Safety in Health Care: The Impact of Operating Room Design.

The science of operating room design has grown over the past 20 years due to the realization that the physical environment influences health care provider performance and patient outcomes. Medical errors occur when the normal workflow in an operating room is disrupted as providers must overcome sub-optimal conditions. All aspects of the physical environment can impact operating room flow. Studying the layout, contents, ergonomics, and environmental parameters of the operating can lead improved work conditions resulting improved patient and provider safety. At the forefront of operating room design science is the use of simulation and the evaluation of new technologies.

Visualization of the biphasic calcium wave during fertilization in Caenorhabditis elegans using a genetically encoded calcium indicator.

Fertilization is a critical step in development, yet internal fertilization events are notoriously difficult to visualize. Taking advantage of the calcium response that is a hallmark of sperm-egg fusion, we adapted the genetically encoded calcium indicator jGCaMP7s to visualize the moment of fertilization in Caenorhabditis elegans using fluorescence. We termed this tool the 'CaFE' reporter, for 'calcium during fertilization in C. elegans'. The CaFE reporter produced a robust signal that recapitulated the previously reported, biphasic nature of the calcium wave and had no significant deleterious effects on worm physiology or fecundity. Calcium waves were not observed at the restrictive temperature in the spe-9(hc88) strain, in which sperm can still trigger meiotic maturation but can no longer fuse with the oocyte. Demonstrating the utility of the CaFE reporter, we analyzed polyspermy induced by inhibition of egg-3 via RNAi and observed late calcium waves in the uterus. This finding provides support to the idea that calcium release is not restricted to the first sperm fusion event during polyspermy. Establishment of the CaFE reporter in the genetically tractable and optically transparent worm provides a powerful tool to dissect the oocyte-to-embryo transition inside a living animal.

Retraction: Colloidal Cobalt Phosphide Nanocrystals as Trifunctional Electrocatalysts for Overall Water Splitting Powered by a Zinc-Air Battery.

Adv. Mater. 2018, 30, 1705796 https://doi.org/10.1002/adma.201705796 The above article, published online on January 15, 2018, in Wiley Online Library (https://doi.org/10.1002/adma.201705796), has been retracted by agreement between the authors, the journal Editor in Chief Jos Lenders, and Wiley-VCH GmbH. The retraction has been agreed on following concerns raised by a third party and a subsequent investigation at Wake Forest University. Data integrity issues were found in Figures 1a, S2b, and S17. As a result, the authors consider the conclusions of this article invalid.

Usability of existing global and national data for flood related vulnerability assessment in Indonesia.

Public climatic data are rapidly growing in volume and complexity at global and national scales but these data remain underutilized for vulnerability assessment. We aim to explore how flood records from Dartmouth Flood Observatory, a global flood monitoring database, can be linked with a national disaster database maintained by the Indonesian National Board for Disaster Management, to aid local vulnerability assessment in Indonesia. We focused on physical damage to structures and agricultural crops from flooding and examined spatiotemporal patterns of a vulnerability metric derived from principal component analysis. We identified the most vulnerable areas based on emerging hot spot analysis and detected sporadic hotspots (i.e. on again then off again) of flooding in Jakarta and West Java. Using our derived metric, we identified oscillating cold spots (i.e. a cold spot that was previously a hot spot) of vulnerability in Banten, Jakarta, West Java, and Central Java. The detection of nonhomogeneous spatiotemporal trends in flooding and vulnerability demonstrate potential usability of public climate data and help to outline directions for novel research.

Acute and chronic toxicity of imidacloprid in the pollinator fly, Eristalis tenax L., assessed using a novel oral bioassay.

Imidacloprid is a neonicotinoid neurotoxin that remains widely used worldwide and persists in the environment, resulting in chronic exposure to non-target insects. To accurately map dose-dependent effects of such exposure across taxa, toxicological assays need to assess relevant modes of exposure across indicator species. However, due to the difficulty of these experiments, contact bioassays are most frequently used to quantify dose. Here, we developed a novel naturalistic feeding bioassay to precisely measure imidacloprid ingestion and its toxicity for acute and chronic exposure in a dipteran, Eristalis tenax L., an important member of an under-represented pollinator group. Flies which ingested imidacloprid dosages lower than 12.1 ng/mg all showed consistent intake volumes and learned improved feeding efficiency over successive feeding sessions. In contrast, at doses of 12.1 ng/mg and higher flies showed a rapid onset of severe locomotive impairment which prevented them from completing the feeding task. Neither probability of survival nor severe locomotive impairment were significantly higher than the control group until doses of 1.43 ng/mg or higher were reached. We were unable to measure a median lethal dose for acute exposure (72 h) due to flies possessing a relatively high tolerance for imidacloprid. However, with chronic exposure (18 days), mortality went up and an LD50 of 0.41 ng/mg was estimated. Severe locomotive impairment (immobilisation) tended to occur earlier and at lower dosages than lethality, with ED50s of 7.82 ng/mg and 0.17 ng/mg for acute and chronic exposure, respectively. We conclude that adult Eristalis possess a much higher tolerance to this toxin than the honeybees that they mimic. The similarity of the LD50 to other dipterans such as the fruitfly and the housefly suggests that there may be a phylogenetic component to pesticide tolerance that merits further investigation. The absence of obvious adverse effects at sublethal dosages also underscores a need to develop better tools for quantifying animal behaviour to evaluate the impact of insecticides on foraging efficiency in economically important species.

Spontaneous Cell Cluster Formation in Human iPSC-Derived Neuronal Spheroid Networks Influences Network Activity.

Three-dimensional neuronal culture systems such as spheroids, organoids, and assembloids constitute a branch of neuronal tissue engineering that has improved our ability to model the human brain in the laboratory. However, the more elaborate the brain model, the more difficult it becomes to study functional properties such as electrical activity at the neuronal level, similar to the challenges of studying neurophysiology in vivo We describe a simple approach to generate self-assembled three-dimensional neuronal spheroid networks with defined human cell composition on microelectrode arrays. Such spheroid networks develop a highly three-dimensional morphology with cell clusters up to 60 µm in thickness and are interconnected by pronounced bundles of neuronal fibers and glial processes. We could reliably record from up to hundreds of neurons simultaneously per culture for ≤90 d. By quantifying the formation of these three-dimensional structures over time, while regularly monitoring electrical activity, we were able to establish a strong link between spheroid morphology and network activity. In particular, the formation of cell clusters accelerates formation and maturation of correlated network activity. Astrocytes both influence electrophysiological network activity as well as accelerate the transition from single cell layers to cluster formation. Higher concentrations of astrocytes also have a strong effect of modulating synchronized network activity. This approach thus represents a practical alternative to often complex and heterogeneous organoids, providing easy access to activity within a brain-like 3D environment.Significance StatementNeuronal "organoid" cultures with multiple cell types grown on elaborate three-dimensional scaffolds have become popular tools to generate brain-like properties in vitro but bring with them similar problems concerning access to physiological function as real brain tissue. Here, we developed a new approach to form simple brain-like spheroid networks from human neurons, but using the normal supporting cells of the brain, astrocytes, as the scaffold. By growing these cultures on conventional microelectrode arrays, we were able to observe development of complex patterns of electrical activity for months. Our results highlight how formation of three-dimensional structures accelerated the formation of synchronized neuronal network activity and provide a promising new simple model system for studying interactions between known human cell types in vitro.

Structure activity relationships leading to the identification of the indirect activator of AMPK, R419.

Using an in-cell AMPK activation assay, we have developed structure-activity relationships around a hit pyridine dicarboxamide 5 that resulted in 40 (R419). A particular focus was to retain the on-target potency while also improving microsomal stability and reducing off-target activities, including hERG inhibition. We were able to show that removing a tertiary amino group from the piperazine unit of hit compound 5 improved microsomal stability while hERG inhibition was improved by modifying the substitution of the central core pyridine ring. The SAR resulted in 40, which continues to maintain on-target potency. Compound 40 was able to activate AMPK in vivo after oral administration and showed efficacy in animal models investigating activation of AMPK as a therapy for glucose control (both db/db and DIO mouse models).

Preattentive facilitation of target trajectories in a dragonfly visual neuron.

The ability to pursue targets in visually cluttered and distraction-rich environments is critical for predators such as dragonflies. Previously, we identified Centrifugal Small-Target Motion Detector 1 (CSTMD1), a dragonfly visual neuron likely involved in such target-tracking behaviour. CSTMD1 exhibits facilitated responses to targets moving along a continuous trajectory. Moreover, CSTMD1 competitively selects a single target out of a pair. Here, we conducted in vivo, intracellular recordings from CSTMD1 to examine the interplay between facilitation and selection, in response to the presentation of paired targets. We find that neuronal responses to both individual trajectories of simultaneous, paired targets are facilitated, rather than being constrained to the single, selected target. Additionally, switches in selection elicit suppression which is likely an important attribute underlying target pursuit. However, binocular experiments reveal these results are constrained to paired targets within the same visual hemifield, while selection of a target in one visual hemifield establishes ocular dominance that prevents facilitation or response to contralaterally presented targets. These results reveal that the dragonfly brain preattentively represents more than one target trajectory, to balance between attentional flexibility and resistance against distraction.

Integrating experience with databases, bioinformatics, and wet lab exercises for students in an introductory genetics course.

Students often have no exposure to the incredible amount of genomic and proteomic data that is freely and easily accessible online. Becoming familiar with these resources, and seeing how they could be applied to a specific research question, is a prerequisite for students to apply them to their own scientific development. Many students have to "see it" and "do it" before they "get it." This paper describes a teaching laboratory for undergraduate Genetics students that combines exploration of several publicly available databases with some simple bioinformatic exercises and "'real" live experience in a wet lab exercise. The goal is to teach skills in applying genomic data to a real scientific question. In this exercise, students identify a target protein after exploring several protein and signal transduction databases, such as the Kyoto Encyclopedia of Genes and Genomes database. They then search for the encoding RNA in a newly available sea star mature egg transcriptome database and for the DNA in an existing sea star genome database. The students design primers against specific regions or domains in their target RNA and amplify these by reverse transcription PCR against RNA purified from fresh sea star eggs. The PCR reactions are analyzed by agarose gel electrophoresis. It is hoped that the combination of the computational biology exercises with the real lab work will excite the students and stimulate them to explore this exciting new biology further.

A Smartphone App for Parental Management of Adolescent Conduct Problems: Randomized Clinical Trial of iKinnect.

OBJECTIVE: This study evaluates iKinnect, a linked caregiver-teen mobile app system designed to address serious adolescent conduct problems through a focus on key targets of evidence-based treatments for juvenile offending, such as parent expectation setting, monitoring, consistency, and positive reinforcement. Additional gamification and autonomy-supporting features are designed to maximize youth engagement. Digital therapeutics such as mobile apps have great potential to expand access to effective interventions, particularly for youth who engage in serious conduct problems and substance abuse, since most never receive an evidence-based treatment and few apps exist for these concerns. METHODS: This randomized clinical trial used a short-term (12 week) longitudinal design with four time points. Recruited was a U.S. national sample of teens (n = 72, age 13-17, 59.7% male, 68.1% White) receiving services for a serious conduct problem and their primary caregiver. The efficacy of iKinnect, used by parent and teen dyads, was measured against an active control condition, Life360, an app that provided mutual GPS-based location tracking to dyads. RESULTS: Across 12 weeks of app use, youth who used iKinnect showed significantly greater reductions in alcohol use, marijuana use, school delinquency, status offenses, and general delinquency than did controls. Parents who used iKinnect Reported greater improvements in structure/rule clarity and discipline consistency relative to control parents. Teen and parent iKinnect app use and acceptability ratings were high. CONCLUSIONS: Real-world use of iKinnect in future applications can, like other emerging digital health technologies, help to expand the reach of evidence-based interventions to children, youth, and families.Registered at clinicaltrials.gov (NCT03065517).

Correction: Synthesis of lead-free Cs3Sb2Br9 perovskite alternative nanocrystals with enhanced photocatalytic CO2 reduction activity.

Correction for 'Synthesis of lead-free Cs3Sb2Br9 perovskite alternative nanocrystals with enhanced photocatalytic CO2 reduction activity' by Chang Lu et al., Nanoscale, 2020, 12, 2987-2991, https://doi.org/10.1039/C9NR07722G.

Peripheral Joint Radiofrequency Ablation.

This article provides a detailed description of peripheral joint radiofrequency ablation and its contemporary use in the treatment of chronic knee, hip, and shoulder pain. Special attention is given to anatomy and innervation of the joints discussed, technical approach, selection criteria, contraindications, and patient outcomes.

Dragonfly Neurons Selectively Attend to Targets Within Natural Scenes.

Aerial predators, such as the dragonfly, determine the position and movement of their prey even when both are moving through complex, natural scenes. This task is likely supported by a group of neurons in the optic lobe which respond to moving targets that subtend less than a few degrees. These Small Target Motion Detector (STMD) neurons are tuned to both target size and velocity, whilst also exhibiting facilitated responses to targets traveling along continuous trajectories. When presented with a pair of targets, some STMDs generate spiking activity that represent a competitive selection of one target, as if the alternative does not exist (i.e., selective attention). Here, we describe intracellular responses of CSTMD1 (an identified STMD) to the visual presentation of targets embedded within cluttered, natural scenes. We examine CSTMD1 response changes to target contrast, as well as a range of target and background velocities. We find that background motion affects CSTMD1 responses via the competitive selection between features within the natural scene. Here, robust discrimination of our artificially embedded "target" is limited to scenarios when its velocity is matched to, or greater than, the background velocity. Additionally, the background's direction of motion affects discriminability, though not in the manner observed in STMDs of other flying insects. Our results highlight that CSTMD1's competitive responses are to those features best matched to the neuron's underlying spatiotemporal tuning, whether from the embedded target or other features in the background clutter. In many scenarios, CSTMD1 responds robustly to targets moving through cluttered scenes. However, whether this neuronal system could underlie the task of competitively selecting slow moving prey against fast-moving backgrounds remains an open question.

Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications.

BACKGROUND: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. MATERIALS AND METHODS: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells. RESULTS: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers. CONCLUSION: We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.

Stress response gene family expansions correlate with invasive potential in teleost fish.

The bluegill sunfish Lepomis macrochirus and the closely related redear sunfish Lepomis microlophus have important ecological and recreational value and are widely used for research and aquaculture. While both species have been introduced outside of their native ranges, only the bluegill is considered invasive. Here, we report de novo transcriptome assemblies for these fish as a resource for sunfish biology. Comparative analyses of the transcriptomes revealed an unexpected, bluegill-specific expansion in the HSP70 and HSP90 molecular chaperone gene families. These expansions were not unique to the bluegill as expansions in HSP70s and HSP90s were identified in the genomes of other teleost fish using the NCBI RefSeq database. To determine whether gene family expansions are specific for thermal stress responses, GST and SOD gene families that are associated with oxidative stress responses were also analyzed. Species-specific expansions were also observed for these gene families in distinct fish species. Validating our approach, previously described expansions in the MHC gene family were also identified. Intriguingly, the number of HSP70 paralogs was positively correlated with thermotolerance range for each species, suggesting that these expansions can impact organismal physiology. Furthermore, fish that are considered invasive contained a higher average number of HSP70 paralogs than non-invasive fish. Invasive fish also had higher average numbers of HSP90, MHC and GST paralogs, but not SOD paralogs. Taken together, we propose that expansions in key cellular stress response gene families represent novel genetic signatures that correlate with invasive potential.

Validation of the INDDEX24 mobile app v. a pen-and-paper 24-hour dietary recall using the weighed food record as a benchmark in Burkina Faso.

Effective nutrition policies require timely, accurate individual dietary consumption data; collection of such information has been hampered by cost and complexity of dietary surveys and lag in producing results. The objective of this work was to assess accuracy and cost-effectiveness of a streamlined, tablet-based dietary data collection platform for 24-hour individual dietary recalls (24HR) administered using INDDEX24 platform v. a pen-and-paper interview(PAPI) questionnaire, with weighed food record (WFR) as a benchmark. This cross-sectional comparative study included women 18-49 years old from rural Burkina Faso (n 116 INDDEX24; n 115 PAPI). A WFR was conducted; the following day, a 24HR was administered by different interviewers. Food consumption data were converted into nutrient intakes. Validity of 24HR estimates of nutrient and food group consumption was based on comparison with WFR using equivalence tests (group level) and percentages of participants within ranges of percentage error (individual level). Both modalities performed comparably estimating consumption of macro- and micronutrients, food groups and quantities (modalities' divergence from WFR not significantly different). Accuracy of both modalities was acceptable (equivalence to WFR significant at P < 0·05) at group level for macronutrients, less so for micronutrients and individual-level consumption (percentage within ±20 % for WFR, 17-45 % for macronutrients, 5-17 % for micronutrients). INDDEX24 was more cost-effective than PAPI based on superior accuracy of a composite nutrient intake measure (but not gram amount or item count) due to lower time and personnel costs. INDDEX24 for 24HR dietary surveys linked to dietary reference data shows comparable accuracy to PAPI at lower cost.

A new, fluorescence-based method for visualizing the pseudopupil and assessing optical acuity in the dark compound eyes of honeybees and other insects.

Recent interest in applying novel imaging techniques to infer optical resolution in compound eyes underscores the difficulty of obtaining direct measures of acuity. A widely used technique exploits the principal pseudopupil, a dark spot on the eye surface representing the ommatidial gaze direction and the number of detector units (ommatidia) viewing that gaze direction. However, dark-pigmented eyes, like those of honeybees, lack a visible pseudopupil. Attempts over almost a century to estimate optical acuity in this species are still debated. Here, we developed a method to visualize a stable, reliable pseudopupil by staining the photoreceptors with fluorescent dyes. We validated this method in several species and found it to outperform the dark pseudopupil for this purpose, even in pale eyes, allowing more precise location of the gaze centre. We then applied this method to estimate the sampling resolution in the frontal part of the eye of the honeybee forager. We found a broad frontal acute zone with interommatidial angles below 2° and a minimum interommatidial angle of 1.3°, a broader, sharper frontal acute zone than previously reported. Our study provides a new method to directly measure the sampling resolution in most compound eyes of living animals.

Modeling Nonlinear Dendritic Processing of Facilitation in a Dragonfly Target-Tracking Neuron.

Dragonflies are highly skilled and successful aerial predators that are even capable of selectively attending to one target within a swarm. Detection and tracking of prey is likely to be driven by small target motion detector (STMD) neurons identified from several insect groups. Prior work has shown that dragonfly STMD responses are facilitated by targets moving on a continuous path, enhancing the response gain at the present and predicted future location of targets. In this study, we combined detailed morphological data with computational modeling to test whether a combination of dendritic morphology and nonlinear properties of NMDA receptors could explain these observations. We developed a hybrid computational model of neurons within the dragonfly optic lobe, which integrates numerical and morphological components. The model was able to generate potent facilitation for targets moving on continuous trajectories, including a localized spotlight of maximal sensitivity close to the last seen target location, as also measured during in vivo recordings. The model did not, however, include a mechanism capable of producing a traveling or spreading wave of facilitation. Our data support a strong role for the high dendritic density seen in the dragonfly neuron in enhancing non-linear facilitation. An alternative model based on the morphology of an unrelated type of motion processing neuron from a dipteran fly required more than three times higher synaptic gain in order to elicit similar levels of facilitation, despite having only 20% fewer synapses. Our data support a potential role for NMDA receptors in target tracking and also demonstrate the feasibility of combining biologically plausible dendritic computations with more abstract computational models for basic processing as used in earlier studies.