1,967 research outputs found
Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice
Cortical interneurons are generated predominantly in the medial ganglionic eminence (MGE) and migrate through the ventral and dorsal telencephalon before taking their final positions within the developing cortical plate. Previously we demonstrated that interneurons from Robo1 knockout (Robo1(-/-) ) mice contain reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less responsive to the chemorepulsive actions of semaphorin ligands expressed in the striatum and affecting their course of migration (Hernandez-Miranda et al. [2011] J. Neurosci. 31:6174-6187). Earlier studies have highlighted the importance of Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1 in this process. We observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1(-/-) mice compared with wild-type littermates at E14.5 and E18.5. Although the level of apoptosis was similar in the mutant and control forebrain, proliferation was significantly reduced in the former. Furthermore, progenitor cells in the MGE of PlexinA1(-/-) mice appeared to be poorly anchored to the ventricular surface and showed reduced adhesive properties, which may account for the observed reduction in proliferation. Together our data uncover a novel role for PlexinA1 in forebrain development. J. Comp. Neurol., 2015. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc
Power output, cadence, and torque are similar between the forward standing and traditional sprint cycling positions
Purpose: Compare power output, cadence, and torque in the seated, standing, and forward standing cycling sprint positions. Methods: On three separated occasions (ie, one for each position), 11 recreational male road cyclists performed a 14 seconds sprint before and directly after a high-intensity lead-up. Power output, cadence, and torque were measured during each sprint. Results: No significant differences in peak and mean power output were observed between the forward standing (1125.5 ± 48.5 W and 896.0 ± 32.7 W, respectively) and either the seated or standing positions (1042.5 ± 46.8 W and 856.5 ± 29.4 W; 1175.4 ± 44.9 W and 927.5 ± 28.9 W, respectively). Power output was higher in the standing, compared with the seated position. No difference was observed in cadence between positions. At the start of the sprint before the lead-up, peak torque was higher in the standing position vs the forward standing position; and peak torque occurred later in the pedal revolution for both the forward standing and standing positions when compared with the seated position. At the start of the sprint after the lead-up, peak torque occurred later in the forward standing position when compared with both the seated and standing position. At the end of the sprint, no difference in torque was found between the forward standing and standing position either before or after the lead-up. Conclusion: Sprinting in the forward standing sprint position does not impair power output, cadence, and torque when compared with the seated and standing sprint positions
Patient-Specific Monitoring and Trend Analysis of Model-Based Markers of Fluid Responsiveness in Sepsis: A Proof-of-Concept Animal Study
© 2019, Biomedical Engineering Society. Total stressed blood volume (SBVT) and arterial elastance (Ea) are two potentially important, clinically applicable metrics for guiding treatment in patients with altered hemodynamic states. Defined as the total pressure generating blood in the circulation, SBVT is a potential direct measurement of tissue perfusion, a critical component in treatment of sepsis. Ea is closely related to arterial tone thus provides insight into cardiac efficiency. However, it is not clinically feasible or ethical to measure SBVT in patients, so a three chambered cardiovascular system model using measured left ventricle pressure and volume, aortic pressure and central venous pressure is implemented to identify SBVT and Ea from clinical data. SBVT and Ea are identified from clinical data from six (6) pigs, who have undergone clinical procedures aimed at simulating septic shock and subsequent treatment, to identify clinically relevant changes. A novel, validated trend analysis method is used to adjudge clinically significant changes in state in the real-time Ea and SBVT traces. Results matched hypothesised increases in SBVT during fluid therapy, with a mean change of + 21% during initial therapy, and hypothesised decreases during endotoxin induced sepsis, with a mean change of − 29%. Ea displayed the hypothesised reciprocal behaviour with a mean changes of − 12 and + 30% during initial therapy and endotoxin induced sepsis, respectively. The overall results validate the efficacy of SBVT in tracking changes in hemodynamic state in septic shock and fluid therapy
Heteroskedasticity testing through a comparison of Wald statistics
This paper shows that a test for heteroskedasticity within the context of classical linear regression can be based on the difference between Wald statistics in heteroskedasticity-robust and nonrobust forms. The test is asymptotically distributed under the null hypothesis of homoskedasticity as chi-squared with one degree of freedom. The power of the test is sensitive to the choice of parametric restriction used by the Wald statistics, so the supremum of a range of individual test statistics is proposed. Two versions of a supremum-based test are considered: the first version does not have a known asymptotic null distribution, so the bootstrap is employed to approximate its empirical distribution. The second version has a known asymptotic distribution and, in some cases, is asymptotically pivotal under the null. A simulation study illustrates the use and finite-sample performance of both versions of the test. In this study, the bootstrap is found to provide better size control than asymptotic critical values, namely with heavy-tailed, asymmetric distributions of the covariates. In addition, the use of well-known modifications of the heteroskedasticity consistent covariance matrix estimator of OLS coefficients is also found to benefit the tests’ overall behaviour.info:eu-repo/semantics/publishedVersio
A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale
In this era of complete genomes, our knowledge of neuroanatomical circuitry
remains surprisingly sparse. Such knowledge is however critical both for basic
and clinical research into brain function. Here we advocate for a concerted
effort to fill this gap, through systematic, experimental mapping of neural
circuits at a mesoscopic scale of resolution suitable for comprehensive,
brain-wide coverage, using injections of tracers or viral vectors. We detail
the scientific and medical rationale and briefly review existing knowledge and
experimental techniques. We define a set of desiderata, including brain-wide
coverage; validated and extensible experimental techniques suitable for
standardization and automation; centralized, open access data repository;
compatibility with existing resources, and tractability with current
informatics technology. We discuss a hypothetical but tractable plan for mouse,
additional efforts for the macaque, and technique development for human. We
estimate that the mouse connectivity project could be completed within five
years with a comparatively modest budget.Comment: 41 page
Management of primary hepatic malignancies during the COVID-19 pandemic: recommendations for risk mitigation from a multidisciplinary perspective
Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19
Differential postural effects of plantar-flexor muscles fatigue under normal, altered and improved vestibular and neck somatosensory conditions
The aim of the present study was to assess the effects of plantar-flexor
muscles fatigue on postural control during quiet standing under normal, altered
and improved vestibular and neck somatosensory conditions. To address this
objective, young male university students were asked to stand upright as still
as possible with their eyes closed in two conditions of No Fatigue and Fatigue
of the plantar-flexor muscles. In Experiment 1 (n=15), the postural task was
executed in two Neutral head and Head tilted backward postures, recognized to
degrade vestibular and neck somatosensory information. In Experiment 2 (n=15),
the postural task was executed in two conditions of No tactile and Tactile
stimulation of the neck provided by the application of strips of adhesive
bandage to the skin over and around the neck. Centre of foot pressure
displacements were recorded using a force platform. Results showed that (1) the
Fatigue condition yielded increased CoP displacements relative to the No
Fatigue condition (Experiment 1 and Experiment 2), (2) this destabilizing
effect was more accentuated in the Head tilted backward posture than Neutral
head posture (Experiment 1) and (3) this destabilizing effect was less
accentuated in the condition of Tactile stimulation than that of No tactile
stimulation of the neck (Experiment 2). In the context of the multisensory
control of balance, these results suggest an increased reliance on vestibular
and neck somatosensory information for controlling posture during quiet
standing in condition of altered ankle neuromuscular function
Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review
Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern.
Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care.
Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research.
Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements.
Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas
Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.
Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation
Physiological modeling, tight glycemic control, and the ICU clinician: what are models and how can they affect practice?
Critically ill patients are highly variable in their response to care and treatment. This variability and the search for improved outcomes have led to a significant increase in the use of protocolized care to reduce variability in care. However, protocolized care does not address the variability of outcome due to inter- and intra-patient variability, both in physiological state, and the response to disease and treatment. This lack of patient-specificity defines the opportunity for patient-specific approaches to diagnosis, care, and patient management, which are complementary to, and fit within, protocolized approaches
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