Many prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have developed strategies to bypass immunity, including anti-CRISPR (Acr) ...proteins; yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we report the discovery of new Acrs by assaying candidate genes adjacent to a conserved Acr-associated (Aca) gene, aca5, against a panel of six type I systems: I-F (Pseudomonas, Pectobacterium, and Serratia), I-E (Pseudomonas and Serratia), and I-C (Pseudomonas). We uncover 11 type I-F and/or I-E anti-CRISPR genes encoded on chromosomal and extrachromosomal MGEs within Enterobacteriaceae and Pseudomonas, and an additional Aca (aca9). The acr genes not only associate with other acr genes, but also with genes encoding inhibitors of distinct bacterial defense systems. Thus, our findings highlight the potential exploitation of acr loci neighborhoods for the identification of previously undescribed anti-defense systems.
OBJECTIVE:To analyze the clinical findings, response to therapy, and outcomes of patients with cerebral vascular amyloid-β (Aβ) deposition with and without inflammatory vascular infiltration.
...METHODS:We report 78 consecutive patients with cerebral vascular Aβ deposition examined at Mayo Clinic Rochester over 25 years (1987 through 2011). Specimens reviewed by a neuropathologist showed 40 with vascular Aβ peptide without inflammation (cerebral amyloid angiopathy CAA), 28 with granulomatous vasculitis (Aβ-related angiitis or ABRA), and 10 with perivascular CAA-related inflammation. We also matched findings in 118 consecutive patients with primary CNS vasculitis (PCNSV) without Aβ seen over 25 years (1983 through 2007).
RESULTS:Compared to the 40 with CAA, the 28 with ABRA were younger at diagnosis (p = 0.05), had less altered cognition (p = 0.02), fewer neurologic deficits (p = 0.02), and fewer intracranial hemorrhages (<0.001), but increased gadolinium leptomeningeal enhancement (p = 0.01) at presentation, and less mortality and disability at last follow-up (p < 0.001). Compared with PCNSV, the 28 patients with ABRA were older at diagnosis (p < 0.001), had a higher frequency of altered cognition (p = 0.05), seizures/spells (p = 0.006), gadolinium leptomeningeal enhancement (p < 0.001), and intracerebral hemorrhage (p = 0.02), lower frequency of hemiparesis (p = 0.01), visual symptoms (p = 0.04), and MRI evidence of cerebral infarction (p = 0.003), but higher CSF protein levels (p = 0.03). Results of treatment and outcomes in ABRA and PCNSV were similar.
CONCLUSIONS:ABRA appears to represent a distinct subset of PCNSV.
Heat related morbidity and mortality, especially during extreme heat events, are increasing due to climate change. More Americans die from heat than from all other natural disasters combined. ...Identifying the populations and locations that are under high risk of heat vulnerability is important for urban planning and design policy making as well as health interventions. An increasing number of heat vulnerability/risk models and indices (HV/R) have been developed based on indicators related to population heat susceptibility such as sociodemographic and environmental factors. The objectives of this study are to summarize and analyze current HV/R's construction, calculation, and validation, evaluate the limitation of these methods, and provide directions for future HV/R and related studies. This systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework and used 5 datasets for the literature search. Journal articles that developed indices or models to assess population level heat-related vulnerability or risks in the past 50 years were included. A total of 52 papers were included for analysis on model construction, data sources, weighting schemes and model validation. By synthesizing the findings, we suggested: (1) include relevant and accurately measured indicators; (2) select rational weighting methods and; (3) conduct model validation. We also concluded that it is important for future heat vulnerability models and indices studies to: (1) be conducted in more tropical areas; (2) include a comprehensive understanding of energy exchanges between landscape elements and humans; and (3) be applied in urban planning and policy making practice.
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•Review indicator selection, weighting method, and validation of heat vulnerability and risk models and indices (HV/R) using PRISMA framework.•Lack of consistency in theory interpretation and indicator selections•Both explicit and statistical weighting methods used in constructing HV/Rs have biases.•No standard criteria to state the efficiency of assessing or predicting heat vulnerability.•HV/R need to include relevant and accurately measured indicators, select rational weighting methods and conduct model validation.
•During heat waves now and in the future urban microclimates put human health at risk.•Intercepting solar radiation is the most effective way to reduce the heat load on people.•Reducing air ...temperature is the second most effective way to reduce heat loads.•Evidence-based climate-responsive design can make parks more thermally comfortable.
Many inhabitants of cities throughout the world suffer from health problems and discomfort that are caused by overheating of urban areas, and there is compelling evidence that these problems will be exacerbated by global climate change. Most cities are not designed to ameliorate these effects although it is well-known that this is possible, especially through evidence-based climate-responsive design of urban open spaces. Urban parks and green spaces have the potential to provide thermally comfortable environments and help reduce vulnerability to heat stress. However, in order for them to provide this function, parks must be designed within the context of the prevailing climate and predicted future climates. To analyze the effects of elements that alter microclimate in parks, we used human energy budget simulations. We modelled the outdoor human energy budget in a range of warm to hot climate zones and interpreted the results in terms of thermal comfort and health vulnerability. Reduction of solar radiant input with trees had the greatest effect in all test cities. Reduction in air temperature was the second-most important component, and in some climates was nearly as important as incorporating shade. We then conducted similar modelling using predicted climates for the middle of the century, emphasizing the importance of city-level efforts for park design to assist in minimizing future climate-related urban health risks. These simulations suggested that heat waves in many climates will produce outdoor environments where people will be in extreme danger of heat stress, but that appropriately designed parks can reduce the threat.
We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of ...UIAs and to assess agreement for this model among specialists in UIA management and research.
An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement).
The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval CI 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033).
This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.
Here we describe a simple route to creating conformal sulphated zirconia monolayers throughout an SBA-15 architecture that confers efficient acid-catalysed one-pot conversion of glucose to ethyl ...levulinate.
Many children growing up in cities are spending less time outdoors to escape the heat. This is contributing to childhood obesity and the prospect of a range of diseases in adulthood. When landscape ...architects and urban designers use a human thermal comfort model to test their designs for children’s comfort, they would have to use a model essentially designed to simulate healthy adults. Yet there are many differences between the body of a child and an adult. The aim of this paper was to modify the thermal comfort model COMFA into a children’s energy budget model through the consideration of the heat exchange of a child. The energy budget of a child can be up to 21 W/m
2
higher than adults in hot summertime conditions, and 26 W/m
2
lower in cold conditions. The model was validated through field studies of 65 children (32 boys and 33 girls) aged from 7-12 years old in 9 days from March to June in 2019, in 68 different microclimates ranging from cool to hot. A 5-point thermal comfort scale of energy budget for children was created using multinomial logistic regression, which revealed that children have a different range of thermal acceptability than adults. The frequency distribution of the actual thermal sensation and the predicted thermal comfort was improved using the new scale. The actual thermal sensation responses from children and the predicted thermal sensation using the model was determined to be positively significantly related. The accuracy of the model was 93.26%. This study has provided an effective children’s energy budget model to predict children’s thermal comfort. Its application can contribute to the design of thermally comfortable children’s outdoor play areas by landscape architects and urban designers.
Abstract
BACKGROUND
There are conflicting data between natural history studies suggesting a very low risk of rupture for small, unruptured intracranial aneurysms and retrospective studies that have ...identified a much higher frequency of small, ruptured aneurysms than expected.
OBJECTIVE
To use the prospective International Study of Unruptured Intracranial Aneurysms cohort to identify morphological characteristics predictive of unruptured intracranial aneurysm rupture.
METHODS
A case-control design was used to analyze morphological characteristics associated with aneurysm rupture in the International Study of Unruptured Intracranial Aneurysms database. Fifty-seven patients with ruptured aneurysms during follow-up were matched (by size and location) with 198 patients with unruptured intracranial aneurysms without rupture during follow-up. Twelve morphological metrics were measured from cerebral angiograms in a blinded fashion.
RESULTS
Perpendicular height (P = .008) and size ratio (ratio of maximum diameter to the parent vessel diameter; P = .01) were predictors of aneurysm rupture on univariate analysis. Aspect ratio, daughter sacs, multiple lobes, aneurysm angle, neck diameter, parent vessel diameter, and calculated aneurysm volume were not statistically significant predictors of rupture. On multivariate analysis, perpendicular height was the only significant predictor of rupture (Chi-square 7.1, P-value .008).
CONCLUSION
This study underscores the importance of other morphological factors, such as perpendicular height and size ratio, that may influence unruptured intracranial aneurysm rupture risk in addition to greatest diameter and anterior vs posterior location.
Cervical artery dissection (CeAD) represents up to 15% to 25% of ischemic strokes in people under the age of 50 years. Noninvasive vessel imaging is increasingly used in clinical practice, but the ...impact on the frequency of detection of CeAD is unknown. In 2006, the yearly incidence rate of CeAD was estimated at 2.6 per 100 000 person-years, but the current incidence is unknown.
In this population-based retrospective observational cohort study, we utilized the resources of the Rochester Epidemiology Project to ascertain all adult residents of Olmsted County, MN, diagnosed with internal carotid artery dissection and common carotid artery dissection or vertebral artery dissection from 2002 to 2020. Patients with only intracranial involvement or CeAD following major trauma were excluded. Age-adjusted sex-specific and age- and sex-adjusted incidence rates were estimated using the US White 2010 decennial census, with rates expressed per 100 000 person-years. We assessed longitudinal trends by dividing the data into 5-year time intervals, with the last being a 4-year interval.
We identified 123 patients with a diagnosis of CeAD. There were 63 patients with internal carotid artery dissection, 54 with vertebral artery dissection, 2 with concurrent internal carotid artery dissection and vertebral artery dissection, and 4 with common carotid artery dissection. There were 63 (51.2%) female patients and 60 (48.8%) male patients. The average age at diagnosis was 50.2 years (SD, 15.1 95% CI, 20.1-90.5 years). The incidence rate of spontaneous CeAD encompassing all locations was 4.69 per 100 000 person-years (2.43 for internal carotid artery dissection and 2.01 for vertebral artery dissection). The incidence rate increased from 2.30 per 100 000 person-years from 2002 to 2006 to 8.93 per 100 000 person-years from 2017 to 2020 (
<0.0001). The incidence rate for female patients rose from 0.81 per 100 000 person-years from 2002 to 2006 to 10.17 per 100 000 person-years from 2017 to 2020.
The incidence rate of spontaneous CeAD increased nearly 4-fold over a 19-year period from 2002 to 2020. The incidence rate in women rose over 12-fold. The increase in incidence rates likely reflects the increased use of noninvasive vascular imaging.
Effects of select medications on hemorrhage risk in patients with cerebral or spinal cavernous malformations (CMs) are unknown.
From a single-institution prospective cohort of patients with CM ...(2015–2021), demographics, mode of clinical presentation, and radiographic data were collected. Follow-up was performed with electronic medical record review, in-person visits, and written surveys. Select medication use was ascertained from the time of CM diagnosis to a censor date of first prospective symptomatic hemorrhage, complete surgical excision of sporadic form CM, last follow-up, or death. Using Cox proportional hazards regression model, we assessed effects of antithrombotic agents, fish oil, selective serotonin reuptake inhibitors (SSRIs), vitamin E and D supplementation, statins, and beta blockers on prospective hemorrhage risk.
The study included 364 patients with spinal or cerebral CM (58.0% female; 20.0% familial form; 42.3% presentation to medical attention owing to hemorrhage; 25.8% brainstem location). During a follow-up of 2018 patient-years, 103 prospective hemorrhages occurred. No studied medications increased the prospective CM hemorrhage risk. Antithrombotics, vitamin D supplementation, fish oil, and SSRI were associated with lower hemorrhage risk even after adjusting for age at diagnosis, hemorrhage at diagnosis, and brainstem location.
Use of select medications with antithrombotic properties do not increase the risk of CM hemorrhage. Vitamin D supplementation, any antithrombotic agent, fish oil, and SSRI were associated with a lower prospective hemorrhage risk. Further studies should evaluate the mechanism of action and potential benefit of these select medications.
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