Relative Risk Profiles Research Articles

Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

A comparison of the substance use related risk and protective factor profiles for American Indian and White American youth: a mixed studies review.

American Indian youth are disproportionately impacted by substance use compared to White American youth in the United States. This mixed studies review focused on gathering data to examine the similarities and differences between the risk and protective factor profiles for substance use among American Indian and White American youth aged 10-21. A scan of the existing literature was needed to review substance use related risk and protective factors for American Indian and White American youth. Search phrases were created to ensure maximum relevant results from existing literature through 2021. After deduplication, an appraisal tool was utilized to review 343 records. A total of 19 articles were deemed relevant. Data from relevant articles was recorded and categorized into the levels of the Social Ecological Model. Significant and salient risk and protective factors of substance use for both American Indian and White American youth presented at the individual, interpersonal (family/non-family), and community levels of the Social Ecological Model. A total of 84 factors were found from relevant articles, 55 risk factors and 29 protective factors. When comparing the American Indian and White American youth profiles, a total of 29 unique differences between American Indian (n = 21) and White American youth (n = 8) were identified. Results from this review can be utilized to inform Tribal leaders, stakeholders, and policymakers, which will ultimately influence health intervention strategies and prioritizations. Given the limited evidence though, researchers should be responsive to Tribal communities' call to action for utilizing a culturally rooted approach.

Elucidating the primary mechanisms of high-intensity interval training for improved cardiac fitness in obesity.

Obesity is a global and rising multifactorial pandemic associated with the emergence of several comorbidities that are risk factors for malignant cardiac remodeling and disease. High-intensity interval training (HIIT) has gained considerable attention due to its favorable outcomes of cardiometabolic health in individuals with overweight or obese. The primary aim of this review is to discuss the fundamental processes through which HIIT improves cardiac impairment in individuals with obesity to develop viable treatments for obesity management. In this review, a multiple database search and collection were conducted from the earliest record to January 2013 for studies included the qualitative component of HIIT intervention in humans and animals with overweight/obesity related to cardiac remodeling and fitness. We attempt to integrate the main mechanisms of HIIT in cardiac remolding improvement in obesity into an overall sequential hypothesis. This work focus on the ameliorative effects of HIIT on obesity-induced cardiac remodeling with respect to potential and pleiotropic mechanisms, including adipose distribution, energy metabolism, inflammatory response, insulin resistance, and related risk profiles in obesity. In conclusion, HIIT has been shown to reduce obesity-induced risks of cardiac remodeling, but the long-term effects of HIIT on obesity-induced cardiac injury and disease are presently unknown. Collective understanding highlights numerous specific research that are needed before the safety and effectiveness of HIIT can be confirmed and widely adopted in patient with obesity.

Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform

COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves. We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups. 18 895 870 adults were included in wave one, 19 014 720 in wave two, 18 932 050 in wave three, 19 097 970 in wave four, and 19 226 475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4·48 deaths (95% CI 4·41-4·55) in wave one to 2·69 (2·66-2·72) in wave two, 0·64 (0·63-0·66) in wave three, 1·01 (0·99-1·03) in wave four, and 0·67 (0·64-0·71) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19·85 deaths per 1000 person-years to 44·41 deaths per 1000 person-years, compared with from 0·05 deaths per 1000 person-years to 15·93 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease). There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups. UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

The impact of age on genetic risk for common diseases

Inherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Previous work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the longitudinal relationship between genetic relative risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic relative risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their relative risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying relative risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic relative risk. The predominant pattern shows genetic risk factors having the greatest relative impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants, although the magnitude and form of the decrease varies among diseases. As a consequence, for diseases where genetic relative risk decreases over age, genetic risk factors have stronger explanatory power among younger populations, compared to older ones. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.

On the Mechanics of sustainability: ESG Rating and company performance

ESG is the core concept in the field of green finance that has attracted much attention in recent years. Based on traditional financial indicators, ESG aims to integrate environmental, social, and governance factors. By examining the potential for long-term and sustainable value growth of the company, it can effectively help prevent and control downside risks, obtain long-term returns, and discover economic growth. However, there are currently many international ESG rating systems, lacking a unified framework, transparency of their rating methodologies, data sources, and a consensus on how to evaluate the ESG related risk profiles. This research intends to find how ESG Rating is constructed from company performance. In the study, we mainly did the review and illustration of MSCI & RepRisk ESG Rating. We can identify limited mechanisms that could hinder us to simulate ESG rating under various circumstances. For RepRisk, we could only identify the formula in the last step of generating RepRisk Rating: Scale RRR = 0.5 𑁦 (country sector aver+|||| peak RRI). For MSCI, we could only identify the rating construction methodologies based on various factors. However, we believe that the blockchain is supportive of eliminating these limitations, and we aim to explore the possibility of constructing an ESG rating system for blockchain for our next step.

Complications of cranioplasty following decompressive craniectomy for traumatic brain injury: systematic review and meta-analysis.

Decompressive craniectomy (DC) is a common neurosurgical intervention for severe traumatic brain injury (TBI), as well as malignant stroke, malignancy and infection. DC necessitates subsequent cranioplasty. There are significant demographic differences between TBI and non-TBI patients undergoing cranioplasty, which may influence their relative risk profiles for infection, aseptic bone flap resorption (aBFR) and re-operation. Perform a meta-analysis to determine the relative infection, aBFR and re-operation risk profiles of TBI patients as compared to other indications for DC. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, EMBASE and Google Scholar were searched until 26/11/2020. Studies detailing rates of infection, re-operation and/or aBFR in specific materials and the post-TBI population were included, while studies in paediatrics or craniosynostosis repair were excluded. Twenty-six studies were included. There was no difference in relative risk of infection between TBI and non-TBI cohorts (RR 0.81, 95% CI 0.57-1.17), with insignificant heterogeneity (I2 = 33%). TBI was a risk factor for aBFR (RR 1.54, 95% CI 1.25-1.89), with no significant heterogeneity (I2 = 13%). TBI was a risk factor for re-operation in the autologous sub-group (RR 1.49, 95% CI 1.05-2.11) but not in the alloplastic sub-group (RR = 0.86, 95% CI 0.34-2.18). Heterogeneity was insignificant (I2 = 11%). TBI is a risk factor for aBFR and re-operation following cranioplasty. Use of an alloplastic graft for primary cranioplasty in these patients may partially mitigate this increased risk.

Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model.

In postmenopausal women, hormonal decline changes muscle function and structure. The non-steroidal selective androgen receptor modulators (SARMs) Ostarine (OS) and Ligandrol (LG) have been shown to increase muscle mass and physical function while showing a relative low risk profile. Information about their effects on muscle structure and metabolism is lacking. To analyze this, two experiments were performed using ovariectomized rats as a standard model for postmenopausal conditions. In each experiment, 3-month old Sprague-Dawley rats were divided into five groups (n = 12 to 15). One group remained intact (Non-OVX), the other four groups were ovariectomized (OVX) and remained untreated for eight (OS Experiment) or nine (LG Experiment) weeks. Thereafter, rats of three of the four OVX groups were treated with OS or LG (with doses of 0.04, 0.4, or 4 mg/kg body weight/day) for 5 weeks. Then, uterus, gastrocnemius, and soleus muscles were weighed, fiber size, capillary density, and enzyme activity (lactate dehydrogenase [LDH], citrate synthase [CS], and complex I) were analyzed. In the LG experiment, intramuscular fat content was determined in the quadriceps femoris muscle. All OS treatments resulted in a higher capillary density in the gastrocnemius and longissimus muscles compared with the Non-OVX and the OVX rats, whereas all LG treatments showed a higher capillary density compared with the Non-OVX group. Muscle fiber size and distribution patterns were not changed under either SARM. The CS activity was higher in the longissimus muscle under OS treatment. LG resulted in a higher activity of CS in the gastrocnemius and of LDH in the longissimus muscle. Both SARMs showed an uterotrophic effect, OS at 4 and 0,4 mg dosages, LG at 4 mg dosage. In sum, beneficial effect on muscle vascularization was observed for both SARMs with a stronger impact for OS. LG showed more effect on muscle metabolism. However, a higher muscle weight and intramuscular fat content observed after LG treatment (4 mg) as well as an uterotrophic effect of both SARMs at higher dosages could be considered as an unfavorable side effects and might be a limitation for their application at these dosages.

Structured Risk Modelling of Naval Aviation Program Life Cycle Integration and Operation

A strategic capability of contemporary naval ships is the ability to launch and recover embarked aircraft such as helicopters in a maritime environment. Such operations are enormously challenging due to deck motion, limited landing space, visibility, ship’s superstructure, etc. This places extreme pressure on the pilot, ship’s crew and the platforms alike, making such shipboard operations the most dangerous of all helicopter flight missions. Therefore, the design and integration of equipment, systems and aids to ensure such operations are done as safely as is practicably possible presents ship builders, aircraft manufacturers, engineers and pilots with some extremely demanding and complex problems. Major naval ship design/build programmes that include an aviation capability will inevitably need to engage resources across multiple disciplines that include, but not limited to, engineering, design, logistics, administration, procurement, legal, alliance partners and the customer to manage project risks from the outset. This research highlights the need for a holistic/Systems Engineering approach that recognises risks across the wider ship programme, which can only be managed/resolved by cross-discipline collaboration. This paper presents a novel methodology to elicit risks qualitatively and models the relative risk profile of an aviation project throughout the ship programme life cycle. The use of an enterprise model based on the three “P” element methodology (3PE), product, process, people within an environment, has been developed. Furthermore, the research outlines a continuous management and visualisation approach that enables a process of dynamic analysis to both reduce and mitigate residual risks progressively throughout the project lifecycle to acceptable levels.

The Differentiation of Etiologies of Pulmonary Arterial Hypertension amongst Males and Females

There are limited studies which have studied the etiological differentiation of pulmonary arterial hypertension in large patient sample. To understand the association pattern of etiologies of pulmonary arterial hypertension. The National Inpatient Sample (NIS) was used to identify all patients 18 years and older hospitalized in 2016 with primary or secondary diagnosis of pulmonary arterial hypertension (PAH) by ICD-10 code I270. We then sought to differentiate etiologies of PAH among males and females. We looked for difference in relative risk profile, geographical distribution and outcomes including length of stay (LOS), mortality, Elixhauser mortality score and readmission score. Categorical variables were assessed with Chi square testing and continuous variables with two sample t-tests. Analyses were conducted using SAS v 9.4. A total of 10,300 patients with primary or secondary diagnosis of pulmonary arterial hypertension were identified, of which 31% were males and 69% females. This distribution was observed across the US (Figure 1A). In terms of prevalence, men were primarily in the Mountain states, whereas women were primarily in the Pacific states (Figure 1B/C). Males were more likely to have HIV related pulmonary hypertension (0.78% vs 0.14%, p=0.0208), whereas females were more likely to have scleroderma related pulmonary hypertension (1.1% vs 4.08%, p=0.0003). Males were likely to have atrial fibrillation (37.25% vs 32.29%, p=0.0316), coronary artery disease (43.51% vs 27.25%, p < 0.0001), smoking (35.68% vs 25.85%, p < 0.0001), and sleep apnea (26.29% vs 21.55%, p=0.0181), relative to females. There were no significant differences in relation to LOS, total hospital charges, mortality or readmission. Pulmonary arterial hypertension in males was more likely to be associated with HIV, coronary artery disease, atrial fibrillation, sleep apnea and smoking whereas among females, it was more likely to be associated with scleroderma.

Impact of Iron Deficiency Anemia in Patients with Pulmonary Arterial Hypertension

The impact of iron deficiency anemia on hospital length of stay and in hospitalization mortality has not been investigated in patients whose main reason for admission is pulmonary arterial hypertension. We sought to compare the outcomes in hospitalization in patients with pulmonary arterial hypertension (PAH) with a diagnosis of iron deficiency anemia (IDA) versus those without from a large sample database. The National Inpatient Sample (NIS) was used to identify all patients hospitalized 18 years of age and older in 2016 with a primary or secondary diagnosis of PAH by ICD-10 code I270. Within each hospitalization, the diagnosis of IDA was further identified using ICD-10 code D50.xx. We then examined the relative risk profile, and outcomes of interests including length of stay (LOS), total charges, number of diagnoses, Elixhauser[EC1] mortality, readmission score and in hospital mortality of each group. Categorical variables were analyzed with logistic regression models while continuous variables were assessed using two sample t-tests. All analyses were conducted using SAS v 9.4 and accounted for the NIS sampling design and updated hospital trend weights. A total of 10,300 patients with a primary or secondary diagnosis of PAH were identified, and of those, 8.45% had a diagnosis of IDA[EC2] . The cohort with IDA had a majority of women (80% vs 68%, p=<0.0001[EC3]), and were more likely to be black (24.5% vs 18.4%, p<0.0001). The number of hospital diagnoses in the IDA group was higher as well (17.0 vs 19.24, p=<0.0001). The IDA cohort were more likely to obese (28.74% vs 23.12%, p = 0.0061), have heart failure (52.30% vs 46.24%, p=0.0350), and have high risk features such as a pericardial effusion (6.32% vs 2.97%, p=0.0015). The IDA cohort were also more likely to be readmitted (mean readmission scores 35.19, p<0.0001), but there was no significant difference in length of stay, in hospital mortality, or hospital charges. Patients with primary pulmonary hypertension and IDA are more likely to be female and non-Caucasian, obese, have heart failure, or pericardial effusion, higher number of co-morbidities, and are more likely to be readmitted that those without IDA.

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer

Purpose/objective(s)To examine the therapeutic ratio and mortality profile over time in a radiotherapy randomized trial in stage III-IV larynx/pharynx cancer with long-term follow-up. Materials/methodsFrom 1988 to 1995, 331 cases were randomized to either hyperfractionated (HF) (58 Gy/40 fractions, twice daily) or conventional (CF) (51 Gy/20 fractions, once daily) radiotherapy. Overall survival (OS), locoregional (LRC), distant control (DC), ≥Grade 3 late toxicity (LT), and relative mortality risk profile over time were compared between both arms. ResultsMedian follow-up was 13.6 years. HF had a 10% improved OS at 5-years (40% vs 30%, p = 0.04), but the benefit diminished to 3% at 10-years (21% vs 18%). A trend towards higher LRC with HF remained (5-year: 49% vs 40%; 10-year: 49% vs 39%, p = 0.05). DC rates were unchanged (5-year: 87% vs 85%; 10-year: 87 vs 84%, p = 0.56). LT rates were similar (HF vs CF: 5-year: 9% vs 12%; 10-year: 11% vs 14%, p = 0.27). Multivariable analysis confirmed that HF reduced mortality risk by 31% [HR 0.69 (0.55–0.88), p < 0.01] and locoregional failure risk by 35% [HR 0.65 (0.48–0.89), p < 0.01]. Index cancer mortality (5-year: 46% vs 51%; 10-year: 49% vs 55%) was lower in the HF arm. Competing mortality (mostly smoking-related) was also numerically lower with HF at 5-years (14% vs 19%) but became similar at 10-years (30% vs 28%). ConclusionsThis trial confirms that HF with augmented total dose has a durable 10% effect size on LRC with comparable LT. OS benefit is evident at 5-years (10%) but relative mortality risk profile changes in longer follow-up.

Evaluation of European Deposit Insurance Scheme Funding Based on Risk Analysis

In this paper, we carry out a quantitative analysis of the financing measures proposed for the European Deposit Insurance Scheme (EDIS) regarding the target level of the fund and the contribution scheme of member entities. We estimate the loss distribution of the EDIS considering different sources of systemic risk associated with the correlations between bank assets inside and outside the eurozone countries, and we analyse the sensitivity of the results to bank portfolio risk. We determine the variations in the cost of insurance due to the relative risk profile of banks in the Banking Union and the loss-absorbing capacity of the contribution made by countries with the methodologies proposed by the European Banking Authority (2015). Our findings show how the interconnection between banks of different countries has an important influence on accumulated losses in the tail of the distribution, although the correlation within a country exerts a stronger effect. Both aspects must be considered in the calibration of the target level of the fund to avoid underestimating financing needs. Likewise, deterioration in the quality of bank portfolios produces a significant reduction in the fund's loss-absorbing capacity, which calls into question its soundness in times of economic recession. Finally, we assess the impact of the new contribution scheme on moral hazard and the possibility of cross-border subsidies between the countries of the Banking Union.

Influence of relative injury risk profiles on anterior cruciate ligament and medial collateral ligament strain during simulated landing leading to a noncontact injury event

BackgroundAthletes have traditionally been subdivided into risk classifications for ACL injury relative to the biomechanical traits they display during landing. This investigation aimed to discern whether these separate risk classifications elicit strain differences on the ACL and MCL during landing. It was hypothesized that the higher risk simulation profiles would exhibit greater ACL strain and that the ACL would exhibit greater strain than the MCL under all conditions. MethodThe mechanical impact simulator was used to simulate landing on a cohort of 46 cadaveric specimens. The simulator applied external joint loads to the knee prior to impulse delivery. These loads were organized into a series of profiles derived from in vivo motion capture previously performed on a cohort of 44 athletes and represented various risk classifications. Strain gauges were implanted on the ACL and MCL and simulations performed until a structural failure was elicited. Differences were assessed with Kruskal-Wallis tests. FindingsThe highest-risk profiles tended to exhibit greater peak ACL strain and change in ACL strain than the baseline- and moderate-risk profiles. Specimens that failed during lower-risk simulations expressed greater strain at these loads than specimens that completed higher-risk simulations. The ACL recorded greater strain than the MCL throughout all simulation profiles. InterpretationThis behavior justifies why neuromuscular interventions have greater impact on higher-risk athletes and supports the continued screening and targeted training of those athletes that express greater injury risk. The loading disparity between ACL and MCL justifies their limited concomitant injury rate.

Heterogeneity in mortality: a survey with an actuarial focus

Heterogeneity in mortality is due to differences among the individuals, which are caused by various risk factors. Some risk factors are observable while others are unobservable. The set of observable risk factors clearly depends on the type of population addressed. The impact of observable risk factors on individual mortality, in particular when they also constitute “rating factors” in the calculation of premiums and other actuarial values, is usually expressed approximately, according to some pragmatic approach. For example, additive or multiplicative adjustments to the average age-specific mortality are frequently adopted. Heterogeneity due to unobservable risk factors can conversely be expressed by adopting the concept of individual “frailty”, which, however, can be interpreted and consequently modeled in several ways, according to the causes which are considered as originating the frailty itself: congenital characteristics, environmental features, lifestyle aspects, etc. In this paper, we provide a survey of scientific contributions on heterogeneity in mortality, focusing on modeling both observable and unobservable heterogeneity. We start with an overview of methodological contributions to heterogeneity and frailty modeling, coming from both the demographical and the actuarial context. We then shift to contributions analyzing the impact of frailty, in its various interpretations, on the results (cash flows, profits, etc.) of life insurance and life annuity portfolios and related risk profiles.

Morphometric measurements of extracranial and intracranial atherosclerotic disease: A population-based autopsy study

Background and aimsIntracranial (IAD) and extracranial atherosclerotic diseases (EAD) have been mostly investigated using imaging methods. Autopsy studies allow for a direct and complete evaluation of the atherosclerotic disease. We aimed to investigate the frequency of IAD and EAD, their association, and related risk profiles in a large cross-sectional autopsy study. MethodsWe measured the intima-media thickness and stenosis of the common (CCA) and internal carotid arteries (ICA), using morphometric measurements. The main outcome was stenosis (≥50%) in the artery with the largest obstruction among the 12 cerebral arteries. We used multivariable logistic regression models to investigate the association between EAD and IAD. ResultsIn 661 participants (mean age = 71.3 ± 11.7 y, 51% male), stenosis was more common in IAD than in EAD (59% vs. 51%). EAD was associated with Caucasian race, hypertension, and smoking, while IAD was associated with older age, less years of education, hypertension, diabetes, and a previous history of stroke. Stenosis in CCA and ICA was associated with more than two times the odds of having stenosis in the intracranial arteries (CCA: OR = 2.32, 95% CI = 1.64; 3.28; ICA: OR = 2.51, 95% CI = 1.76; 3.57). ConclusionsIn this population-based autopsy study, IAD was common, even more common than EAD, but correlated with EAD.

SUN-P054: Malnutrition and Related Risk Profiles in Older Adults from Different Settings: an Enable-Study

SUN-P054: Malnutrition and Related Risk Profiles in Older Adults from Different Settings: an Enable-Study

Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex.

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.

Is the search for right-to-left shunt still worthwhile?

Patent foramen ovale (PFO) is a common disembryogenic defect with well-attested prevalence but dubious etiopathogenetic linkage with cryptogenic stroke and different clinical conditions. Transcranial color-coded Doppler (TCCD) assures high accuracy in diagnosing right-to-left shunt (RLS) and its functional aspects. Aim of the study was to evaluate RLS prevalence and degree in subjects submitted to TCCD for conditions theoretically associated or caused by paradoxical embolism to the brain. PFO assessment, performed in 10 major diagnostic categories and a control group, followed a standardized protocol with a 10 or 20 microbubbles (MB) cutoff to identify any or only large RLS, respectively. Among 2113 patients, a significant larger RLS prevalence was found in stroke (53.3%), TIA (45.7%) and migraine with aura (39.7%) when compared with non-migraineurs controls (25.5%). RLS degree was significantly higher in stroke and TIA patients: The ROC curve from MB load data helped to identify new cutoff values for both normal breathing (42 MB) and Valsalva (139 MB) tests. From logistic regression, a family history for PFO, ASA, and male gender appeared independent predictors of a RLS. By contrast, RLS seemed independent of white matter abnormalities presence on brain neuroimaging or stroke mimics. In addition to recently defined criteria, genetically determined inheritable traits and epidemiologic characteristics (male gender) should be taken into account when assessing PFO and related cerebrovascular risk profile. A newly defined threshold in TCCD MB count is suggested to discriminate shunts related to stroke and TIA from innocent ones.

The landscape of metastatic progression patterns across major human cancers.

The majority of patients with solid malignancies die from metastatic burden. However, our current understanding of the mechanisms and resulting patterns of dissemination is limited. Here, we analyzed patterns of metastatic progression across 16 major cancer types in a cohort of 1008 patients with metastatic cancer autopsied between 2000 and 2013 to assess cancer specific progression patterns of disease and related risk predictions. The frequency and location of metastases were evaluated in and across 1) 16 major cancers, 2) smoking- and non-smoking-related cancers and 3) adeno- and squamous cell carcinoma. Associations between primary and secondary sites were analyzed by the fractional and the relative risk methods. We detected significantly different cancer specific patterns of metastatic progression with specific relative risk profiles for secondary site involvement. Histology and smoking etiology influenced these patterns. Backward analysis showed that metastatic patterns help to predict unknown primary sites. Solid malignancies maintain a unique and recurrent organ tropism to specific secondary sites which does not appear to be strongly influenced by advances in cancer medicine as shown by comparison with previous data sets. The delineated landscape of metastatic progression patterns is a comprehensive data resource to both clinical and basic scientists which aids fostering new hypotheses for cancer research and cancer therapies.