A matrix perturbation view of the small world phenomenon

We use techniques from applied matrix analysis to study small world cutoff in a Markov chain. Our model consists of a periodic random walk plus uniform jumps. This has a direct interpretation as a teleporting random walk, of the type used by search engines to locate web pages, on a simple ring network. More loosely, the model may be regarded as an analogue of the original small world network of Watts and Strogatz [Nature, 393 (1998), pp. 440-442]. We measure the small world property by expressing the mean hitting time, averaged over all states, in terms of the expected number of shortcuts per random walk. This average mean hitting time is equivalent to the expected number of steps between a pair of states chosen uniformly at random. The analysis involves nonstandard matrix perturbation theory and the results come with rigorous and sharp asymptotic error estimates. Although developed in a different context, the resulting cutoff diagram agrees closely with that arising from the mean-field network theory of Newman, Moore, and Watts [Phys. Rev. Lett., 84 (2000), pp. 3201-3204]

Ischemic Stroke and Depression

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH–D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 ± 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 ± 6.7 years). We required a SIGH–D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH–D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke

Violence prevention accelerators for children and adolescents in South Africa:A path analysis using two pooled cohorts

Background: The INSPIRE framework was developed by 10 global agencies as the first global package for preventing and responding to violence against children. The framework includes seven complementary strategies. Delivering all seven strategies is a challenge in resource limited contexts. Consequently, governments are requesting additional evidence to inform which ‘accelerator’ provisions can simultaneously reduce multiple types of violence against children. Methods and Findings: We pooled data from two prospective South African adolescent cohorts including Young Carers (2010-2012), and Mzantsi Wakho (2014-2017). The combined sample size was 5034 adolescents. Each cohort measured six self-reported violence outcomes: sexual abuse, transactional sexual exploitation, physical abuse, emotional abuse, community violence victimisation, and youth lawbreaking; and seven self-reported INSPIRE-aligned protective factors: positive parenting, parental monitoring and supervision, food security at home, basic economic security at home, free schooling, free school meals, and abuse response services. Associations between hypothesised protective factors and violence outcomes were estimated jointly in a sex-stratified multivariate path model, controlling for baseline outcomes and socio-demographics, and correcting for multiple hypothesis testing using the Benjamini-Hochberg procedure. We calculated adjusted probability estimates conditional on the presence of no, one, or all protective factors significantly associated with reduced odds of at least three forms of violence in the path model. Adjusted risk differences (ARD) and risk ratios (ARR) with 95% confidence intervals (CI) were also calculated. The sample mean age was 13.54 years and 56.62% were female. There was 4% loss to follow up. Positive parenting, parental monitoring and supervision, and food security at home, were each associated with lower odds of three or more violence outcomes (p Conclusion: In this cohort study, we found that positive and supervisory caregiving, and food security at home are associated with reduced risk of multiple forms of violence against children. The presence of all three of these factors may be linked to greater risk reduction as compared to the presence of one, or none of these factors. Policies promoting action on positive and supervisory caregiving, and food security at home are likely to support further efficiencies in the delivery of INSPIRE.</p

Effects of depression on employment and social outcomes: a Mendelian randomisation study

Background: Depression is associated with socioeconomic disadvantage. However, whether and how depression exerts a causal effect on employment remains unclear. We used Mendelian randomisation (MR) to investigate whether depression affects employment and related outcomes in the UK Biobank dataset. Methods: We selected 227 242 working-age participants (40–64 in men, 40–59 years for women) of white British ethnicity/ancestry with suitable genetic data in the UK Biobank study. We used 30 independent genetic variants associated with depression as instruments. We conducted observational and two-sample MR analyses. Outcomes were employment status (employed vs not, and employed vs sickness/disability, unemployment, retirement or caring for home/family); weekly hours worked (among employed); Townsend Deprivation Index; highest educational attainment; and household income. Results: People who had experienced depression had higher odds of non-employment, sickness/disability, unemployment, caring for home/family and early retirement. Depression was associated with reduced weekly hours worked, lower household income and lower educational attainment, and increased deprivation. MR analyses suggested depression liability caused increased non-employment (OR 1.16, 95% CI 1.06 to 1.26) and sickness/disability (OR 1.56, 95% CI 1.34 to 1.82), but was not causal for caring for home/family, early retirement or unemployment. There was little evidence from MR that depression affected weekly hours worked, educational attainment, household income or deprivation. Conclusions: Depression liability appears to cause increased non-employment, particularly by increasing disability. There was little evidence of depression affecting early retirement, hours worked or household income, but power was low. Effective treatment of depression might have important economic benefits to individuals and society

Witnessed violence and youth behavior problems: A multi‐informant study.

Witnessed violence has significant negative consequences for youth behavior and mental health. However, many findings on the impact of witnessed violence have been based on a single informant. There is a general lack of consistency between caregiver and youth reports on both witnessed violence and behavioral problems. This study included data from both caregivers and youth and incorporated a multi-source analytic approach to simultaneously examine the association between youth witnessed violence and externalizing and internalizing behavior problems. Data from 875 caregivers and 812 youth were collected as part of the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Findings showed that youth reported more witnessed violence than did their caregivers, and caregivers reported more externalizing and internalizing behavior problems than did youth. Further, the source of information had a significant impact on the association between witnessed violence and internalizing behaviors. These findings highlight the need to incorporate multiple sources and multi-informant analytic techniques to eliminate methodological limitations to understanding the effect of witnessed violence on youth behavioral problems

PINK1 cleavage at position A103 by the mitochondrial protease PARL

Mutations in PTEN-induced kinase 1 (PINK1) cause early onset autosomal recessive Parkinson's disease (PD). PINK1 is a 63 kDa protein kinase, which exerts a neuroprotective function and is known to localize to mitochondria. Upon entry into the organelle, PINK1 is cleaved to produce a ∼53 kDa protein (ΔN-PINK1). In this paper, we show that PINK1 is cleaved between amino acids Ala-103 and Phe-104 to generate ΔN-PINK1. We demonstrate that a reduced ability to cleave PINK1, and the consequent accumulation of full-length protein, results in mitochondrial abnormalities reminiscent of those observed in PINK1 knockout cells, including disruption of the mitochondrial network and a reduction in mitochondrial mass. Notably, we assessed three N-terminal PD-associated PINK1 mutations located close to the cleavage site and, while these do not prevent PINK1 cleavage, they alter the ratio of full-length to ΔN-PINK1 protein in cells, resulting in an altered mitochondrial phenotype. Finally, we show that PINK1 interacts with the mitochondrial protease presenilin-associated rhomboid-like protein (PARL) and that loss of PARL results in aberrant PINK1 cleavage in mammalian cells. These combined results suggest that PINK1 cleavage is important for basal mitochondrial health and that PARL cleaves PINK1 to produce the ΔN-PINK1 fragment

Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Cardiovascular dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children. DATA SOURCES Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded. DATA EXTRACTION Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member. RESULTS Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction

Frequency and Clinical Determinants of Dementia after Ischemic Stroke

Objective: To investigate the frequency and clinical determinants of dementia after ischemic stroke. Methods: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 ± 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. Results: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). Conclusions: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors’ cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke

Trajectories of Adverse Childhood Experiences and Self-Reported Health at Age 18

Despite growing evidence of links between adverse childhood experiences (ACEs) and long-term health outcomes, there has been limited longitudinal investigation of such links in youth. The purpose of these analyses was to describe the patterns of exposure to ACEs over time and their links to youth health

Adverse Childhood Experiences and Child Health in Early Adolescence

1) Examine the relationship between previous adverse childhood experiences and somatic complaints and health problems in early adolescence, and 2) examine the role of the timing of adverse exposures