Residue codes of extremal Type II Z_4-codes and the moonshine vertex operator algebra

In this paper, we study the residue codes of extremal Type II Z_4-codes of length 24 and their relations to the famous moonshine vertex operator algebra. The main result is a complete classification of all residue codes of extremal Type II Z_4-codes of length 24. Some corresponding results associated to the moonshine vertex operator algebra are also discussed.Comment: 21 pages, shortened from v

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis.

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Behavioral determinants as predictors of return to work after long-term sickness absence: an application of the theory of planned behavior

Background The aim of this prospective, longitudinal cohort study was to analyze the association between the three behavioral determinants of the theory of planned behavior (TPB) model-attitude, subjective norm and self-efficacy-and the time to return-to-work (RTW) in employees on long-term sick leave. Methods The study was based on a sample of 926 employees on sickness absence (maximum duration of 12 weeks). The employees filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. The TPB-determinants were measured at baseline. Work attitude was measured with a Dutch language version of the Work Involvement Scale. Subjective norm was measured with a self-structured scale reflecting a person's perception of social support and social pressure. Self-efficacy was measured with the three subscales of a standardised Dutch version of the general self-efficacy scale (ALCOS): willingness to expend effort in completing the behavior, persistence in the face of adversity, and willingness to initiate behavior. Cox proportional hazards regression analyses were used to identify behavioral determinants of the time to RTW. Results Median time to RTW was 160 days. In the univariate analysis, all potential prognostic factors were significantly associated (P < 0.15) with time to RTW: work attitude, social support, and the three subscales of self-efficacy. The final multivariate model with time to RTW as the predicted outcome included work attitude, social support and willingness to expend effort in completing the behavior as significant predictive factors. Conclusions This prospective, longitudinal cohort-study showed that work attitude, social support and willingness to expend effort in completing the behavior are significantly associated with a shorter time to RTW in employees on long-term sickness absence. This provides suggestive evidence for the relevance of behavioral characteristics in the prediction of duration of sickness absence. It may be a promising approach to address the behavioral determinants in the development of interventions focusing on RTW in employees on long-term sick leave

An exploration of socio-economic and food characteristics of high trans fatty acid consumers in the Dutch and UK national surveys after voluntary product reformulation

Trans fatty acids (TFA) increase the risk of mortality and chronic diseases. TFA intakes have fallen since reformulation, but may still be high in certain, vulnerable, groups. This paper investigates socio-economic and food consumption characteristics of high TFA consumers after voluntary reformulation in the Netherlands and UK. Post-reformulation data of adults aged 19–64 was analysed in two national surveys: the Dutch National Food Consumption Survey (DNFCS) collected 2007–2010 using 2*24hr recalls (N = 1933) and the UK National Diet and Nutrition Survey (NDNS) years 3&4 collected 2010/11 and 2011/12 using 4-day food diaries (N = 848). The socio-economic and food consumption characteristics of the top 10% and remaining 90% TFA consumers were compared. Means of continuous data were compared using t-tests and categorical data means using chi-squared tests. Multivariate logistic regression models indicated which socio-demographic variables were associated with high TFA consumption. In the Dutch analyses, women and those born outside the Netherlands were more likely to be top 10% TFA consumers than men and Dutch-born. In the UK unadjusted analyses there was no significant trend in socio-economic characteristics between high and lower TFA consumers, but there were regional differences in the multivariate logistic regression analyses. In the Netherlands, high TFA consumers were more likely to be consumers of cakes, buns & pastries; cream; and fried potato than the remaining 90%. Whereas in the UK, high TFA consumers were more likely to be consumers of lamb; cheese; and dairy desserts and lower crisps and savoury snack consumers. Some socio-demographic differences between high and lower TFA consumers were evident post-reformulation. High TFA consumers in the Dutch 2007–10 survey appeared more likely to obtain TFA from artificial sources than those in the UK survey. Further analyses using more up-to-date food composition databases may be needed

Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

Background: Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care progra

Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease

Background: Clostridium difficile infections (CDI) are a significant health problem to humans and food animals. Clostridial toxins ToxA and ToxB encoded by genes tcdA and tcdB are located on a pathogenicity locus known as the PaLoc and are the major virulence factors of C. difficile. While toxin-negative strains of C. difficile are often isolated from faeces of animals and patients suffering from CDI, they are not considered to play a role in disease. Toxin-negative strains of C. difficile have been used successfully to treat recurring CDI but their propensity to acquire the PaLoc via lateral gene transfer and express clinically relevant levels of toxins has reinforced the need to characterise them genetically. In addition, further studies that examine the pathogenic potential of toxin-negative strains of C. difficile and the frequency by which toxin-negative strains may acquire the PaLoc are needed. Results: We undertook a comparative genomic analysis of five Australian toxin-negative isolates of C. difficile that lack tcdA, tcdB and both binary toxin genes cdtA and cdtB that were recovered from humans and farm animals with symptoms of gastrointestinal disease. Our analyses show that the five C. difficile isolates cluster closely with virulent toxigenic strains of C. difficile belonging to the same sequence type (ST) and have virulence gene profiles akin to those in toxigenic strains. Furthermore, phage acquisition appears to have played a key role in the evolution of C. difficile. Conclusions: Our results are consistent with the C. difficile global population structure comprising six clades each containing both toxin-positive and toxin-negative strains. Our data also suggests that toxin-negative strains of C. difficile encode a repertoire of putative virulence factors that are similar to those found in toxigenic strains of C. difficile, raising the possibility that acquisition of PaLoc by toxin-negative strains poses a threat to human health. Studies in appropriate animal models are needed to examine the pathogenic potential of toxin-negative strains of C. difficile and to determine the frequency by which toxin-negative strains may acquire the PaLoc

Insulin/IGF and Sex Hormone Axes in Human Endometrium and Associations with Endometrial Cancer Risk Factors

Given an ordered set of points and an ordered set of geometric objects in the plane, we are interested in finding a non-crossing matching between point-object pairs. In this paper, we address the algorithmic problem of determining whether a non-crossing matching exists between a given point-object pair. We show that when the objects we match the points to are finite point sets, the problem is NP-complete in general, and polynomial when the objects are on a line or when their size is at most 2. When the objects are line segments, we show that the problem is NP-complete in general, and polynomial when the segments form a convex polygon or are all on a line. Finally, for objects that are straight lines, we show that the problem of finding a min-max non-crossing matching is NP-complete. © 2012 Elsevier B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe