We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
Aims
Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Method
Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
Results
Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
Conclusions
Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Policy measures to slow the spread of coronavirus disease 2019 (COVID-19), such as curfews and business closures, may have negative effects on mental health. Populations in low- and middle-income countries (LMICs) may be particularly affected due to high rates of poverty and less comprehensive welfare systems, but the evidence is scarce. We evaluated predictors of depression, anxiety, and psychological distress in Uganda, which implemented one of the world's most stringent lockdowns.
Methods
We conducted a mobile phone-based cross-sectional survey from December 2020 through April 2021 among individuals aged 18 years or over in Uganda. We measured depression, anxiety, and psychological distress using the Patient Health Questionnaire (PHQ)-2, the Generalized Anxiety Disorder (GAD)-2, and the PHQ-4. We applied linear regression to assess associations between experiences of COVID-19 (including fear of infection, social isolation, income loss, difficulty accessing medical care, school closings, and interactions with police) and PHQ-4 score, adjusted for sociodemographic characteristics.
Results
29.2% of 4066 total participants reported scores indicating moderate psychological distress, and 12.1% reported scores indicating severe distress. Distress was most common among individuals who were female, had lower levels of education, and lived in households with children. Related to COVID-19, PHQ-4 score was significantly associated with difficulty accessing medical care, worries about COVID-19, worries about interactions with police over lockdown measures, and days spent at home.
Conclusions
There is an urgent need to address the significant burden of psychological distress associated with COVID-19 and policy responses in LMICs. Pandemic mitigation strategies must consider mental health consequences.
South Africa has embarked on major health policy reform to deliver universal health coverage through the establishment of National Health Insurance (NHI). The aim is to improve access, remove financial barriers to care, and enhance care quality. Health technology assessment (HTA) is explicitly identified in the proposed NHI legislation and will have a prominent role in informing decisions about adoption and access to health interventions and technologies. The specific arrangements and approach to HTA in support of this legislation are yet to be determined. Although there is currently no formal national HTA institution in South Africa, there are several processes in both the public and private healthcare sectors that use elements of HTA to varying extents to inform access and resource allocation decisions. Institutions performing HTAs or related activities in South Africa include the National and Provincial Departments of Health, National Treasury, National Health Laboratory Service, Council for Medical Schemes, medical scheme administrators, managed care organizations, academic or research institutions, clinical societies and associations, pharmaceutical and devices companies, private consultancies, and private sector hospital groups. Existing fragmented HTA processes should coordinate and conform to a standardized, fit-for-purpose process and structure that can usefully inform priority setting under NHI and for other decision makers. This transformation will require comprehensive and inclusive planning with dedicated funding and regulation, and provision of strong oversight mechanisms and leadership.
OBJECTIVES/GOALS: Despite advances in precision medicine and understanding of the molecular pathways, melanoma remains the deadliest skin cancer, warranting identification of novel biomarkers. In this study, we performed bioinformatic analysis of melanoma patient tumors to identify novel dysregulated gene and micro-RNA (miRNA) targets responsible for survival. METHODS/STUDY POPULATION: Genetic sequencing data for 594 patient samples of melanoma and normal skin tissue from 10 databases were accessed using the NCBI Gene Expression Omnibus. Genes and miRNA that were significantly dysregulated (adjusted p-value < 0.05, log fold change > ± 2) in melanoma compared to normal skin were identified using the GEO2R program. Dataset expression profiles were cross-referenced to identify genetic elements dysregulated in at least 50% of datasets and filtered for association with poor survival using R2 Genomics Analysis and Visualization Platform. DAVID 6.8 provided pathway analysis of dysregulated genes. miRTarBase linked genes associated with poor survival and dysregulated miRNA from our database analysis. RESULTS/ANTICIPATED RESULTS: Bioinformatic analysis revealed consistent differential regulation of 205 genes (down=177 and up=28) and 38 miRNA across datasets with fold change >2 (bonf. p<0.05). Pathway analysis indicated that PPAR, phosphatidylinositol signaling, Rap1 signaling, and p53 signaling pathways were enriched by downregulated genes while the NF-kB pathway was enriched up regulated genes. Survival analysis of the differentially regulated genes identified 11 downregulated (ACSL1, CEBPA, CES4A, CRIP1, GATA3, HLADQB2, PTGS1, PYCARD, PPARG, PKP3, RSSF6) and 3 upregulated (DUXAP10, SLC2A3 and PRAME) hub genes to be associated with poor overall survival. Out of the 13 miRNA associated with hub genes, five miRNA (hsa-miR-125b-5p, hsa-miR-130b-3p, hsa-miR-26n-5p, hsa-miR-30b, hsa-miR-30c) were linked to multiple hub genes. DISCUSSION/SIGNIFICANCE: Our analysis identified 14 hub genes (regulators of PPARA, adipocyte differentiation, and transcriptional pathways) as well as miRNAs hsa-miR-30c (regulator of PTGS1 and SLC2A3) and hsa-let-7i-5p (regulator of ASCL1) as potential therapeutic targets. Further studies for validation of the targets are needed for clinical translation in melanoma.
Islamic attitudes and policies concerning the Jews in the Middle Ages have been the subject of heated debate in recent decades. Some see a benign, tolerant Islam, protecting its Jewish and other non-Muslim subjects from violence and respecting their religion and religious institutions. Others see conflict, intolerance, persecution, and even antisemitism. The first image harks back to the nineteenth century, a time when Jewish historians tended to paint an exaggerated picture of a “golden age” of Jewish-Muslim harmony, taking al-Andalus, or Muslim Spain, as the model. The idea stemmed from the disappointment Central European Jewish intellectuals felt as Emancipation-era promises of political and cultural equality remained unfulfilled. Historians exploited the tolerance they ascribed to Islam to chastise their Christian neighbors for failing to rise to the standards set by non-Christian society hundreds of years earlier.
Intelligence is an elusive concept. For well over a century, what exactly intelligence is and how best to measure it has been debated (see Sternberg & Kaufman, 2011). In one predominant factorization of the components of intelligence it is separated into fluid and crystalized categories, with fluid intelligence measuring one’s reasoning and problem-solving ability, and crystallized intelligence measuring lifetime knowledge (Cattell, 1971). Influential theories of intelligence, particularly fluid intelligence, have proposed that aspects of cognitive control, most notably working memory, are the drivers of intelligent behavior (Conway, Getz, Macnamara, & Engel de Abreu, 2011; Conway, Kane, & Engle, 2003; Kane & Engle, 2002; Kovacs & Conway, 2016). More specifically, it is thought that the control aspect of working memory, the central executive proposed by Baddeley and Hitch (1974), is the basis for the types of cognitive processes tapped by intelligence assessments (Conway et al., 2003; Kane & Engle, 2002). It has further been proposed that the control process underlying intelligence may not be a single process, but instead a cluster of domain-general control processes, including attentional control, interference resolution, updating of relevant information, and others (Conway et al., 2011; Kovacs & Conway, 2016). Here, we focus on what we have learned about how intelligence emerges from brain function, taking the perspective that cognitive control ability and intelligence are supported by similar brain mechanisms, namely integration, efficiency, and plasticity. These mechanisms are best investigated using brain network methodology. From a network neuroscience perspective, integration refers to interactions across distinct brain networks; efficiency refers to the speed at which information can be transferred across the brain; and plasticity refers to the ability of brain networks to reconfigure, or rearrange, into an organization that is optimal for the current context. Therefore, we review relevant literature relating brain network function to both intelligence and cognitive control, as well as literature relating intelligence to cognitive control. Given the strong link between fluid intelligence, in particular, and cognitive control, we focus mainly on literature probing fluid intelligence in this chapter.
Total cost estimates for crime in the USA are both out-of-date and incomplete. We estimated incidence and costs of personal crimes (both violent and non-violent) and property crimes in 2017. Incidence came from national arrest data, multi-state estimates of police-reported crimes per arrest, national victimization and road crash surveys, and police underreporting studies. We updated and expanded upon published unit costs. Estimated crime costs totaled $2.6 trillion ($620 billion in monetary costs plus quality of life losses valued at $1.95 trillion; 95 % uncertainty interval $2.2–$3.0 trillion). Violent crime accounted for 85 % of costs. Principal contributors to the 10.9 million quality-adjusted life years lost were sexual violence, physical assault/robbery, and child maltreatment. Monetary expenditures caused by criminal victimization represent 3 % of Gross Domestic Product – equivalent to the amount spent on national defense. These estimates exclude the additional costs of preventing and avoiding crime such as enhanced lighting and burglar alarms. They also exclude crimes against businesses and most white-collar and corporate offenses.
Through legislative changes, tariff wars, and executive actions, the Trump Administration has injected a new urgency into international technology and supply chain management, particularly between the United States and China. Analytically, the situation invites a perspective that links practical/on-the-ground responses by commercial actors in the politics of technological competition between superpowers, i.e. a discussion that bridges the gap between policy and process. This article therefore approaches management of supply chain disruption in terms of a key security issue motivating recent changes to the trade environment: the protection of intellectual property. After reviewing critical policy developments and trade statistics, we draw upon data on IP-intensive industries from global patent offices, trade classifications for products made by these IP-intensive industries, and concordance data on patent classifications to illustrate the centrality of IP to extended supply chains. With these key relationships in mind, we outline specific opportunities that intellectual property licensing provides for managing supply chain linkages between the United States and China in the current geopolitical environment. Viewing intellectual property as both a driver of and a solution to trade difficulties highlights the sorts of cross-jurisdictional nuances that can better inform policy and business decisions alike in the broader international trade regime.
Research in developmental neuropsychiatric conditions has revealed morphological and functional divergences in the brain. In some cases, the divergences occur due to one or two highly penetrant genomic mutations. In case such as autism, mutations in varied sets of genes may produce a convergent autism behavioral phenotype. It is thus likely that there may be other forms of non-genomic regulation of gene expression during development affecting behavioral outcome. Epigenetic gene regulation is one such mechanism that can permanently switch on or switch off gene expression, and these epigenetic changes can be inherited from one cell stage to another during differentiation, mimicking the effects of genomic mutations. Epigenetic gene regulation occurring during early developmental stages of cellular differentiation, which are highly sensitive to environmental cues, is the primary mechanism responsible for the phenomenon known as evolutionary development or “evo-devo.” This chapter discusses these mechanisms in the context of autism and the environmental factors that influence it.
Integration of research experiences into the undergraduate classroom can result in increased recruitment, retention, and motivation of science students. 'Big data' science initiatives, such as the Paleobiology Database (PBDB), can provide inexpensive and accessible research opportunities. This Element provides an introduction to what the PBDB is, how to use it, how it can be deployed in introductory and advanced courses, and examples of how it has been used in undergraduate research. The PBDB aims to provide information on all fossil organisms, across the tree of life, around the world, and through all of geologic time. The PBDB Resource Page contains a range of PBDB tutorials and activities for use in physical geology, historical geology, paleontology, sedimentology, and stratigraphy courses. As two-year colleges, universities, and distance-based learning initiatives seek research-based alternatives to traditional lab exercises, the PBDB can provide opportunities for hands-on science activities.
A once-dominant family of interpretations of the beginnings of Japanese and Russian development claimed that policies adopted by the two states were inadequate to modernize agrarian property relations, and so both states were required to mediate between premodern agriculture and “hot-house” modern industry. More recent accounts have insisted that despite the limited reforms to agrarian property relations, agriculture in both countries in fact dynamically participated in economic development. This paper contends that these revised accounts’ one-sided focus on market opportunities leaves unresolved key puzzles. Why did productivity growth jump higher after the Meiji reforms in Japan? Why did only some regions participate in agricultural development in Russia? To answer these questions, this paper argues it is necessary to return attention to the ways agrarian property relations did and did not change following reforms adopted by the two states in the 1860s and 1870s. The key theoretical upshot of this analysis is that the initiation of capitalist development required a political process in which institutions that had previously guaranteed non-market access of rural households to subsistence were dismantled in favor of the domination of market relations.
This paper identifies the individual components of social harm associated with a hypothetical racially targeted police encounter. Individuals who believe they are being targeted by police because they are members of a racial minority may suffer from fear of physical harm and humiliation by the encounter itself. However, the very fact that individuals will be racially targeted for a police encounter also causes harm to other members of the minority group even if they are not directly subject to an unwarranted encounter. In addition to fear and anxiety over the risk of such an encounter, they will often undertake costly avoidance behaviors to reduce their risk, or to mitigate the risk of any harm if such an encounter occurs. In addition, other members of society who value a nondiscriminatory policing policy might be willing to pay to reduce such unwarranted police encounters, and hence suffer a loss from this policing policy. In addition to discussing possible methodologies for estimating these cost components, this paper raises several issues that must be resolved – such as how to deal with the difference between perceived and actual racially targeted police encounters.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
Methods
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Results
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
Conclusions
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
Taylor's law (TL) originated as an empirical pattern in ecology. In many sets of samples of population density, the variance of each sample was approximately proportional to a power of the mean of that sample. In a family of nonnegative random variables, TL asserts that the population variance is proportional to a power of the population mean. TL, sometimes called fluctuation scaling, holds widely in physics, ecology, finance, demography, epidemiology, and other sciences, and characterizes many classical probability distributions and stochastic processes such as branching processes and birth-and-death processes. We demonstrate analytically for the first time that a version of TL holds for a class of distributions with infinite mean. These distributions, a subset of stable laws, and the associated TL differ qualitatively from those of light-tailed distributions. Our results employ and contribute to the methodology of Albrecher and Teugels (2006) and Albrecher et al. (2010). This work opens a new domain of investigation for generalizations of TL.
In a family, parameterized by θ, of non-negative random variables with finite, positive second moment, Taylor's law (TL) asserts that the population variance is proportional to a power of the population mean as θ varies: σ2 (θ) = a[μ(θ)]b, a > 0. TL, sometimes called fluctuation scaling, holds widely in science, probability theory, and stochastic processes. Here we report diverse examples of TL with b = 2 (equivalent to a constant coefficient of variation) arising from a difference of random variables in normed vector spaces of dimension 1 and larger. In these examples, we compute a exactly using, in some cases, a simple, new technique. These examples may prove useful in future models that involve differences of random variables, including models of the spatial distribution and migration of human populations.
The Munro Review of Child Protection approached the problem of child
protection from an understanding based upon systems analysis. Risk
assessment in psychiatry has similarities to the assessment by social
workers of child protection issues. Psychiatry as a profession could learn
from the Review, and, in doing so, be supported in recovering and
communicating the requirements for good clinical practice.
This paper reports on a benefit-cost analysis of a targeted intervention program, the YouthBuild USA Offender Project (YBOP), aimed at low-income, criminal offenders who are 16–24 years old. Using data on 388 participants, we find: (1) evidence of reduced recidivism and improved educational outcomes that exceed our expectations based on similar cohorts and (2) evidence consistent with a positive benefit-cost ratio, indicating that every dollar spent on the YBOP is estimated to produce a return on investment between $7.20 and $21.60, with benefits to society ranging between $174,000 and $281,000 per participant at a cost to society between $13,000 and $24,000.
In radar receivers, the low noise amplifier (LNA) must provide very low noise figure and high gain to successfully receive very low signals reflected off of illuminated targets. Obtaining low noise figure and high gain, unfortunately, is a well-known trade-off that has been carefully negotiated by design engineers for years. This paper presents a fundamental solution method for the source reflection coefficient providing the maximum available gain under a given noise figure constraint, and also for the lowest possible noise figure under a gain constraint. The design approach is based solely on the small-signal S-parameters and noise parameters of the device; no additional measurements or information are required. This method is demonstrated through examples. The results are expected to find application in design of LNAs and in real-time reconfigurable amplifiers for microwave communication and radar receivers.
The ipsilateral primary motor cortex (M1) plays a role in voluntary movement. In our studies, we used repetitive transcranial magnetic stimulation (rTMS) to study the effects of transient disruption of the ipsilateral M1 on the performance of finger sequences in right-handed normal subjects. Stimulation of the M1 ipsilateral to the movement induced timing errors in both simple and complex sequences performed with either hand, but with complex sequences, the effects were more pronounced with the left-sided stimulation. Recent studies in both animals and humans have confirmed the traditional view that ipsilateral projections from M1 to the upper limb are mainly directed to truncal and proximal muscles, with little evidence for direct connections to distal muscles. The ipsilateral motor pathway appears to be an important mechanism for functional recovery after focal brain injury during infancy, but its role in functional recovery for older children and adults has not yet been clearly demonstrated. There is increasing evidence from studies using different methodologies such as rTMS, functional imaging and movement-related cortical potentials, that M1 is involved in ipsilateral hand movements, with greater involvement in more complex tasks and the left hemisphere playing a greater role than the right.