Relational Concurrent Refinement II: Internal Operations and Outputs

Two styles of description arise naturally in formal specification: state-based and behavioural. In state-based notations, a system is characterised by a collection of variables, and their values determine which actions may occur throughout a system history. Behavioural specifications describe the chronologies of actions -- interactions between a system and its environment. The exact nature of such interactions is captured in a variety of semantic models with corresponding notions of refinement; refinement in state based systems is based on the semantics of sequential programs and is modelled relationally. Acknowledging that these viewpoints are complementary, substantial research has gone into combining the paradigms. The purpose of this paper is to do three things. First, we survey recent results linking the relational model of refinement to the process algebraic models. Specifically, we detail how variations in the relational framework lead to relational data refinement being in correspondence with traces-divergences, singleton failures and failures-divergences refinement in a process semantics. Second, we generalise these results by providing a general flexible scheme for incorporating the two main ''erroneous'' concurrent behaviours: deadlock and divergence, into relational refinement. This is shown to subsume previous characterisations. In doing this we derive relational refinement rules for specifications containing both internal operations and outputs that corresponds to failures-divergences refinement. Third, the theory has been formally specified and verified using the interactive theorem prover KIV

Australia's Dengue Risk Driven by Human Adaptation to Climate Change

Current and projected rainfall reduction in southeast Australia has seen the installation of large numbers of government-subsidised and ad hoc domestic water storage containers that could create the possibility of the mosquito Ae. aegypti expanding out of Queensland into southern Australian's urban regions. By assessing the past and current distribution of Ae. aegypti in Australia, we construct distributional models for this dengue vector for our current climate and projected climates for 2030 and 2050. The resulting mosquito distribution maps are compared to published theoretical temperature limits for Ae. aegypti and some differences are identified. Nonetheless, synthesising our mosquito distribution maps with dengue transmission climate limits derived from historical dengue epidemics in Australia suggests that the current proliferation of domestic water storage tanks could easily result in another range expansion of Ae. aegypti along with the associated dengue risk were the virus to be introduced

The Meningococcal Vaccine Candidate Neisserial Surface Protein A (NspA) Binds to Factor H and Enhances Meningococcal Resistance to Complement

Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH) to fH-binding protein (fHbp) is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a ∼17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA), a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep) I chain of lipooligosaccharide (LOS), or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6–7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components

Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands

Trachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation-follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population. We conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1-9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis. We observed a moderate prevalence of TF in children aged 1-9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation-intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1-9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains. The low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study

Nilotinib-Induced Keratosis Pilaris

Nilotinib is a second-generation Bcr-Abl tyrosine kinase inhibitor (TKI) that is approved for the treatment of imatinib-resistant chronic myeloid leukaemia expressing the Bcr-Abl mutation. Cutaneous adverse drug reactions occur more frequently in patients using this medication. We present a case of nilotinib-induced keratosis pilaris that did not have accompanying symptoms of alopecia or pruritus. Greater recognition of this association is needed so that appropriate treatment can be instituted to ensure a good oncologic outcome

Solar Elastosis in Its Papular Form: Uncommon, Mistakable

Solar elastosis is a degenerative condition of elastic tissue in the dermis due to prolonged sun exposure. There are a variety of clinical manifestations of solar elastosis. In its most common form, solar elastosis manifests as yellow, thickened, coarsely wrinkled skin. We report two uncommon cases of severe solar elastosis with a papular morphology. Its presentation can closely mimic a host of cutaneous disorders and thus, although it is helpful to be cognizant of this entity, it is still crucial to biopsy these lesions to avoid missing a more sinister condition

Increased lucerne nodulation in acid soils with Sinorhizobium meliloti and lucerne tolerant to low pH and high aluminium

Acidic conditions with damaging levels of available aluminium (Al3+) currently limit lucerne (Medicago sativa) production on soils in the New Zealand high country and in large areas of Australia. Increased lucerne nodulation could be achieved by using an Al3+-tolerant strain of Sinorhizobium meliloti to inoculate an Al3+-tolerant lucerne line. The Al3+ tolerance of the current commercial Australasian inoculant strain for lucerne, S. meliloti RRI128, was compared with strain SRDI736, selected in Australia for tolerance to low pH. Four Al3+ levels (0, 2, 4 and 8 µm) were created at pH 5.1 in a hydroponic system. The rhizobial strains were evaluated on SARDI AT7, a lucerne line selected for improved growth and nodulation in acidic solution culture with Al3+, and on Stamina 5, a commercial cultivar commonly grown in Australasia. SARDI AT7 when inoculated with strain SRDI736 produced more nodules per plant (3.6 vs 2.4) and had higher nodulation percentage (>80% vs <50%) at all Al3+ levels than when inoculated with RRI128. The percentage of nodulated Stamina 5 plants after inoculation with the commercial strain was lower than after inoculation with strain SRDI736 (10–16% vs 25–70%) at all Al3+ levels. The potential of S. meliloti strains SRDI736, SRDI672 and RRI128 and rates of lime to increase lucerne nodulation and dry matter production in soils of low pH (3mg kg–1 soil) was also investigated in a pot trial. Lime had a more consistent effect than inoculant strain for increasing nodulation. At 0.5 and 2 t lime ha–1, plants inoculated with strains SRDI672and SRDI736 had more nodules per plant than plants inoculated with the commercial strain. At 4 t lime ha–1, the number of nodules per plant was highest for all three inoculants, and there were no differences among them. This confirms the importance of lime to increase lucerne nodulation in low-pH, high-Al3+ soils. However, where liming is uneconomic or impractical, the results show that it was possible to select rhizobial strains to increase lucerne nodulation in acidic soils with damaging levels of available Al3+

Basaloid follicular hamartoma: clinical, dermoscopic, and histopathological characteristics of case

Basaloid follicular hamartoma (BFH) is a rare benignadnexal tumor with variable clinical presentation.We report a case of a 64-year-old man, whopresented with an incidental finding of a 3mmhyperpigmented macule on his cheek. Dermoscopyrevealed a structureless blue lesion. Histopathologyexamination showed interconnecting lobules andcords of bland pigmented epithelial cells within thedermal stroma, with the presence of pseudohorncysts. The lesional cells were faintly positive for Bcl2on immunohistochemical staining. These findingswere consistent with basaloid follicular hamartoma.Histological differential diagnoses include benignlesions such as trichoepithelioma, and malignantlesions such as basal cell carcinoma (BCC)