randomized controlled trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and PSYCHinfo.</p> <p>Results</p> <p>The update yielded 66 studies new eligible studies with 74 comparisons. The new studies ranged considerably in quality. Client reminders, small media, and provider audit and feedback appear to be effective interventions to increase the uptake of screening for three cancers. One-on-one education and reduction of structural barriers also appears effective, but their roles with CRC and cervical screening, respectively, are less established. More study is required to assess client incentives, mass media, group education, reduction of out-of-pocket costs, and provider incentive interventions.</p> <p>Conclusion</p> <p>The new evidence generally aligns with the evidence and conclusions from the original systematic reviews. This review served as the evidentiary foundation for an implementation guideline. Poor reporting, lack of precision and consistency in defining operational elements, and insufficient consideration of context and differences among populations are areas for additional research.</p

Infection by a foliar endophyte elicits novel arabidopside-based plant defence reactions in its host, Cirsium arvense

Endophytic fungi live asymptomatically within plants. They are usually regarded as non-pathogenic or even mutualistic, but whether plants respond antagonistically to their presence remains unclear, particularly in the little-studied associations between endophytes and nong-raminoid herbaceous plants. We investigated the effects of the endophyte Chaetomium cochlioides on leaf chemistry in Cirsium arvense. Plants were sprayed with spores; leaf material from both subsequent new growth and the sprayed leaves was analysed 2 wk later. Infection frequency was 91% and63% for sprayed and new growth, respectively, indicating that C. cochlioides rapidly infects new foliage. Metabolomic analyses revealed marked changes in leaf chemistry with infection, especially in new growth. Changes in several novel oxylipin metabolites were detected, including arabi-dopsides reported here for the first time in a plant species other than Arabidopsis thaliana,and a jasmonate-containing galactolipid. The production of these metabolites in response to endophyte presence, particularly in newly infected foliage, suggests that endophytes elicit similar chemical responses in plants to those usually produced following wounding, herbivory and pathogen invasion. Whether en-dophytes benefit their hosts may depend on a complex series of chemically mediated interactions between the plant, the endophyte, other microbial colonists and natural enemies

Microbial sharing between pediatric patients and therapy dogs during hospital animal-assisted intervention programs

Microbial sharing between humans and animals has been demonstrated in a variety of settings. However, the extent of microbial sharing that occurs within the healthcare setting during animal-assisted intervention programs is unknown. Understanding microbial transmission between patients and therapy dogs can provide important insights into potential health benefits for patients, in addition to addressing concerns regarding potential pathogen transmission that limits program utilization. This study evaluated for potential microbial sharing between pediatric patients and therapy dogs and tested whether patient-dog contact level and a dog decolonization protocol modified this sharing. Patients, therapy dogs, and the hospital environment were sampled before and after every group therapy session and samples underwent 16S rRNA sequencing to characterize microbial communities. Both patients and dogs experienced changes in the relative abundance and overall diversity of their nasal microbiome, suggesting that the exchange of microorganisms had occurred. Increased contact was associated with greater sharing between patients and therapy dogs, as well as between patients. A topical chlorhexidine-based dog decolonization was associated with decreased microbial sharing between therapy dogs and patients but did not significantly affect sharing between patients. These data suggest that the therapy dog is both a potential source of and a vehicle for the transfer of microorganisms to patients but not necessarily the only source. The relative contribution of other potential sources (e.g., other patients, the hospital environment) should be further explored to determine their relative importance

Defining success in graduate school

[Response to Weiner OD (2014) How should we be selecting our graduate students. Mol Biol Cell 25:429–430. doi: 10.1091/mbc.E13-11-0646.