Investigative decision-making in public corruption cases: Factors influencing case outcomes

Public corruption undermines the rule of law that is crucial to the maintenance of governmental legitimacy and peaceful co-existence. As political divisiveness has grown, politicians have called public corruption investigations “witch hunts” and part of partisan politics, rather than a search for justice. Contemporary attacks on law enforcement charge that they are acting with political motivation which further undermines the legitimacy of these investigations. It is important for research to delve into how the investigative processes maintain their fact-finding missions in support of the rule of law. This study addresses how public corruption investigations occur and how the investigations themselves are conducted. First, federal prosecution data are used to understand the frequency of investigations over the last thirty years. Second, interviews with 40 former investigators and prosecutors examines the process, protocols, tools and resources needed for successful corruption investigations. Investigations require interagency cooperation (especially at different levels of government) and particular attention to the use of investigative tools that ensure the legitimacy of the law in the eyes of the accused, the courts and the general public. In addition, a decline in public corruption cases is seen in recent years with the US prosecution effort diverted to immigration cases

Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy.

ObjectivesTo examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy.DesignOpen-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study.MethodsHIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms.ResultsAll eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046).ConclusionSBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy

Benefits and limitations of text messages to stimulate higher learning among community providers: participants’ views of an mHealth intervention to support continuing medical education in Vietnam

BACKGROUND: A randomized controlled trial was conducted in 2015 to evaluate a mobile continuing medical education (mCME) intervention that provided daily text messages to community-based physicians’ assistants (CBPAs) in Thai Nguyen Province, Vietnam. Although the intervention failed to improve medical knowledge over a 6-month period, a companion qualitative study provided insights on the views and experiences of intervention participants. METHODS: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) among participants randomized to receive text messages containing either simple medical facts or quiz questions. Trained interviewers collected data immediately following the conclusion of the trial in December 2015. Using semi-structured question guides, respondents were queried on their views of the intervention, positive and negative, and perceived impacts of the intervention. During analysis, after learning that the intervention had failed to increase knowledge among participants, we also examined reasons for lack of improvement in medical knowledge. All analyses were performed in NVivo using a thematic approach. RESULTS: A total of 70 CBPAs engaged in one of 8 FGDs or an IDI. One-half were men; average age among all respondents was 40 years. Most (81%) practiced in rural settings and most (51%) focused on general medicine. The mean length of work experience was 3 years. All respondents made positive comments about the intervention; convenience, relevance, and quick feedback (quiz format) were praised. Downsides encompassed lack of depth of information, weak interaction, technology challenges, and challenging/irrelevant messages. Respondents described perceived impacts encompassing increased motivation, knowledge, collegial discussions, Internet use to search for more information, and clinical skills. Overall, they expressed a desire for the intervention to continue and recommended expansion to other medical professionals. Overreliance on the text messages, lack of effective self-study, and technical/language-based barriers may be potential explanations for intervention failure. CONCLUSION: As a form of mCME, daily text messages were well-received by community-level health care providers in Vietnam. This mCME approach appears very promising in low-resource environments or where traditional forms of CME are impractical. Future models might consider enhancements to foster linkages to relevant medical materials, improve interaction with medical experts, and tailor medical content to the daily activities of medical staff

Radiation Induces Diffusible Feeder Cell Factor(s) That Cooperate with ROCK Inhibitor to Conditionally Reprogram and Immortalize Epithelial Cells

Both feeder cells and Rho kinase inhibition are required for the conditional reprogramming and immortalization of human epithelial cells. In the present study, we demonstrated that the Rho kinase inhibitor Y-27632, significantly suppresses keratinocyte differentiation and extends life span in serum-containing medium but does not lead to immortalization in the absence of feeder cells. Using Transwell culture plates, we further demonstrated that physical contact between the feeder cells and keratinocytes is not required for inducing immortalization and, more importantly, that irradiation of the feeder cells is required for this induction. Consistent with these experiments, conditioned medium was shown to induce and maintain conditionally immortalized cells, which was accompanied by increased telomerase expression. The activity of conditioned medium directly correlated with radiation-induced apoptosis of the feeder cells. Thus, the induction of conditionally reprogrammed cells is mediated by a combination of Y-27632 and a diffusible factor (or factors) released by apoptotic feeder cells

Deploying and Optimizing Embodied Simulations of Large-Scale Spiking Neural Networks on HPC Infrastructure

Simulating the brain-body-environment trinity in closed loop is an attractive proposal to investigate how perception, motor activity and interactions with the environment shape brain activity, and vice versa. The relevance of this embodied approach, however, hinges entirely on the modeled complexity of the various simulated phenomena. In this article, we introduce a software framework that is capable of simulating large-scale, biologically realistic networks of spiking neurons embodied in a biomechanically accurate musculoskeletal system that interacts with a physically realistic virtual environment. We deploy this framework on the high performance computing resources of the EBRAINS research infrastructure and we investigate the scaling performance by distributing computation across an increasing number of interconnected compute nodes. Our architecture is based on requested compute nodes as well as persistent virtual machines; this provides a high-performance simulation environment that is accessible to multi-domain users without expert knowledge, with a view to enable users to instantiate and control simulations at custom scale via a web-based graphical user interface. Our simulation environment, entirely open source, is based on the Neurorobotics Platform developed in the context of the Human Brain Project, and the NEST simulator. We characterize the capabilities of our parallelized architecture for large-scale embodied brain simulations through two benchmark experiments, by investigating the effects of scaling compute resources on performance defined in terms of experiment runtime, brain instantiation and simulation time. The first benchmark is based on a large-scale balanced network, while the second one is a multi-region embodied brain simulation consisting of more than a million neurons and a billion synapses. Both benchmarks clearly show how scaling compute resources improves the aforementioned performance metrics in a near-linear fashion. The second benchmark in particular is indicative of both the potential and limitations of a highly distributed simulation in terms of a trade-off between computation speed and resource cost. Our simulation architecture is being prepared to be accessible for everyone as an EBRAINS service, thereby offering a community-wide tool with a unique workflow that should provide momentum to the investigation of closed-loop embodiment within the computational neuroscience community.journal articl

Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory markers and impact on HIV persistence by cell-dependent mechanisms, and show unique effects of MVC in duodenal immunity driven by higher drug tissue penetration and possibly by class-dependent effects