Scalable spin squeezing in a dipolar Rydberg atom array.

The standard quantum limit bounds the precision of measurements that can be achieved by ensembles of uncorrelated particles. Fundamentally, this limit arises from the non-commuting nature of quantum mechanics, leading to the presence of fluctuations often referred to as quantum projection noise. Quantum metrology relies on the use of non-classical states of many-body systems to enhance the precision of measurements beyond the standard quantum limit1,2. To do so, one can reshape the quantum projection noise-a strategy known as squeezing3,4. In the context of many-body spin systems, one typically uses all-to-all interactions (for example, the one-axis twisting model4) between the constituents to generate the structured entanglement characteristic of spin squeezing5. Here we explore the prediction, motivated by recent theoretical work6-10, that short-range interactions-and in particular, the two-dimensional dipolar XY model-can also enable the realization of scalable spin squeezing. Working with a dipolar Rydberg quantum simulator of up to N = 100 atoms, we demonstrate that quench dynamics from a polarized initial state lead to spin squeezing that improves with increasing system size up to a maximum of -3.5 ± 0.3 dB (before correcting for detection errors, or roughly -5 ± 0.3 dB after correction). Finally, we present two independent refinements: first, using a multistep spin-squeezing protocol allows us to further enhance the squeezing by roughly 1 dB, and second, leveraging Floquet engineering to realize Heisenberg interactions, we demonstrate the ability to extend the lifetime of the squeezed state by freezing its dynamics.

First Measurement of ν_{e} and ν_{µ} Interaction Cross Sections at the LHC with FASER's Emulsion Detector.

The first results of the study of high-energy electron neutrino (ν_{e}) and muon neutrino (ν_{µ}) charged-current interactions in the FASERν emulsion-tungsten detector of the FASER experiment at the LHC are presented. A 128.8 kg subset of the FASERν volume was analyzed after exposure to 9.5 fb^{-1} of sqrt[s]=13.6 TeV pp data. Four (eight) ν_{e} (ν_{µ}) interaction candidate events are observed with a statistical significance of 5.2σ (5.7σ). This is the first direct observation of ν_{e} interactions at a particle collider and includes the highest-energy ν_{e} and ν_{µ} ever detected from an artificial source. The interaction cross section per nucleon σ/E_{ν} is measured over an energy range of 560-1740 GeV (520-1760 GeV) for ν_{e} (ν_{µ}) to be (1.2_{-0.7}^{+0.8})×10^{-38} cm^{2} GeV^{-1} [(0.5±0.2)×10^{-38} cm^{2} GeV^{-1}], consistent with standard model predictions. These are the first measurements of neutrino interaction cross sections in those energy ranges.

First Direct Observation of Collider Neutrinos with FASER at the LHC.

We report the first direct observation of neutrino interactions at a particle collider experiment. Neutrino candidate events are identified in a 13.6 TeV center-of-mass energy pp collision dataset of 35.4 fb^{-1} using the active electronic components of the FASER detector at the Large Hadron Collider. The candidates are required to have a track propagating through the entire length of the FASER detector and be consistent with a muon neutrino charged-current interaction. We infer 153_{-13}^{+12} neutrino interactions with a significance of 16 standard deviations above the background-only hypothesis. These events are consistent with the characteristics expected from neutrino interactions in terms of secondary particle production and spatial distribution, and they imply the observation of both neutrinos and anti-neutrinos with an incident neutrino energy of significantly above 200 GeV.

Exploration of current pharmacy practice in cardio-oncology: Experiences & perspectives.

INTRODUCTION: Cardiovascular complications can occur in oncology patients secondary to certain cancer therapies. Pharmacists are involved in the care of oncology patients who are at risk of or experiencing cardiotoxicity related to their cancer therapy. Our study aimed to understand how pharmacists in Canada care to these patients and to explore their experiences, perceptions, and challenges. METHODS: Canadian pharmacists currently involved in the care of patients receiving cancer treatments and at risk of or experiencing cardiotoxicity were invited to participate in a 30-min telephone interview using an interview guide. A combination of inductive and deductive reasoning was applied using two coders who independently reviewed the transcribed interviews and identified key concepts and themes. RESULTS: Eight pharmacists were interviewed. Perceived benefits included sharing specialized knowledge and conducting safety assessments. Perceived challenges were the lack of role recognition and resources and fractured continuity of care. Proposed future directions were to play a more substantial role in direct medication management, creation of specific guidance and tools to support the clinical decision-making process, and to understand how pharmacists at other sites were providing care through the creation of a community of practice. CONCLUSIONS: As patient-focused medication specialists, pharmacists help guide clinical decision-making, assess cardiac risk factors, and offer individualized education to meet the holistic needs of oncology patients at risk of or experiencing cardiotoxicities. The creation of a cardio-oncology community of practice may allow pharmacists with a common interest to connect, share learnings, and collaborate on how to continue to advance the delivery of care.

A scoping review of the globally available tools for assessing health research partnership outcomes and impacts.

BACKGROUND: Health research partnership approaches have grown in popularity over the past decade, but the systematic evaluation of their outcomes and impacts has not kept equal pace. Identifying partnership assessment tools and key partnership characteristics is needed to advance partnerships, partnership measurement, and the assessment of their outcomes and impacts through systematic study. OBJECTIVE: To locate and identify globally available tools for assessing the outcomes and impacts of health research partnerships. METHODS: We searched four electronic databases (Ovid MEDLINE, Embase, CINAHL + , PsychINFO) with an a priori strategy from inception to June 2021, without limits. We screened studies independently and in duplicate, keeping only those involving a health research partnership and the development, use and/or assessment of tools to evaluate partnership outcomes and impacts. Reviewer disagreements were resolved by consensus. Study, tool and partnership characteristics, and emerging research questions, gaps and key recommendations were synthesized using descriptive statistics and thematic analysis. RESULTS: We screened 36 027 de-duplicated citations, reviewed 2784 papers in full text, and kept 166 studies and three companion reports. Most studies originated in North America and were published in English after 2015. Most of the 205 tools we identified were questionnaires and surveys targeting researchers, patients and public/community members. While tools were comprehensive and usable, most were designed for single use and lacked validity or reliability evidence. Challenges associated with the interchange and definition of terms (i.e., outcomes, impacts, tool type) were common and may obscure partnership measurement and comparison. Very few of the tools identified in this study overlapped with tools identified by other, similar reviews. Partnership tool development, refinement and evaluation, including tool measurement and optimization, are key areas for future tools-related research. CONCLUSION: This large scoping review identified numerous, single-use tools that require further development and testing to improve their psychometric and scientific qualities. The review also confirmed that the health partnership research domain and its measurement tools are still nascent and actively evolving. Dedicated efforts and resources are required to better understand health research partnerships, partnership optimization and partnership measurement and evaluation using valid, reliable and practical tools that meet partners' needs.

How are health research partnerships assessed? A systematic review of outcomes, impacts, terminology and the use of theories, models and frameworks.

BACKGROUND: Accurate, consistent assessment of outcomes and impacts is challenging in the health research partnerships domain. Increased focus on tool quality, including conceptual, psychometric and pragmatic characteristics, could improve the quantification, measurement and reporting partnership outcomes and impacts. This cascading review was undertaken as part of a coordinated, multicentre effort to identify, synthesize and assess a vast body of health research partnership literature. OBJECTIVE: To systematically assess the outcomes and impacts of health research partnerships, relevant terminology and the type/use of theories, models and frameworks (TMF) arising from studies using partnership assessment tools with known conceptual, psychometric and pragmatic characteristics. METHODS: Four electronic databases were searched (MEDLINE, Embase, CINAHL Plus and PsycINFO) from inception to 2 June 2021. We retained studies containing partnership evaluation tools with (1) conceptual foundations (reference to TMF), (2) empirical, quantitative psychometric evidence (evidence of validity and reliability, at minimum) and (3) one or more pragmatic characteristics. Outcomes, impacts, terminology, definitions and TMF type/use were abstracted verbatim from eligible studies using a hybrid (independent abstraction-validation) approach and synthesized using summary statistics (quantitative), inductive thematic analysis and deductive categories (qualitative). Methodological quality was assessed using the Quality Assessment Tool for Studies with Diverse Designs (QATSDD). RESULTS: Application of inclusion criteria yielded 37 eligible studies. Study quality scores were high (mean 80%, standard deviation 0.11%) but revealed needed improvements (i.e. methodological, reporting, user involvement in research design). Only 14 (38%) studies reported 48 partnership outcomes and 55 impacts; most were positive effects (43, 90% and 47, 89%, respectively). Most outcomes were positive personal, functional, structural and contextual effects; most impacts were personal, functional and contextual in nature. Most terms described outcomes (39, 89%), and 30 of 44 outcomes/impacts terms were unique, but few were explicitly defined (9, 20%). Terms were complex and mixed on one or more dimensions (e.g. type, temporality, stage, perspective). Most studies made explicit use of study-related TMF (34, 92%). There were 138 unique TMF sources, and these informed tool construct type/choice and hypothesis testing in almost all cases (36, 97%). CONCLUSION: This study synthesized partnership outcomes and impacts, deconstructed term complexities and evolved our understanding of TMF use in tool development, testing and refinement studies. Renewed attention to basic concepts is necessary to advance partnership measurement and research innovation in the field. Systematic review protocol registration: PROSPERO protocol registration: CRD42021137932 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=137932 .

Individualized tracking of self-directed motor learning in group-housed mice performing a skilled lever positioning task in the home cage.

Skilled forelimb function in mice is traditionally studied through behavioral paradigms that require extensive training by investigators and are limited by the number of trials individual animals are able to perform within a supervised session. We developed a skilled lever positioning task that mice can perform within their home cage. The task requires mice to use their forelimb to precisely hold a lever mounted on a rotary encoder within a rewarded position to dispense a water reward. A Raspberry Pi microcomputer is used to record lever position during trials and to control task parameters, thus making this low-footprint apparatus ideal for use within animal housing facilities. Custom Python software automatically increments task difficulty by requiring a longer hold duration, or a more accurate hold position, to dispense a reward. The performance of individual animals within group-housed mice is tracked through radio-frequency identification implants, and data stored on the microcomputer may be accessed remotely through an active internet connection. Mice continuously engage in the task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials to learn to hold the lever within a 10° range for 1.5 s and were able to further refine movement accuracy by limiting their error to a 5° range within each trial. These results demonstrate the feasibility of autonomously training group-housed mice on a forelimb motor task. This paradigm may be used in the future to assess functional recovery after injury or cortical reorganization induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost system for fully autonomous training of group-housed mice on a forelimb motor task. We demonstrate the feasibility of tracking both end-point, as well as kinematic performance of individual mice, with each performing thousands of trials over 2.5 mo. The task is run and controlled by a Raspberry Pi microcomputer, which allows for cages to be monitored remotely through an active internet connection.

Administrator Perspectives on ICU-to-Ward Transfers and Content Contained in Existing Transfer Tools: a Cross-sectional Survey.

BACKGROUND: The transfer of critically ill patients from the intensive care unit (ICU) to hospital ward is challenging. Shortcomings in the delivery of care for patients transferred from the ICU have been associated with higher healthcare costs and poor satisfaction with care. Little is known about how hospital ward providers, who accept care of these patients, perceive current transfer practices nor which aspects of transfer they perceive as needing improvement. OBJECTIVE: To compare ICU and ward administrator perspectives regarding ICU-to-ward transfer practices and evaluate the content of transfer tools. DESIGN: Cross-sectional survey design. PARTICIPANTS: We administered a survey to 128 medical and/or surgical ICU and 256 ward administrators to obtain institutional perspectives on ICU transfer practices. We performed qualitative content analysis on ICU transfer tools received from respondents. KEY RESULTS: In total, 108 (77%) ICU and 160 (63%) ward administrators responded to the survey. The ICU attending physician was reported to be "primarily responsible" for the safety (93% vs. 91%; p = 0.515) of patient transfers. ICU administrators more commonly perceived discharge summaries to be routinely included in patient transfers than ward administrators (81% vs. 60%; p = 0.006). Both groups identified information provided to patients/families, patient/family participation during transfer, and ICU-ward collaboration as opportunities for improvement. A minority of hospitals used ICU-to-ward transfer tools (11%) of which most (n = 21 unique) were designed to communicate patient information between providers (71%) and comprised six categories of information: demographics, patient clinical course, corrective aids, mobility at discharge, review of systems, and documentation of transfer procedures. CONCLUSION: ICU and ward administrators have similar perspectives of transfer practices and identified patient/family engagement and communication as priorities for improvement. Key information categories exist.

Patient, family and provider experiences with transfers from intensive care unit to hospital ward: a multicentre qualitative study.

BACKGROUND: Transfer of patient care from an intensive care unit (ICU) to a hospital ward is often challenging, high risk and inefficient. We assessed patient and provider perspectives on barriers and facilitators to high-quality transfers and recommendations to improve the transfer process. METHODS: We conducted semistructured interviews of participants from a multicentre prospective cohort study of ICU transfers conducted at 10 hospitals across Canada. We purposively sampled 1 patient, 1 family member of a patient, 1 ICU provider, and 1 ward provider at each of the 8 English-speaking sites. Qualitative content analysis was used to derive themes, subthemes and recommendations. RESULTS: The 35 participants described 3 interrelated, overarching themes perceived as barriers or facilitators to high-quality patient transfers: resource availability, communication and institutional culture. Common recommendations suggested to improve ICU transfers included implementing standardized communication tools that streamline provider-provider and provider-patient communication, using multimodal communication to facilitate timely, accurate, durable and mutually reinforcing information transfer; and developing procedures to manage delays in transfer to ensure continuity of care for patients in the ICU waiting for a hospital ward bed. INTERPRETATION: Patient and provider perspectives attribute breakdown of ICU-to-ward transfers of care to resource availability, communication and institutional culture. Patients and providers recommend standardized, multimodal communication and transfer procedures to improve quality of care.

Re-Establishment of Cortical Motor Output Maps and Spontaneous Functional Recovery via Spared Dorsolaterally Projecting Corticospinal Neurons after Dorsal Column Spinal Cord Injury in Adult Mice.

Motor cortical plasticity contributes to spontaneous recovery after incomplete spinal cord injury (SCI), but the pathways underlying this remain poorly understood. We performed optogenetic mapping of motor cortex in channelrhodopsin-2 expressing mice to assess the capacity of the cortex to re-establish motor output longitudinally after a C3/C4 dorsal column SCI that bilaterally ablated the dorsal corticospinal tract (CST) containing ∼96% of corticospinal fibers but spared ∼3% of CST fibers that project via the dorsolateral funiculus. Optogenetic mapping revealed extensive early deficits, but eventual reestablishment of motor cortical output maps to the limbs at the same latency as preoperatively by 4 weeks after injury. Analysis of skilled locomotion on the horizontal ladder revealed early deficits followed by partial spontaneous recovery by 6 weeks after injury. To dissociate between the contributions of injured dorsal projecting versus spared dorsolateral projecting corticospinal neurons, we established a transient silencing approach to inactivate spared dorsolaterally projecting corticospinal neurons specifically by injecting adeno-associated virus (AAV)-expressing Cre-dependent DREADD (designer receptor exclusively activated by designer drug) receptor hM4Di in sensorimotor cortex and AAV-expressing Cre in C7/C8 dorsolateral funiculus. Transient silencing uninjured dorsolaterally projecting corticospinal neurons via activation of the inhibitory DREADD receptor hM4Di abrogated spontaneous recovery and resulted in a greater change in skilled locomotion than in control uninjured mice using the same silencing approach. These data demonstrate the pivotal role of a minor dorsolateral corticospinal pathway in mediating spontaneous recovery after SCI and support a focus on spared corticospinal neurons as a target for therapy. SIGNIFICANCE STATEMENT: Spontaneous recovery can occur after incomplete spinal cord injury (SCI), but the pathways underlying this remain poorly understood. We performed optogenetic mapping of motor cortex after a cervical SCI that interrupts most corticospinal transmission but results in partial recovery on a horizontal ladder task of sensorimotor function. We demonstrate that the motor cortex can reestablish output to the limbs longitudinally. To dissociate the roles of injured and uninjured corticospinal neurons in mediating recovery, we transiently silenced the minor dorsolateral corticospinal pathway spared by our injury. This abrogated spontaneous recovery and resulted in a greater change in skilled locomotion than in uninjured mice using the same approach. Therefore, uninjured corticospinal neurons substantiate remarkable motor cortical plasticity and partial recovery after SCI.

Development and Validation of Quality Criteria for Providing Patient- and Family-centered Injury Care.

OBJECTIVE: The aim of this study was to develop and evaluate the content validity of quality criteria for providing patient- and family-centered injury care. BACKGROUND: Quality criteria have been developed for clinical injury care, but not patient- and family-centered injury care. METHODS: Using a modified Research AND Development Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Methodology, a panel of 16 patients, family members, injury and quality of care experts serially rated and revised criteria for patient- and family-centered injury care identified from patient and family focus groups. The criteria were then sent to 384 verified trauma centers in the United States, Canada, Australia, and New Zealand for evaluation. RESULTS: A total of 46 criteria were rated and revised by the panel over 4 rounds of review producing 14 criteria related to clinical care (n = 4; transitions of care, pain management, patient safety, provider competence), communication (n = 3; information for patients/families; communication of discharge plans to patients/families, communication between hospital and community providers), holistic care (n = 4; patient hygiene, kindness and respect, family access to patient, social and spiritual support) and end-of-life care (n = 3; decision making, end-of-life care, family follow-up). Medical directors, managers, or coordinators representing 254 trauma centers (66% response rate) rated 12 criteria to be important (95% of responses) for patient- and family-centered injury care. Fewer centers rated family access to the patient (80%) and family follow-up after patient death (65%) to be important criteria. CONCLUSIONS: Fourteen-candidate quality criteria for patient- and family-centered injury care were developed and shown to have content validity. These may be used to guide quality improvement practices.

Reconciling patient and provider priorities for improving the care of critically ill patients: A consensus method and qualitative analysis of decision making.

BACKGROUND: Providers have traditionally established priorities for quality improvement; however, patients and their family members have recently become involved in priority setting. Little is known about how to reconcile priorities of different stakeholder groups into a single prioritized list that is actionable for organizations. OBJECTIVE: To describe the decision-making process for establishing consensus used by a diverse panel of stakeholders to reconcile two sets of quality improvement priorities (provider/decision maker priorities n=9; patient/family priorities n=19) into a single prioritized list. DESIGN: We employed a modified Delphi process with a diverse group of panellists to reconcile priorities for improving care of critically ill patients in the intensive care unit (ICU). Proceedings were audio-recorded, transcribed and analysed using qualitative content analysis to explore the decision-making process for establishing consensus. SETTING AND PARTICIPANTS: Nine panellists including three providers, three decision makers and three family members of previously critically ill patients. RESULTS: Panellists rated and revised 28 priorities over three rounds of review and reached consensus on the "Top 5" priorities for quality improvement: transition of patient care from ICU to hospital ward; family presence and effective communication; delirium screening and management; early mobilization; and transition of patient care between ICU providers. Four themes were identified as important for establishing consensus: storytelling (sharing personal experiences), amalgamating priorities (negotiating priority scope), considering evaluation criteria and having a priority champion. CONCLUSIONS: Our study demonstrates the feasibility of incorporating families of patients into a multistakeholder prioritization exercise. The approach described can be used to guide consensus building and reconcile priorities of diverse stakeholder groups.

Developing a framework to guide the de-adoption of low-value clinical practices in acute care medicine: a study protocol.

BACKGROUND: Healthcare systems have difficulty incorporating scientific evidence into clinical practice, especially when science suggests that existing clinical practices are of low-value (e.g. ineffective or harmful to patients). While a number of lists outlining low-value practices in acute care medicine currently exist, less is known about how best to initiate and sustain the removal of low-value clinical practices (i.e. de-adoption). This study will develop a comprehensive list of barriers and facilitators to the de-adoption of low-value clinical practices in acute care facilities to inform the development of a framework to guide the de-adoption process. METHODS: The proposed project is a multi-stage mixed methods study to develop a framework to guide the de-adoption of low-value clinical practices in acute care medicine that will be tested in a representative sample of acute care settings in Alberta, Canada. Specifically, we will: 1) conduct a systematic review of the de-adoption literature to identify published barriers and facilitators to the de-adoption of low-value clinical practices in acute care medicine and any associated interventions proposed (Phase one); 2) conduct focus groups with acute care stakeholders to identify important themes not published in the literature and obtain a comprehensive appreciation of stakeholder perspectives (Phase two); 3) extend the generalizability of focus group findings by conducting individual stakeholder surveys with a representative sample of acute care providers throughout the province to determine which barriers and facilitators identified in Phases one and two are most relevant in their clinical setting (Phase three). Identified barriers and facilitators will be catalogued and integrated with targeted interventions in a framework to guide the process of de-adoption in each of four targeted areas of acute care medicine (Emergency Medicine, Cardiovascular Health and Stroke, Surgery and Critical Care Medicine). Analyses will be descriptive using a combination of qualitative and quantitative analyses. DISCUSSION: There is a growing body of literature suggesting that the de-adoption of ineffective or harmful practices from patient care is integral to the delivery of high quality care and healthcare sustainability. The framework developed in this study will map barriers and facilitators to de-adoption to the most appropriate interventions, allowing stakeholders to effectively initiate, execute and sustain this process in an evidence-based manner.

Ministrokes in channelrhodopsin-2 transgenic mice reveal widespread deficits in motor output despite maintenance of cortical neuronal excitability.

We evaluated the effects of ministrokes targeted to individual pial arterioles on motor function in Thy-1 line 18 channelrhodopsin-2 (ChR2) transgenic mice within the first hours after ischemia. Using optogenetics, we directly assessed both the excitability and motor output of cortical neurons in a manner independent of behavioral state or training. Occlusion of individual arterioles within the motor cortex led to a ministroke that was verified using laser speckle contrast imaging. Surprisingly, ministrokes targeted to a relatively small region of the forelimb motor map, with an ischemic core of 0.07 ± 0.03 mm(2), impaired motor responses evoked from points across widespread areas of motor cortex even 1.5 mm away. Contrasting averaged ChR2-evoked electroencephalographic, spinal (ChR2 evoked potential), and electromyographic responses revealed a mismatch between measures of cortical excitability and motor output within 60 min after stroke. This mismatch suggests that apparently excitable cortical neurons (even >1 mm into peri-infarct areas, away from the infarct core) were impaired in their capacity to generate spinal potentials leading to even more severe deficits in motor output at muscles. We suggest that ischemia, targeted to a subset of motor cortex, leads to relatively small reductions in excitability within motor cortex, and cumulative depression of both descending spinal circuits and motor output in response to the activation of widespread cortical territories even outside of the area directly affected by the ischemia.

A micro-architecture for binocular disparity and ocular dominance in visual cortex.

In invertebrate predators such as the praying mantis and vertebrate predators such as wild cats the ability to detect small differences in inter-ocular retinal disparities is a critical means for accurately determining the depth of moving objects such as prey. In mammals, the first neurons along the visual pathway that encode binocular disparities are found in the visual cortex. However, a precise functional architecture for binocular disparity has never been demonstrated in any species, and coarse maps for disparity have been found in only one primate species. Moreover, the dominant approach for assaying the developmental plasticity of binocular cortical neurons used monocular tests of ocular dominance to infer binocular function. The few studies that examined the relationship between ocular dominance and binocular disparity of individual cells used single-unit recordings and have provided conflicting results regarding whether ocular dominance can predict the selectivity or sensitivity to binocular disparity. We used two-photon calcium imaging to sample the response to monocular and binocular visual stimuli from nearly every adjacent neuron in a small region of the cat visual cortex, area 18. Here we show that local circuits for ocular dominance always have smooth and graded transitions from one apparently monocular functional domain to an adjacent binocular region. Most unexpectedly, we discovered a new map in the cat visual cortex that had a precise functional micro-architecture for binocular disparity selectivity. At the level of single cells, ocular dominance was unrelated to binocular disparity selectivity or sensitivity. When the local maps for ocular dominance and binocular disparity both had measurable gradients at a given cortical site, the two gradient directions were orthogonal to each other. Together, these results indicate that, from the perspective of the spiking activity of individual neurons, ocular dominance cannot predict binocular disparity tuning. However, the precise local arrangement of ocular dominance and binocular disparity maps provide new clues regarding how monocular and binocular depth cues may be combined and decoded.

Live imaging and analysis of postnatal mouse retinal development.

BACKGROUND: The explanted, developing rodent retina provides an efficient and accessible preparation for use in gene transfer and pharmacological experimentation. Many of the features of normal development are retained in the explanted retina, including retinal progenitor cell proliferation, heterochronic cell production, interkinetic nuclear migration, and connectivity. To date, live imaging in the developing retina has been reported in non-mammalian and mammalian whole-mount samples. An integrated approach to rodent retinal culture/transfection, live imaging, cell tracking, and analysis in structurally intact explants greatly improves our ability to assess the kinetics of cell production. RESULTS: In this report, we describe the assembly and maintenance of an in vitro, CO2-independent, live mouse retinal preparation that is accessible by both upright and inverted, 2-photon or confocal microscopes. The optics of this preparation permit high-quality and multi-channel imaging of retinal cells expressing fluorescent reporters for up to 48h. Tracking of interkinetic nuclear migration within individual cells, and changes in retinal progenitor cell morphology are described. Follow-up, hierarchical cluster screening revealed that several different dependent variable measures can be used to identify and group movement kinetics in experimental and control samples. CONCLUSIONS: Collectively, these methods provide a robust approach to assay multiple features of rodent retinal development using live imaging.

Displacement of sensory maps and disorganization of motor cortex after targeted stroke in mice.

BACKGROUND AND PURPOSE: Recovery from stroke is hypothesized to involve the reorganization of surviving cortical areas. To study the functional organization of sensorimotor cortex at multiple time points before and after stroke, we performed longitudinal light-based motor mapping of transgenic mice expressing light-sensitive channelrhodopsin-2 in layer 5 cortical neurons. METHODS: Pulses of light stimulation were targeted to an array of cortical points, whereas evoked forelimb motor activity was recorded using noninvasive motion sensors. Intrinsic optical signal imaging produced maps of the forelimb somatosensory cortex. The resulting motor and sensory maps were repeatedly generated for weeks before and after small (0.2 mm3) photothrombotic infarcts were targeted to forelimb motor or sensory cortex. RESULTS: Infarcts targeted to forelimb sensory or motor areas caused decreased motor output in the infarct area and spatial displacement of sensory and motor maps. Strokes in sensory cortex caused the sensory map to move into motor cortex, which adopted a more diffuse structure. Stroke in motor cortex caused a compensatory increase in peri-infarct motor output, but did not affect the position or excitability of sensory maps. CONCLUSIONS: After stroke in motor cortex, decreased motor output from the infarcted area was offset by peri-infarct excitability. Sensory stroke caused a new sensory map to form in motor cortex, which maintained its center position, despite becoming more diffuse. These data suggest that surviving regions of cortex are able to assume functions from stroke-damaged areas, although this may come at the cost of alterations in map structure.

Developing a patient and family-centred approach for measuring the quality of injury care: a study protocol.

BACKGROUND: Quality indicators (QI) are used in health care to measure quality of service and performance improvement. Health care professionals and organizations caring for patients with injuries need information regarding the quality of care provided and the outcomes experienced in order to target improvement efforts. However, very little is known about the quality of injury care provided to individual patients and populations and even less about patients' perspectives on quality of care. The absence of QIs that incorporate patient or family preferences, needs or values has been identified as an important gap in the science and practice of injury quality improvement. The primary objective of this research protocol is to develop and evaluate the first set of patient and family-centred QIs of injury care for critically injured patients METHODS/DESIGN: This mixed methods study is comprised of three Sub-Studies. Sub-Study A will utilize focus group methodology to describe the preferences, needs and values of critically injured patients and their family members regarding the quality of health care delivered. Qualitative content analysis of the transcripts will begin after the first completed focus group and will draw on grounded theory using a process of open, axial and selective coding. A panel of stakeholders will be assembled during Sub-Study B to review the themes identified from the focus groups and develop a catalogue of potential patient and family-centred QIs of injury care using the RAND/UCLA Appropriateness Method (RAM). The QIs developed by the stakeholder panel will be pilot tested in Sub-Study C using surveys of patients and their family members to determine construct validity, intra-rater reliability and clinical sensibility. DISCUSSION: Measuring the quality of injury care is but a first step towards improving patient outcomes. This research will develop the first set of patient and family-centred QIs of injury care. To improve patient care, we need accessible, reliable indicators of quality that are important to patients, and that can then be used to establish quality of care benchmarks, to flag potential problems or successes, follow trends over time and identify disparities across organizations, communities, populations and regions.