Bridges Out of Poverty as an Anti-Poverty Strategy in Kennett Square, Pennsylvania

This paper explores the initial results of the Bridges Out of Poverty (“Bridges”) community framework as implemented by the organization Kennett Area Community Service in Kennett Square, Pennsylvania. The aim of this research is to provide perspective on Bridges Out of Poverty’s contribution to the understanding of poverty in the United States and its potential as an antipoverty intervention. It does so first through an exploration of the historical and current discussion on poverty and anti-poverty interventions in the United States, followed by research on the Bridges model itself and its implementation in Kennett Square. This latter research includes content analysis of Bridges publications, interviews with Bridges leaders across the United States, additional interviews with those involved in the initial Bridges programming in Kennett Square, and finally survey data collected by Kennett Area Community Service in the beginning stages of program implementation. The research finds that by situating the individual-level effects of poverty in structural context, Bridges has the potential to change the conversation on poverty in the communities engaging with its framework. While Bridges’ stated goals reach into the level of large-scale structural impact, I find that the change inspired by Bridges is primarily happening on the community level, and with bigger impacts happening as they “trickle up” from local contexts. I argue, therefore, that Bridges has potential as a set of tools to bring a critical analysis of poverty to circles where it is often overlooked, and in doing so to change mindsets and practices that address poverty at the local level

Generalized Permutohedra from Probabilistic Graphical Models

A graphical model encodes conditional independence relations via the Markov properties. For an undirected graph these conditional independence relations can be represented by a simple polytope known as the graph associahedron, which can be constructed as a Minkowski sum of standard simplices. There is an analogous polytope for conditional independence relations coming from a regular Gaussian model, and it can be defined using multiinformation or relative entropy. For directed acyclic graphical models and also for mixed graphical models containing undirected, directed and bidirected edges, we give a construction of this polytope, up to equivalence of normal fans, as a Minkowski sum of matroid polytopes. Finally, we apply this geometric insight to construct a new ordering-based search algorithm for causal inference via directed acyclic graphical models.Comment: Appendix B is expanded. Final version to appear in SIAM J. Discrete Mat

Differentially Private Model Selection with Penalized and Constrained Likelihood

In statistical disclosure control, the goal of data analysis is twofold: The released information must provide accurate and useful statistics about the underlying population of interest, while minimizing the potential for an individual record to be identified. In recent years, the notion of differential privacy has received much attention in theoretical computer science, machine learning, and statistics. It provides a rigorous and strong notion of protection for individuals' sensitive information. A fundamental question is how to incorporate differential privacy into traditional statistical inference procedures. In this paper we study model selection in multivariate linear regression under the constraint of differential privacy. We show that model selection procedures based on penalized least squares or likelihood can be made differentially private by a combination of regularization and randomization, and propose two algorithms to do so. We show that our private procedures are consistent under essentially the same conditions as the corresponding non-private procedures. We also find that under differential privacy, the procedure becomes more sensitive to the tuning parameters. We illustrate and evaluate our method using simulation studies and two real data examples

Enhancement of cancer chemotherapy in vitro by intense ultrawideband electric field pulses

Experiments have been performed to enhance the Jurkat cell-killing effects of the cancer chemotherapy agent bleomycin using electric field pulses of 50–200 kV/cm50–200kV∕cm peak electric field strength, ∼ 150 ns∼150ns duration, and nanosecond rise time. Dramatic increases in cell killing (factors of ∼ 1000∼1000) were observed with a low dose of bleomycin after treatment with trains of ten or more pulses at all electric field strengths tested, compared to pulse-only or drug-only treatments. Cell death occurred within 24 h24h for treated cells, with some evidence of membrane phosphatidylserine externalization at 6 h6h postexposure but no significant increase in caspase activity, indicating that the primary mode of cell death was not caspase-mediated apoptosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87477/2/094701_1.pd

A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop

In human mitochondria the transcription machinery generates the RNA primers needed for initiation of DNA replication. A critical feature of the leading-strand origin of mitochondrial DNA replication is a CG-rich element denoted conserved sequence block II (CSB II). During transcription of CSB II, a G-quadruplex structure forms in the nascent RNA, which stimulates transcription termination and primer formation. Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. We here demonstrate that the unusual behavior of the RNA primer is explained by the formation of a stable G-quadruplex structure, involving the CSB II region in both the nascent RNA and the non-template DNA strand. Based on our data, we suggest that G-quadruplex formation between nascent RNA and the non-template DNA strand may be a regulated event, which decides the fate of RNA primers and ultimately the rate of initiation of DNA synthesis in human mitochondria

Phosphatidylinositol 3‐kinase and Akt effectors mediate insulin‐like growth factor‐I neuroprotection in dorsal root ganglia neurons

Insulin‐like growth factor‐I (IGF‐I) protects neurons of the peripheral nervous system from apoptosis, but the underlying signaling pathways are not well understood. We studied IGF‐I mediated signaling in embryonic dorsal root ganglia (DRG) neurons. DRG neurons express IGF‐I receptors (IGF‐IR), and IGF‐I activates the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway. High glucose exposure induces apoptosis, which is inhibited by IGF‐I through the PI3K/Akt pathway. IGF‐I stimulation of the PI3K/Akt pathway phosphorylates three known Akt effectors: the survival transcription factor cyclic AMP response element binding protein (CREB) and the pro‐apoptotic effector proteins glycogen synthase kinase‐3β (GSK‐3β) and forkhead (FKHR). IGF‐I regulates survival at the nuclear level through accumulation of phospho‐Akt in DRG neuronal nuclei, increased CREB‐mediated transcription, and nuclear exclusion of FKHR. High glucose increases expression of the pro‐apoptotic Bcl protein Bim (a transcriptional target of FKHR). However, IGF‐I does not regulate Bim or anti‐apoptotic Bcl‐xL protein expression levels, which suggests that IGF‐I neuroprotection is not through regulation of their expression. High glucose also induces loss of the initiator caspase‐9 and increases caspase‐3 cleavage, effects blocked by IGF‐I. These data suggest that IGF‐I prevents apoptosis in DRG neurons by regulating PI3K/Akt pathway effectors, including GSK‐3β, CREB, and FKHR, and by blocking caspase activation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154325/1/fsb2fj041581fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154325/2/fsb2fj041581fje-sup-0001.pd

The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa

BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458); the Harvard University Center for AIDS Research (P30 AI42851); National Institutes of Health (K24 AR 02123); the Doris Duke Charitable Foundation (Clinical Scientist Development Award); the Harvard University Program on AID

Causality in digital medicine

Ben Glocker (an expert in machine learning for medical imaging, Imperial College London), Mirco Musolesi (a data science and digital health expert, University College London), Jonathan Richens (an expert in diagnostic machine learning models, Babylon Health) and Caroline Uhler (a computational biology expert, MIT) talked to Nature Communications about their research interests in causality inference and how this can provide a robust framework for digital medicine studies and their implementation, across different fields of application

Pionic Deuterium

The strong interaction shift and broadening in pionic deuterium have been remeasured with high statistics by means of the (3p-1s) X-ray transition using the cyclotron trap and a high-resolution crystal spectrometer. Preliminary results are (-2325+/-31) meV (repulsive) for the shift and (1171+23/-49} meV for the width, which yields precise values for the pion-deuteron scattering length and the threshold parameter for pion production.Comment: Conf. Proc. Few Body 19 (FB19), August 31 - September 5, 2009, Bonn, Germany 9 pages, 13 figure

Incorporating spatial dependence into a multicellular tumor spheroid growth model

Recent models for organism and tumor growth yield simple scaling laws based on conservation of energy. Here, we extend such a model to include spatial dependence to model necrotic core formation. We adopt the allometric equation for tumor volume with a reaction-diffusion equation for nutrient concentration. In addition, we assume that the total metabolic energy and average cellular metabolic rate depend on nutrient concentration in a Michaelis-Menten-like manner. From experimental results, we relate the necrotic volume to nutrient consumption and estimate both the time and nutrient concentration at necrotic core formation. Based on experimental results, we demand that the necrotic core radius varies linearly with tumor radius after core formation and extend the equations for tumor volume and nutrient concentration to the postnecrotic core regime. In particular, we obtain excellent agreement with experimental data and the final steady-state viable rim thickness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87333/2/124701_1.pd