Control theory helps to resolve the measles paradox

Measles virus (MV) is a highly contagious respiratory morbillivirus that results in many disabilities and deaths. A crucial challenge in studying MV infection is to understand the so-called ‘measles paradox’—the progression of the infection to severe immunosuppression before clearance of acute viremia, which is also observed in canine distemper virus (CDV) infection. However, a lack of models that match in vivo data has restricted our understanding of this complex and counter-intuitive phenomenon. Recently, progress was made in the development of a model that fits data from acute measles infection in rhesus macaques. This progress motivates our investigations to gain additional insights from this model into the control mechanisms underlying the paradox. In this paper, we investigated analytical conditions determining the control and robustness of viral clearance for MV and CDV, to untangle complex feedback mechanisms underlying the dynamics of acute infections in their natural hosts. We applied control theory to this model to help resolve the measles paradox. We showed that immunosuppression is important to control and clear the virus. We also showed under which conditions T-cell killing becomes the primary mechanism for immunosuppression and viral clearance. Furthermore, we characterized robustness properties of T-cell immunity to explain similarities and differences in the control of MV and CDV. Together, our results are consistent with experimental data, advance understanding of control mechanisms of viral clearance across morbilliviruses, and will help inform the development of effective treatments. Further the analysis methods and results have the potential to advance understanding of immune system responses to a range of viral infections such as COVID-19

Can translocated native fishes retain their trophic niche when confronted with a resident invasive?

Diet interactions between native and non-native fishes may influence the establishment of native species within their historical range (i.e., reintroduction). Therefore, we illustrated the food web structure of and followed the transition of the federally endangered humpback chub Gila cypha into a novel food web following translocation and determined the potential for a non-native species, rainbow trout Oncorhynchus mykiss, to influence translocation success. Humpback chub and rainbow trout used resources high in the food web and assimilated similar proportions of native fishes, suggesting non-native rainbow trout may occupy an ecological role similar to humpback chub. Subsequently, humpback chub may be well suited to colonise tributaries because of their ability to consume resources high in the food web. Additionally, diet partitioning may occur between all members of the fish community as indicated by separation in trophic niche space and little trophic overlap; although all species, particularly bluehead sucker Catostomus discobolus, used a broad range of food resources. Rainbow trout stomach content analysis corroborated stable isotope analysis and suggested rainbow trout diet consisted of aquatic and terrestrial macroinvertebrates, while larger rainbow trout (\u3e120 mm total length) consumed a greater proportion of fish (incidence of piscivory = 5.3%). Trophic interactions may reveal an underutilized niche space or biotic resistance to the establishment of translocated native fishes. Continued translocation of humpback chub into tributaries appears to be one option for conservation. However, successful establishment of humpback chub may depend on continued removal of non-native trout, increasing availability of diet sources at higher trophic levels

Peak height pattern in dichloro-rhodamine and energy transfer dye terminator sequencing

Establishing the pattern in peak heights within local sequence contexts improves the accuracy of base calling and the identification of DNA sequence variations in dye-terminator cycle sequencing. We have systematically examined pairs of sequence-tagged sites (STSs) that vary at only a single nucleotide to determine how base changes influence the peak heights of neighboring bases in sequencing traces generated by two recently commercialized dye-terminator chemistries, the dichloro-rhodamine (dRhodamine) and the energy transfer (BigDye) terminators. For sequencing traces generated with the dRhodamine terminators, the peak height of a particular base in 28 of 64 possible 3-base windows (44%) can be predicted by knowing just one or two bases 5\u27 to the base in question. For those generated with the BigDye terminators, the peak height of a particular base in 23 of 64 possible 3-base windows (36%) can be predicted by knowing the local sequence context. When the peak heights are binned slightly differently, 75% (48 out of 64 cases) of the base peaks generated by both dRhodamine and BigDye terminators fall in the middle half, confirming that the peak patterns of these two new dye terminator chemistries are much more even than those found in the original rhodamine dye terminator sequences

Achieving provider engagement: providers' perceptions of implementing and delivering integrated care

The literature on integrated care is limited with respect to practical learning and experience. Although some attention has been paid to organizational processes and structures, not enough is paid to people, relationships, and the importance of these in bringing about integration. Little is known, for example, about provider engagement in the organizational change process, how to obtain and maintain it, and how it is demonstrated in the delivery of integrated care. Based on qualitative data from the evaluation of a large-scale integrated care initiative in London, United Kingdom, we explored the role of provider engagement in effective integration of services. Using thematic analysis, we identified an evolving engagement narrative with three distinct phases: enthusiasm, antipathy, and ambivalence, and argue that health care managers need to be aware of the impact of professional engagement to succeed in advancing the integrated care agenda

Workplace violence in Queensland, Australia: the results of a comparative study

[Abstract]: This paper presents the results on workplace violence from a larger study undertaken in 2004. Comparison is made with the results of a similar study undertaken in 2001. The study involved the random sampling of 3000 nurses from the Queensland Nurses’ Union’s membership in the public (acute hospital and community nursing), private (acute hospital and domiciliary nursing) and aged care sectors (both public and private aged care facilities). The self-reported results suggest an increase in workplace violence in all three sectors. Whilst there are differences in the sources of workplace violence across the sectors, the major causes of workplace violence are: clients/patients, visitors/relatives, other nurses, nursing management and medical practitioners. Associations were also found between workplace violence and gender, the designation of the nurse, hours of employment, the age of the nurse, morale and perceptions of workplace safety. Whilst the majority of nurses reported that policies were in place for the management of workplace violence, these policies were not always adequate

Continuous Uniform Finite Time Stabilization of Planar Controllable Systems

Continuous homogeneous controllers are utilized in a full state feedback setting for the uniform finite time stabilization of a perturbed double integrator in the presence of uniformly decaying piecewise continuous disturbances. Semiglobal strong $\mathcal{C}^1$ Lyapunov functions are identified to establish uniform asymptotic stability of the closed-loop planar system. Uniform finite time stability is then proved by extending the homogeneity principle of discontinuous systems to the continuous case with uniformly decaying piecewise continuous nonhomogeneous disturbances. A finite upper bound on the settling time is also computed. The results extend the existing literature on homogeneity and finite time stability by both presenting uniform finite time stabilization and dealing with a broader class of nonhomogeneous disturbances for planar controllable systems while also proposing a new class of homogeneous continuous controllers

AmpliTaq DNA polymerase, FS dye-terminator sequencing: Analysis of peak height patterns

Taq DNA polymerases in which the phenylalanine is substituted by a tyrosine at position 667 (Taq F667Y) are members of a new class of DNA polymerases that incorporate chain-terminating dideoxyribonucleoside triphosphates (ddNTPs) much more efficiently than the wild-type Taq DNA polymerase. Improved incorporation of ddNTPs into DNA during cycle sequencing using AmpliTaq DNA polymerase, FS (Taq-FS, a member of the Taq F667Y family), and dye-labeled primers results in nearly uniform peak heights in the sequencing trace. This is not the case when dye-labeled ddNTPs are used in Taq-FS cycle sequencing reactions. While the rate of dye-terminator incorporation is more efficient with Taq-FS, the peak pattern is still highly variable and different from that produced by the wild-type enzyme. We have systematically examined pairs of sequence-tagged sites that vary at only a single nucleotide to determine how base changes influence the peak heights of neighboring bases in sequencing traces generated by the Taq-FS dye-terminator chemistry. In 31 of 64 possible 3-base windows (48%), we find that the peak height of a particular base can be predicted by knowing just one or two bases 5\u27 to the base in question. We have also compared and contrasted the peak patterns produced by the Taq-FS enzyme with those previously identified for the wild-type enzyme. Establishing the patterns in peak heights within local sequence contexts can improve the accuracy of base-calling and the identification of polymorphisms/mutations when using the Taq-FS dye-terminator cycle-sequencing chemistry