External store effects on the stability of fighter and interceptor airplanes

Some criteria for external carriage of missiles for fighter aircraft intended for aerial combat missions and for fighter-interceptor missions are considered. The mission requirements discussed include the short-range fighter-interceptor, the short-range interceptor, the medium-range interceptor, and the long-range interceptor. Missiles types considered to be compatible with the various point mission designs include the short-range missile, the medium-range missile, and the long-range missile. From the study, it appears that point mission design aircraft can be arranged in such a way that the required external-store arrangement will not impair the stability of the aircraft. An extensive reference list of NASA external store research is included

Orthotopic liver transplantation at Groote Schuur Hospital : a serial analysis of biliary cytokines and biochemical parameters

Orthotopic liver transplantation is the treatment of choice for many patients with end-stage liver disease. Despite advances in immunosuppression, acute rejection remains common (up to 70%) and results in significant patient morbidity. It is frequently difficult to distinguish abnormal liver function due to rejection from that due to infection, biliary obstruction or ischaemic injury without performing invasive procedures such as a liver biopsy or angiography which may be Clinically, the diagnosis of rejection is usually once the immunological process is already hazardous. made late, established. In this study, we evaluated standard biochemical parameters and cytokine concentrations (IL-1, IL-6 and TNF-alpha) in serial samples of bile obtained post-operatively via the Ttubes of patients following orthotopic liver transplantation in order to determine whether there are any biochemical or immunological pointers to the early diagnosis of rejection which would enable earlier administration of appropriate antirejection therapy. Biliary cytokines did not prove to be useful and reliable markers of early rejection. Serial measurement of biliary bilirubin levels showed an early and significant decrease a few days prior to rejection, and were a more sensitive marker of graft function than serum bilirubin levels

Diagonal and Low-Rank Matrix Decompositions, Correlation Matrices, and Ellipsoid Fitting

In this paper we establish links between, and new results for, three problems that are not usually considered together. The first is a matrix decomposition problem that arises in areas such as statistical modeling and signal processing: given a matrix $X$ formed as the sum of an unknown diagonal matrix and an unknown low rank positive semidefinite matrix, decompose $X$ into these constituents. The second problem we consider is to determine the facial structure of the set of correlation matrices, a convex set also known as the elliptope. This convex body, and particularly its facial structure, plays a role in applications from combinatorial optimization to mathematical finance. The third problem is a basic geometric question: given points $v_1,v_2,...,v_n\in \R^k$ (where $n > k$) determine whether there is a centered ellipsoid passing \emph{exactly} through all of the points. We show that in a precise sense these three problems are equivalent. Furthermore we establish a simple sufficient condition on a subspace $U$ that ensures any positive semidefinite matrix $L$ with column space $U$ can be recovered from $D+L$ for any diagonal matrix $D$ using a convex optimization-based heuristic known as minimum trace factor analysis. This result leads to a new understanding of the structure of rank-deficient correlation matrices and a simple condition on a set of points that ensures there is a centered ellipsoid passing through them.Comment: 20 page

Performance Evaluation and Optimization of Math-Similarity Search

Similarity search in math is to find mathematical expressions that are similar to a user's query. We conceptualized the similarity factors between mathematical expressions, and proposed an approach to math similarity search (MSS) by defining metrics based on those similarity factors [11]. Our preliminary implementation indicated the advantage of MSS compared to non-similarity based search. In order to more effectively and efficiently search similar math expressions, MSS is further optimized. This paper focuses on performance evaluation and optimization of MSS. Our results show that the proposed optimization process significantly improved the performance of MSS with respect to both relevance ranking and recall.Comment: 15 pages, 8 figure

A decade of hepatitis C at the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa, in the pre-direct-acting antivirals era

Background. Hepatitis C virus (HCV) in South Africa (SA) is incompletely characterised and understood. Epidemiological and clinical data will better inform our understanding and assist national policy decision-making. Against the background of more than two decades of clinical challenges in HCV management, the advent of direct-acting antivirals (DAAs) now makes HCV elimination plausible.Objectives. To better understand the base from which we come, we elected to review and characterise our HCV experience at Groote Schuur Hospital (GSH), Cape Town, SA, in the pegylated interferon (Peg-IFN) and ribavirin (RBV) management era.Methods. Patients with chronic HCV infection attending the GSH Liver Clinic from 2002 to 2014 were included in the analysis. Relevant data were extracted from a registry and existing clinical records were accessed. Two brands of Peg-IFN were available, and patients treated with the first-generation add-on protease inhibitor telaprevir were included.Results. A total of 238 patients were included in the analysis (median (interquartile range) 47 (37 - 58) years, 60.5% males). Males were significantly younger than females (43.5 (35 - 52) years v. 55 (42 - 64) years, respectively) (p<0.0001). The majority were white (55.9%) or of mixed ancestry (21.8%), 16.4% were HIV co-infected, 3.7% were hepatitis B virus (HBV) co-infected, and 1 patient (0.4%) was triple-infected with HCV, HBV and HIV. The most likely mode of HCV acquisition was blood or blood product exposure prior to 1992 (32.8%) and injecting drug use (17.6%), while 30.3% of patients had no clear risk factor identifiable. Genotypes (GTs) 1 - 5 were observed, with GT-1 (34.9%) predominating. Of patients who were biopsied (n=90), 30.0% had ≥F3 fibrosis, with 15.6% cirrhotic. With IL28B polymorphisms, the heterozygous CT (23.9%) and CC (15.5%) genotypes were most frequent. Of the patients, 32.6% accessed Peg-IFN/RBV-based therapy, 6.5% (n=5) with add-on telaprevir. GT-1 (35.1%) was most prevalent in the treatment group, followed by GT-3 (26.0%) and GT-5 (18.2%); 10.0% were HIV co-infected. The overall sustained virological response (SVR) rate was 75.3%, with 37.0% of GT-1 patients not achieving SVR. Of the patients treated, 49.4% experienced adverse events, including cytopenias (32.5%) and depression (15.6%), and 23.4% required cell support in the form of erythropoietin and/or granulocyte-macrophage colony-stimulating factor.Conclusions. HCV patients in the Peg-IFN/RBV management era typified the epidemiology of HCV. GT distribution was pangenotypic, and treatment outcomes were encouraging despite treatment challenges. Patient selection, IL28B and sensible support of cytopenias probably accounted for these favourable outcomes. However, numbers treated were limited, and the DAA era of therapy allows for rapid expansion of therapy with now growing numbers of patients and a changing local epidemiology.

Towards the elimination of hepatitis B and hepatocellular carcinoma

Hepatitis B (HBV) remains a global health problem despite the availability of effective vaccines since 1982 and effective antiviral therapy. The global burden of disease is substantial, with HBV resulting in 887 220 deaths in 2015: acute hepatitis (87 076), cirrhosis (462 690) and hepatocellular carcinoma (337 454). The World Health Organization has a vision to eliminate viral hepatitis as a public health threat by 2030. Although HBV and its associated complications of cirrhosis, liver failure and hepatocellular carcinoma are entirely vaccine preventable, there is no cure for chronic hepatitis B as yet. HBV elimination strategies will need to focus on effective and implementable preventive and therapeutic strategies such as upscaling HBV birth-dose vaccination, full HBV vaccine coverage, vaccination of high-risk groups, prevention of mother-to-child transmission, and identification of HBV-infected individuals and linkage to care with sustainable access to antiviral therapy

A natural history of efavirenz drug-induced liver injury

Background. Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, has been a component of first-line antiretroviral therapy (ART) in the South African HIV/AIDS programme since 2004. It is extensively used in ART programmes in other low- and middle-income countries. The natural history of the previously recognised EFV drug-induced liver injury (DILI) is not known.Objectives. To define and establish a causality assessment for EFV DILI and document its natural history by detailing a patient cohort. All relevant features characterising the patterns of clinical and histological injury, the duration of clinical and biochemical recovery and the associated mortality rate were documented. Factors associated with specific histological patterns of liver injury were analysed.Methods. Patients were prospectively included after meeting causality and inclusion criteria for EFV DILI. Clinical, demographic and liver histological features (where possible) were documented from the time of presentation and throughout follow-up. Prednisone at 0.25 - 0.5 mg/kg was initiated at the discretion of the treating hepatologist.Results. Fifty patients were prospectively included in the analysis. The median age was 34 (interquartile range (IQR) 29 - 39) years, males being older than females (p=0.014). Most (92%) were female, and 86% were of black African ethnicity. The median duration of ART at presentation was 6 months, with half of the women having initiated ART during pregnancy, at a median gestation of 24 (IQR 11 - 36) weeks. The median CD4 nadir at ART treatment initiation was 517 cells/µL, with no significant difference in CD4 nadir between those who were pregnant and those who were not (p=0.6). The median RUCAM (Roussel Uclaf Causality Assessment Method) score was 7, and among the 75% of patients who had liver biopsies, three histological patterns were identified: submassive necrosis (60%), nonspecific hepatitis (35%), and mixed cholestatic hepatitis (5%). On multivariate analysis, predictors for the development of submassive necrosis included younger age (<30 years; p=0.045), ART initiation in pregnancy (p=0.02), and a baseline CD4 count >350 cells/µL (p=0.018). For the nonspecific hepatitis group, pregnancy was also an associated factor (p=0.04). The mortality rate was 14%, with a median time from admission to death of 15 days. The median (IQR) time to initial hospital discharge was a lengthy 33 (24 - 52) days. Biochemical recovery was prolonged, necessitating a follow-up period of more than a year at an outpatient specialist clinic, with 86% of patients initiating a protease inhibitor-based ART regimen successfully.Conclusions. EFV DILI is a severe drug complication of ART with appreciable mortality and significant inpatient morbidity, requiring prolonged hospitalisation and follow-up

Immune tolerance and immunosuppression in solid organ transplantation

Organ transplantation is the treatment of choice for patients with end-stage organ failure. Most of them will require lifelong immunosuppression to prevent both acute and chronic rejection. T-cell recognition of the allograft major histocompatibility complex antigens is the central event initiating cellular rejection of the allograft, and subsequent full T-cell activation requires three signals.Immunosuppressive regimens currently used in clinical practice are nonspecific and target T-cell activation, clonal expansion or differentiation into effector T cells. While these therapeutic regimens have advanced considerably and one-year graft survival figures for most solid organ transplants (SOTs) are >90%, the long-term graft survival remains fair owing to graft loss from chronic rejection. The ‘holy grail’ of SOT is therefore the development of a permanent specific immune tolerance against donor allogeneic antigens without the long-term use of immunosuppression