Factors associated with survival to hospital discharge following endoscopic treatment for synovial sepsis in 214 horses.

REASONS FOR PERFORMING STUDY: To determine risk factors involved in survival to hospital discharge of cases of synovial sepsis. OBJECTIVES: Investigate pre-, intra- and post operative factors involved in short-term survival of horses undergoing endoscopic treatment for synovial sepsis. STUDY DESIGN: Retrospective case series. METHODS: Clinical data were obtained for horses (>6 months old) undergoing endoscopic surgery as part of management for synovial sepsis over a 7-year period in a single hospital population. Descriptive data were generated for pre-, intra- and post operative variables. Multivariable logistic regression analysis was used to develop 3 models related to presurgical, surgical and post surgical stages of management with outcome defined as survival to hospital discharge. RESULTS: Two hundred and fourteen horses were included. In Model 1 (preoperative variables), increased preoperative synovial fluid total protein (TP) was associated with nonsurvival (OR 0.88, 95% CI 0.83-0.94, P<0.001) whereas the presence of a wound on admission was associated with survival (OR 4.75, 95% CI 1.21-18.65, P = 0.02). Model 2 (intraoperative variables) revealed that factors associated with decreased survival were anaesthetic induction outside of normal working hours (OR 0.36, 95% CI 0.15-0.88 P = 0.02) and presence of moderate/severe synovial inflammation at surgery (OR 0.28, 95% CI 0.12-0.67, P = 0.004). Model 3 (post operative variables) showed that increased post operative synovial fluid TP (OR 0.94, 95% CI 0.90-0.98, P = 0.013) and undertaking more than one endoscopic surgery for treatment (OR 0.19, 95% CI 0.05-0.70, P = 0.005) were associated with nonsurvival. Cut-off values for predicting survival were 55-60 g/l for preoperative and 50-55 g/l for post operative TP measurements. CONCLUSIONS: This study has identified factors associated with altered likelihood of survival to hospital discharge following endoscopic surgery for synovial sepsis. Prognosis for survival to hospital discharge can be based on evidence from this study at the key stages of management of horses with synovial sepsis.

Adipose tissue-derived adiponectin expression is significantly associated with increased post operative mortality in horses undergoing emergency abdominal surgery.

REASONS FOR PERFORMING STUDY: Adipose tissue is an important source of inflammatory cytokines (adipokines) and adiposity has been identified as having a significant effect on human morbidity and mortality. Obesity is also an emerging welfare problem in the UK horse population, but the role that it plays in secondary diseases is unclear. OBJECTIVES: To examine the expression of inflammation-related adipokine genes in retroperitoneal adipose tissue of horses undergoing emergency abdominal surgery and to explore associations with adiposity and post operative survival. METHODS: Retroperitoneal adipose tissue samples were obtained from 76 horses undergoing emergency abdominal surgery. Real-time PCR was used to measure gene expression for leptin, adiponectin, tumour necrosis factor-alpha, macrophage chemoattractant protein-1, macrophage inhibitory factor, serum amyloid A, haptoglobin and interleukin-1. Multivariate patterns of adipokine expression were explored with principal component analysis (PCA), whilst univariable associations with post operative survival were tested in a Cox proportional hazards model. RESULTS: Leptin gene expression was higher in overweight and obese horses than in lean animals. Expression of mRNA encoding adiponectin mRNA in visceral adipose tissue was positively associated with increased post operative mortality (hazard ratio 1.31, 95% CI 1.05-1.65). However, PCA did not demonstrate multivariable patterns of adipokine gene expression from visceral adipose tissue associated with body mass index or with survival. CONCLUSIONS: In horses presented with acute intestinal disease, increased adiponectin gene expression from retroperitoneal adipose tissue is associated with an increased risk of mortality. Obesity assessed by BMI had no association with increased post operative mortality in horses with primary gastrointestinal disease. POTENTIAL RELEVANCE: Further study is warranted on the expression and effects of adipokines, particularly adiponectin, and correlation with postoperative outcome.

Sequence-structure relationships in DNA oligomers: a computational approach.

A collective-variable model for DNA structure is used to predict the conformation of a set of 30 octamer, decamer, and dodecamer oligomers for which high-resolution crystal structures are available. The model combines an all-atom base pair representation with an empirical backbone, emphasizing the role of base stacking in fixing sequence-dependent structure. We are able to reproduce trends in roll and twist to within 5 degrees across a large database of both A- and B-DNA oligomers. A genetic algorithm approach is used to search for global minimum structures and this is augmented by a grid search to identify local minimums. We find that the number of local minimums is highly sequence dependent, with certain sequences having a set of minimums that span the entire range between canonical A- and B-DNA conformations. Although the global minimum does not always agree with the crystal structure, for 24 of the 30 oligomers, we find low-energy local minimums that match the experimental step parameters. Discrepancies throw some light on the role of crystal packing in determining the solid-state conformation of double-helical DNA.

Sequence-dependent DNA structure: dinucleotide conformational maps.

We have used a computational model to calculate the potential energy surface for dinucleotide steps in double helical DNA as a function of the two principal degrees of freedom, slide and shift. By using a virtual bond to model the constraints imposed by the sugar-phosphate backbone, twist, roll, tilt and rise can be simultaneously optimised for any given values of slide and shift. Thus we have been able to construct complete conformational maps for all step types. For some steps, the maps agree well with experimental data from X-ray crystal structures, but other steps appear to be strongly perturbed by the effects of context (conformational coupling with the neighbouring steps). The optimised values of twist and roll show sequence-dependent variations consistent with the crystal structure data. The conformational maps allow us to construct adiabatic paths, and hence calculate the flexibility of each step with respect to slide and shift. Again the results agree well with the available experimental assignments of flexibility: YR steps, CA/TG and CG, are the most flexible and RR steps, such as AA, the least flexible.

Sequence-dependent DNA structure: tetranucleotide conformational maps.

A database of X-ray crystal structures of double helical DNA oligomers has been used to analyse the role of the sugar-phosphate backbone in coupling the conformational properties of neighbouring dinucleotide steps. The base step parameters which are most strongly coupled to the backbone degrees of freedom are slide and shift, and these are the two dinucleotide step parameters which show strong correlations along a sequence: the value of slide follows the values in the neighbouring steps, whereas shift tends to alternate. This conformational coupling is mediated by the shared furanose rings at the step junctions: a change in the value of slide causes a change in the mean value of the same strand 3' and 5'-chi torsion angle, and a change in the mean value of the 3' and 5' sugar pseudo-rotation phase angle, P; a change in the value of shift causes a difference between the same strand 3' and 5'-chi in A-DNA and a difference between the 3' and 5'-P in B-DNA. We have used a database of tetranucleotide X-ray crystal structures to parameterise a simple model for the coupling of slide and shift. Using this junction model together with our dinucleotide step potential energy maps described previously, we can in principle calculate the structure of any DNA oligomer. The parameterisation indicates that the rotational step parameters are accurate to within 5 degrees, and the translational step parameters are accurate to within 0.5 A. The model has been used to study the potential energy surfaces of all possible tetranucleotide sequences, and the calculations agree well with the experimental data from X-ray crystal structures. Some dinucleotide steps are context independent (AA/TT, AT and TA), because the conformational properties of all possible neighbouring steps are compatible. When the conformational properties of the neighbours are not compatible, the behaviour of a step cannot be understood at the dinucleotide level. Thus the conformations of CG, GC and GG/CC are all strongly context dependent. The remaining mixed sequence steps show weakly context-dependent behaviour. The approach allows the calculation of the relative stability and flexibility of tetranucleotide sequences, and the results indicate why TATA is used as an origin of replication. Clear predictions are made about sequences which have not yet been characterised crystallographically. In particular, poly(CCA).poly(TGG) is predicted to have an unusual structure which lies between the C and D-DNA polymorphs.

Sequence-dependent DNA structure: the role of the sugar-phosphate backbone.

A detailed analysis of the coupling between the conformational properties of the sugar-phosphate backbone and the base stacking interactions in dinucleotide steps of double helical DNA is described. In X-ray crystal structures of oligonucleotides, the backbone shows one major degree of freedom, consisting of the torsion angles chi, delta, zeta and the pseudorotation phase angle, P. The remaining torsion angles (beta, epsilon, alpha and gamma) comprise two less important degrees of freedom. The base stacking interactions show three degrees of freedom: slide-roll-twist, shift-tilt, and rise (which is more or less constant). Coupling is observed between the base and backbone degrees of freedom. The major base stacking mode, slide-roll-twist, is coupled to the major backbone mode, chi-P-delta-zeta. The secondary base stacking mode, shift-tilt, is coupled to epsilon and zeta and to a lesser extent to the chi-P-delta-zeta mode. We show that the length of the backbone, C, given by the same strand C1'-C1' separation, is an excellent single parameter descriptor for the conformation of the backbone and the way in which it is coupled to the base stacking geometry. The slide-roll-twist motion relates to changes in the mean backbone length, C, and the shift-tilt motion to the difference between the lengths of the two backbone strands, DeltaC. We use this observation to develop a simple virtual bond model which describes the coupling of the backbone conformations and the base stacking geometry. A semi-flexible bond is used to connect the same strand C1'-C1' atoms. Analysis of the X-ray crystal structure database, simple geometric considerations and model building experiments all show that this bond is flexible with respect to slide, shift and propeller but rigid with respect to the other 14 local base stacking parameters. Using this simple model for the backbone in conjunction with potential energy calculations of the base stacking interactions, we show that it is possible to predict accurately the values of these 14 base step parameters, given values of slide, shift and propeller. We also show that the base step parameters fall into three distinct groups: roll, tilt and rise are determined solely by the base stacking interactions and are independent of the backbone; twist is insensitive to the base stacking interactions and is determined solely by the constraints of a relatively rigid fixed length backbone; slide and shift are the primary degrees of freedom and cannot be predicted accurately at the dinucleotide level because they are influenced by the conformations of neighbouring steps in a sequence. We have found that the context effect on slide is mediated by the chi torsion angles while the context effect on shift results from a BI to BII transition in the backbone. We have therefore reduced the dimensionality of the dinucleotide step problem to two parameters, slide and shift.

Malaria parasites enhance blood-feeding of their naturally infected vector Anopheles punctulatus.

We investigated the blood-feeding behaviour of a natural population of the human-feeding mosquito Anopheles punctulatus in Iguruwe, Papua New Guinea. In particular we investigated the relationship between the mosquitoes' blood-feeding behaviour and their infection by the malaria parasites Plasmodium falciparum and P. vivax. Female mosquitoes were caught at 4 times of the night, the amount of blood they had obtained was measured and their status of infection was evaluated. Among uninfected mosquitoes the bloodmeal size steadily increased through the night, possibly because they were progressively less likely to be disturbed by human activity as the night drew on. Infected mosquitoes, on the other hand, tended to feed maximally at all times of the night. This suggests that infected mosquitoes were more tenacious in their blood-feeding behaviour, being either less readily disturbed during a bout of feeding (and thus feeding longer) or more likely to return to continue their feed following disturbance (and thus feeding several times). Either change would increase the parasites' rate of transmission. We conclude that in this natural situation the two species of malaria parasites modified the mosquitoes' behaviour with the effect of increasing their own transmission.

Predicting the distribution of tsetse flies in West Africa using temporal Fourier processed meteorological satellite data.

An example is given of the application of remotely-sensed, satellite data to the problems of predicting the distribution and abundance of tsetse flies in West Africa. The distributions of eight species of tsetse, Glossina morsitans, G. longipalpis, G. palpalis, G. tachinoides, G. pallicera, G. fusca, G. nigrofusca and G. medicorum in Côte d'Ivoire and Burkina Faso, were analysed using discriminant analysis applied to temporal Fourier-processed surrogates for vegetation, temperature and rainfall derived from meteorological satellites. The vegetation and temperature surrogates were the normalized difference vegetation index and channel-4-brightness temperature, respectively, from the advanced, very-high-resolution radiometers on board the National Oceanic and Atmospheric Administration's polar-orbiting, meteorological satellites. For rainfall the surrogate was the Cold-Cloud-Duration (CCD) index derived from the geostationary, Meteosat satellite series. The presence or absence of tsetse was predicted with accuracies ranging from 67%-100% (mean = 82.3%). A further data-set, for the abundance of five tsetse species across the northern part of Côte d'Ivoire (an area of about 140,000 km2), was analysed in the same way, and fly-abundance categories predicted with accuracies of 30%-100% (mean = 73.0%). The thermal data appeared to be the most useful of the predictor variables, followed by vegetation and rainfall indices. Refinements of the analytical technique and the problems of extending the predictions through space and time are discussed.

Remotely sensed surrogates of meteorological data for the study of the distribution and abundance of arthropod vectors of disease.

This paper gives an overview of how certain meteorological data used in studies of the population dynamics of arthropod vectors of disease may be predicted using remotely sensed, satellite data. Details are given of the stages of processing necessary to convert digital data arising from satellite sensors into ecologically meaningful information. Potential sources of error in these processing steps are also highlighted. Relationships between ground-measured meteorological variables (saturation deficit, ground temperature and rainfall) and data from both the National Oceanic and Atmospheric Administration's, polar-orbiting, meteorological satellites and the geostationary, Meteosat satellite are defined and examples detailed for Africa. Finally, the current status of existing satellite platforms and future satellite missions are reviewed and potential data availability discussed. How such satellite-based predictions have proved valuable in understanding the distribution of tsetse fly species in Côte d'Ivoire and Burkina Faso will be the subject of a future review.

Mating patterns in malaria parasite populations of Papua New Guinea.

Description of the genetic structure of malaria parasite populations is central to an understanding of the spread of multiple-locus drug and vaccine resistance. The Plasmodium falciparum mating patterns from madang, Papua New Guinea, where intense transmission of malaria occurs, are described here. A high degree of inbreeding occurs in the absence of detectable linkage disequilibrium. This contrasts with other studies, indicating that the genetic structure of malaria parasite populations is neither clonal nor panmictic but will vary according to the transmission characteristics of the region.

Responses of tsetse to ox sebum: a video study in the field.

The behaviour of tsetse (mainly Glossina pallidipes Austen) around odour-baited targets, with or without a coating of ox sebum, was recorded in the field using video. The addition of sebum increased the total time a fly was in contact with the target, as well as the time spent flying around and landing on it. When carbon dioxide was released as part of the attractant odour plume, the presence of sebum on the target increased the number of landings made by each fly, but did not significantly affect the duration of each contact. When carbon dioxide was absent from the odour plume, sebum did not affect the number of landings made by flies but the duration of each contact with the target did increase. Evidence for an interactive effect of sebum and carbon dioxide was obtained. In addition, the presence of sebum on the target increased the percentage of landed flies which walked on its surface; such behaviour may represent an 'inspection' of the artificial host. The potential tsetse control application of the current findings are discussed.