Efficacy of albendazole against the whipworm Trichuris trichiura - a randomised, controlled trial

Objectives and design. To test the efficacy of albendazole against the whipworm Trichuris trichiura for  school-based deworming in the south-western Cape, South Africa. Children infected with Trichuris were  randomised to 3 doses of albendazole (400; 800 or 1 200 mg), each repeated 4 times. The boy I girl ratio was 1. A group not infected With worms was treated with placebo, creating a negative control. Subjects and setting. Pupils at a primary school serving a wineproducing area approximately 90 km east of Cape Town.Outcome measures. Trichuris cure rates and reduction in the number of eggs/gin faeces, as well as the  infection dynamics of Trichuris and Ascaris during treatment with placebo.Results. Albendazole treatment was associated with Trichuris cure rates of 23% (400 mg), 56% (800  mg) and 67% (1 200 mg) after the final treatment. The corresponding reductions in the number of eggs/g of faeces were 96.8%, 99.3% and 99.7%. Environmental pollution by human faeces was confirmed because worm egg-negative children in the placebo group became egg-positive while the study was in progress.Conclusion. The 400 mg stat dose had a low Trichuris cure rate. To repeat the dose on 2 or 3 days would  increase cost, reduce compliance and complicate management. Albendazole cannot be used in deworming programmes in South Africa because it is a Schedule 4 prescription medicine. De-scheduling is needed urgently, particularly because of high efficacy against hookworm in KwaZulu-Natal and  neighbouring countries

Searching for faces differs from categorization: Evidence from scenes and eye movements

This study examined whether the detection of frontal, ¾ and profile face views differs from their categorization as faces. Experiment 1 compared three tasks that required observers to determine the presence or absence of a face but varied in the extent to which they had to search for faces in simple displays and small or large scenes to make this decision. Performance was equivalent for all face views in simple displays and small scenes, but was notably slower for profile views when this required the search for faces in extended scene displays. This search effect was confirmed in Experiment 2, which compared observers’ eye movements with their response times to faces in visual scenes. These results demonstrate that the categorization of faces at fixation is dissociable from the detection of faces in space. Consequently, we suggest that face detection should be studied with extended visual displays, such as natural scenes

The aa-theorem and the Asymptotics of 4D Quantum Field Theory

We study the possible IR and UV asymptotics of 4D Lorentz invariant unitary quantum field theory. Our main tool is a generalization of the Komargodski-Schwimmer proof for the $a$-theorem. We use this to rule out a large class of renormalization group flows that do not asymptote to conformal field theories in the UV and IR. We show that if the IR (UV) asymptotics is described by perturbation theory, all beta functions must vanish faster than $(1/|\ln\mu|)^{1/2}$ as $\mu \to 0$ ($\mu \to \infty$). This implies that the only possible asymptotics within perturbation theory is conformal field theory. In particular, it rules out perturbative theories with scale but not conformal invariance, which are equivalent to theories with renormalization group pseudocycles. Our arguments hold even for theories with gravitational anomalies. We also give a non-perturbative argument that excludes theories with scale but not conformal invariance. This argument holds for theories in which the stress-energy tensor is sufficiently nontrivial in a technical sense that we make precise.Comment: 41 pages, 2 figures. v2: Arguments clarified, some side comments corrected, connection to previous work by Jack and Osborn described, conclusions unaffecte

Protein S-Bacillithiolation Functions in Thiol Protection and Redox Regulation of the Glyceraldehyde-3-Phosphate Dehydrogenase Gap in Staphylococcus aureus Under Hypochlorite Stress

Aims: Bacillithiol (BSH) is the major low-molecular-weight thiol of the human pathogen Staphylococcus aureus. In this study, we used OxICAT and Voronoi redox treemaps to quantify hypochlorite-sensitive protein thiols in S. aureus USA300 and analyzed the role of BSH in protein S-bacillithiolation.  Results: The OxICAT analyses enabled the quantification of 228 Cys residues in the redox proteome of S. aureus USA300. Hypochlorite stress resulted in >10% increased oxidation of 58 Cys residues (25.4%) in the thiol redox proteome. Among the highly oxidized sodium hypochlorite (NaOCl)-sensitive proteins are five S-bacillithiolated proteins (Gap, AldA, GuaB, RpmJ, and PpaC). The glyceraldehyde-3-phosphate (G3P) dehydrogenase Gap represents the most abundant S-bacillithiolated protein contributing 4% to the total Cys proteome. The active site Cys151 of Gap was very sensitive to overoxidation and irreversible inactivation by hydrogen peroxide (H2O2) or NaOCl in vitro. Treatment with H2O2 or NaOCl in the presence of BSH resulted in reversible Gap inactivation due to S-bacillithiolation, which could be regenerated by the bacilliredoxin Brx (SAUSA300_1321) in vitro. Molecular docking was used to model the S-bacillithiolated Gap active site, suggesting that formation of the BSH mixed disulfide does not require major structural changes.  Conclusion and Innovation: Using OxICAT analyses, we identified 58 novel NaOCl-sensitive proteins in the pathogen S. aureus that could play protective roles against the host immune defense and include the glycolytic Gap as major target for S-bacillithiolation. S-bacillithiolation of Gap did not require structural changes, but efficiently functions in redox regulation and protection of the active site against irreversible overoxidation in S. aureus. Antioxid. Redox Signal. 28, 410–430

Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Scenario-Based Design Theorizing:The Case of a Digital Idea Screening Cockpit

As ever more companies encourage employees to innovate, a surplus of ideas has become reality in many organizations – often exceeding the available resources to execute them. Building on insights from a literature review and a 3-year collaboration with a banking software provider, the paper suggests a Digital Idea Screening Cockpit (DISC) to address this challenge. Following a design science research approach, it suggests a prescriptive design theory that provides practitioner-oriented guidance for implementing a DISC. The study shows that, in order to facilitate the assessment, selection, and tracking of ideas for different stakeholders, such a system needs to play a dual role: It needs to structure decision criteria and at the same be flexible to allow for creative expression. Moreover, the paper makes a case for scenario-based design theorizing by developing design knowledge via scenarios

Individually Modified Saliva Delivery Changes the Perceived Intensity of Saltiness and Sourness

Individuals vary largely in their salivary flow and composition, and given the importance of saliva on perception of taste, this might influence how the tastant stimuli are perceived. We therefore hypothesise that altering the individual salivary flow rates has an impact on the perceived taste intensity. In this study, we investigated the role of saliva amount on the perceived taste intensity by excluding parotid saliva and adding artificial saliva close to the parotid duct at preset flow rates. Significant decreases in perception with increasing salivary flow rates were observed for citric acid and sodium chloride. This can partially be explained by a dilution effect which is in line with previous studies on detectable concentration differences. However, since the bitterness and sweetness remained unaffected by the salivary flow conditions and the dilution effect was comparable to that of saltiness, further explanation is needed. Furthermore, we investigated whether the suppression of taste intensity in binary mixtures (taste–taste interactions) could possibly be caused by the increased salivary flow rate induced by an additional taste attribute. The results show, however, that suppression of taste intensity in binary mixtures was not affected by the rate of salivation. This was more likely to be explained by psychophysics

Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage

Osteoarthritis (OA) is a degenerative disease which causes pain and stiffness in joints. OA progresses through excessive degradation of joint cartilage, eventually leading to significant joint degeneration and loss of function. Cytokines, a group of cell signalling proteins, present in raised concentrations in OA joints, can be classified into pro-inflammatory and anti-inflammatory groups. They mediate cartilage degradation through several mechanisms, primarily the up-regulation of matrix metalloproteinases (MMPs), a group of collagen-degrading enzymes. In this paper we show that the interactions of cytokines within cartilage have a crucial role to play in OA progression and treatment. We develop a four-variable ordinary differential equation model for the interactions between pro- and anti-inflammatory cytokines, MMPs and fibronectin fragments (Fn-fs), a by-product of cartilage degradation and upregulator of cytokines. We show that the model has four classes of dynamic behaviour: homoeostasis, bistable inflammation, tristable inflammation and persistent inflammation. We show that positive and negative feedbacks controlling cytokine production rates can determine either a pre-disposition to OA or initiation of OA. Further, we show that manipulation of cytokine, MMP and Fn-fs levels can be used to treat OA, but we suggest that multiple treatment targets may be essential to halt or slow disease progression

Arabidopsis MKS1 Is Involved in Basal Immunity and Requires an Intact N-terminal Domain for Proper Function

Innate immune signaling pathways in animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. MAP kinase 4 (MPK4) functions downstream of innate immune receptors via a nuclear substrate MKS1 to regulate the activity of the WRKY33 transcription factor, which in turn controls the production of anti-microbial phytoalexins.We investigate the role of MKS1 in basal resistance and the importance of its N- and C-terminal domains for MKS1 function. We used the information that mks1 loss-of-function partially suppresses the mpk4 loss-of-function phenotype, and that transgenic expression of functional MKS1 in mpk4/mks1 double mutants reverted the mpk4 dwarf phenotype. Transformation of mks1/mpk4 with mutant versions of MKS1 constructs showed that a single amino acid substitution in a putative MAP kinase docking domain, MKS1-L32A, or a truncated MKS1 version unable to interact with WRKY33, were deficient in reverting the double mutant to the mpk4 phenotype. These results demonstrate functional requirement in MKS1 for the interaction with MPK4 and WRKY33. In addition, nuclear localization of MKS1 was shown to depend on an intact N-terminal domain. Furthermore, loss-of-function mks1 mutants exhibited increased susceptibility to strains of Pseudomonas syringae and Hyaloperonospora arabidopsidis, indicating that MKS1 plays a role in basal defense responses.Taken together, our results indicate that MKS1 function and subcellular location requires an intact N-terminus important for both MPK4 and WRKY33 interactions