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Osteoarthritis (OA) was recently defined as an epidemic, and the lack of effective treatment is highly correlated to the limited knowledge regarding the underlying pathophysiology. Failure to regenerate upon trauma is thought to be one of the underlying causes for degenerative diseases, including OA. To investigate why lesions within an OA environment fail to heal, a heterogeneous cell population was isolated from the synovial fluid (SF) of OA patients. The cells’ ability to undergo processes required for functional tissue regeneration was evaluated in the presence or absence of autologous SF. The obtained mechanistic findings were then used for the development of an immunomodulatory cell treatment, aimed to restore the pro-regenerative environment. Intra-articular injection in a clinical compassionate use study showed that the treatment restored the articular cartilage and joint homeostasis of OA patients. These findings confirm the role of pro-regenerative immune cells and their targeted influence on progenitor cells for degenerative joint disease therapies.

Supplemental Digital Content is available in the text., Background: Stakeholder involvement in health care research has been shown to improve research development, processes, and dissemination. The literature is developing on stakeholder engagement methods and preliminarily validated tools for evaluating stakeholder level of engagement have been proposed for specific stakeholder groups and settings. Objectives: This paper describes the methodology for engaging a Study Advisory Committee (SAC) in research and reports on the use of a stakeholder engagement survey for measuring level of engagement. Methods: Stakeholders with previous research connections were recruited to the SAC during the planning process for a multicenter randomized control clinical trial, which is ongoing at the time of this writing. All SAC meetings undergo qualitative analysis, while the Stakeholder Engagement Survey instrument developed by the Patient-Centered Outcomes Research Institute (PCORI) is distributed annually for quantitative evaluation. Results: The trial’s SAC is composed of 18 members from 3 stakeholder groups: patients and their caregivers; patient advocacy organizations; and health care payers. After an initial in-person meeting, the SAC meets quarterly by telephone and annually in-person. The SAC monitors research progress and provides feedback on all study processes. The stakeholder engagement survey reveals improved engagement over time as well as continued challenges. Conclusions: Stakeholder engagement in the research process has meaningfully contributed to the study design, patient recruitment, and preliminary analysis of findings.

For many people the emergency department (ED) is the first point of access to healthcare for acute needs and a recurring location for many with chronic healthcare needs. While the ED is well placed to identify unmet needs it can also be a net that people slip through when faced with uncoordinated and expensive healthcare challenges. Thus the ED has a responsibility to set patients on a safe and meaningful care trajectory, which can only be done in consultation and partnership with the patients themselves. The purpose of this article is to present crucial aspects of patient engagement that are essential for future research to foster an environment of colearning and respect that encourages ongoing involvement by patients, families, and staff.

Patient-centered emergency diagnostic imaging relies on efficient communication and multispecialty care coordination to ensure optimal imaging utilization. The construct of the emergency diagnostic imaging care coordination cycle with three main phases (pretest, test, and posttest) provides a useful framework to evaluate care coordination in patient-centered emergency diagnostic imaging. This article summarizes findings reached during the patient-centered outcomes session of the 2015 Academic Emergency Medicine consensus conference "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The primary objective was to develop a research agenda focused on 1) defining component parts of the emergency diagnostic imaging care coordination process, 2) identifying gaps in communication that affect emergency diagnostic imaging, and 3) defining optimal methods of communication and multidisciplinary care coordination that ensure patient-centered emergency diagnostic imaging. Prioritized research questions provided the framework to define a research agenda for multidisciplinary care coordination in emergency diagnostic imaging.

The AAFP recently released an updated clinical practice guideline on the pharmacologic management of atrial fibrillation. An executive summary appears below. ### Executive Summary Atrial fibrillation (AF) is one of the most common arrhythmia types in adults worldwide, with an estimated 2.7–6.1

Although the Patient Protection and Affordable Care Act and other laws have promoted the use of shared decision making (SDM) in recent years, few specific policies have addressed the opportunities and challenges of utilizing SDM in the emergency department (ED). Policies relating to physician payment, quality measurement, and medical-legal risks each present unique challenges to adoption of SDM in the ED. This article summarizes findings from a health policy breakout session of the 2016 Academic Emergency Medicine consensus conference “Shared Decision Making in the Emergency Department: Development of a Policy-Relevant, Patient-Centered Research Agenda.” The objectives were to (1) describe federal and state policies that influence utilization or assessment of SDM; (2) identify policies and policy-focused knowledge gaps that serve as barriers to adoption of emergency department SDM; and (3) to define a consensus-based, policy-focused research agenda to support adoption of SDM in emergency care.

Influences from the visual (AEV), auditory (FAES), and somatosensory (SIV) divisions of the cat anterior ectosylvian sulcus (AES) play a critical role in rendering superior colliculus (SC) neurons capable of multisensory integration. However, it is not known whether this is accomplished via their independent sensory-specific action or via some cross-modal cooperative action that emerges as a consequence of their convergence on SC neurons. Using visual–auditory SC neurons as a model, we examined how selective and combined deactivation of FAES and AEV affected SC multisensory (visual–auditory) and unisensory (visual–visual) integration capabilities. As noted earlier, multisensory integration yielded SC responses that were significantly greater than those evoked by the most effective individual component stimulus. This multisensory “response enhancement” was more evident when the component stimuli were weakly effective. Conversely, unisensory integration was dominated by the lack of response enhancement. During cryogenic deactivation of FAES and/or AEV, the unisensory responses of SC neurons were only modestly affected; however, their multisensory response enhancement showed a significant downward shift and was eliminated. The shift was similar in magnitude for deactivation of either AES subregion and, in general, only marginally greater when both were deactivated simultaneously. These data reveal that SC multisensory integration is dependent on the cooperative action of distinct subsets of unisensory corticofugal afferents, afferents whose sensory combination matches the multisensory profile of their midbrain target neurons, and whose functional synergy is specific to rendering SC neurons capable of synthesizing information from those particular senses.

While research over the last 30 years has shown that sermons have a minimal influence on listeners, denominational differences in sermon effectiveness have been unexplored. We surveyed Anglican and Elim members (representing Mainline and Pentecostal Christians respectively) to compare their responses to sermons, and the sermon features and themes they prefer. The results revealed higher sermon effectiveness responses from Elim participants. The data also showed that Anglicans desired significant intellectual content and discussion of social issues compared with Elim members who gave higher ratings on almost all other features and themes. However, participants from both churches responded to sermons in a predominantly emotional (rather than cognitive or behavioural) way, and most wanted to hear sermons on grace and forgiveness. We conclude by noting the need for evaluations of sermon effectiveness that reflect preachers' and listeners' motivations.

Converging cortical influences from the anterior ectosylvian sulcus and the rostral lateral suprasylvian sulcus were shown to have a multisensory-specific role in the integration of sensory information in superior colliculus (SC) neurons. These observations were based on changes induced by cryogenic deactivation of these cortico-SC projections. Thus, although the results indicated that they played a critical role in integrating SC responses to stimuli derived from different senses (i.e., visual–auditory), they played no role in synthesizing its responses to stimuli derived from within the same sense (visual–visual). This was evident even in the same multisensory neurons. The results suggest that very different neural circuits have evolved to code combinations of cross-modal and within-modal stimuli in the SC, and that the differences in multisensory and unisensory integration are likely caused by differences in the configuration of each neuron's functional inputs rather than to any inherent differences among the neurons themselves. The specificity of these descending influences was also apparent in the very different ways in which they affected responses to the component cross-modal stimuli and their actual integration. Furthermore, they appeared to target only multisensory neurons and not their unisensory neighbors.

Diagnostic imaging is integral to the evaluation of many emergency department (ED) patients. However, relatively little effort has been devoted to patient-centered outcomes research (PCOR) in emergency diagnostic imaging. This article provides background on this topic and the conclusions of the 2015 Academic Emergency Medicine consensus conference PCOR work group regarding "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The goal was to determine a prioritized research agenda to establish which outcomes related to emergency diagnostic imaging are most important to patients, caregivers, and other key stakeholders and which methods will most optimally engage patients in the decision to undergo imaging. Case vignettes are used to emphasize these concepts as they relate to a patient's decision to seek care at an ED and the care received there. The authors discuss applicable research methods and approaches such as shared decision-making that could facilitate better integration of patient-centered outcomes and patient-reported outcomes into decisions regarding emergency diagnostic imaging. Finally, based on a modified Delphi process involving members of the PCOR work group, prioritized research questions are proposed to advance the science of patient-centered outcomes in ED diagnostic imaging.

For years the Reitrage was discussed in hushed tones as being a triumphant masterpiece by Martin Heidegger. This essay takes the form of a light-hearted dialogue between two individuals of different philosophical stripehaving a lunchtime reading group conversation over some specific lines of the Beitrage text. The result highlights how difficult and rewarding it is both to give a close reading of the original text, and to communicate with others not ensconced in the nomenclature of this particular thinker.

Ring opening as practiced in hydrocracking of naphthenic molecules results from multiple cleavages of both endo- and exocyclic C–C bonds. Selective ring opening requires that only one endocyclic C–C bond per naphthene ring be severed, preserving thereby reactant molecular weight. The products of selective ring opening are alkanes and alkylnaphthenes. Over hydrocracking catalysts the yield of alkanes with the same number of carbon atoms as the reactant naphthenes is unacceptably low as a result of extensive dealkylation of alkylnaphthenes and secondary cracking of alkanes. Alkylcyclopentanes, in contrast, selectively ring open by hydrogenolysis over a number of noble metal catalysts. Under similar reaction conditions the selective ring-opening rates of alkylcyclohexanes are, however, one to two orders slower than those of alkylcyclopentanes. Addition of a ring-contraction acidity function converts alkylcyclohexanes into more easily ring-opened alkylcyclopentanes, greatly facilitating selective ring opening. Selective ring-opening rates and selectivities are optimum when ring isomerization occurs by a nonbranching ring contraction. Branching ring contraction, creating increased numbers of ring substituents, is detrimental to both ring-opening rates and selectivities. When an effective acidity function is coupled with a high-activity hydrogenolysis metal, such as iridium, the resulting bifunctional catalyst system greatly outperforms conventional hydrocracking catalysts for the selective conversion of naphthenes to alkanes.

Summary Over the past few years, several premium sand-control screens have been introduced into the market. The proliferation of new screens has raised questions about how to choose the proper sand-control screen for a particular formation. To address this concern, a project was initiated at ChevronTexaco Exploration Production Technology Co. (EPTC) to devise a method to evaluate sand-control screens. As a result of this program, a method has been standardized for the evaluation of sand-control screens. The method, known as the screen efficiency (SE) test, shows the relationship between normalized sand-control characteristics (i.e., sand-control factor) of the screens and the normalized length of time it takes a screen to plug under a certain set of conditions (i.e., the performance factor). The results of SE tests to evaluate several sand-control screens for a North Sea and a west Africa field are discussed in the paper. The data in this paper also document that the numerical ratings given by the manufacturers are generally not very useful in understanding the sand-control rating of the particular screen or in comparing screens from different manufacturers. In addition, the effect of particle size distribution and sand concentration on the relative performance of sand-control screens was demonstrated by a comparison of SE plots of sands from the North Sea and west Africa fields.

The spatial register of the different receptive fields of multisensory neurons in the superior colliculus (SC) plays a significant role in determining the responses of these neurons to cross-modal stimulus combinations. Spatially coincident visual-auditory stimuli fall within these overlapping receptive fields and generally produce response enhancements that exceed the individual modality-specific responses and can exceed their sum. Yet, in this context, it has not been clear how "spatial coincidence" is operationally defined. Given the large size of SC receptive fields, visual and auditory stimuli could be within their respective receptive fields even when there are substantial spatial disparities between them. Indeed, previous observations have raised the possibility that there may be a second level of determinism in how SC neurons deal with the relative spatial locations of within-field cross-modal stimuli; specifically, that multisensory response enhancements become progressively weaker as the within-field visual and auditory stimuli become increasingly disparate. While the present experiments demonstrated that SC multisensory neurons have heterogeneous receptive fields, and that the greatest number of impulses evoked were by stimuli that fell within the area of cross-modal receptive field overlap, they also indicate that there is no systematic relationship between cross-modal stimulus disparity and the magnitude of multisensory response enhancement. Thus, two within-field cross-modal stimuli produced the same proportionate change (i.e., multisensory response enhancement) when they were widely disparate as they did when they overlapped one another in space. These observations indicate that cross-modal spatial coincidence can be defined operationally by the borders of an SC neuron's receptive fields regardless of the size of those receptive fields and/or the absolute spatial disparity between within-field cross-modal stimuli.

An observational study was conducted at 18 transplant centers in the United States and Canada to characterize the platelet recovery of patients receiving myeloablative therapy and stem cell transplantation and to determine the clinical variables influencing recovery, determine platelet utilization and cost, and incidence of hemorrhagic events. The study included 789 evaluable patients transplanted in 1995. Clinical, laboratory, and outcome data were obtained from the medical records. Variables associated with accelerated recovery in multivariate models included (1) higher CD34 count; (2) higher platelet count at the start of myeloablative therapy; (3) graft from an HLA-identical sibling donor; and (4) prior stem cell transplant. Variables associated with delayed recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic veno-occlusive disease; and (4) use of posttransplant growth factors. Disease type also influenced recovery. Recipients of peripheral blood stem cells (PBSC) had faster recovery and fewer platelet transfusion days than recipients of bone marrow (BM). The estimated average 60-day platelet transfusion cost per patient was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was found that 11% of all patients had a significant hemorrhagic event during the first 60 days posttransplant, contributing to death in 2% of patients. In conclusion, clinical variables influencing platelet recovery should be considered in the design and interpretation of clinical strategies to accelerate recovery. Enhancing platelet recovery is not likely to have a significant impact on 60-day mortality but could significantly decrease health care costs and potentially improve patient quality of life.

Kadunce, Daniel C., J. William Vaughan, Mark T. Wallace, Gyorgy Benedek, and Barry E. Stein. Mechanisms of within- and cross-modality suppression in the superior colliculus. J. Neurophysiol. 78: 2834–2847, 1997. The present studies were initiated to explore the basis for the response suppression that occurs in cat superior colliculus (SC) neurons when two spatially disparate stimuli are presented simultaneously or in close temporal proximity to one another. Of specific interest was examining the possibility that suppressive regions border the receptive fields (RFs) of unimodal and multisensory SC neurons and, when activated, degrade the neuron's responses to excitatory stimuli. Both within- and cross-modality effects were examined. An example of the former is when a response to a visual stimulus within its RF is suppressed by a second visual stimulus outside the RF. An example of the latter is when the response to a visual stimulus within the visual RF is suppressed when a stimulus from a different modality (e.g., auditory) is presented outside its (i.e., auditory) RF. Suppressive regions were found bordering visual, auditory, and somatosensory RFs. Despite significant modality-specific differences in the incidence and effectiveness of these regions, they were generally quite potent regardless of the modality. In the vast majority (85%) of cases, responses to the excitatory stimulus were degraded by ≥50% by simultaneously stimulating the suppressive region. Contrary to expectations and previous speculations, the effects of activating these suppressive regions often were quite specific. Thus powerful within-modality suppression could be demonstrated in many multisensory neurons in which cross-modality suppression could not be generated. However, the converse was not true. If an extra-RF stimulus inhibited center responses to stimuli of a different modality, it also would suppress center responses to stimuli of its own modality. Thus when cross-modality suppression was demonstrated, it was always accompanied by within-modality suppression. These observations suggest that separate mechanisms underlie within- and cross-modality suppression in the SC. Because some modality-specific tectopetal structures contain neurons with suppressive regions bordering their RFs, the within-modality suppression observed in the SC simply may reflect interactions taking place at the level of one input channel. However, the presence of modality-specific suppression at the level of one input channel would have no effect on the excitation initiated via another input channel. Given the modality-specificity of tectopetal inputs, it appears that cross-modality interactions require the convergence of two or more modality-specific inputs onto the same SC neuron and that the expression of these interactions depends on the internal circuitry of the SC. This allows a cross-modality suppressive signal to be nonspecific and to degrade any and all of the neuron's excitatory inputs.

Bell's palsy, named after the Scottish anatomist, Sir Charles Bell, is the most common acute mono-neuropathy, or disorder affecting a single nerve, and is the most common diagnosis associated with facial nerve weakness/paralysis. Bell's palsy is a rapid unilateral facial nerve paresis (weakness) or paralysis (complete loss of movement) of unknown cause. The condition leads to the partial or complete inability to voluntarily move facial muscles on the affected side of the face. Although typically self-limited, the facial paresis/paralysis that occurs in Bell's palsy may cause significant temporary oral incompetence and an inability to close the eyelid, leading to potential eye injury. Additional long-term poor outcomes do occur and can be devastating to the patient. Treatments are generally designed to improve facial function and facilitate recovery. There are myriad treatment options for Bell's palsy, and some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, numerous diagnostic tests available are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy.The primary purpose of this guideline is to improve the accuracy of diagnosis for Bell's palsy, to improve the quality of care and outcomes for patients with Bell's palsy, and to decrease harmful variations in the evaluation and management of Bell's palsy. This guideline addresses these needs by encouraging accurate and efficient diagnosis and treatment and, when applicable, facilitating patient follow-up to address the management of long-term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. The guideline is intended for all clinicians in any setting who are likely to diagnose and manage patients with Bell's palsy. The target population is inclusive of both adults and children presenting with Bell's palsy. ACTION STATEMENTS: The development group made a strong recommendation that (a) clinicians should assess the patient using history and physical examination to exclude identifiable causes of facial paresis or paralysis in patients presenting with acute-onset unilateral facial paresis or paralysis, (b) clinicians should prescribe oral steroids within 72 hours of symptom onset for Bell's palsy patients 16 years and older, (c) clinicians should not prescribe oral antiviral therapy alone for patients with new-onset Bell's palsy, and (d) clinicians should implement eye protection for Bell's palsy patients with impaired eye closure. The panel made recommendations that (a) clinicians should not obtain routine laboratory testing in patients with new-onset Bell's palsy, (b) clinicians should not routinely perform diagnostic imaging for patients with new-onset Bell's palsy, (c) clinicians should not perform electrodiagnostic testing in Bell's palsy patients with incomplete facial paralysis, and (d) clinicians should reassess or refer to a facial nerve specialist those Bell's palsy patients with (1) new or worsening neurologic findings at any point, (2) ocular symptoms developing at any point, or (3) incomplete facial recovery 3 months after initial symptom onset. The development group provided the following options: (a) clinicians may offer oral antiviral therapy in addition to oral steroids within 72 hours of symptom onset for patients with Bell's palsy, and (b) clinicians may offer electrodiagnostic testing to Bell's palsy patients with complete facial paralysis. The development group offered the following no recommendations: (a) no recommendation can be made regarding surgical decompression for patients with Bell's palsy, (b) no recommendation can be made regarding the effect of acupuncture in patients with Bell's palsy, and (c) no recommendation can be made regarding the effect of physical therapy in patients with Bell's palsy.