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.

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.

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.

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.