•There is a wide range of total T2 and large lesion T2 (≥5 mm) count in patients with familial or presumed familial cerebral cavernous malformation (CCM) syndrome.•Tobacco use in patients with ...familial CCM is associated with 5 or more large T2 lesion count.•Hypertension, Hyperlipidemia and Diabetes did not influence total T2 lesion count in patients with familial CCM.
Background: Familial cerebral cavernous malformation (CCM) syndrome is characterized by multiple, non-contiguous cavernous malformations. The lesion burden may affect morbidity. Our aim was to identify risk factors for high lesion burden in these patients. Methods: Patients with radiologically confirmed CCM were screened between 2015 and 2023. Only familial or presumed familial CCM patients were included. Demographic information and medical history at the time of diagnosis were evaluated. The first diagnostic MRI was used to determine T2 total and T2 large lesion (≥5 mm) count. Chi-square was used to determine risk factors for total T2 large lesion count ≥5. Results: Of 107 patients with familial or presumed familial CCM (55.1 % female, age 42.4 years), the median total T2 lesion count and large lesion count was 4 (range: 1–109) and 2 (range: 0–50) respectively. Current tobacco use was a risk factor for T2 large lesion count ≥5. Conclusion: Further studies combining familial cohorts and assessing length of exposure may be useful to confirm tobacco as a risk factor for T2 large lesion formation in familial CCM.
Our goal was to describe the prospective risk and timing of symptomatic hemorrhage in a large cohort of followed patients with intracerebral cavernous malformations (ICMs).
All patients between 1989 ...and 1999 with the radiographic diagnosis of intracerebral cavernous malformation were identified retrospectively. The records and radiographic data were reviewed, and follow-up after diagnosis was obtained. An incidence rate was used to calculate annual risk of symptomatic hemorrhage. Predictive factors for outcomes used univariate and multivariable analysis with p < 0.05.
A total of 292 patients were identified (47.3%male) with 2,035 patient years of follow-up. Seventy-four patients presented with hemorrhage, 108 with symptoms not related to hemorrhage (seizure or focal deficit), and 110 as asymptomatic. The overall annual rate of hemorrhage in those presenting initially with hemorrhage, with symptoms not related to hemorrhage, or as an incidental finding was 6.19%, 2.18%, and 0.33%, respectively. Patients who presented initially with symptomatic hemorrhage (hazard ratio 5.14; 95% confidence interval CI 2.54-10.4; p < 0.001) were at higher risk for future hemorrhage, and hemorrhage risk decreased with time. Male gender (hazard ratio 2.36; 95% CI 1.14-4.89; p = 0.02), and multiplicity of ICMs (hazard ratio 2.65; 95% CI 1.30-5.43; p = 0.01) also increased the risk of hemorrhage. The median time from first to second hemorrhage was 8 months.
This study provides an estimate of prospective annual symptomatic hemorrhage risk in patients with ICMs stratified by initial presenting symptom. Prior hemorrhage, male gender, and multiplicity of ICMs may predict future hemorrhage. Hemorrhage risk decreases with time in those initially presenting with hemorrhage.
Much has been written about the initial radiologic features of cavernous malformations, but less known are the radiologic natural history and evolution of the lesions, particularly when they ...initially present with hemorrhage. We aimed to describe the typical evolution of a sporadic, hemorrhagic brain cavernous malformation with time.
From our institutional review board-approved cavernous malformation registry, we assessed initial clinical and radiologic features and the subsequent MR imaging evolution of 51 patients with sporadic, hemorrhagic brain cavernous malformations (with follow-up brain MRIs available for review).
The initial MR imaging demonstrated mostly Zabramski type I lesions (94.2%) with T1 hyperintensity (94.2%) and associated edema (76.5%). Eight patients (15.6%) rebled in the first year with lesions characterized by new T1 hyperintensity (100%), edema (61.5%), and growth (median, 4 mm). By 90 days, most lesions had changed from Zabramski type I to type II or III (65.2%). While 76.5% had edema associated with the acute hemorrhage, none had persistent edema beyond 90 days unless rebleeding occurred. Across time, the frequency of T1 hyperintensity decreased from 94.2% at baseline to 73.9%, 57.1%, and 50.0% at <90, 91-365, and >365 days. DWI intensity at baseline and <90, 91-365, and >365 days was hypointense at 53.1%, 56.5%, 70.1%, and 81.2%, respectively.
Hemorrhagic cavernous malformation demonstrates a characteristic pattern of evolution on follow-up imaging. Knowing this evolution helps to analyze the timing of imaging in relation to the clinical presentation and may help distinguish true cavernous malformation hemorrhagic evolution from mimics and guide appropriate timing of interval-imaging follow-up after symptomatic bleeds in untreated patients.
Background and purpose
The full spectrum of causes of convexal subarachnoid hemorrhage (cSAH) requires further investigation. Therefore, our objective was to describe the spectrum of clinical and ...imaging features of patients with non‐traumatic cSAH.
Methods
A retrospective observational study of consecutive patients with non‐traumatic cSAH was performed at a tertiary referral center. The underlying cause of cSAH was characterized and clinical and imaging features that predict a specific etiology were identified. The frequency of future cSAH or intracerebral hemorrhage (ICH) was determined.
Results
In all, 88 patients median age 64 years (range 25–85) with non‐traumatic cSAH were identified. The most common causes were reversible cerebral vasoconstriction syndrome (RCVS) (26, 29.5%), cerebral amyloid angiopathy (CAA) (23, 26.1%), indeterminate (14, 15.9%) and endocarditis (9, 10.2%). CAA patients commonly presented at an older age than RCVS patients (75 years versus 51 years, P < 0.0001). Thirteen patients (14.7%) had recurrent cSAH, and 12 patients (13.6%) had a subsequent ICH. However, the risk was high amongst those with CAA compared to those caused by RCVS, with recurrent cSAH in 39.1% and subsequent lobar ICH in 43.5% of CAA cases.
Conclusions
Our study demonstrates the clinical diversity of cSAH. Older age, sensorimotor dysfunction and stereotyped spells suggest CAA as the underlying cause. Younger age and thunderclap headache predict RCVS. Yet, various other causes also need to be considered in the differential diagnosis.
Click here for the corresponding questions to this CME article.
Among patients with vertebrobasilar dolichoectasia is a subset of patients with disease affecting the anterior circulation as well. We hypothesized that multivessel intracranial dolichoectasia may ...represent a distinct phenotype from single-territory vertebrobasilar dolichoectasia. The purpose of this study was to characterize clinical characteristics and angiographic features of this proposed distinct phenotype termed "diffuse intracranial dolichoectasia" and compare them with those in patients with isolated vertebrobasilar dolichoectasia.
We retrospectively reviewed a consecutive series of patients with diffuse intracranial dolichoectasia and compared their demographics, vascular risk factors, additional aneurysm prevalence, and clinical outcomes with a group of patients with vertebrobasilar dolichoectasia. "Diffuse intracranial dolichoectasia" was defined as aneurysmal dilation of entire vascular segments involving ≥2 intracranial vascular beds. Categoric and continuous variables were compared by using χ
and Student
tests, respectively.
Twenty-five patients had diffuse intracranial dolichoectasia, and 139 had vertebrobasilar dolichoectasia. Patients with diffuse intracranial dolichoectasia were older than those with vertebrobasilar dolichoectasia (70.9 ± 14.2 years versus 60.4 ± 12.5 years,
= .0002) and had a higher prevalence of abdominal aortic aneurysms (62.5% versus 14.3%,
= .01), other visceral aneurysms (25.0% versus 0%,
< .0001), and smoking (68.0% versus 15.9%,
< .0001). Patients with diffuse intracranial dolichoectasia were more likely to have aneurysm growth (46.2% versus 21.5%,
= .09) and rupture (20% versus 3.5%,
= .007) at follow-up. Patients with diffuse intracranial dolichoectasia were less likely to have good neurologic function at follow-up (24.0% versus 57.6%,
= .004) and were more likely to have aneurysm-related death (24.0% versus 7.2%,
= .02).
The natural history of patients with diffuse intracranial dolichoectasia is significantly worse than that in those with isolated vertebrobasilar dolichoectasia. Many patients with diffuse intracranial dolichoectasia had additional saccular and abdominal aortic aneurysms. These findings suggest that diffuse intracranial dolichoectasia may be a distinct vascular phenotype secondary to a systemic arteriopathy affecting multiple vascular beds.
The Golden (British Columbia, Canada) meteorite fall occurred on October 4, 2021 at 0534 UT with the first recovered fragment (1.3 kg) landing on an occupied bed. The associated fireball was recorded ...by numerous cameras permitting reconstruction of its trajectory and orbit. The fireball entered the atmosphere at a 54° angle from the horizontal at a speed of 18 km s−1. The fireball reached a peak brightness of −14, having first become luminous at a height of >84 km and ending at 18 km altitude. Analysis of the infrasonic record of the bolide produced an estimated mass of 78−65+157 kg while modeling of the fireball light curve suggests an initial mass near 70 kg. The fireball experienced a major flare near 31 km altitude where more than half its mass was lost in the form of dust and gram‐sized fragments under a dynamic pressure of 3.3 MPa. The strength and fragmentation behavior of the fireball were similar to those reported for other meteorite‐producing fireballs (Borovička et al., 2020). Seven days after the fireball occurred, an additional 0.9 kg fragment was recovered during the second day of dedicated searching guided by initial trajectory and dark flight calculations. Additional searching in the fall and spring of 2021–2022 located no additional fragments. The meteorite is an unbrecciated, low‐shock (S2) ordinary chondrite of intermediate composition, typed as an L/LL5 with a grain density of ~3530 k gm−3, an average bulk density of 3150 kg m−3 and calculated porosity of ~10%. From noble gas measurements, the cosmic ray exposure age is 25 ± 4 Ma while gas retention ages are all >2 Ga. Short‐lived radionuclides and noble gas measurements of the pre‐atmospheric size overlap with estimates from infrasound and light curve modeling producing a preferred pre‐atmospheric mass of 70–200 kg. The orbit of Golden has a high inclination (23.5°) and is consistent with delivery from the inner main belt. The highest probability (60%) of an origin is from the Hungaria group. We propose that Golden may originate among the background S‐type asteroids found interspersed in the Hungaria region. The current collection of 18 L/LL—chondrite orbits shows a strong preference for origins in the inner main belt, suggesting multiple parent bodies may be required to explain the diversity in CRE ages and shock states.
Human campylobacteriosis is the leading bacterial gastrointestinal illness in Canada; environmental transmission has been implicated in addition to transmission via consumption of contaminated food. ...Information about Campylobacter spp. occurrence at the watershed scale will enhance our understanding of the associated public health risks and the efficacy of source water protection strategies. The overriding purpose of this study is to provide a quantitative framework to assess and compare the relative public health significance of watershed microbial water quality associated with agricultural BMPs. A microbial monitoring program was expanded from fecal indicator analyses and Campylobacter spp. presence/absence tests to the development of a novel, 11-tube most probable number (MPN) method that targeted Campylobacter jejuni, Campylobacter coli, and Campylobacter lari. These three types of data were used to make inferences about theoretical risks in a watershed in which controlled tile drainage is widely practiced, an adjacent watershed with conventional (uncontrolled) tile drainage, and reference sites elsewhere in the same river basin. E. coli concentrations (MPN and plate count) in the controlled tile drainage watershed were statistically higher (2008–11), relative to the uncontrolled tile drainage watershed, but yearly variation was high as well. Escherichia coli loading for years 2008–11 combined were statistically higher in the controlled watershed, relative to the uncontrolled tile drainage watershed, but Campylobacter spp. loads for 2010–11 were generally higher for the uncontrolled tile drainage watershed (but not statistically significant). Using MPN data and a Bayesian modelling approach, higher mean Campylobacter spp. concentrations were found in the controlled tile drainage watershed relative to the uncontrolled tile drainage watershed (2010, 2011). A second-order quantitative microbial risk assessment (QMRA) was used, in a relative way, to identify differences in mean Campylobacter spp. infection risks among monitoring sites for a hypothetical exposure scenario. Greater relative mean risks were obtained for sites in the controlled tile drainage watershed than in the uncontrolled tile drainage watershed in each year of monitoring with pair-wise posterior probabilities exceeding 0.699, and the lowest relative mean risks were found at a downstream drinking water intake reference site. The second-order modelling approach was used to partition sources of uncertainty, which revealed that an adequate representation of the temporal variation in Campylobacter spp. concentrations for risk assessment was achieved with as few as 10 MPN data per site. This study demonstrates for the first time how QMRA can be implemented to evaluate, in a relative sense, the public health implications of controlled tile drainage on watershed-scale water quality.
Map of the experimental controlled (CTD) and uncontrolled (UCTD) tile drainage watersheds. The grey shade codes delineate tile drainage catchment areas. Display omitted
► Human campylobacteriosis can be transmitted through the environment. ► This study provides a novel investigation of land use management on Campylobacter spp. in surface water. ► Risk assessment was used to identify water monitoring requirements in the context of public health. ► Second-order modelling was used to address variability and uncertainty in a risk framework. ► The public health risk framework is heuristic, and can be used to understand issues that influence water quality.
The design of a general-purpose PreAmplifier-DIscriminator ASIC chip, PADI, is presented in this article. PADI is intended to be used as Front-End-Electronics (FEE) for reading out the timing ...Resistive-Plate Chambers (RPCs) in the time-of-flight (ToF) wall of the CBM detector for the future FAIR facility in Darmstadt-Germany, which will comprise about 100,000 channels in a 150 m 2 area. The evolution of this 0.18 μm CMOS technology design will be presented, from the first prototype PADI-1 to the last one, PADI-8, as well as its features and test results.
Many Cryptosporidium species/genotypes are not considered infectious to humans, and more realistic estimations of seasonal infection risks could be made using human infectious species/genotype ...information to inform quantitative microbial risk assessments (QMRA). Cryptosporidium oocyst concentration and species/genotype data were collected from three surface water surveillance programs in two river basins South Nation River, SN (2004-09) and Grand River, GR (2005-13) in Ontario, Canada to evaluate seasonal infection risks. Main river stems, tributaries, agricultural drainage streams, water treatment plant intakes, and waste water treatment plant effluent impacted sites were sampled. The QMRA employed two sets of exposure data to compute risk: one assuming all observed oocysts were infectious to humans, and the other based on the fraction of oocysts that were C. hominis and/or C. parvum (dominant human infectious forms of the parasite). Viability was not considered and relative infection risk was evaluated using a single hypothetical recreational exposure. Many sample site groupings for both river systems, had significant seasonality in Cryptosporidium occurrence and concentrations (p ≤ 0.05); occurrence and concentrations were generally highest in autumn for SN, and autumn and summer for GR. Mean risk values (probability of infection per exposure) for all sites combined, for each river system, were roughly an order of magnitude lower (avg. of SN and GR 5.3 × 10−5) when considering just C. parvum and C. hominis oocysts, in relation to mean infection risk (per exposure) assuming all oocysts were infectious to humans (5.5 × 10−4). Seasonality in mean risk (targeted human infectious oocysts only) was most strongly evident in SN (e.g., 7.9 × 10−6 in spring and 8.1 × 10−5 in summer). Such differences are important if QMRA is used to quantify effects of water safety/quality management practices where inputs from a vast array of fecal pollution sources can readily occur. Cryptosporidium seasonality in water appears to match the seasonality of human infections from Cryptosporidium in the study regions. This study highlights the importance of Cryptosporidium species/genotype data to help determine surface water pollution sources and seasonality, as well as to help more accurately quantify human infection risks by the parasite.
•Order of magnitude less infection risk when just pathogenic genotypes considered.•Seasonality of waterborne Cryptosporidium and associated infection risks.•Cryptosporidium in surface water is correlated with seasonal infection rates.
This study quantifies future changes in tropospheric ozone (O3) using
a simple parameterisation of source–receptor relationships based on
simulations from a range of models participating in the Task ...Force on
Hemispheric Transport of Air Pollutants (TF-HTAP) experiments. Surface and
tropospheric O3 changes are calculated globally and across 16 regions
from perturbations in precursor emissions (NOx, CO, volatile organic compounds – VOCs)
and methane (CH4) abundance only, neglecting any impact from climate
change. A source attribution is provided for each source region along with an
estimate of uncertainty based on the spread of the results from the models.
Tests against model simulations using the Hadley Centre Global Environment
Model version 2 – Earth system configuration (HadGEM2-ES) confirm that the approaches
used within the parameterisation perform well for most regions. The
O3 response to changes in CH4 abundance is slightly larger in
the TF-HTAP Phase 2 than in the TF-HTAP Phase 1 assessment (2010) and provides
further evidence that controlling CH4 is important for limiting
future O3 concentrations. Different treatments of chemistry and
meteorology in models remain one of the largest uncertainties in calculating
the O3 response to perturbations in CH4 abundance and
precursor emissions, particularly over the Middle East and south Asia
regions. Emission changes for the future Evaluating the CLimate and Air Quality
ImPacts of Short-livEd Pollutants (ECLIPSE) scenarios and a subset of
preliminary Shared Socioeconomic Pathways (SSPs) indicate that surface
O3 concentrations will increase regionally by 1 to 8 ppbv in 2050.
Source attribution analysis highlights the growing importance of CH4
in the future under current legislation. A change in the global tropospheric
O3 radiative forcing of +0.07 W m−2 from 2010 to 2050 is
predicted using the ECLIPSE scenarios and SSPs, based solely on changes in
CH4 abundance and tropospheric O3 precursor emissions and
neglecting any influence of climate change. Current legislation is shown to
be inadequate in limiting the future degradation of surface ozone air quality
and enhancement of near-term climate warming. More stringent future emission
controls provide a large reduction in both surface O3 concentrations
and O3 radiative forcing. The parameterisation provides a simple tool
to highlight the different impacts and associated uncertainties of local and
hemispheric emission control strategies on both surface air quality and the
near-term climate forcing by tropospheric O3.
PDF
