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Assessment of the best flow model to characterize diffuse correlation spectroscopy data acquired directly on the brain. - Biomedical optics express
Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique capable of monitoring tissue perfusion. The normalized temporal intensity autocorrelation function generated by DCS is typically characterized by assuming that the movement of erythrocytes can be modeled as a Brownian diffusion-like process instead of by the expected random flow model. Recently, a hybrid model, referred to as the hydrodynamic diffusion model, was proposed, which combines the random and Brownian flow models. The purpose of this study was to investigate the best model to describe autocorrelation functions acquired directly on the brain in order to avoid confounding effects of extracerebral tissues. Data were acquired from 11 pigs during normocapnia and hypocapnia, and flow changes were verified by computed tomography perfusion (CTP). The hydrodynamic diffusion model was found to provide the best fit to the autocorrelation functions; however, no significant difference for relative flow changes measured by the Brownian and hydrodynamic diffusion models was observed.
Efficacy of Selective Brain Cooling Using a Nasopharyngeal Method in Piglets. - Neurocritical care
Mild hypothermia is an effective neuroprotective strategy for a variety of acute brain injuries. Cooling the nasopharynx may offer the capability to cool the brain selectively due to anatomic proximity of the internal carotid artery to the cavernous sinus. This study investigated the feasibility and efficiency of nasopharyngeal brain cooling by continuously blowing room temperature or cold air at different flow rates into the nostrils of normal newborn piglets.Experiments were conducted on thirty piglets (nÂ =Â 30, weightÂ =Â 2.7Â Â±Â 1.5Â kg). Piglets were anesthetized with 1-2Â % isoflurane and were randomized to receive one of four different nasopharyngeal cooling treatments: I. Room temperature at a flow rate of 3-4Â LÂ min(-1) (nÂ =Â 6); II. -1Â Â±Â 2Â Â°C at a flow rate of 3-4Â LÂ min(-1) (nÂ =Â 6); III. Room temperature at a flow rate of 14-15Â LÂ min(-1) (nÂ =Â 6); IV. -8Â Â±Â 2Â Â°C at a flow rate of 14-15Â LÂ min(-1) (nÂ =Â 6). To control for the normal thermal regulatory response of piglets without nasopharyngeal cooling, a control group of piglets (nÂ =Â 6) had their brain temperature monitored without nasopharyngeal cooling. The duration of treatment was 60Â min, with additional 30Â min of observation.In group I, median cooling rate was 1.7Â Â±Â 0.9Â Â°C/h by setting the flow rate of room temperature air to 3-4Â LÂ min(-1). Results of comparing different temperatures and flow rates in the nasopharyngeal cooling approach reveal that the brain temperature could be reduced rapidly at a rate of 5.5Â Â±Â 1.1Â Â°C/h by blowing -8Â Â±Â 2Â Â°C air at a flow rate of 14-15Â LÂ min(-1).Nasopharyngeal cooling via cooled insufflated air can lower the brain temperature, with higher flows and lower temperatures of insufflated air being more effective.
RFX transcription factors are essential for hearing in mice. - Nature communications
Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. To understand the role of RFX in hearing, we generate Rfx1/3 conditional knockout mice. We show that these mice are deaf secondary to rapid loss of initially well-formed outer HCs. These data identify an essential role for RFX in hearing and survival of the terminally differentiating outer HCs.
Acute Multi-modal Neuroimaging in a Porcine Model of Endothelin-1-Induced Cerebral Ischemia: Defining the Acute Infarct Core. - Translational stroke research
In a porcine ischemic stroke model, we sought to compare the acute predicted infarct core volume (PIV) defined by CT perfusion (CTP)-hemodynamic parameters and MR-diffusion-weighted imaging (MR-DWI)/apparent diffusion coefficient (ADC), with the true infarct core volume (TIV) as defined by histology. Ten Duroc-cross pigs had a CTP scan prior to injection of endothelin-1 (ET-1) into the left striatum. CTP scans were used to monitor ischemic progression. A second dose of ET-1 was injected 2 h from the first injection. The animal was moved to a 3-T MRI scanner where DWI was performed. CTP imaging was acquired immediately after the MR imaging. Next, the brain was removed and stained with tetrazolium chloride (TTC). Linear regression and Bland-Altman plots were used to correlate the PIV measured by each imaging modality to that of the TIV from the histological gold standard. The CTP-cerebral blood flow (CBF) parameter had the highest R (2) value and slope closest to unity, while the CTP-cerebral blood volume (CBV) had the lowest R(2) value and slope furthest away from unity. The CTP-CBF â€¢ CBV product parameter had a higher R(2) value but lower slope than both MR parameers. The best Bland-Altman agreement was observed with the CTP-CBF parameter. PIV from MR-DWI, ADC, and CTP-CBF overestimated the TIV defined with histology. We show that the PIV defined with absolute gray and white matter CT-CBF thresholds correlates best with the TIV and is similar to both MR-DWI and ADC-defined PIVs. Further, the acute CBF â€¢ CBV mismatch may not indicate penumbral tissue in the acute stroke setting.
Pre-entry student clinical placement demand: can it be met? - Australian health review : a publication of the Australian Hospital Association
Objectives The Clinical Education Workload Management Initiative (the Initiative) is a unique, multiprofessional, jurisdiction-wide approach and reform process enshrined within an industrial agreement. The Initiative enabled significant investment in allied health clinical education across Queensland public health services to address the workload associated with providing pre-entry clinical placements. This paper describes the outcomes of a quality review activity to measure the impact of the Initiative on placement capacity and workload management for five allied health professions. Data related to several key factors impacting on placement supply and demand in addition to qualitative perspectives from workforce surveys are reported. Methods Data from a range of quality review actions including collated placement activity data, and workforce and student cohort statistics were appraised. Stakeholder perspectives reported in surveys were analysed for emerging themes. Results Placement offers showed an upward trend in the context of increased university program and student numbers and in contrast with a downward trend in full-time equivalent (FTE) staff numbers. Initiative-funded positions were identified as a major factor in individual practitioners taking more students, and staff and managers valued the Initiative-funded positions' support before and during placements, in the coordination of placements, and in building partnerships with universities. Conclusions The Initiative enabled a co-ordinated response to meeting placement demand and enhanced collaborations between the health and education sectors. Sustaining pre-entry student placement provision remains a challenge for the future. What is known about the topic? The literature clearly identifies factors impacting on increasing demand for clinical placements and a range of strategies to increase clinical placement capacity. However, reported initiatives have mostly been ad hoc or reactive responses, often isolated within services or professions. What does this paper add? This paper describes implementation of a clinical placement capacity building initiative within public sector health services developed from a unique opportunity to provide funding through an industrial agreement. The Initiative aimed to address the workload associated with clinical education of pre-entry students and new graduates. What are the implications for practitioners? This paper demonstrates that systematic commitment to, and funding of, clinical education across a jurisdiction's public health services is able to increase placement capacity, even when staffing numbers are in decline.
Functional trajectories in the year before hospice. - Annals of family medicine
We undertook a study to identify distinct functional trajectories in the year before hospice, to determine how patients with these trajectories differ according to demographic characteristics and hospice diagnosis, and to evaluate the association between these trajectories and subsequent outcomes.From an ongoing cohort study of 754 community-living persons aged 70 years or older, we evaluated data on 213 persons who were subsequently enrolled in hospice from March 1998 to December 2011. Disability in 13 basic, instrumental, and mobility activities was assessed during monthly telephone interviews through June 2012.In the year before hospice, we identified 5 clinically distinct functional trajectories, representing worsening cumulative burden of disability: late decline (10.8%), accelerated (10.8%), moderate (21.1%), progressively severe (24.9%), and persistently severe (32.4%). Participants with a cancer diagnosis (34.7%) had the most favorable functional trajectories (ie, lowest burden of disability), whereas those with neurodegenerative disease (21.1%) had the worst. Median survival in hospice was only 14 days and did not differ significantly by functional trajectory. Compared with participants in the persistently severe trajectory, those in the moderate trajectory had the highest likelihood of surviving and being independent in at least 1 activity in the month after hospice admission (adjusted odds ratio = 5.5; 95% CI, 1.9-35.9).The course of disability in the year before hospice differs greatly among older persons but is particularly poor among those with neurodegenerative disease. Late admission to hospice (as shown by the short survival), coupled with high levels of severe disability before hospice, highlight potential unmet palliative care needs for many older persons at the end of life.Â© 2015 Annals of Family Medicine, Inc.
Developing competencies for pediatric hospice and palliative medicine. - Pediatrics
In 2006, hospice and palliative medicine (HPM) became an officially recognized subspecialty. This designation helped initiate the Accreditation Council of Graduate Medical Education Outcomes Project in HPM. As part of this process, a group of expert clinician-educators in HPM defined the initial competency-based outcomes for HPM fellows (General HPM Competencies). Concurrently, these experts recognized and acknowledged that additional expertise in pediatric HPM would ensure that the competencies for pediatric HPM were optimally represented. To fill this gap, a group of pediatric HPM experts used a product development method to define specific Pediatric HPM Competencies. This article describes the development process. With the ongoing evolution of HPM, these competencies will evolve. As part of the Next Accreditation System, the Accreditation Council of Graduate Medical Education uses milestones as a framework to better define competency-based, measurable outcomes for trainees. Currently, there are no milestones specific to HPM, although the field is designing curricular milestones with multispecialty involvement, including pediatrics. These competencies are the conceptual framework for the pediatric content in the HPM milestones. They are specific to the pediatric HPM subspecialist and should be integrated into the training of pediatric HPM subspecialists. They will serve a foundational role in HPM and should inform a wide range of emerging innovations, including the next evolution of HPM Competencies, development of HPM curricular milestones, and training of adult HPM and other pediatric subspecialists. They may also inform pediatric HPM outcome measures, as well as standards of practice and performance for pediatric HPM interdisciplinary teams.Copyright Â© 2014 by the American Academy of Pediatrics.
CT perfusion imaging as an early biomarker of differential response to stereotactic radiosurgery in C6 rat gliomas. - PloS one
The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model.Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, Nâ€Š=â€Š8) or stereotactic radiosurgery (Nâ€Š=â€Š25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival >15 days were designated as responders while those with survival â‰¤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline.Early signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P<0.04). Responders to stereotactic radiosurgery showed lower relative blood volume (rBV), and permeability-surface area (PS) product on day 7 post-stereotactic radiosurgery when compared to controls and non-responders (P<0.05). rBV and PS on day 7 showed correlations with overall survival (P<0.05), and were predictive of survival with 92% accuracy.Response to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation.
Sleep disorders and fatigue: special issues in the older adult with cancer. - Cancer journal (Sudbury, Mass.)
Older adults with cancer reporting fatigue and sleep disorders often have coexisting geriatric syndromes and are at high risk of further functional decline. This review summarizes special considerations in the diagnosis and treatment of sleep disorders and fatigue when older persons with cancer present with multiple comorbidities, polypharmacy, dementia, delirium, and/or falls. Physicians caring for these older adults need to be aware of the unique diagnostic and treatment concerns in this population so that these patients can receive optimal care.
The Quality Improvement Knowledge Application Tool Revised (QIKAT-R). - Academic medicine : journal of the Association of American Medical Colleges
Quality improvement (QI) has been part of medical education for over a decade. Assessment of QI learning remains challenging. The Quality Improvement Knowledge Application Tool (QIKAT), developed a decade ago, is widely used despite its subjective nature and inconsistent reliability. From 2009 to 2012, the authors developed and assessed the validation of a revised QIKAT, the "QIKAT-R."Phase 1: Using an iterative, consensus-building process, a national group of QI educators developed a scoring rubric with defined language and elements. Phase 2: Five scorers pilot tested the QIKAT-R to assess validity and inter- and intrarater reliability using responses to four scenarios, each with three different levels of response quality: "excellent," "fair," and "poor." Phase 3: Eighteen scorers from three countries used the QIKAT-R to assess the same sets of student responses.Phase 1: The QI educators developed a nine-point scale that uses dichotomous answers (yes/no) for each of three QIKAT-R subsections: Aim, Measure, and Change. Phase 2: The QIKAT-R showed strong discrimination between "poor" and "excellent" responses, and the intra- and interrater reliability were strong. Phase 3: The discriminative validity of the instrument remained strong between excellent and poor responses. The intraclass correlation was 0.66 for the total nine-point scale.The QIKAT-R is a user-friendly instrument that maintains the content and construct validity of the original QIKAT but provides greatly improved interrater reliability. The clarity within the key subsections aligns the assessment closely with QI knowledge application for students and residents.
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