Objective
To create a multidimensional tool to prognosticate long‐term functional, cognitive, and quality of life outcomes after spontaneous subarachnoid hemorrhage (SAH) using data up to 48 hours ...after admission.
Methods
Data were prospectively collected for 1,619 consecutive patients enrolled in the SAH outcome project July 1996 to March 2014. Linear models (LMs) were applied to identify factors associated with outcome in 1,526 patients with complete data. Twelve‐month functional, cognitive, and quality of life outcomes were measured using the modified Rankin scale (mRS), Telephone Interview for Cognitive Status, and Sickness Impact Profile. Based on the LM residuals, we constructed the FRESH score (Functional Recovery Expected after Subarachnoid Hemorrhage). Score performance, discrimination, and internal validity were tested using the area under the receiver operating characteristic curve (AUC), Nagelkerke and Cox/Snell R2, and bootstrapping. For external validation, we used a control population of SAH patients from the CONSCIOUS‐1 study (n = 413).
Results
The FRESH score was composed of Hunt & Hess and APACHE‐II physiologic scores on admission, age, and aneurysmal rebleed within 48 hours. Separate scores to prognosticate 1‐year cognition (FRESH‐cog) and quality of life (FRESH‐quol) were developed controlling for education and premorbid disability. Poor functional outcome (mRS = 4–6) for score levels 1 through 9 respectively was present in 3, 6, 12, 38, 61, 83, 92, 98, and 100% at 1‐year follow‐up. Performance of FRESH (AUC = 0.90), FRESH‐cog (AUC = 0.80), and FRESH‐quol (AUC = 0.78) was high. External validation of our cohort using mRS as endpoint showed satisfactory results (AUC = 0.77). To allow for convenient score calculation, we built a smartphone app available for free download.
Interpretation
FRESH is the first clinical tool to prognosticate long‐term outcome after spontaneous SAH in a multidimensional manner. Ann Neurol 2016;80:46–58
Following centuries of exploitation, basking sharks (Cetorhinus maximus) are considered by IUCN as Endangered in the Northeast Atlantic, where they have now been substantially protected for over two ...decades. However, the present size of this population remains unknown. We investigated the use of photo-identification of individuals' dorsal fins, combined with mark-recapture methodology, to investigate the size of populations of basking shark within the west coast of Scotland. From a total of 921 encounters photographed between 2004 and 2011, 710 sharks were found to be individually identifiable based on dorsal fin damage and natural features. Of these, only 41 individuals were re-sighted, most commonly both within days of, and close to the site of, the initial encounter. A smaller number were re-sighted after longer periods of up to two years. A comparison of the distinguishing features of individuals on first recording and subsequent re-sighting showed that in almost all cases these features remained little changed, suggesting the low re-sighting rate was not due to a loss of distinguishing features. Because of the low number of re-sighting we were not able to produce reliable estimates for the long-term regional population. However, for one 50 km diameter study area between the islands of Mull, Coll and Tiree, we were able to generate closed-population estimates for 6-9 day periods in 2010 of 985 (95% CI = 494-1683), and in 2011 of 201 (95% CI = 143-340). For the same 2011 period an open-population model generated a similar estimate of 213 (95% CI = 111-317). Otherwise the low rate and temporal patterning of re-sightings support the view that such local basking shark populations are temporary, dynamic groupings of individuals drawn from a much larger regional population than previously supposed. The study demonstrated the feasibility and limitations of photo-identification as a non-invasive technique for identifying individual basking sharks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Accurate behavioral assessments of consciousness carry tremendous significance in guiding management, but are extremely challenging in acutely brain‐injured patients. We evaluated whether ...electroencephalography (EEG) and multimodality monitoring parameters may facilitate assessment of consciousness in patients with subarachnoid hemorrhage.
Methods
A retrospective analysis was performed of 83 consecutively treated adults with subarachnoid hemorrhage. All patients were initially comatose and had invasive brain monitoring placed. Behavioral assessments were performed during daily interruption of sedation and categorized into 3 groups based on their best examination as (1) comatose, (2) arousable (eye opening or attending toward a stimulus), and (3) aware (command following). EEG features included spectral power and complexity measures. Comparisons were made using bootstrapping methods and partial least squares regression.
Results
We identified 389 artifact‐free EEG clips following behavioral assessments. Increasing central gamma, posterior alpha, and diffuse theta‐delta oscillations differentiated patients who were arousable from those in coma. Command following was characterized by a further increase in central gamma and posterior alpha, as well as an increase in alpha permutation entropy. These EEG features together with basic neurological examinations (eg, pupillary light reflex) contributed heavily to a linear model predicting behavioral state, whereas brain physiology measures (eg, brain oxygenation), structural injury, and clinical course added less.
Interpretation
EEG measures of behavioral states provide distinctive signatures that complement behavioral assessments of patients with subarachnoid hemorrhage shortly after the injury. Our data support the hypothesis that impaired connectivity of cortex with both central thalamus and basal forebrain underlies decreasing levels of consciousness. Ann Neurol 2016;80:541–553
Objective
Recognition of potential for neurological recovery in patients who remain comatose after cardiac arrest is challenging and strains clinical decision making. Here, we utilize an approach ...that is based on physiological principles underlying recovery of consciousness and show correlation with clinical recovery after acute anoxic brain injury.
Methods
A cohort study of 54 patients admitted to an Intensive Care Unit after cardiac arrest who underwent standardized bedside behavioral testing (Coma Recovery Scale – Revised CRS‐R) during EEG monitoring. Blinded to all clinical variables, artifact‐free EEG segments were selected around maximally aroused states and analyzed using a multi‐taper method to assess frequency spectral content. EEG spectral features were assessed based on pre‐defined categories that are linked to anterior forebrain corticothalamic integrity. Clinical outcomes were determined at the time of hospital discharge, using Cerebral Performance Categories (CPC).
Results
Ten patients with ongoing seizures, myogenic artifacts or technical limitations obscuring recognition of underlying cortical dynamic activity were excluded from primary analysis. Of the 44 remaining patients with distinct EEG spectral features, 39 (88%) fit into our predefined categories. In these patients, spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness and favorable clinical outcome at the time of hospital discharge (P = 0.014).
Interpretation
Predicted transitions of neocortical dynamics that indicate functional integrity of anterior forebrain corticothalamic circuitry correlate with clinical outcomes in postcardiac‐arrest patients. Our results support a new biologically driven approach toward better understanding of neurological recovery after cardiac arrest.
The voluntary allocation of attention to environmental inputs is a crucial mechanism of healthy cognitive functioning, and is probably influenced by an observer's level of interest in a stimulus. For ...example, an individual who is passionate about soccer but bored by botany will obviously be more attentive at a soccer match than an orchid show. The influence of monetary rewards on attention has been examined, but the impact of more common motivating factors (i.e. the level of interest in the materials under observation) remains unclear, especially during development. Here, stimulus sets were designed based on survey measures of the level of interest of adolescent participants in several item classes. High‐density electroencephalography was recorded during a cued spatial attention task in which stimuli of high or low interest were presented in separate blocks. The motivational impact on performance of a spatial attention task was assessed, along with event‐related potential measures of anticipatory top‐down attention. As predicted, performance was improved for the spatial target detection of high interest items. Further, the impact of motivation was observed in parieto‐occipital processes associated with anticipatory top‐down spatial attention. The anticipatory activity over these regions was also increased for high vs. low interest stimuli, irrespective of the direction of spatial attention. The results also showed stronger anticipatory attentional and motivational modulations over the right vs. left parieto‐occipital cortex. These data suggest that motivation enhances top‐down attentional processes, and can independently shape activations in sensory regions in anticipation of events. They also suggest that attentional functions across hemispheres may not fully mature until late adolescence.
This work examined the influence of level of interest in anticipated stimuli on established ERP indices of spatial attention in adolescents. Results showed significantly greater accuracy in target detection for high versus low interest stimuli, as well as enhanced amplitude in parieto‐occipital processes related to anticipatory spatial attention. This provides a foundation for future work with developmentally disabled populations using level of interest in stimuli as incentive to potentially regulate atypical attentional processes.
The morbidity, mortality, and monetary cost associated with intracerebral hemorrhage (ICH) is devastatingly high. Several scoring systems have been proposed to prognosticate outcomes after ICH, ...although the original ICH Score is still the most widely used. However, recent research suggests that systemic physiologic factors, such as those included in the Acute Physiology and Chronic Health Evaluation II score, may also influence outcome. In addition, no scoring systems to date have included premorbid functional status. Therefore, we propose a scoring system that incorporates these factors to prognosticate 3-month and 12-month functional outcomes.
We used the Random Forest machine-learning technique to identify factors from a dataset of more than 200 data points per patient that were most strongly affiliated with functional outcome. We then used linear regression to create an initial model based on these factors and modified weightings to improve accuracy. Our scoring system was compared with the ICH Score for prognosticating functional outcomes.
Two separate scoring systems (Intracerebral Hemorrhage Outcomes Project 3 ICHOP3 and ICHOP12) were developed for 3-month and 12-month functional outcomes using Glasgow Coma Scale, National Institutes of Health Stroke Scale, Acute Physiology and Chronic Health Evaluation II, premorbid modified Rankin Scale (mRS), and hematoma volume (3-month only). Patient outcomes were dichotomized into good (mRS score, 0–3) and poor (mRS score, 4–6) categories based on functional status. Areas under the curve in the derivation cohort for predicting mRS score were 0.89 (3-month) and 0.87 (12-month); both were significantly more discriminatory than the original ICH Score.
The ICHOP scores may provide more comprehensive evaluation of a patient's long-term functional prognosis by taking into account systemic physiologic factors as well as premorbid functional status.
A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial ...tuning will depend on the consistency and accuracy of the eye movement system. Anomalies in fixation patterns and the ballistics of eye movements are well documented in autism spectrum disorder (ASD), with off‐center fixations a hallmark of the phenotype. We hypothesized that these atypicalities might affect the development of visuo‐spatial maps and specifically that peripheral inputs might receive altered processing in ASD. Using high‐density recordings of visual evoked potentials (VEPs) and a novel system‐identification approach known as VESPA (visual evoked spread spectrum analysis), we assessed sensory responses to centrally and peripherally presented stimuli. Additionally, input luminance was varied to bias responsiveness to the magnocellular system, given previous suggestions of magnocellular‐specific deficits in ASD. Participants were 22 ASD children (7–17 years of age) and 31 age‐ and performance‐IQ‐matched neurotypical controls. Both VEP and VESPA responses to central presentations were indistinguishable between groups. In contrast, peripheral presentations resulted in significantly greater early VEP and VESPA amplitudes in the ASD cohort. We found no evidence that anomalous enhancement was restricted to magnocellular‐biased responses. The extent of peripheral response enhancement was related to the severity of stereotyped behaviors and restricted interests, cardinal symptoms of ASD. The current results point to differential visuo‐spatial cortical mapping in ASD, shedding light on the consequences of peculiarities in gaze and stereotyped visual behaviors often reported by clinicians working with this population.
A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial tuning will depend on the consistency and accuracy of the eye‐movement system.
Abstract The formation of scar tissue due to dedifferentiation of smooth muscle cells (SMCs) is one of the major issues faced when engineering bladder tissue. Furthermore, cell sources for ...regenerating the SMC layer are also limiting. Here we explore if human mesenchymal stem cells (MCSs), cultured in enzymatically degradable poly(ethylene glycol) (PEG) hydrogel scaffolds can be differentiated into SMC-like cells. We explored the degree to which a less synthetic SMC phenotype can be achieved when primary human SMCs are cultured within these scaffolds, It was observed that when both MSCs and SMCs are cultured in the PEG hydrogel scaffolds, but not on traditional tissue culture plastic, they up-regulate markers associated with the less synthetic SMC phenotype, decreased expression of α5 integrin and THY-1, and increased expression of α- smooth muscle actin ( α SMA) and myosin. Furthermore, we show that MSCs and SMCs cultured in the PEG hydrogels are able to proliferate and express matrix metalloproteinases for up to 21 d in culture, the duration of the study. This study addresses the importance of the cellular microenvironment on cell fate, and proposes synthetic instructive biomaterials as a means to direct cell differentiation and circumvent scar tissue formation during bladder reconstruction.
High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could ...provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exposure to a broad spectrum of patient cases is a mainstay of undergraduate medical education. This study aimed to assess how many primary care-specific clinical pictures final-year medical students ...in traditional block rotations had encountered, and how this changed after a curricular change that included the implementation of a four-year longitudinal clerkship in primary care.
Final-year students before, and after, implementation of the clerkship were asked which of the clinical pictures most relevant to primary care they had seen. We compared the overall proportions of clinical pictures seen by the two cohorts.
In the first cohort, 96 (66%) students responded, and 94 (65%) in the second. Before the curricular change, students had encountered a mean of 26.3 of the 34 primary care-specific clinical pictures (77.2%). After implementation of the longitudinal clerkship, this increased by 1.1 (4.2%, P = 0.038). Among the eight clinical pictures seen the least by students in the first cohort, we found a significant increase in the proportion of students seeing polymalgia rheumatica, frozen shoulder, epicondylitis and Dupuytren's contracture after the clerkship's implementation.
The undergraduate longitudinal clerkship in primary care broadened the spectrum of clinical pictures seen by medical students, to include more clinical pictures commonly seen in primary care.
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