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We propose a hierarchical Bayesian model for analyzing multi-site experimental fMRI studies. Our method takes the hierarchical structure of the data (subjects are nested within sites, and there are multiple observations per subject) into account and allows for modeling between-site variation. Using posterior predictive model checking and model selection based on the deviance information criterion (DIC), we show that our model provides a good fit to the observed data by sharing information across the sites. We also propose a simple approach for evaluating the efficacy of the multi-site experiment by comparing the results to those that would be expected in hypothetical single-site experiments with the same sample size.
Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.
Participants and Methods:
Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.
Results:
Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.
Conclusions:
Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:
240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:
In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:
These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
Surveillance of non–ventilator-associated hospital-acquired pneumonia (NV-HAP) is complicated by subjectivity and variability in diagnosing pneumonia. We compared a fully automatable surveillance definition using routine electronic health record data to manual determinations of NV-HAP according to surveillance criteria and clinical diagnoses.
Methods:
We retrospectively applied an electronic surveillance definition for NV-HAP to all adults admitted to Veterans’ Affairs (VA) hospitals from January 1, 2015, to November 30, 2020. We randomly selected 250 hospitalizations meeting NV-HAP surveillance criteria for independent review by 2 clinicians and calculated the percent of hospitalizations with (1) clinical deterioration, (2) CDC National Healthcare Safety Network (CDC-NHSN) criteria, (3) NV-HAP according to a reviewer, (4) NV-HAP according to a treating clinician, (5) pneumonia diagnosis in discharge summary; and (6) discharge diagnosis codes for HAP. We assessed interrater reliability by calculating simple agreement and the Cohen κ (kappa).
Results:
Among 3.1 million hospitalizations, 14,023 met NV-HAP electronic surveillance criteria. Among reviewed cases, 98% had a confirmed clinical deterioration; 67% met CDC-NHSN criteria; 71% had NV-HAP according to a reviewer; 60% had NV-HAP according to a treating clinician; 49% had a discharge summary diagnosis of pneumonia; and 82% had NV-HAP according to any definition according to at least 1 reviewer. Only 8% had diagnosis codes for HAP. Interrater agreement was 75% (κ = 0.50) for CDC-NHSN criteria and 78% (κ = 0.55) for reviewer diagnosis of NV-HAP.
Conclusions:
Electronic NV-HAP surveillance criteria correlated moderately with existing manual surveillance criteria. Reviewer variability for all manual assessments was high. Electronic surveillance using clinical data may therefore allow for more consistent and efficient surveillance with similar accuracy compared to manual assessments or diagnosis codes.
While unobscured and radio-quiet active galactic nuclei are regularly being found at redshifts
$z > 6$
, their obscured and radio-loud counterparts remain elusive. We build upon our successful pilot study, presenting a new sample of low-frequency-selected candidate high-redshift radio galaxies (HzRGs) over a sky area 20 times larger. We have refined our selection technique, in which we select sources with curved radio spectra between 72–231 MHz from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. In combination with the requirements that our GLEAM-selected HzRG candidates have compact radio morphologies and be undetected in near-infrared
$K_{\rm s}$
-band imaging from the Visible and Infrared Survey Telescope for Astronomy Kilo-degree Infrared Galaxy (VIKING) survey, we find 51 new candidate HzRGs over a sky area of approximately
$1200\ \mathrm{deg}^2$
. Our sample also includes two sources from the pilot study: the second-most distant radio galaxy currently known, at
$z=5.55$
, with another source potentially at
$z \sim 8$
. We present our refined selection technique and analyse the properties of the sample. We model the broadband radio spectra between 74 MHz and 9 GHz by supplementing the GLEAM data with both publicly available data and new observations from the Australia Telescope Compact Array at 5.5 and 9 GHz. In addition, deep
$K_{\rm s}$
-band imaging from the High-Acuity Widefield K-band Imager (HAWK-I) on the Very Large Telescope and from the Southern Herschel Astrophysical Terahertz Large Area Survey Regions
$K_{\rm s}$
-band Survey (SHARKS) is presented for five sources. We discuss the prospects of finding very distant radio galaxies in our sample, potentially within the epoch of reionisation at
$z \gtrsim 6.5$
.
Suprastomal granulation tissue is a common complication of long-term tracheostomy. It may be associated with bleeding, aphonia, airway obstruction and delayed decannulation.
Methods
This study describes the experience of a tertiary paediatric medical centre with CoblationTM-assisted suprastomal granulation tissue excision.
Results
Thirteen children (mean age, 5.7 years) who underwent the procedure from 2013 to 2019 because of delayed decannulation or aphonia were included. Lumen obstruction ranged from 50 to 90 per cent, with a mean of 68.8 per cent. After the procedure, decannulation was successfully performed in 7 patients, and voice quality improved in 10 patients. There were no peri- or post-operative complications.
Conclusion
This is the largest series to date that describes Coblation used for the treatment of suprastomal granuloma. Coblation has advantages of high precision, relatively low temperature (thereby avoiding thermal injury to adjacent tissue), haemostatic resection and feasibility for use for even large granulomas. The promising results should prompt further studies in larger samples.
Pediatric patients with epilepsy have an increased risk of ictal, postictal or interictal psychotic symptoms. We describe a child with mild epilepsy who was hospitalized in our Pediatric ward with acute severe psychosis. His epilepsy was well controlled and he was known to have a 4 mm large frontal cystic lesion per brain MRI. He did not have overt seizures upon admission, but his EEG showed non-convulsive, high voltage spike/slow wave activity. Treatment with valproic acid led to concomitant resolution of the psychotic symptoms and EEG abnormalities. Several months later psychotic symptoms recurred, this time in a milder form, again associated with the same EEG pattern. Lamotrigine was added to the treatment regimen and both symptoms and electrographic changes resolved. No change was noted on repeat MRI.
This child presents an unusual relationship between acute psychosis and markedly abnormal EEG, both resolving with anti-epileptic medication, and a potential causative relationship to a frontal lesion. We discuss this unusual connection between the psychiatric (psychosis), epileptic (non-convulsive status epilepticus) and organic brain (frontal benign lesion) disorders in this child.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
To determine if hypoperfusion abnormalities on single photon emission computed tomography (SPECT) are associated with poorer cognitive function at baseline or increased risk of decline in cognitive function and progression to dementia in memory-impaired but non-demented elderly subjects meeting the criteria for aging associated cognitive decline (AACD).
Design:
Cross sectional study of 36 AACD subjects comparing hexamethyl propylene-amine oxime (HMPAO) SPECT results rated by visual inspection with base line cognitive functioning. Prospective study of these AACD subjects with clinical and neuropsychological follow-up over 35 months.
Setting:
The memory clinic and nuclear medicine unit of a university teaching hospital.
Subjects:
Thirty-six subjects meeting the criteria for AACD recruited from patients seen on a physician referral basis.
Main outcome measures:
1) Baseline cognitive function as measured by the Mini Mental State Examination (MMSE), Boston naming, Logical Memory I subtest of the WAIS-R, and verbal fluency, correlated with SPECT status. 2) Decline in cognitive function as measured by clinical exam and the MMSE, with progression to dementia on follow-up being correlated with SPECT status at baseline.
Results:
18 of the 36 subjects progressed to dementia (probable Alzheimer's Disease) over follow-up. No correlation was found between the presence or absence of SPECT abnormality and MMSE or other cognitive measures. There was no correlation between the presence or absence of SPECT abnormality at initial examination, and cognitive decline according to the MMSE, or with the occurrence of clinical dementia on follow-up.
Conclusions:
We conclude that SPECT abnormalities assessed by visual inspection do not correlate with severity of impairment in AACD individuals, and are not useful in predicting progression to dementia in AACD subjects.
We used a terrestrial radar interferometer (TRI) at Helheim Glacier, Greenland, in August 2013, to study the effects of tidal forcing on the terminal zone of this tidewater glacier. During our study period, the glacier velocity was up to 25 m d–1. Our measurements show that the glacier moves out of phase with the semi-diurnal tides and the densely packed melange in the fjord. Here detrended glacier displacement lags behind the forecasted tidal height by ∼8 hours. The transition in phase lag between the glacier and the melange happens within a narrow (∼500 m) zone in the fjord in front of the ice cliff. The TRI data also suggest that the impact of tidal forcing decreases rapidly up-glacier of the terminus. A flowline model suggests this pattern of velocity perturbation is consistent with weak ice flowing over a weakly nonlinear bed.
A previous small study suggested that Brain Network Activation (BNA), a novel ERP-based brain network analysis, may have diagnostic utility in attention deficit hyperactivity disorder (ADHD). In this study we examined the diagnostic capability of a new advanced version of the BNA methodology on a larger population of adults with and without ADHD.
Method
Subjects were unmedicated right-handed 18- to 55-year-old adults of both sexes with and without a DSM-IV diagnosis of ADHD. We collected EEG while the subjects were performing a response inhibition task (Go/NoGo) and then applied a spatio-temporal Brain Network Activation (BNA) analysis of the EEG data. This analysis produced a display of qualitative measures of brain states (BNA scores) providing information on cortical connectivity. This complex set of scores was then fed into a machine learning algorithm.
Results
The BNA analysis of the EEG data recorded during the Go/NoGo task demonstrated a high discriminative capacity between ADHD patients and controls (AUC = 0.92, specificity = 0.95, sensitivity = 0.86 for the Go condition; AUC = 0.84, specificity = 0.91, sensitivity = 0.76 for the NoGo condition).
Conclusions
BNA methodology can help differentiate between ADHD and healthy controls based on functional brain connectivity. The data support the utility of the tool to augment clinical examinations by objective evaluation of electrophysiological changes associated with ADHD. Results also support a network-based approach to the study of ADHD.
The 2014 Ebola virus disease (EVD) outbreak in West Africa remains the most deadly in history. Emergency departments (EDs) are more likely to come into contact with potential EVD patients. It is important for EDs to be prepared to care for suspected EVD patients. Our objective was to understand the perceived challenges experienced by Washington State ED medical directors in EVD preparedness.
Methods
An anonymous, electronic survey was sent to a convenience sample of ED medical directors across Washington State between November and February of 2014–2015. The perceived challenges of and attitudes toward EVD preparations were assessed and reported as stratified proportions.
Results
Of 85 medical directors contacted, 59 responses (69%) were received. This included EDs with annual patient volumes of <20,000 (20 hospitals, 34%), 20,000 to 40,000 (21 hospitals, 36%), 41,000 to 60,000 (4 hospitals, 6.8%), and >60,000 (12 hospitals, 20%). Among the perceived challenges in EVD preparations were spatial modifications (eg, building an anteroom for donning and doffing of personal protective equipment) and waste management planning. Ninety-five percent of respondents moderately or strongly agreed that it is important to have a predesignated hospital to care for EVD patients.
Conclusions
Washington State ED medical directors have faced significant challenges in ensuring their EDs are prepared to safely care for suspected EVD patients. Attitudes toward EVD preparations are mixed. Varying levels of perceived importance may represent an additional barrier to statewide EVD preparedness. (Disaster Med Public Health Preparedness. 2016;10:662–668)
To evaluate the association between hospital room square footage and acquisition of nosocomial Clostridium difficile infection (CDI).
METHODS
A case-control study was conducted at a university hospital during the calendar year of 2011. Case patients were adult inpatients with nosocomial CDI. Control patients were hospitalized patients without CDI and were randomly selected and matched to cases in a 2:1 ratio on the basis of hospital length of stay in 3-day strata. A multivariate model was developed using conditional logistic regression to evaluate risk factors for nosocomial CDI.
RESULTS
A total of 75 case patients and 150 control patients were included. On multivariate analyses, greater square footage of the hospital room was associated with a significantly increased risk of acquiring CDI (odds ratio for every 50 ft2 increase, 3.00; 95% CI, 1.75–5.16; P<.001). Other factors associated with an increased risk of CDI were location in a single room (odds ratio, 3.43; 95% CI, 1.31–9.05; P=.01), malignant tumor (4.56; 1.82–11.4; P=.001), and receipt of cefepime (2.48; 1.06–5.82; P=.04) or immunosuppressants (6.90; 2.07–23.0; P=.002) within the previous 30 days.
CONCLUSIONS
Greater room square footage increased the risk of acquisition of CDI in the hospital setting, likely owing to increased environmental contamination and/or difficulty in effective disinfection. Future studies are needed to determine feasible and effective cleaning protocols based on patient and room characteristics.
Is human immunodeficiency virus still a terminal condition? Recent advances in treatment have significantly reduced both mortality and morbidity associated with HIV, but these treatments have not been successful in eradicating the virus itself. As such, HIV has evolved into a chronic condition that is complicated by neurocognitive factors. Cognitive difficulties associated with HIV are characterized by a subcortical pattern with primary deficits in information processing speed and psychomotor speed. These deficits interfere with the ability of patients to complete important instrumental activities of daily living even in the absence of dementia. Treatment of HIV improves neurocognitive functioning, but the regimens are complex and patient adherence is critical. Cognitive factors can negatively impact treatment adherence, which in turn results in poorer immunological, cognitive, and psychiatric outcome. This cycle emphasizes the important interrelationships between symptom expression and treatment outcome in patients with HIV. The nature of these relationships will change with further developments in treatment regimens such as once-daily dosing. Less complex treatment approaches should improve health outcome as well as provide additional opportunities to further understand the impact of HIV on brain function.
Concussion is a form of traumatic brain injury that has been defined as a “trauma-induced alteration in mental status that may or may not involve loss of consciousness.” Terms such as getting a “ding” or getting your “bell rung” are sometimes used as colloquialisms for concussion, but inappropriately downplay the seriousness of the injury. It is estimated that between 1.6 and 3.8 million concussions occur annually in the United States as a result of participation in sports or recreational activities. To date, there are no objective, biological markers for concussion; rather, the current diagnosis of concussion is dependent upon symptom reporting by the athlete. In the acute phase, concussions can result in a broad spectrum of symptoms that can be transient or last for days, weeks, or even months. Symptom prolongation is generally referred to as post-concussion syndrome.
NASA's NuSTAR observatory is the first focusing hard X-ray telescope. Launched in June 2012, NuSTAR is sensitive in the 3–79 keV range with unprecedented ~17″ FWHM angular resolution above 12 keV, a result of its multilayer-coated optics and 10-m focal length. With its large effective area (900 cm2 at 10 keV), NuSTAR has point-source sensitivity ~100 times better than previous hard X-ray telescopes. Here we describe NuSTAR and its planned work on rotation-powered pulsars and magnetars during its nominal 2-yr baseline mission that has just commenced.