Outcome after palliative cardiac surgery in a developing country

The outcome of 121 children who underwent palliative cardiac surgery at the Red Cross War Memorial Children's Hospital over a 5 year period, 1980 1984, was retrospectively examined. 79 children had systemic artery to pulmonary artery shunt operations (SPS), 40 had pulmonary artery bands (PAB) and 2 had surgical septectomies. SPS was most often done for children with Tetralogy of Fallot (TOF, 26 cases) or complex univentricular hearts with right ventricular outflow tract obstruction (27 cases). PAB was done chiefly for ventricular septa! defects, alone (VSD, 8 cases) or with coarctation of the aorta (9 cases). Children were referred from a wide area with 63 cases being referred from other major centres and foreign countries. Overall, 36 children died (30 % mortality): 5 died at surgery, 6 within 48 hours of surgery, a further 5 within 31 days; and 20 died after 31 days. SPS and PAB had the same early mortality rates ( 13 % ) • SPS had higher late and overall mortality rates (20 and 33 %) than PAB (10 and 23 %). Age at operation was found to be the most significant determinant of the overall mortality rate: children less than six months had a mortality of 42 % and those over 6 months, 13 % • The children were grouped into those with lesions which were probably correctable and those that were unlikely to be so, based on diagnosis and age at surgery: those with correctable lesions had a lower overall mortality (22 %) than those with uncorrectable lesions (43 %). Where the surgery was performed as an emergency, there was a higher overall and early mortality (55 and 35 respectively), compared to those operations which were performed electively ( 25 and 9 % ) • The presence of other medical conditions, for example congenital abnormalities and infections, was also a determinant of death (44 % mortality if other medical condition present, 26 % if absent). sex, population group, home address and type of surgery performed did not significantly affect mortality when examined by multivariate analysis. Using routine methods of follow up, it was initially thought that 17 % of all patients (22 % of survivors) were lost to follow up. An important determinant of this was the referral centre. 31 % of cases from other major centres and 20 % of foreign cases were lost, as compared to 8 % of cases from smaller towns near Cape Town and 2 % of children from Cape Town. Population group (35 % Blacks, 14 % Coloureds and 7 % Whites were lost), and palliative operation (23 % SPS, and 5 % PAB lost) were also significant determinants. It was possible to trace 12 of the 20 children who were thought to be lost to follow. 8 had died, 3 were still awaiting correction and 1 was traced and received corrective surgery. The records of the children who underwent cardiac surgery in 1987 were also analysed. There was no difference in the demographic characteristics of either group, and the early mortality was the same. This study shows that the outcome after palliative cardiac surgery is poor, with a high mortality rate and children often being lost to follow up. The decision to palliate rather than to correct a congenital heart defect must be made after balancing these risks with those of early correction for the particular surgical team. Should palliative surgery be undertaken, careful follow up is essential to ensure that complications of palliation do not set in and that corrective surgery is done at the optimal time

Appellate Review under the New Felony Sentencing Guidelines: Where Do We Stand

Now that it has been more than four years since Senate Bill 2 became effective, this is a good time to analyze the cases to see where courts stand in their interpretations of the guidelines. This article will review the case law and show how different courts have dealt with the legislation. My analysis concentrates on one aspect of the guidelines in particular: the standard of review that appeals courts have used to determine the propriety of sentences. To illustrate my points, I focus on the issue of when judges can impose maximum prison sentences under the guidelines, one of the most frequently litigated issues before our court. After initially analyzing the origins and development of Senate Bill 2, I will show that courts have not used consistent standards of review. This inconsistency, I argue, is especially problematic because it will result in inconsistent sentences for convicted felons, whose sentences will be greatly influenced by the section of the state, or appellate district, where their crimes occurred-just what Senate Bill 2 was designed to avoid

Improving Lay Helper Effectiveness: Teaching Living Prayer as a Gateway to a Focused Kingdom Lifestyle

It is common for those entering counseling at the Lake Church Counseling Center to lack intimacy with God. When one lacks intimacy with God, they are in imminent danger of becoming influenced exclusively by the world\u27s thinking in one or more areas of life. It is the effort of the LCCC to provide services to those suffering from emotional, spiritual, relational, and personal development struggles. Initially, the counseling center treats such conditions using Living Prayer to help clients strengthen their connection with God and transition to behaviors influenced only by the kingdom of God. This project aims to help Lake Church members learn to use Living Prayer as a gateway to a focused kingdom lifestyle. The intervention\u27s value is that a more focused kingdom lifestyle benefits anyone experiencing a life struggle and that those who will eventually attend counseling sessions at the LCCC will already be familiar with Living Prayer. To deploy the Living Prayer concept to all church members, the researcher selected a group of lay leaders already involved in supporting those with struggles. The group attended a four-hour training seminar followed by a four-week trial period. After the seminar and the trial period, surveys revealed that participants overwhelmingly embraced Living Prayer and their new role as Living Prayer Coaches. The results of this project demonstrate that lay leaders and helpers value training programs aimed at improving their proficiencies and augmenting their gifts

Alternative Media and Normative Theory: A Case of Ferguson, Missouri

This paper, based on in-depth interviews with journalists at alternative and advocacy papers in St. Louis as well as interviews with live streaming protestors, a new breed of citizen journalist, applies six characteristics commonly associated with the alternative press to coverage of the protests and police crackdown in Ferguson, Missouri, between August 9, 2014, and March 2015. Journalists from the alternative newspaper in St. Louis focused on progressive or radical values less than the literature predicted. The African-American newspaper in St. Louis found itself influencing the national and global agenda regarding Ferguson and the ongoing oppression of blacks in the city and surrounding municipalities. Mobile media-savvy protesters broadcast police actions from the front lines of dissent in nearly constant live streams day after day from August to November, altering the scope of counternarrative and providing distilled counter­propaganda. In this study, researchers provide a snapshot of the alternative/advocacy press as it rose to fill in gaps in coverage and to find untold stories in one of the most widely broadcast events of 2014

Mechanisms of Human Immunodeficiency Virus (HIV) Persistence and Strategies to Elicit Cytotoxic T Lymphocyte-Mediated Clearance of HIV-Infected Cells

Human immunodeficiency virus (HIV), the cause of a decades-long pandemic responsible for over 30 million deaths and 38 million ongoing infections, establishes a chronic infection for which there is no cure. While the development of combination antiretroviral therapy (ART) has radically transformed the course of the pandemic, individuals living with HIV must maintain therapy for the remainder of their lives. This is the result of cells harboring latent HIV proviruses, which are stably integrated in the host cell DNA but remain transcriptionally silent. These latent proviruses are not targeted by ART and evade clearance by the host immune response, but can begin to express viral genes and re-establish an ongoing infection in the event of ART interruption. The leading theoretical framework to achieve an HIV cure is the “shock and kill” approach, in which latent proviruses are therapeutically reactivated to express viral genes and subsequently killed by the cytopathic effects of the virus or the host immune response. The latent reservoir of replication-competent HIV is found in a multitude of quiescent cell types residing in diverse tissues, including resting memory CD4+ T cells and hematopoietic stem and progenitor cells (HSPCs). Understanding the mechanisms regulating HIV latency and reactivation in quiescent cells will enable the development of targeted latency reversing agents (LRAs). Chapter 2 describes two modifications to in vitro cultures that independently maintain primary HSPCs in a quiescent state. These quiescent HSPCs are susceptible to HIV infection, but preferentially harbor latent proviruses that have a significantly reduced likelihood of spontaneous reactivation. Latent proviruses in quiescent cells are resistant to therapeutic reactivation by histone deacetylase inhibition or P-TEFb activation, but are responsive to NFkB activation. Collectively, this work provides a path forward to identify mechanisms contributing to latency and latency reversal in quiescent primary cells. In the event that a potent shock or sequential shocks successfully induce HIV gene expression in every cell harboring a replication-competent provirus, these cells need to be killed before the latent reservoir can be reseeded. Cytotoxic T lymphocytes (CTLs) are the main effectors of the adaptive immune system responsible for eliminating HIV-infected cells by recognizing HIV peptides presented by MHC-I on the cell surface. HIV evades these responses through the activity of the accessory protein Nef, which downregulates MHC-I by redirecting it to the lysosome instead of the plasma membrane. The work described in Chapter 3 led to the identification of concanamycin A (CMA) as a potent inhibitor of HIV Nef. CMA counteracted Nef at sub-nanomolar concentrations that did not interfere with lysosomal acidification or degradation and were non-toxic in primary cell cultures. CMA specifically reversed Nef-mediated downregulation of MHC-I, but not CD4, and cells treated with CMA showed reduced formation of the AP-1:Nef:MHC-I complex required for MHC-I downregulation. CMA restored expression of diverse allotypes of MHC-I in Nef-expressing cells and inhibited Nef alleles from divergent clades of HIV and SIV, including from primary patient isolates. Importantly, restoration of MHC-I in HIV-infected cells was accompanied by enhanced CTL-mediated clearance of infected cells comparable to genetic deletion of Nef. Thus, CMA is a promising lead compound for therapeutic inhibition of Nef to enhance immune-mediated clearance of HIV-infected cells.PHDImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/166108/1/markmp_1.pd

An attractive model: simulating fuzzy dark matter with attractive self-interactions

Fuzzy Dark Matter (FDM) comprised of ultralight ($m \sim 10^{-22}~\rm{eV}$) boson particles has received significant attention as a viable alternative to Cold Dark Matter (CDM), as it approximates CDM on large scales ($\gtrsim 1$ Mpc) while potentially resolving some of its small-scale problems via kiloparsec-scale quantum interference. However, the most basic FDM model, with one free parameter (the boson mass), is subject to a tension: small boson masses yield the desired cores of dwarf galaxies but underpredict structure in the Lyman-$\alpha$ forest, while large boson masses render FDM effectively identical to CDM. This Catch-22 problem may be alleviated by considering an axion-like particle with attractive particle self-interactions. We simulate an idealized FDM halo with self-interactions parameterized by an energy decay constant $f \sim 10^{15}~\rm{GeV}$ related to the axion symmetry-breaking conjectured to solve the strong-CP problem in particle physics. We observe solitons, a hallmark of FDM, condensing within a broader halo envelope, and find that the density profile and soliton mass depend on self-interaction strength. We propose generalized formulae to extend those from previous works to include self-interactions. We also investigate a critical mass threshold predicted for strong interactions at which the soliton collapses into a compact, unresolved state. We find that the collapse happens quickly and its effects are initially contained to the central region of the halo.Comment: 20 pages, 16 figures; to be submitted to MNRA

Ectromelia Virus Infections of Mice as a Model to Support the Licensure of Anti-Orthopoxvirus Therapeutics

The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the “Animal Efficacy Rule”. One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. In this review we outline how mousepox has been used as a model for smallpox. We also discuss mousepox in the context of mouse strain, route of infection, infectious dose, disease progression, and recovery from infection

Improving snow albedo processes in WRF/SSiB regional climate model to assess impact of dust and black carbon in snow on surface energy balance and hydrology over western U.S.

Two important factors that control snow albedo are snow grain growth and presence of light‐absorbing impurities (aerosols) in snow. However, current regional climate models do not include such processes in a physically based manner in their land surface models. We improve snow albedo calculations in the Simplified Simple Biosphere (SSiB) land surface model coupled with the Weather Research and Forecasting (WRF) regional climate model (RCM), by incorporating the physically based SNow ICe And Radiative (SNICAR) scheme. SNICAR simulates snow albedo evolution due to snow aging and presence of aerosols in snow. The land surface model is further modified to account for deposition, movement, and removal by meltwater of such impurities in the snowpack. This paper presents model development technique, validation with in situ observations, and preliminary results from RCM simulations investigating the impact of such impurities in snow on surface energy and water budgets. By including snow‐aerosol interactions, the new land surface model is able to realistically simulate observed snow albedo, snow grain size, dust in snow, and surface water and energy balances in offline simulations for a location in western U.S. Preliminary results with the fully coupled RCM show that over western U.S., realistic aerosol deposition in snow induces a springtime average radiative forcing of 16 W/m2 due to a 6% albedo reduction, a regional surface warming of 0.84°C, and a snowpack reduction of 11 mm.Key PointsIncluding snow aging and aerosols in snow improves offline and WRF snow simulationsDust and black/organic carbon exerts nontrivial radiative forcing in western U.S.RCM simulation shows temperature increase and snow mass loss from aerosols in snowPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111782/1/jgrd52045.pd