The Development of an Age-Structured Model for Trachoma Transmission Dynamics, Pathogenesis and Control

Trachoma is the worldwide leading infectious cause of blindness and is due to repeated conjunctival infection with Chlamydia trachomatis bacteria. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular disease outcomes require long-term monitoring. We present a mathematical model of trachoma transmission and disease to predict the impact of interventions on blinding trachoma. The model is based on the concept of multiple re-infections leading to progressive scarring of the eye and the potentially blinding disease sequelae. It includes aspects of trachoma natural history such as an increasing rate of recovery from infection, and a decreasing chlamydial load with subsequent infections. The model reproduces key features of trachoma epidemiology such as the age-profile of infection prevalence; a shift in the prevalence peak toward younger ages in higher-transmission environments; and a rising profile of the prevalence of the severe sequelae (scarring, trichiasis), as well as estimates of the number of infections experienced before these sequelae appear. The model can be used to examine the outcomes of various control strategies on infection and disease and can help to plan treatment interventions for different endemic settings

Identification of Novel Single Nucleotide Polymorphisms in Inflammatory Genes as Risk Factors Associated with Trachomatous Trichiasis

infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5′UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3–22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele.Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs

Understanding Interorganizational Learning Based on Social Spaces and Learning Episodes

Different organizational settings have been gaining ground in the world economy, resulting in a proliferation of different forms of strategic alliances that translate into a growth in the number of organizations that have started to deal with interorganizational relationships with different actors. These circumstances reinforce Crossan, Lane, White and Djurfeldt (1995) and Crossan, Mauer and White (2011) in exploring what authors refer to as the fourth, interorganizational, level of learning. These authors, amongst others, suggest that the process of interorganizational learning (IOL) warrants investigation, as its scope of analysis needs widening and deepening. Therefore, this theoretical essay is an attempt to understand IOL as a dynamic process found in interorganizational cooperative relationships that can take place in different structured and unstructured social spaces and that can generate learning episodes. According to this view, IOL is understood as part of an organizational learning continuum and is analyzed within the framework of practical rationality in an approach that is less cognitive and more social-behavioral

Polymorphisms in the tumor necrosis factor-alpha gene promoter may predispose to severe silicosis in black South African miners.

Susceptibility to silicosis is in part genetically determined. Polymorphisms in the promoter region of tumor necrosis factor (TNF)-alpha, a cytokine with a central role in the pathophysiology of silicosis, have been associated with predisposition to several infectious and inflammatory diseases. Polymorphisms at positions -308, -238, and -376 in the TNF-alpha promoter region were compared in nine patients with severe silicosis with International Labour Office (ILO) grade 3 nodularity, 112 patients with less severe silicosis (ILO grades 1/1 to 2/2), and 120 black South African gold miners without silicosis (ILO grades 0/0) in an age-frequency-matched case- control study. There were no significant differences between miners with less severe silicosis and controls at any loci in the TNF-alpha promoter region, but miners with severe silicosis were significantly more likely than controls to have -238A (33% versus 6%, Fisher's exact p value = 0.022) and -376A (33% versus 5%, Fisher's exact p value = 0.016). These alleles were in linkage disequilibrium (p < 0.001), and so were not independent. The association remained significant (Fisher's exact p values = 0.011 and 0.011, respectively) when analysis was limited to the majority tribe (Basotho), which included all subjects with severe silicosis. Subjects with severe silicosis were also significantly more likely to have the -308A allele (Fisher's exact p value = 0.034), but this result was confounded by ethnicity and was not significant within Basotho tribe members (Fisher's exact p value = 0.15). TNF-alpha promoter polymorphisms are associated with severe, but not less severe, silicosis in this population. A predominant effect on disease severity, rather than on disease frequency, appears to be a general feature of promoter polymorphism in diseases in which TNF-alpha has a critical role

Effects of sleep reduction on spatial attention

To investigate the effects exerted by sleep loss on specific attentive components the performance to a simple reaction time task and to a cued reaction time task were recorded at regular intervals during days following either 8 or 3 h of uninterrupted sleep. Eleven subjects took part in the experiment. The results show that, notwithstanding a general reduction of alertness produced by sleep curtailment (as indicated by the increase of reaction times in the simple reaction time task), in the cued reaction time task only the reaction times to invalidly cued targets significantly increase, while no difference is observed when attention is summoned by a valid cue. This result suggests that the mechanisms underlying orienting of attention are differentially affected by the reduction of alertness level