Knowledge of actions of inhaled corticosteroids in patients who did not persist drug treatment early

Objective To evaluate, among new users of inhaled corticosteroids that did not persist treatment, knowledge of inhaled corticosteroids' actions and whether they were instructed on the use of their inhaler. Setting Fifteen community pharmacies in The Netherlands. Methods Patients were interviewed by telephone. Their general practitioners provided diagnostic information and automated dispensing records were retrieved. Main outcome measures Knowledge of patients about the actions of inhaled corticosteroids. Results 230 (80.1%) of 287 patients were willing to participate. The majority (79.1%) of 230 patients was not aware of the anti-inflammatory actions of inhaled corticosteroids. Most patients were instructed on the use of their inhaler, predominantly by their physician (53%) or pharmacy (35.2%). Conclusions Although most patients reported inhaler instruction by at least one health care provider, the majority was unaware of inhaled corticosteroids' actions. Physicians and pharmacists should reconsider the instructions they provide especially to patients who should continuously use inhaled corticosteroids

A Philosophically Plausible Formal Interpretation of Intuitionistic Logic

This study addresses the mediating role of settlement patterns in the relationship between urbanization and start-up activity. Places do not operate in a vacuum and to understand the effect of 'own' density on start-up patterns, we need to account for the urban spillovers or borrowed size that they may experience from other places nearby. The results can explain the empirical ambiguity in the relationship between urbanization and start-up patterns: the relationship between urbanization and start-up rates becomes more similar between countries when controlling for country-specific settlement patterns by including a spatially lagged urbanization variable and variables measuring the distance to urban centers. Accounting for the relative location of places and relevant sorting effects, we find that 'own' density has a consistently negative effect on start-up activity. Yet, access to other places has a generally positive effect. This implies that nearby regions profit from the advantages offered by urban environments without having to deal with the costs involved

Localisation and origin of the bacteriochlorophyll-derived photosensitizer in the retina of the deep-sea dragon fish Malacosteus niger

Most deep-sea fish have a single visual pigment maximally sensitive at short wavelengths, approximately matching the spectrum of both downwelling sunlight and bioluminescence. However, Malcosteus niger produces far-red bioluminescence and its longwave retinal sensitivity is enhanced by red-shifted visual pigments, a longwave reflecting tapetum and, uniquely, a bacteriochlorophyllderived photosensitizer. The origin of the photosensitizer, however, remains unclear. We investigated whether the bacteriochlorophyll was produced by endosymbiotic bacteria within unusual structures adjacent to the photoreceptors that had previously been described in this species. However, microscopy, elemental analysis and SYTOX green staining provided no evidence for such localised retinal bacteria, instead the photosensitizer was shown to be distributed throughout the retina. Furthermore, comparison of mRNA from the retina of Malacosteus to that of the closely related Pachystomias microdon (which does not contain a bacterichlorophyll-derived photosensitzer) revealed no genes of bacterial origin that were specifically up-regulated in Malacosteus. Instead up-regulated Malacosteus genes were associated with photosensitivity and may relate to its unique visual ecology and the chlorophyll-based visual system. We also suggest that the unusual longwave-reflecting, astaxanthin-based, tapetum of Malacosteus may protect the retina from the potential cytotoxicity of such a system

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Equilibrium configurations of two charged masses in General Relativity

An asymptotically flat static solution of Einstein-Maxwell equations which describes the field of two non-extreme Reissner - Nordstr\"om sources in equilibrium is presented. It is expressed in terms of physical parameters of the sources (their masses, charges and separating distance). Very simple analytical forms were found for the solution as well as for the equilibrium condition which guarantees the absence of any struts on the symmetry axis. This condition shows that the equilibrium is not possible for two black holes or for two naked singularities. However, in the case when one of the sources is a black hole and another one is a naked singularity, the equilibrium is possible at some distance separating the sources. It is interesting that for appropriately chosen parameters even a Schwarzschild black hole together with a naked singularity can be "suspended" freely in the superposition of their fields.Comment: 4 pages; accepted for publication in Phys. Rev.

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.

Complex Adaptations Can Drive the Evolution of the Capacitor [PSI+], Even with Realistic Rates of Yeast Sex

The [PSI+] prion may enhance evolvability by revealing previously cryptic genetic variation, but it is unclear whether such evolvability properties could be favored by natural selection. Sex inhibits the evolution of other putative evolvability mechanisms, such as mutator alleles. This paper explores whether sex also prevents natural selection from favoring modifier alleles that facilitate [PSI+] formation. Sex may permit the spread of “cheater” alleles that acquire the benefits of [PSI+] through mating without incurring the cost of producing [PSI+] at times when it is not adaptive. Using recent quantitative estimates of the frequency of sex in Saccharomyces paradoxus, we calculate that natural selection for evolvability can drive the evolution of the [PSI+] system, so long as yeast populations occasionally require complex adaptations involving synergistic epistasis between two loci. If adaptations are always simple and require substitution at only a single locus, then the [PSI+] system is not favored by natural selection. Obligate sex might inhibit the evolution of [PSI+]-like systems in other species

Practice development plans to improve the primary care management of acute asthma: randomised controlled trial

Background: Our professional development plan aimed to improve the primary care management of acute asthma, which is known to be suboptimal. Methods: We invited 59 general practices in Grampian, Scotland to participate. Consenting practices were randomised to early and delayed intervention groups. Practices undertook audits of their management of all acute attacks (excluding children under 5 years) occurring in the 3 months preceding baseline, 6-months and 12-months study time-points. The educational programme [including feedback of audit results, attendance at a multidisciplinary interactive workshop, and formulation of development plan by practice teams] was delivered to the early group at baseline and to the delayed group at 6 months. Primary outcome measure was recording of peak flow compared to best/predicted at 6 months. Analyses are presented both with, and without adjustment for clustering. Results: 23 consenting practices were randomised: 11 to early intervention. Baseline practice demography was similar. Six early intervention practices withdraw before completing the baseline audit. There was no significant improvement in our primary outcome measure (the proportion with peak flow compared to best/predicted) at either the 6 or 12 month time points after adjustment for baseline and practice effects. However, the between group difference in the adjusted combined assessment score, whilst non-significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p = 0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE 0.28) p = 0.02). Conclusion: We demonstrated no significant benefit at the a priori 6-month assessment point, though improvement in the objective assessment of attacks was shown after 12 months. Our practice development programme, incorporating audit, feedback and a workshop, successfully engaged the healthcare team of participating practices, though future randomised trials of educational interventions need to recognise that effecting change in primary care practices takes time. Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care