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At least 721 records · Page 40

Climate-disease connections: Rift Valley Fever in Kenya

All known Rift Valley fever(RVF) outbreaks in Kenya from 1950 to 1998 followed periods of abnormally high rainfall. On an interannual scale, periods of above normal rainfall in East Africa are associated with the warm phase of the El Nino/Southern Oscillation (ENSO) phenomenon. Anomalous rainfall floods mosquito-breeding habitats called dambos, which contain transovarially infected mosquito eggs. The eggs hatch Aedes mosquitoes that transmit the RVF virus preferentially to livestock and to humans as well. Analysis of historical data on RVF outbreaks and indicators of ENSO (including Pacific and Indian Ocean sea surface temperatures and the Southern Oscillation Index) indicates that more than three quarters of the RVF outbreaks have occurred during warm ENSO event periods. Mapping of ecological conditions using satellite normalized difference vegetation index (NDVI) data show that areas where outbreaks have occurred during the satellite recording period (1981-1998) show anomalous positive departures in vegetation greenness, an indicator of above-normal precipitation. This is particularly observed in arid areas of East Africa, which are predominantly impacted by this disease. These results indicate a close association between interannual climate variability and RVF outbreaks in Kenya.

Rift Valley Fever/epidemiology/transmission↗

Association of Cortical ß-Amyloid Protein in the Absence of Insoluble Deposits With Alzheimer Disease.

IMPORTANCE: ß-Amyloid deposits are a pathologic hallmark of Alzheimer disease (AD). However, the extent to which cortical ß-amyloid protein in the absence of insoluble deposits is associated with classic features of AD appear to be unknown. OBJECTIVE: To examine the associations of cortical ß-amyloid protein in the absence of insoluble deposits with cognitive decline, neurofibrillary tangles, other age-associated neuropathologic conditions, and APOE. DESIGN, SETTING, AND PARTICIPANTS: This analysis combines data from 2 community-based clinicopathologic cohort studies of aging. The Religious Orders Study started in 1994, and the Rush Memory and Aging Project started in 1997. Both studies are ongoing. Participants without known dementia were enrolled and agreed to annual clinical evaluations and brain donation after death. Primary analyses focused on individuals without ß-amyloid deposits. Data analyses occurred in mid-September 2018. MAIN OUTCOMES AND MEASURES: ß-Amyloid protein abundance was measured by targeted proteomics using selected reaction monitoring. ß-Amyloid deposits were detected using immunohistochemistry. Other neuropathologic indices were quantified via uniform structured evaluation. Linear mixed models were used to examine the association of ß-amyloid protein with cognitive decline. Regression models examined the protein associations with neuropathologic outcomes and the APOE genotype. RESULTS: By mid-September 2018, 3575 older persons were enrolled, and 1559 had died and undergone brain autopsy. Proteomic data were collected in 1208 individuals, and 5 with missing cognitive scores were excluded. Of the remaining 1203, primary analyses focused on 148 individuals (12.3%) without ß-amyloid deposits. In this group, the mean (SD) age at death was 87.0 (7.0) years, and 84 individuals (56.8%) were women. In the absence of ß-amyloid deposits, we did not observe an association of ß-amyloid protein with decline in episodic memory, but the protein was associated with faster rates of decline in processing speed (mean [SE] change, -0.014 [0.005]; P?=?.008) and visuospatial abilities (mean [SE] change, -0.013 [0.005]; P?=?.006). We did not observe protein association with paired helical filament tau tangle density. The protein was associated with amyloid angiopathy (odds ratio, 1.38 [95% CI, 1.15-1.67]; P?<?.001) but no other brain pathology. The associations with cognitive decline were unchanged after controlling for amyloid angiopathy. Neither APOE e4 nor a polygenic Alzheimer risk score was associated with ß-amyloid protein. CONCLUSIONS AND RELEVANCE: Cortical ß-amyloid protein was associated with faster cognitive decline in the absence of ß-amyloid deposits, which supports the role of cortical soluble ß-amyloid as a neurotoxic agent in aging. The lack of protein association with paired helical filament tau tangles, episodic memory decline, or strong genetic drivers of deposited ß-amyloid suggests an underlying neuropathologic change that may differ from that of AD.

Alzheimer’s disease, Insoluble deposits↗

Individuals with Alzheimer's disease and low tau burden: Characteristics and implications

Abnormal amyloid-beta (Aβ) and tau deposition define Alzheimer's Disease (AD), but non-elevated tau is relatively frequent in patients on the AD pathway. We examined characteristics and regional patterns of 397 Aβ+ unimpaired and impaired individuals with low tau (A+T-) in relation to their higher tau counterparts (A+T+). Seventy-one percent of Aβ+ unimpaired and 42% of impaired Aβ+ individuals were categorized as A+T- based on global tau. In impaired individuals only, A+T- status was associated with older age, male sex, and greater cardiovascular risk. α-synuclein was linked to poorer cognition, particularly when tau was low. Tau burden was most frequently elevated in a common set of temporal regions regardless of T+/T- status. Low tau is relatively common in patients on the AD pathway and is linked to comorbidities that contribute to impairment. These findings have implications for the selection of individuals for Aβ- and tau-modifying therapies.

60 APPLIED LIFE SCIENCES↗

A multilayer network analysis of Alzheimer's disease pathogenesis: Roles for p‐tau, synaptic peptides, and physical activity

INTRODUCTION: In the aging brain, cognitive abilities emerge from the coordination of complex pathways arising from a balance between protective lifestyle and environmental factors and accumulation of neuropathologies. METHODS: As part of the Rush Memory and Aging Project (n = 440), we measured accelerometer-based actigraphy, cognitive performance, and after brain autopsy, selected reaction monitoring mass spectrometry. Multilevel network analysis was used to examine the relationships among the molecular machinery of vesicular neurotransmission, Alzheimer's disease (AD) neuropathology, cognition, and late-life physical activity. RESULTS: Synaptic peptides involved in neuronal secretory function were the most influential contributors to the multilayer network, reflecting the complex interdependencies among AD pathology, synaptic processes, and late-life cognition. Older adults with lower physical activity evidenced stronger adverse relationships among phosphorylated tau peptides, markers of synaptic integrity, and tangle pathology. DISCUSSION: Network-based approaches simultaneously model interdependent biological processes and advance understanding of the role of physical activity in age-associated cognitive impairment. Highlights: Network-based approaches simultaneously model interdependent biological processes. Secretory synaptic peptides were influential contributors to the multilayer network. Older adults with lower physical activity had adverse relationships among pathology. There was interdependence among phosphorylated tau, synaptic integrity, and tangles. Network methods elucidate the role of physical activity in cognitive impairment.

60 APPLIED LIFE SCIENCES↗

Role of tau versus TDP-43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease

Hippocampal atrophy on magnetic resonance imaging is an important biomarker in Alzheimer's disease (AD). While hippocampal atrophy was thought to result from tau tangles in AD, different neuropathologies can lead to hippocampal atrophy, especially TAR DNA-binding protein 43 (TDP-43) pathology. In this narrative review, we evaluate existing studies on the relative contribution of tau and TDP-43 pathology to medial temporal lobe (MTL) atrophy. We report a clear association of both tau and TDP-43 neuropathology with MTL atrophy, even after correcting for other neuropathologies. Next, we discuss a potential synergism between tau and TDP-43 and the relative timing of the effects of both neuropathologies. Finally, avenues for future research will be discussed. A better understanding of the interplay between tau and TDP-43 neuropathologies and their effect on atrophy will help with the development of more specific biomarkers for limbic-predominant age-related TDP-43 encephalopathy and pinpointing of the optimal timing for testing anti-tau and anti-TDP-43 treatments in trials.

60 APPLIED LIFE SCIENCES↗

Contact heterogeneities in feral swine: implications for disease management and future research

Abstract Contact rates vary widely among individuals in socially structured wildlife populations. Understanding the interplay of factors responsible for this variation is essential for planning effective disease management. Feral swine ( Sus scrofa ) are a socially structured species which pose an increasing threat to livestock and human health, and little is known about contact structure. We analyzed 11 GPS data sets from across the United States to understand the interplay of ecological and demographic factors on variation in co‐location rates, a proxy for contact rates. Between‐sounder contact rates strongly depended on the distance among home ranges (less contact among sounders separated by >2 km; negligible between sounders separated by >6 km), but other factors causing high clustering between groups of sounders also seemed apparent. Our results provide spatial parameters for targeted management actions, identify data gaps that could lead to improved management and provide insight on experimental design for quantitating contact rates and structure.

60 APPLIED LIFE SCIENCES↗

Efficacy and Safety of a Novel Vascular Closure Device (Glubran 2 Seal) After Diagnostic and Interventional Angiography in Patients with Peripheral Arterial Occlusive Disease

To prospectively evaluate safety and efficacy of a novel vascular closure device (Glubran 2 Seal) after peripheral angiography in patients with peripheral arterial occlusive disease (PAOD). From December 2010 to June 2011, all consecutive patients with PAOD undergoing peripheral angiography were prospectively enrolled onto the study after percutaneous antegrade or retrograde puncture of the common femoral artery. After angiography, the Glubran 2 Seal device was used to achieve hemostasis. The following data were registered: technical success and manual compression duration, patients' discomfort (scale 0-5), operators' technical difficulty (scale 0-5), and vascular complications. The site of hemostasis was evaluated by clinical inspection and color-coded Duplex ultrasound performed 1 day and 1 month after the procedure. One hundred seventy-eight patients were enrolled (112 male, mean age 70.8 years) with a total of 206 puncture sites, including 104 (50.5 %) antegrade accesses. The device was successful in 198(96.1 %) of 206 procedures, with 8 cases of manual compression lasting longer than 5 min (maximum 20 min). No major vascular complications were observed, resulting in 100 % procedural success. Minor complications occurred in seven procedures (3.4 %), including two cases of pseudoaneurysms, successfully treated by ultrasound-guided glue injection. The mean {+-} standard deviation score for patients' discomfort was 0.9 {+-} 0.7, whereas the mean score for operators' difficulty was 1.2 {+-} 0.9. In patients with PAOD, the Glubran 2 Seal represents a simple, painless, and efficient vascular closure device, able to achieve hemostasis both in antegrade and retrograde accesses.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Budget Impact Model for Paclitaxel-eluting Stent in Femoropopliteal Disease in France

The Zilver PTX drug-eluting stent (Cook Ireland Ltd., Limerick, Ireland) represents an advance in endovascular treatments for atherosclerotic superficial femoral artery (SFA) disease. Clinical data demonstrate improved clinical outcomes compared to bare-metal stents (BMS). This analysis assessed the likely impact on the French public health care budget of introducing reimbursement for the Zilver PTX stent. A model was developed in Microsoft Excel to estimate the impact of a progressive transition from BMS to Zilver PTX over a 5-year horizon. The number of patients undergoing SFA stenting was estimated on the basis of hospital episode data. The analysis from the payer perspective used French reimbursement tariffs. Target lesion revascularization (TLR) after primary stent placement was the primary outcome. TLR rates were based on 2-year data from the Zilver PTX single-arm study (6 and 9 %) and BMS rates reported in the literature (average 16 and 22 %) and extrapolated to 5 years. Net budget impact was expressed as the difference in total costs (primary stenting and reinterventions) for a scenario where BMS is progressively replaced by Zilver PTX compared to a scenario of BMS only. The model estimated a net cumulative 5-year budget reduction of Euro-Sign 6,807,202 for a projected population of 82,316 patients (21,361 receiving Zilver PTX). Base case results were confirmed in sensitivity analyses. Adoption of Zilver PTX could lead to important savings for the French public health care payer. Despite higher initial reimbursement for the Zilver PTX stent, fewer expected SFA reinterventions after the primary stenting procedure result in net savings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

High Spatial Resolution MRI of Cystic Adventitial Disease of the Iliofemoral Vein Communicating with the Hip Joint

Venous cystic adventitial disease (CAD) is an extremely rare entity, and so far less than 20 cases have been described in the literature. Herein, we describe the imaging findings of CAD of iliofemoral vein in a 51-year-old woman who presented with leg swelling with special emphasis on high spatial resolution MRI, which demonstrated communication of the cyst with the hip joint. To our knowledge, this is the first description of high spatial resolution MRI findings in venous CAD supporting a new theory about the pathogenesis of venous CAD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparing Percutaneous Transluminal Angioplasty and Stent Placement for Treatment of Subclavian Arterial Occlusive Disease: A Systematic Review and Meta-Analysis

Background and PurposeSubclavian artery occlusive disease (SAOD) is often associated with cerebrovascular symptoms such as subclavian steal syndrome and stroke. We conducted a systematic review and meta-analysis to compare percutaneous transluminal angioplasty (PTA) and stent placement for the treatment of SAOD.Materials and MethodsWe searched Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through October 16, 2014. From each study, we abstracted baseline patient characteristics, study design variables, and outcome data including rates of technical success, primary patency (≤2 and >2 years follow-up), symptom resolution, and complications. Meta-analysis was performed using a random-effects model.ResultsA total of 35 non-comparative studies with 1726 patients were included. Technical success rate was significantly higher in the stent group than the PTA group (92.8 vs 86.8 %, p = 0.007). Long-term primary patency rates (76.9 vs 79.6 %, p = 0.729) and symptom resolution rates (82.2 vs 73.0 %, p = 0.327) were not statistically different. There was no statistically significant difference in the rates of stroke or death.ConclusionStent placement for treatment of SAOD may be associated with higher rates of technical success but similar rates of symptom resolution and long-term outcomes. The confidence in the available estimates is low. Further comparative studies are needed to guide patients and clinicians in shared decision making.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Endovascular Therapy Research in Lower Limb Peripheral Arterial Disease Published Over a 5-Year Period: Who is Publishing and Where?

IntroductionPeripheral arterial disease (PAD) is being increasingly managed by endovascular therapies. In this study, we identified the clinical services publishing research as well as the journals of publication over a 5-year period.MethodsTwenty keywords and phrases related to endovascular intervention were identified, and a literature search was performed through the PubMed database from January 2009 to January 2014. Inclusion criteria were English language, study population more than five patients, and matching the keyword search. Eligible studies were collated into a database and classified by journal of publication, PubMed number, article title, publishing clinical service, type of publication, country of origin, and authors.Results825 studies from 114 different journals were identified. 297 papers were excluded. Of the 528 included papers, 204 (39%) were published by Vascular Surgery (VS), 157 (30%) by Interventional Radiology (IR), 101 (19%) by Cardiology, 43 (8%) by Angiology, 6 (1%) by Vascular Medicine, and 17 (3%) from miscellaneous services. 283 (54%) studies originated from Europe, 157 (30%) from North America, 76 (14%) from Asia, 6 from Australia, 3 each from South America and Africa. IR published the most papers on PAD endovascular intervention in Europe with VS second while this trend was reversed in the USA. The 528 papers were published in 98 different journals with retrospective case series (72%), the majority.ConclusionIR continues to play a significant research role in endovascular intervention in PAD, particularly in Europe, and specifically in below the knee intervention, pedal intervention, and drug-eluting technologies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

No Increased Mortality After TIPS Compared with Serial Large Volume Paracenteses in Patients with Higher Model for End-Stage Liver Disease Score and Refractory Ascites

Purpose: To compare survival after transjugular intrahepatic portosystemic shunt (TIPS) creation versus serial large volume paracenteses (LVP) in patients with refractory ascites and higher Model for End-Stage Liver Disease (MELD) scores. Materials and Methods: In this retrospective study, from 1/1/2013 to 10/1/2018, 478 patients (294 male; mean age 58, range 23–89) underwent serial LVP (n = 386) or TIPS (n = 92) for ascites. Propensity-matched cohorts were constructed based on age, MELD, Charlson comorbidity index, varices, and hepatic encephalopathy. Survival was analyzed using a Cox proportional hazards model in which MELD score and TIPS were treated as time-dependent covariates. An interaction term was used to assess the impact of TIPS versus serial LVP on survival as a function of increasing MELD. Results: In the overall patient sample, higher MELD score predicted worse survival after either serial LVP or TIPS [hazard ratio (HR) = 1.13; p < 0.001], but there was no significant interaction between TIPS and higher MELD score conferring worse survival (HR = 1.01; p = 0.55). In 92 propensity-matched serial LVP and 92 TIPS patients, higher MELD score predicted worse survival after either serial LVP or TIPS (HR = 1.19; p < 0.001), but there was no significant survival interaction between TIPS and higher MELD (HR = 0.97; p = 0.22). In 30 propensity-matched serial LVP patients and 30 TIPS patients with baseline MELD greater than 18, TIPS did not predict worse survival (HR = 0.97; p = 0.94). Conclusion: Higher MELD predicts poorer survival after either serial LVP or TIPS, but TIPS creation is not associated with worse survival compared to serial LVP in patients with higher MELD scores Level of Evidence: Level 4, case series.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Combined Static and Dynamic Computed Tomography Angiography of Peripheral Artery Occlusive Disease: Comparison with Magnetic Resonance Angiography

PurposeTo compare in patients with known peripheral artery occlusive disease (PAOD), image quality of a combined CTA to a combined MRA protocol, including both static and dynamic acquisitions.Materials and MethodsTwenty-two patients with PAOD were examined with a combined CTA and MRA protocol consisting of static acquisitions (s-CTA, s-MRA) of the entire runoff and dynamic acquisitions (d-CTA, d-MRA) of the calves. Two radiologists compared image quality of the s-MRA versus s-CTA as well as d-MRA versus d-CTA. Image quality was assessed on a segmental basis using a 4-point Likert scale.ResultsFor s-CTA, 76% of segments were rated as excellent or good. For s-MRA, 50% of segments were rated as excellent or good (p < 0.0001). For d-CTA, median image quality score for all segments was rated as excellent for both readers. For d-MRA, median image quality for the different segments ranged from moderate to good. For both d-CTA and d-MRA, the median image quality scores were significantly higher for all segments of the lower limb compared with the static examinations of the lower limb segments (all p values < 0.0001). In patients with PAOD category 4–6, 80% of segments were rated as excellent or good for d-CTA, while 45% of segments were rated as poor or non-diagnostic for d-MRA.ConclusionIn patients with known PAOD, a combined static and dynamic CTA examination improves image quality relative to static and dynamic MRA and should be considered as an alternative to MRA, particularly in patients with advanced stage PAOD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Association of small vessel disease with tau pathology

Emerging evidence suggests that small vessel disease (SVD) is a risk factor for clinical dementia and may contribute to AD neuropathological changes. Watershed brain regions are located at the most distal areas between arterial territories, making them vulnerable to SVD-related changes. We examined the association of pathologic markers of SVD, specifically arteriolosclerosis in watershed brain regions, with AD pathologic changes. Participants (N= 982; mean age-at-death = 90; 69% women) were enrolled as part of one of two cohort studies of aging and dementia. At autopsy, neuropathological evaluation included semi-quantitative grading of arteriolosclerosis pathology from 2 cortical watershed regions: the anterior watershed (AWS) and posterior watershed (PWS), densities for cortical β-amyloid and tau-tangle pathology, and other common age-related pathologies. Linear regression models examined the association of watershed arteriolosclerosis pathology with β-amyloid and tau-tangle burden. In follow-up analyses, available ex-vivo MRI and proteomics data in a subset of decedents were leveraged to examine the association of whole brain measure of WMH, as a presumed MRI marker of SVD, with β-amyloid and tau-tangle burden, as well as to examine the association of watershed arteriolosclerosis with proteomic tau. Watershed arteriolosclerosis was common, with 45% of older persons having moderate-to-severe arteriolosclerosis pathology in the AWS region, and 35% in the PWS. In fully adjusted models that controlled for demographics and common age-related pathologies, an increase in severity of PWS arteriolosclerosis was associated with a higher burden of tau-tangle burden, specifically neocortical tau burden, but not with β-amyloid. AWS arteriolosclerosis was not associated with β-amyloid or tau pathology. Ex-vivo WMH was associated with greater tau-tangle pathology burden but not β-amyloid. Furthermore, PWS arteriolosclerosis was associated with higher abundance of tau phosphopeptides, that promote formation of tau aggregates. These data provide compelling evidence that SVD, specifically posterior watershed arteriolosclerosis pathology, is linked with tau pathological changes in the aging brain.

60 APPLIED LIFE SCIENCES↗

Evaluation of Coronary Artery Disease and Coronary Anomalies with a Handheld Smartphone

The purpose of this study was to determine the diagnostic accuracy of an iPhone for evaluation of the coronary arteries on coronary CT angiography (CTA) in comparison to a standard clinical workstation. Fifty coronary CTA exams were selected to include a range of normal and abnormal cases including both coronary artery disease (CAD) of varying severity and coronary artery anomalies. Two cardiac radiologists reviewed each exam on a standard clinical workstation initially and then on an iPhone 6 after a washout period. Coronary stenosis was evaluated on a 4-point scale and presence of coronary anomalies was recorded. Two additional cardiac radiologists reviewed all cases in consensus on the standard workstation and these results were used as the reference standard. When reader results were compared to the reference standard, there was no significant difference in agreement for per-vessel stenosis scores using either the iPhone or standard clinical workstation. The intraobserver intertechnology agreement on a per-vessel basis for obstructive CAD were 97.4% (299/307, kappa = 0.777) and 97.5% (317/325, kappa = 0.804) for the two readers. All cases of coronary anomalies were identified by both readers regardless of the device used. Coronary CTA examinations can be interpreted on a smartphone with diagnostic accuracy comparable to a standard workstation. 3D visualization app on the iPhone may facilitate urgent coronary CTA review when a workstation is not available.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Synthesis of new N-(pyridin-3-ylmethyl)-2-aminothiazoline derivatives possessing anticholinesterase and antiradical activity as potential multifunctional agents for the treatment of neurodegenerative diseases

New N-(pyridin-3-ylmethyl)-2-aminothiazolines containing various substituents at the 5 position of the thiazoline ring and the 4-tert-butylbenzyl, 4-isopropylbenzyl, or 4-fluorobenzyl moiety at the nitrogen atom of the amino group were synthesized. The inhibitory activity of the synthesized compounds against human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), equine serum butyrylcholinesterase (BChE, EC 3.1.1.8), and porcine liver carboxylesterase (CaE, EC 3.1.1.1) was evaluated and their antioxidant properties were studied by ABTS assay. N-(Pyridin-3-ylmethyl)-2-aminothiazolines proveded to be very weak AChE inhibitors, while their inhibitory activity against BChE and CaE was structure-dependent. 2-Aminothiazolines containing the 4-tert-butylbenzyl moiety are more efficient BChE inhibitors compared to the derivatives containing the 4-isopropylbenzyl or 4-fluorobenzyl substituent. An analysis of the dependence of the esterase profile of N-(pyridin-3-ylmethyl)-2-aminothiazolines on the structure of the substituent at the 5 position of the thiazoline ring of these compounds demonstrated that the derivatives containing the iodomethyl substituent possess the highest anti-BChE activity, the compounds with R{sup 2} = H and R{sup 3} = CH{sub 2}I have the optimal esterase profile. Regardless of the structure of the substituents in the benzyl moiety, all N-(pyridin-3-ylmethyl)-2-aminothiazolines containing the iodomethyl substituent at the 5 position of the thiazoline ring exhibited high radical scavenging activity comparable with that of the standard antioxidant Trolox. N-(Pyridin-3-ylmethyl)-2-aminothiazolines were shown to be a new promising class of compounds for the design of multifunctional agents for the treatment of neurodegenerative diseases.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Impacts of Vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 Variants Alpha and Delta on Coronavirus Disease 2019 Transmission Dynamics in Four Metropolitan Areas of the United States

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. In conclusion, estimated takeoff times are consistent with genomic surveillance data.

60 APPLIED LIFE SCIENCES↗

New Insights in the Control of Low-Density Lipoprotein Cholesterol to Prevent Cardiovascular Disease

Purpose of Review: Low-density lipoprotein cholesterol (LDL-C) is one major cause of cardiovascular disease (CVD). In this review, we discuss current developments in the understanding of LDL-C as lifelong risk factor, treatment targets, and emerging approaches to reduce cardiovascular risk by lowering LDL-C. Recent Findings: Recent evidence underscores the importance of LDL-C lowering in CVD prevention by mechanisms that increase the hepatic clearance of apolipoprotein B-containing lipoproteins from the plasma. Mendelian randomization studies provided evidence on both safety and efficacy of lower LDL-C in the long term. For young individuals, metrics other than 10-year CVD risk are required. Despite this evidence, LDL-C treatment target attainment is poor. Novel approaches are therefore needed. These include individualized strategies and new LDL-C-lowering pharmaceuticals. Summary: Early, long-term treatment with LDL-C-lowering therapies has the potential to markedly reduce CVD incidence and progression. Future research should aim to identify patient characteristics that enable physicians to tailor therapy to each individual patient.

62 RADIOLOGY AND NUCLEAR MEDICINE↗