Abstract
The InterPro database (http://www.ebi.ac.uk/interpro/) classifies protein sequences into families and predicts the presence of functionally important domains and sites. Here, we report ...recent developments with InterPro (version 70.0) and its associated software, including an 18% growth in the size of the database in terms on new InterPro entries, updates to content, the inclusion of an additional entry type, refined modelling of discontinuous domains, and the development of a new programmatic interface and website. These developments extend and enrich the information provided by InterPro, and provide greater flexibility in terms of data access. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB, and discuss how our evaluation of residue coverage may help guide future curation activities.
Data on safety of thrombolysis for acute ischemic stroke (AIS) in patients with hematologic malignancy is not well established. We report our single institution experience with thrombolysis in this ...patient population.
We identified patients with pathology-confirmed hematologic malignancy from 2000-2022. Primary exposure was presence of AIS and receipt of intravenous (IV) thrombolysis. Primary outcome was safety of IV thrombolysis in this patient population. Safety was measured through imaging review for hemorrhagic transformation, post-stroke mortality, and modified Rankin Scale (mRS) at 90 days.
Among 45,894 patients with hematologic malignancy, 1,099 (2.4%) were identified as having a suspected AIS. Twenty (1.8%) received IV tissue plasminogen activator (tPA) for AIS, three underwent endovascular intervention, and 17 had AIS confirmed on MRI. Two patients with confirmed AIS experienced hemorrhagic transformation, one of which was symptomatic. Most patients (n=10, 59%) were functionally independent (mRS 0-2) at 90 days post-stroke, including all patients with active hematologic malignancy at the time of stroke (n=3). Four patients died within 90 days of AIS. None of these deaths were patients with active hematologic malignancy at the time of stroke.
Without other contraindications, IV alteplase should be considered for management of AIS in patients with hematologic malignancy. The safety profile of tPA administration in this patient population may be similar to the general population, whether underlying hematologic malignancy is active or in remission.
Pregnancy as a hemorrhage risk factor in women with cavernous malformations (CMs) is controversial. We describe prospective hemorrhage risk in women who become pregnant after an established CM ...diagnosis.
Beginning in 2015, we recruited consecutive patients with radiologically confirmed CM of the brain or spinal cord to participate in a prospective registry. Participants underwent a baseline and annual medical record review, imaging review, and annual surveys to ascertain pregnancies, deliveries, and neurological complications. We collected prospective hemorrhage data on reproductive age women. We calculated prospective hemorrhage rates on childbearing age patients based on the number of hemorrhages occurring post-CM diagnosis during pregnancy and nonpregnancy, divided by the years of follow-up and censored at last follow-up, age 46, or surgery in sporadic-form CM. The hemorrhage rates were compared and the 95% CI presented with a
value of <0.05.
Of 160 women, 90 presented with CM under the age of 46 (average age 31.6 years; 25.6% familial form; 46.7% with hemorrhage; 24.4% brain stem location). These 90 patients had 136 pregnancies before CM diagnosis; 36 pregnancies occurred at or after the diagnosis of CM. Four patients had a hemorrhage while pregnant or postpartum leading to the first CM diagnosis. During 402.6 years of follow-up while not pregnant, 42 hemorrhages occurred prospectively yielding a 10.4% per year (95% CI, 7.5-14.0) risk of hemorrhage while not pregnant. No hemorrhages occurred during 32 prospective pregnancies (26 live births including 1 twinset and 7 nonviable fetuses) after CM diagnosis during 26.9 years of pregnancy time yielding a rate of 0% per year (95% CI, 0-13.6). We found no statistical difference in the rates of hemorrhage during pregnant and nonpregnant time (
=0.09). No hemorrhage occurred during delivery.
Our prospective data suggest that pregnancy does not increase the risk of hemorrhage in women with a known brain or spinal cord CM and that vaginal delivery is safe in appropriate candidates.
Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, ...the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with cerebral amyloid angiopathy. The annual incidence rate of PCNSV was estimated at 2.4 cases per 1,000,000 person-years. PCNSV appears to consist of several subsets defined by the size of the vessels involved, the clinical characteristics at presentation, MRI findings, and histopathological patterns on biopsy. Early recognition and treatment may reduce poor outcomes.
IMPORTANCE: The prevalence of cerebral cavernous malformation (CCM) is unknown. Case ascertainment in most previous studies was based on autopsy data or clinical convenience samples, often without ...detailed clinical or radiologic information. OBJECTIVE: To determine the prevalence of CCM in a population-based sample of older adults. DESIGN, SETTING, AND PARTICIPANTS: This prospective imaging study included 4721 participants aged 50 to 89 years who were enrolled between January 1, 2004, and December 15, 2015, in the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota. An age- and sex-stratified sampling strategy was used to randomly select participants from Olmsted County using the medical records linkage system of the Rochester Epidemiology Project. Participants were invited to undergo brain magnetic resonance imaging (MRI). Of the 4721 participants, 2715 had an evaluable MRI. All images were reviewed by a board-certified neuroradiologist, and MRI reports were searched for the terms cavernous malformation, cavernous angioma, and cavernoma. Two vascular neurologists reviewed MRIs, and potential CCMs were classified using Zabramski classification. Medical records of the identified individuals with CCM were reviewed along with their demographic information, medical history, and any symptoms referable to the identified CCM lesion. MAIN OUTCOMES AND MEASURES: Prevalence of CCM and clinical and radiologic characteristics of study participants with CCM. RESULTS: Of the 2715 participants who underwent MRI scans, 12 (0.44%) had CCM. With the use of inverse probability weights to adjust for participation bias, the overall prevalence was 0.46% (95% CI, 0.05-0.86). The age-adjusted prevalence was found to be 0.61% (95% CI, 0-1.47) for the 50- to 59-year age group, 0.17% (95% CI, 0-0.50) for the 60- to 69-year age group, 0.45% (95% CI, 0.09-0.81) for the 70- to 79-year age group, and 0.58% (95% CI, 0-1.29) for the 80- to 89-year age group. The sex-adjusted prevalence was 0.41% (95% CI, 0-1.00) for women and 0.51% (95% CI, 0-1.07) for men. Observed frequencies were similar in men and women, with a slight male predominance. Of the 12 participants with CCM, 9 (75%) had a single Zabramski type 2 lesion in a supratentorial location. Only 1 participant (0.037%) was symptomatic from the CCM during the study period. CONCLUSIONS AND RELEVANCE: The findings and data from this study are important for determining the potential number of patients available for cohort studies and anticipated clinical trials in older patients with CCM.
Incidence rates for internal carotid artery dissection (ICAD) have been reported to be 2.6 to 2.9 per 100,000, but reliable epidemiologic data for vertebral artery dissection (VAD) are not available.
...To determine the incidence rate of cervical artery dissection (CAD) in a defined population.
With IRB approval, we used the medical record linkage system of the Rochester Epidemiology Project to identify all patients diagnosed with spontaneous ICAD and VAD for the period of 1987-2003 in Olmsted County, MN.
Of 48 patients with CAD, there were 32 patients with ICAD and 18 patients with VAD. In Olmsted County, the average annual incidence rate for ICAD was 1.72 per 100,000 population (95% CI, 1.13 to 2.32) and for VAD 0.97 per 100,000 population (95% CI, 0.52 to 1.4). The average annual incidence rate for CAD was 2.6 per 100,000 population (95% CI, 1.86 to 3.33). The most frequently encountered symptoms in CAD were head or neck pain (80%), cerebral ischemia (TIA or infarct) (56%), and Horner syndrome (25%). Good outcome (defined as modified Rankin score of 0 to 2) was seen in 92% of patients. No recurrence of dissection was observed during a mean 7.8 years of follow-up.
Internal carotid artery dissection was detected approximately twice as frequently as vertebral artery dissection in the overall study, but in the latter half of the study period, vertebral artery and internal carotid artery dissection incidence rates were equivalent. The majority of cervical artery dissection patients in the community have excellent outcome, and contrary to many tertiary referral series, re-dissection is rare.
•Research Through Designing (RTD) is needed in landscape architecture and urban design.•RTD can generate design relevant knowledge: design guidelines and prototypes.•Urban microclimate responsive ...design is often studied with post-positivist RTD.•In post-positivist RTD complexity is reduced to different degrees, independent of scale.•Post-positivist RTD tests design results through physical or numerical modelling.
‘Research Through Designing’ (RTD) is a research method that is based on the active employment of designing in the research process. Often, RTD is necessary to generate knowledge that is relevant for design such as design guidelines or prototypes. A broad range of RTD methods can be used to produce such results: post-positivist, constructivist, participatory and pragmatist approaches. The aim of this paper is to elucidate the post-positivist RTD methods through the discussion of examples. The examples represent microclimate responsive design research and were derived from an extensive literature review. The typical issues to be dealt with in such studies are discussed: complexity, scale, testing methods and their mutual relations. A distinction is made between RTD methods and other design research for microclimatic improvement. Three studies occurred to be RTD in the literal sense and they provide a methodological model for further research to generate evidence that supports urban microclimate responsive design.
Less than 10% of the plastics generated globally are recycled, while the rest are incinerated, accumulated in landfills, or leak into the environment. New technologies are emerging to chemically ...recycle waste plastics that are receiving tremendous interest from academia and industry. Chemists and chemical engineers need to understand the fundamentals of these technologies to design improved systems for chemical recycling and upcycling of waste plastics. In this paper, we review the entire life cycle of plastics and options for the management of plastic waste to address barriers to industrial chemical recycling and further provide perceptions on possible opportunities with such materials. Knowledge and insights to enhance plastic recycling beyond its current scale are provided. Outstanding research problems and where researchers in the field should focus their efforts in the future are also discussed.
This paper reviewed the entire life cycle of plastics and options for the management of plastic waste to address barriers to industrial chemical recycling and further provide perceptions on possible opportunities with such materials.
The 2020 Olympic Games marathon will be run through the streets of Tokyo on the mornings of August 2nd and 9th, a time of year that is typically hot, sunny, and humid. Few studies have assessed the ...potential impact of extreme heat along the marathon course to understand the multiple factors (e.g., radiation, wind flow) affecting human thermal comfort (TC) as influenced by urban design and vegetation.
The current research establishes a baseline of microclimate conditions and scenarios to estimate the projected TC along the marathon route for spectators. Mobile microclimate data (air and surface temperatures, solar radiation, humidity, wind speed) were collected along the marathon course over 15 periods in the summer of 2016 and aligned with sky view factors (SVF). Human energy budget modeling was applied to provide spatially-explicit heat budget and TC information along the route.
Conditions are expected to create the most discomfort along open, sun-exposed locations, with ~50% of the area along the second half of the course resulting in ‘Hot’ (budget > 200 W m−2) or ‘Very hot’ (budget > 295 W m−2) conditions. The heat strain index frequently rises above 80% in these locations, with high humidity and low wind flow exacerbating discomfort. Buildings and trees producing a low SVF over roads and sidewalks protect spectators from the morning radiant heat, but such locations should be balanced with wind flow to optimize comfort.
The modeling and spatial information can aid in preparing for and mitigating heat stress during the Olympics. Potential solutions can be implemented in collaboration with local organizers and government. This ‘research through design’ strategy can aid in preparing for and mitigating heat illness during the Olympics. Knowledge gained can be extended to other areas of Tokyo to reduce urban heat, and further provide targeted guidance for effective environmental cooling techniques for human health.
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•The 2020 Tokyo Olympics is expected to present heat and humidity challenges.•Spatially-explicit meteorological data provide a baseline of expected conditions.•Spectator thermal comfort varies significantly along the course.•Shade provided by trees and buildings is closely related to thermal comfort.•Enhanced preparedness efforts are needed to limit discomfort and heat illness.
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