Comparing the effectiveness of testing methods in improving programs: the effect of variations in program quality

We compare the efficacy of different testing methods for improving the reliability of software. Specifically, we use modelling to compare “operational” testing, in which test cases are chosen according to their probability of occurring in actual use of the software, against “debug” testing methods, in which the testers look for test cases which they consider likely to cause failure, or that satisfy some coverage criterion. We base our comparisons on the reliability reached by the program at the end of testing. Differently from previous studies, we consider the probability distribution of the achieved reliability, and thus the probability of satisfying specific requirements, rather than just the average reliability achieved. We take account of two sources of variation. The variation between the actual test histories that are possible for a given program and a given test method: and the fact that different programs start testing with different faults and initial reliability levels. By necessity, we use very simplified models of reality. Yet, we can show some interesting conclusions with important practical consequences. In general, there are stronger arguments in favor of operational testing than previous studies have show

Optimal discrimination between transient and permanent faults

An important practical problem in fault diagnosis is discriminating between permanent faults and transient faults. In many computer systems, the majority of errors are due to transient faults. Many heuristic methods have been used for discriminating between transient and permanent faults; however, we have found no previous work stating this decision problem in clear probabilistic terms. We present an optimal procedure for discriminating between transient and permanent faults, based on applying Bayesian inference to the observed events (correct and erroneous results). We describe how the assessed probability that a module is permanently faulty must vary with observed symptoms. We describe and demonstrate our proposed method on a simple application problem, building the appropriate equations and showing numerical examples. The method can be implemented as a run-time diagnosis algorithm at little computational cost; it can also be used to evaluate any heuristic diagnostic procedure by compariso

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldHost defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans

The treatment of hyperinsulinemic hypoglycaemia in adults: an update

Treatment of hyperinsulinemic hypoglycaemia (HH) is challenging due to the rarity of this condition and the difficulty of differential diagnosis. The aim of this article is to give an overview of the recent literature on the management of adult HH

BEYOND WAIST CIRCUMFERENCE IN AN ADULT MALE POPULATION OF SOUTHERN ITALY: IS THERE ANY ROLE FOR SUBSCAPULAR SKINFOLD THICKNESS IN THE RELATIONSHIP BETWEEN INSULIN-LIKE GROWTH FACTOR-1 SYSTEM AND METABOLIC PARAMETERS ?

ABSTRACT Background: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The Insulin-like Growth Factor (IGF)-1 system is deregulated in obese subjects in proportion to their degree of visceral adiposity. Aim : To examine the association among IGF-1, IGF-Binding Protein (BP)1 and 3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. Materials and Methods: A complete database for this analysis was available for 229 (age range 50–82 years) participating at 2002-2004 Olivetti Heart Study follow-up. Results: After adjustment for age, IGF-1 was inversely associated with BMI and waist circumference (p<0.05). IGFBP1 was inversely associated with BMI, waist circumference, SST, Homeostasis Model Assessment (HOMA) index, Fat Mass (FM). HOMA index, age and SST significantly predicted the IGFBP1 plasma levels, with 24% of IGFPB-1 variability explained at a linear regression analysis. Conclusions: IGFBP1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFPB-1 levels. The evaluation of some components of the IGFs system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults

Malignant osteopetrosis: bone marrow transplantation

A osteopetrose é uma osteopatia hereditária caracterizada pela deficiência na reabsorção óssea que ocorre por disfunção dos osteoclastos. Com o acúmulo de material osteóide que oblitera o canal medular, ocorre hematopoiese extramedular (hepato-esplenomegalia), obliteração dos forames dos nervos cranianos (cegueira, surdez, paralisias faciais), macrocefalia, protusão da fronte, hipertelorismo, exoftalmo, aumento da pressão intracraniana, retardo na erupção dentária, atraso no crescimento, atraso no desenvolvimento neuropsicomotor, e a morte ocorre precocemente nos primeiros anos de vida. A única alternativa terapêutica curativa é o transplante de medula óssea (TMO) de doador HLA idêntico, pois restabelece a hematopoiese e a função monócito-macrófago, com melhora das lesões ósseas e anormalidades hematopoiéticas, embora não reverta as alterações sensoriais já instaladas. Os autores relatam casos de duas crianças portadoras de osteopetrose maligna submetidas ao transplante de medula óssea com sucesso. A primeira encontra-se no dia +1260 do TMO, com melhora evidente da radiologia esquelética, sem progressão das deficiências neurológicas que apresentava, e com biópsia óssea sem sinais de osteopetrose. O segundo paciente encontra-se no dia + 700, com sinais de reabsorção óssea e sem progressão dos danos neurológicos. Os autores chamam a atenção para a necessidade de diagnóstico precoce da osteopetrose e o rápido encaminhamento para o transplante de medula óssea antes da instalação de seqüelas neurológicas definitivas.Osteopetrosis is an inherited disorder characterized by the inability to reabsorb and remodel bone due to osteoclast dysfunction. The encroachment by bone and mineralized cartilage of the medullary cavities leads to extramedullary hematopoiesis (hepatosplenomegaly) and cranial-nerve foramina leads to blindness, auditory nerve damage, and occulomotor and facial nerve palsies. Defective bone re-absorption also leads to macrocephaly, frontal bossing, hypertelorism, exophthalmos, increased intracranial pressure, retarded tooth eruption, retarded linear growth and psychomotor delay. Death occurs within the first years of life. The only curative therapy is allogeneic bone marrow transplantation with a HLA-identical donor, which restores hematopoiesis, monocyte-macrophage function and bone recovery, but there is no sensorial deficit restoration once present. The authors report two cases of allogeneic bone marrow transplant for infantile malignant osteopetrosis. The first child, on day 1260 after bone marrow transplantation (BMT), showed radiologic bone recovery and no progression of neurological deficits with a bone biopsy showing no signs of osteopetrosis. The second child showed signs of bone re-absorption and no progression of neurological deficits on day 700. The authors emphasize the importance of early diagnosis of osteopetrosis and the necessity of bone marrow transplantation before neurological deficits have begun

A Review of Subsidence Monitoring Techniques in Offshore Environments

In view of the ever-increasing global energy demands and the imperative for sustainability in extraction methods, this article surveys subsidence monitoring systems applied to oil and gas fields located in offshore areas. Subsidence is an issue that can harm infrastructure, whether onshore or especially offshore, so it must be carefully monitored to ensure safety and prevent potential environmental damage. A comprehensive review of major monitoring technologies used offshore is still lacking; here, we address this gap by evaluating several techniques, including InSAR, GNSSs, hydrostatic leveling, and fiber optic cables, among others. Their accuracy, applicability, and limitations within offshore operations have also been assessed. Based on an extensive literature review of more than 60 published papers and technical reports, we have found that no single method works best for all settings; instead, a combination of different monitoring approaches is more likely to provide a reliable subsidence assessment. We also present selected case histories to document the results achieved using integrated monitoring studies. With the emerging offshore energy industry, combining GNSSs, InSAR, and other subsidence monitoring technologies offers a pathway to achieving precision in the assessment of offshore infrastructural stability, thus underpinning the sustainability and safety of offshore oil and gas operations. Reliable and comprehensive subsidence monitoring systems are essential for safety, to protect the environment, and ensure the sustainable exploitation of hydrocarbon resources

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease