Unifying the Law of Impossibility

On April 10, 1980, the United Nations Convention for the International Sale of Goods was announced. The Convention was the latest in a series of attempts to formulate a uniform law to govern transnational commercial transactions. Because the common- and civil-law systems start with fundamentally different approaches to contracts, the drafters of the Convention were faced with the difficult task of compromising between the two systems to create a hybrid acceptable to both. This Article focuses on the doctrine of impossibility where, on the surface at least, the common- and civil-law (exemplified by German law) approaches appear to be fundamentally different. The Article analyzes impossibility under both systems and then describes the compromise approach taken by the Convention. The Article concludes that the Convention successfully adopted a compromise approach compatible with both common- and civil-law systems. This success should contribute to widespread adoption of the Convention and thus contribute to the unification of the law governing transnational commercial transactions

Immune evasion strategies utilized by Francisella tularensis

Francisella tularensis is a highly pathogenic, gram-negative, facultative intracellular bacterium and the causative agent of tularemia. Francisella has evolved numerous mechanisms to evade host immune responses. One immune evasion mechanism utilized by Francisella is its ability to induce prostaglandin E2 (PGE2) secretion from infected host cells. We identified 20 Francisella genes necessary for the induction of PGE2 secretion in infected host cells. One of the genes necessary for PGE2 induction encodes a highly conserved AAA+ ATPase chaperone protein, ClpB. F. tularensis live vaccine strain (LVS) clpB is attenuated in vivo, despite normal intracellular growth in vitro. LVS clpB fails to inhibit pro-inflammatory cytokine responses in the lung early after inoculation, a process normally inhibited by LVS. The adaptive immune response is also altered compared to LVS with increased IFN-γ or IL-17A production by T cells. Although LVS clpB is attenuated, it induces an immune response that is as protective as LVS following lethal challenge indicating clpB is a potential target for vaccine development. Although the primary immune response is altered during LVS clpB infection, there are no differences in the secondary immune response to LVS. The primary immune response to LVS requires IFN-γ and IL-17A production to control bacterial replication. Few Th17 cells were identified during the secondary response in the lung whereas there were numerous CD4+ and CD8+ T cells producing IFN-γ. IFN-γ production is required for controlling bacterial replication during the secondary response, but IL-17A production is dispensable for survival during re-infection. Francisella also evades host immunity by targeting innate immune cells for infection. Francisella infects different cell types in the lung depending on the route of inoculation; alveolar macrophages are infected following intranasal inoculation while interstitial macrophages and neutrophils are infected in the lung after intradermal inoculation. The lung's cytokine milieu is more pro-inflammatory after intradermal inoculation compared to intranasal inoculation, consistent with the development of a more robust IFN-γ mediated adaptive immune response. A better understanding of the mechanisms of Francisella infection will not only result in understanding important concepts in pathogenesis, but will suggest key pathways to impact for the development of drugs and vaccines.Doctor of Philosoph

Norms of Staff Responses to Falls in Residential Care Homes

The aim of the current research was to review the first-line response to patient falls in the independent care sector in North East England. The authors used an online questionnaire via 'Survey Monkey' software package, and a convenience sample of 24 of 32 independent care sector homes from South Tyneside, representing a 75% response rate. Policies and guidelines for falls were investigated and the findings highlight the disparate responses to incidences in care-home settings. Despite 96% having a policy on falls, only 80% included an assessment of possible injury or harm and 13% included no direct guidance for staff when residents fall. The most common action was to ring emergency services to move patients, even in the absence of physical injury. There was considerable ambiguity around the assessment of injuries and whose responsibility this was, particularly in falls with potentially non-visible injuries. Ambiguity was also present in the management of falls, where there was overlap between accident and falls policies. The current research highlights the need for policy standardisation. There is a potential fiscal impact on emergency ambulance services when they are contacted as the first-line response for falls regardless of the occurrence of injury. This has implications on staff education and the strategic planning of emergency ambulance services. Further consideration on the suitability of falls policies is urgently required

Filament formation in wind-cloud interactions - I. Spherical clouds in uniform magnetic fields

Filamentary structures are ubiquitous in the interstellar medium, yet their formation, internal structure, and longevity have not been studied in detail. We report the results from a comprehensive numerical study that investigates the characteristics, formation, and evolution of filaments arising from magnetohydrodynamic interactions between supersonic winds and dense clouds. Here, we improve on previous simulations by utilizing sharper density contrasts and higher numerical resolutions. By following multiple density tracers, we find that material in the envelopes of the clouds is removed and deposited downstream to form filamentary tails, while the cores of the clouds serve as footpoints and late-stage outer layers of these tails. Aspect ratios 12, subsonic velocity dispersions ∼0.1–0.3 of the wind sound speed, and magnetic field amplifications ∼100 are found to be characteristic of these filaments. We also report the effects of different magnetic field strengths and orientations. The magnetic field strength regulates vorticity production: sinuous filamentary towers arise in non-magnetic environments, while strong magnetic fields inhibit small-scale perturbations at boundary layers making tails less turbulent. Magnetic field components aligned with the direction of the flow favour the formation of pressure-confined flux ropes inside the tails, whilst transverse components tend to form current sheets. Softening the equation of state to nearly isothermal leads to suppression of dynamical instabilities and further collimation of the tail. Towards the final stages of the evolution, we find that small cloudlets and distorted filaments survive the break-up of the clouds and become entrained in the winds, reaching velocities ∼0.1 of the wind speed. Key words: MHD – methods: numerical – stars: winds, outflows – ISM: clouds – ISM: ma

Identification of Francisella novicida mutants that fail to induce prostaglandin E2 synthesis by infected macrophages

Francisella tularensis is the causative agent of tularemia. We have previously shown that infection with F. tularensis Live Vaccine Strain (LVS) induces macrophages to synthesize prostaglandin E2 (PGE2). Synthesis of PGE2 by F. tularensis infected macrophages results in decreased T cell proliferation in vitro and increased bacterial survival in vivo. Although we understand some of the biological consequences of F. tularensis induced PGE2 synthesis by macrophages, we do not understand the cellular pathways (neither host nor bacterial) that result in up-regulation of the PGE2 biosynthetic pathway in F. tularensis infected macrophages. We took a genetic approach to begin to understand the molecular mechanisms of bacterial induction of PGE2 synthesis from infected macrophages. To identify F. tularensis genes necessary for the induction of PGE2 in primary macrophages, we infected cells with individual mutants from the closely related strain F. tularensis subspecies novicida U112 (U112) two allele mutant library. Twenty genes were identified that when disrupted resulted in U112 mutant strains unable to induce the synthesis of PGE2 by infected macrophages. Fourteen of the genes identified are located within the Francisella pathogenicity island (FPI). Genes in the FPI are required for F. tularensis to escape from the phagosome and replicate in the cytosol, which might account for the failure of U112 with transposon insertions within the FPI to induce PGE2. This implies that U112 mutant strains that do not grow intracellularly would also not induce PGE2. We found that U112 clpB::Tn grows within macrophages yet fails to induce PGE2, while U112 pdpA::Tn does not grow yet does induce PGE2. We also found that U112 iglC::Tn neither grows nor induces PGE2. These findings indicate that there is dissociation between intracellular growth and the ability of F. tularensis to induce PGE2 synthesis. These mutants provide a critical entrée into the pathways used in the host for PGE2 induction

Infection with Francisella tularensis LVS clpB Leads to an Altered yet Protective Immune Response

ABSTRACT Bacterial attenuation is typically thought of as reduced bacterial growth in the presence of constant immune pressure. Infection with Francisella tularensis elicits innate and adaptive immune responses. Several in vivo screens have identified F. tularensis genes necessary for virulence. Many of these mutations render F. tularensis defective for intracellular growth. However, some mutations have no impact on intracellular growth, leading us to hypothesize that these F. tularensis mutants are attenuated because they induce an altered host immune response. We were particularly interested in the F. tularensis LVS (live vaccine strain) clpB (FTL_0094) mutant because this strain was attenuated in pneumonic tularemia yet induced a protective immune response. The attenuation of LVS clpB was not due to an intracellular growth defect, as LVS clpB grew similarly to LVS in primary bone marrow-derived macrophages and a variety of cell lines. We therefore determined whether LVS clpB induced an altered immune response compared to that induced by LVS in vivo . We found that LVS clpB induced proinflammatory cytokine production in the lung early after infection, a process not observed during LVS infection. LVS clpB provoked a robust adaptive immune response similar in magnitude to that provoked by LVS but with increased gamma interferon (IFN-γ) and interleukin-17A (IL-17A) production, as measured by mean fluorescence intensity. Altogether, our results indicate that LVS clpB is attenuated due to altered host immunity and not an intrinsic growth defect. These results also indicate that disruption of a nonessential gene(s) that is involved in bacterial immune evasion, like F. tularensis clpB , can serve as a model for the rational design of attenuated vaccines

Delighting, Compelling, Challenging: PQ 2019 exhibits explore artist, viewer, and space

The article informs about the introduction to the wealth of design held within the 2019 Prague Quadrennial. Topics discussed include variety of experiences was surprising and delightful, and many of the broadly varying approaches; contemporary global concerns such as climate change, human interactions, and political unrest; and the theatre and presented it as a natural history museum

Falls in the residential independent care sector—ambiguity in guidelines and policies for healthcare assistants

The need for healthcare assistants (HCAs) to have clear policies and guidelines in relation to when falls occur in domiciliary care settings is paramount. If first-line responses are to be appropriately tailored to patient need and discernment is to be used in determining the necessity for intervention by emergency care workers such as paramedics, then standardised frameworks and policies ought to be clearly apparent across care sectors. Our work focused on the first-line response to patient falls in the independent care sector in a specific geographical region of north-east England. This article provides an insight into what our original findings revealed and how they might be used as a source of reflection for HCAs working in the residential independent care sector. Using a basic questionnaire, we surveyed 24 (75%) of the 32 independent care sector homes in South Tyneside to establish how policies and guidelines in these organisations were understood by staff. Our findings highlight a diverse array of responses to falls in care home settings. While 96% of homes claimed to have a specific policy on falls, only 80% of them included an assessment of possible injury or harm to residents and 13% included no direct guidance for care staff in instances where residents fell and were still on the floor. Even in instances where policies did include direct guidance, there was great variation in available information for staff, especially between domiciliary and care home settings. Most commonly, staff were advised to call an emergency ambulance, even in the absence of injury, if patients were found on the floor. HCAs are working in contexts where there is apparently a high degree of ambiguity around the assessment of injuries sustained as a consequence of falls, particularly where potentially non-visible injuries occur, which are not immediately recognisable or symptomatic. There was also overlap between accident and falls policies, which added a further level of ambiguity to the most appropriate and immediate actions for HCAs to take

“Just ring for an ambulance?" Local survey reveals the behavioural norms of staff from organisations responding to patient falls in the independent residential care sector

Aim: To review the first line response to patient falls that is operational in the independent care sector in a specific geographical region of North East England. Design: Questionnaire survey implemented online via ‘Survey Monkey’ software package. Sample: A convenience sample of 24 of 32 independent care sector homes from South Tyneside, UK participated in the study, representing a 75% response rate. Results: Policies and guidelines for falls in the independent care sector homes were investigated, as understood by care home managers. The findings highlight the disparate responses to falls in the care home settings. Despite 96% of homes having a policy on falls, only 80% of these included an assessment of possible injury or harm to residents and 13% included no direct guidance for care staff in instances where residents fall and are on the floor. For those policies that did include direct guidance, there was a great disparity in available information, especially between domiciliary and residential care home settings. The most common recommended action was to ring emergency services in order to move patients, even in the absence of evidence of physical injury. In the context of residential care home settings there was a high degree of ambiguity around the assessment of sustained injuries and whose responsibility this was. This was particularly evident in relation to falls where potentially non-visible injuries which were subsequently not immediately identifiable. There was also reported ambiguity in relation to the management of falls, where there was overlap between accident policies and falls policies. Conclusions: Our research highlights the need for standardisation of policies and procedures in relation to falls of those living under the care of the independent care sector. At present, there is a disparate set of approaches evident in the contexts of care, which are largely determined by locally devised and implemented policies, which prioritise legalistic and bureaucratic concerns over clinical decision making. Our study highlights the potential fiscal impact on emergency ambulance services in instances where it is commonplace for contacting emergency services to be the first line response to a patient falling to the floor regardless of whether an injury has occurred. This has important implications for the education of independent care sector workers and the strategic planning of emergency ambulance services. Whilst generic frameworks are available, further consideration of the whether falls policies are suited for purpose is urgently required