The governance of overseas surgical collaborations - BFIRST/BSSH.

Clinical governance is the structured approach to maintaining and improving the quality of patient care and is a vital part of global surgery. BFIRST and BSSH closely collaborate with local doctors on a number of overseas projects, seeking to strengthen and develop local knowledge and skills, aiming for an independent local practice in reconstructive and upper limb surgery. Thoughts on essential requirements, improvements and pitfalls in the ethical approach to global collaboratives are presented.

In-process rheometry as a PAT tool for hot melt extrusion.

Real time measurement of melt rheology has been investigated as a Process Analytical Technology (PAT) to monitor hot melt extrusion of an Active Pharmaceutical Ingredient (API) in a polymer matrix. A developmental API was melt mixed with a commercial copolymer using a heated twin screw extruder at different API loadings and set temperatures. The extruder was equipped with an instrumented rheological slit die which incorporated three pressure transducers flush mounted to the die surface. Pressure drop measurements within the die at a range of extrusion throughputs were used to calculate rheological parameters, such as shear viscosity and exit pressure, related to shear and elastic melt flow properties, respectively. Results showed that the melt exhibited shear thinning behavior whereby viscosity decreased with increasing flow rate. Increase in drug loading and set extrusion temperature resulted in a reduction in melt viscosity. Shear viscosity and exit pressure measurements were found to be sensitive to API loading. These findings suggest that this technique could be used as a simple tool to measure material attributes in-line, to build better overall process understanding for hot melt extrusion.

Next generation crop models: A modular approach to model early vegetative and reproductive development of the common bean (Phaseolus vulgaris L).

The next generation of gene-based crop models offers the potential of predicting crop vegetative and reproductive development based on genotype and weather data as inputs. Here, we illustrate an approach for developing a dynamic modular gene-based model to simulate changes in main stem node numbers, time to first anthesis, and final node number on the main stem of common bean (Phaseolus vulgaris L.). In the modules, these crop characteristics are functions of relevant genes (quantitative trait loci (QTL)), the environment (E), and QTL × E interactions. The model was based on data from 187 recombinant inbred (RI) genotypes and the two parents grown at five sites (Citra, FL; Palmira, Colombia; Popayan, Colombia; Isabela Puerto Rico; and Prosper, North Dakota). The model consists of three dynamic QTL effect models for node addition rate (NAR, No. d- 1), daily rate of progress from emergence toward flowering (RF), and daily maximum main stem node number (MSNODmax), that were integrated to simulate main stem node number vs. time, and date of first flower using daily time steps. Model evaluation with genotypes not used in model development showed reliable predictions across all sites for time to first anthesis (R2 = 0.75) and main stem node numbers during the linear phase of node addition (R2 = 0.93), while prediction of the final main stem node number was less reliable (R2 = 0.27). The use of mixed-effects models to analyze multi-environment data from a wide range of genotypes holds considerable promise for assisting development of dynamic QTL effect models capable of simulating vegetative and reproductive development.

Bordetella parapertussis PagP mediates the addition of two palmitates to the lipopolysaccharide lipid A.

Bordetella bronchiseptica PagP (PagPBB) is a lipid A palmitoyl transferase that is required for resistance to antibody-dependent complement-mediated killing in a murine model of infection. B. parapertussis contains a putative pagP homolog (encoding B. parapertussis PagP [PagPBPa]), but its role in the biosynthesis of lipid A, the membrane anchor of lipopolysaccharide (LPS), has not been investigated. Mass spectrometry analysis revealed that wild-type B. parapertussis lipid A consists of a heterogeneous mixture of lipid A structures, with penta- and hexa-acylated structures containing one and two palmitates, respectively. Through mutational analysis, we demonstrate that PagPBPa is required for the modification of lipid A with palmitate. While PagPBB transfers a single palmitate to the lipid A C-3' position, PagPBPa transfers palmitates to the lipid A C-2 and C-3' positions. The addition of two palmitate acyl chains is unique to B. parapertussis. Mutation of pagPBPa resulted in a mutant strain with increased sensitivity to antimicrobial peptide killing and decreased endotoxicity, as evidenced by reduced proinflammatory responses via Toll-like receptor 4 (TLR4) to the hypoacylated LPS. Therefore, PagP-mediated modification of lipid A regulates outer membrane function and may be a means to modify interactions between the bacterium and its human host during infection.

Density, DSC, X-ray and NMR measurements through the gel and lamellar phase transitions of 1-myristoyl-2-stearoyl-sn-glycero-3-phosphatidylcholine (MSPC) and 1-stearoyl-2-myristoyl-sn-glycero-3-phosphatidylcholine (SMPC): observation of slow relaxation processes and mechanisms of phase transitions.

Dialkyl lecithin dispersions in water exhibit two phase transitions upon cooling from the lamellar phase (L(α)). At the main transition (T(M)) the L(α) phase changes to a ripple (gel) phase (P(ß')) which then transforms to a second gel phase (L(ß')) at the "pretransition" (T(P)). We have made accurate density measurements through the various phases for two lecithins having unequal chains: 1-myristoyl-2-stearoyl-sn-glycero-3-phosphatidylcholine (MSPC) and 1-stearoyl-2-myristoyl-sn-glycero-3-phosphatidylcholine (SMPC). The measurements were carried out over five heat/cool cycles from 5 to 55 °C, followed by cooling back to 5 °C. The samples were then held at 50 °C for 24 hours, followed by a further three cool/heat cycles. For SMPC we observe an increase in density of the gel phases over the first 5 cycles, followed by much smaller changes after incubation at 50 °C. The lamellar phase also shows an increase in density, albeit much smaller. This parallels the behaviour of 1,2-di-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-di-myristoyl-sn-glycero-3-phosphatidylcholine (DMPC) reported earlier (Jones et al., Liquid Crystals 32, 1465 (2005)). For MSPC we observe a decrease in density within the gel phases while T(P) almost disappears after the first cycle. The lamellar phase shows little evidence of any change with each cycle. Within the lamellar phases there is a marked reduction in density on approaching T(M), which is attributed to the formation of transitory gel phase domains. Additional measurements by DSC and X-ray diffraction show that the changes in densities are not accompanied by large changes in transition enthalpies or phase structures. NMR data indicate that the pretransitional event within the L(α) phase is accompanied by ordering of the alkyl chains. The results indicate that the exact nature of the lipid alkyl chains could play a key role in the formation of gel phase patches within membrane bilayers. Their detailed chemical structures merit more attention than by simply assuming a uniform "bending energy" to describe the behaviour.

Role of pagL and lpxO in Bordetella bronchiseptica lipid A biosynthesis.

PagL and LpxO are enzymes that modify lipid A. PagL is a 3-O deacylase that removes the primary acyl chain from the 3 position, and LpxO is an oxygenase that 2-hydroxylates specific acyl chains in the lipid A. pagL and lpxO homologues have been identified in the genome of Bordetella bronchiseptica, but in the current structure for B. bronchiseptica lipid A the 3 position is acylated and 2-OH acylation is not reported. We have investigated the role of B. bronchiseptica pagL and lpxO in lipid A biosynthesis. We report a different structure for wild-type (WT) B. bronchiseptica lipid A, including the presence of 2-OH-myristate, the presence of which is dependent on lpxO. We also demonstrate that the 3 position is not acylated in the major WT lipid A structures but that mutation of pagL results in the presence of 3-OH-decanoic acid at this position, suggesting that lipid A containing this acylation is synthesized but that PagL removes most of it from the mature lipid A. These data refine the structure of B. bronchiseptica lipid A and demonstrate that pagL and lpxO are involved in its biosynthesis.

The role of tenodesis in surgery of the upper limb.

This paper describes the presence of tenodesis effects in normal physiology and explores the uses of operative tenodesis in surgery of the upper limb.

Soil organic carbon dynamics and crop yield for different crop rotations in a degraded ferruginous tropical soil in a semi-arid region: a simulation approach.

In recent years, simulation models have been used as a complementary tool for research and for quantifying soil carbon sequestration under widely varying conditions. This has improved the understanding and prediction of soil organic carbon (SOC) dynamics and crop yield responses to soil and climate conditions and crop management scenarios. The goal of the present study was to estimate the changes in SOC for different cropping systems in West Africa using a simulation model. A crop rotation experiment conducted in Farakô-Ba, Burkina Faso was used to evaluate the performance of the cropping system model (CSM) of the Decision Support System for Agrotechnology Transfer (DSSAT) for simulating yield of different crops. Eight crop rotations that included cotton, sorghum, peanut, maize and fallow, and three different management scenarios, one without N (control), one with chemical fertilizer (N) and one with manure applications, were studied. The CSM was able to simulate the yield trends of various crops, with inconsistencies for a few years. The simulated SOC increased slightly across the years for the sorghum-fallow rotation with manure application. However, SOC decreased for all other rotations except for the continuous fallow (native grassland), in which the SOC remained stable. The model simulated SOC for the continuous fallow system with a high degree of accuracy normalized root mean square error (RMSE)=0·001, while for the other crop rotations the simulated SOC values were generally within the standard deviation (s.d.) range of the observed data. The crop rotations that included a supplemental N-fertilizer or manure application showed an increase in the average simulated aboveground biomass for all crops. The incorporation of this biomass into the soil after harvest reduced the loss of SOC. In the present study, the observed SOC data were used for characterization of production systems with different SOC dynamics. Following careful evaluation of the CSM with observed soil organic matter (SOM) data similar to the study presented here, there are many opportunities for the application of the CSM for carbon sequestration and resource management in Sub-Saharan Africa.

Susceptibility of Peruvian mosquitoes to eastern equine encephalitis virus.

Mosquitoes were collected in the Amazon Basin, near Iquitos, Peru, and used in experimental studies to evaluate their susceptibility to strains of eastern equine encephalitis virus (EEEV) that were isolated from mosquitoes captured within 20 km of Iquitos. When fed on hamsters or chickens with a viremia of 4105 plaque-forming units (PFU) of EEEV/ml, Culex pedroi Sirivanakarn and Belkin, Aedesfulvus (Wiedemann), Psorophora albigenu (Peryassu), and Psorophoraferox (Von Humboldt) were susceptible to infection, whereas none of the Aedes serratus (Theobald), Culex vomerifer Komp, Culex gnomatos Sallum, Huchings, and Ferreira, Culex portesi Senevet and Abonnenc, or Culex coronator Dyar and Knab became infected, even though they fed on the same viremic blood sources. When these mosquito species fed on animals with viremias of approximately 10(8) PFU/ml, Cx. pedroi, Ae.II (Brazil-Peru) and a lineage III (Argentina-Panama) isolate of EEEV. This study, combined with the repeated isolation of strains of EEEV from Cx. pedroi captured in the Amazon Basin region of Peru, suggests that Cx. pedroi may be the primary enzootic vector of EEEV in this region.

Chromonic liquid crystal formation by Edicol Sunset Yellow.

The solution and liquid crystalline phases formed by dissolution of the dye Edicol Sunset Yellow (ESY) in water have been examined using optical microscopy, multinuclear NMR (1H, 2H, 13C, 23Na), and X-ray diffraction. From the solution 1H and 13C spectra (particularly 13C), it is clear that the tautomeric form present in all these phases is the hydrazone, NH, structure, not the usually given azo, OH, form. Two chromonic mesophases occur: a nematic (N) phase at approximately 30-40 wt % and a hexagonal (M) phase at approximately 40-45 wt %. X-ray diffraction data show that the aggregates in the mesophases are single molecule stacks, with a typical spacing of approximately 3.5 angstroms, as expected for these systems. The NMR quadrupole splittings (2H2O, 23Na) are similar to those observed for surfactant lyotropic mesophases, suggesting that there are no water molecules or counter ions that are tightly bound to the ESY aggregates. An unusual feature of the X-ray diffraction pattern of the mesophases is the occurrence of diffuse off-axis reflections at approximately 6.8 angstroms. It is proposed that these arise from a head-to-tail packing of the molecules within the stacks.

A simple soil organic-matter model for biomass data assimilation in community-level carbon contracts.

Soil carbon (C) sequestration has been proposed as a transitional win-win strategy to help replenish organic-matter content in depleted agricultural soils and counter increases in atmospheric greenhouse gases. Data assimilation and remote sensing can reduce uncertainty in sequestered C mass estimates, but simple soil organic carbon (SOC) models are required to make operational predictions of tradeable amounts over large, heterogenous areas. Our study compared the performance of RothC26.3 and a reduced compartmental model on an 11-year fertilizer trial in subhumid West Africa. Root mean square error (RMSE) differences of 0.05 Mg C/ha between models on total SOC predictions suggest that for contractual purposes, SOC dynamics can be simulated by a two-pool structure with labile and stable components. Faster (seasonal) and slower (semicentennial and beyond) rates can be approximated by constants as instantaneous and infinite decay. In these systems, simulations indicate that cereal residue incorporation holds most potential for mitigation of transient C loss associated with recent land conversion to agriculture.

Paediatric forearm fractures: the increasing use of elastic stable intra-medullary nails.

This paper entails a clinical review of outcomes and complications of 19 consecutive paediatric patients having undergone elastic stable intramedullary nailing for diaphyseal forearm fractures over a one year period. The mean age of patients was 9 years. The majority were male with a ratio of 17:2. In this group there were two patients with grade 1 open fractures. Four of the fractures required open reduction due to difficulty in reduction and soft tissue interposition. All fractures went on to osseous union with minimal deformity and full recovery. There were three complications which included one EPL rupture requiring delayed repair, one EPB partial rupture repaired at time of surgery, and one superficial radial nerve injury. Two patients also presented with nails penetrating the skin prior to removal. Elastic stable intramedullary nails offer good fixation to control deformity in midshaft forearm fractures for paediatric patients. However there is a high rate of possible complications around the radial insertion point.

Standardizing container classification for immature Aedes aegypti surveillance in Kamphaeng Phet, Thailand.

For the development of community-based vector control programs for dengue prevention, one of the key components is to formulate an adequate classification scheme for the different containers in which immature Aedes mosquitoes develop. Such a standardized scheme would permit more efficient targeting of efforts and resources in the most productive way possible. Based on field data from Kamphaeng Phet, Thailand, we developed a classification method that consists of the shape (S), use (U), and material (M) of the container (SUM-method). We determined that by targeting the four container classes that held the most Ae. aegypti pupae, adult mosquito production could theoretically be reduced by 70%. The classification method may be equally suitable for similar studies elsewhere in the world. Main advantages of the classification scheme are that categorization of containers does not need to be done a priori, that there is no "miscellaneous" class, and that different immature control strategies can be easily and prospectively tested with a local database. We expect that the classification strategy will 1) facilitate comparison of results among different ecological and geographic settings and 2) simplify communication among vector control personnel and affected communities.

Spatial and temporal patterns in the recovery of Aedes aegypti (Diptera: Culicidae) populations after insecticide treatment.

Given that tools for dengue emergency control are limited, continuous evaluation of the effectiveness of insecticide applications in the field is of utmost importance. Such studies will provide a sound basis for defining spraying schemes for public health authorities in dengue-affected countries. In this article, we address the following research questions: How do different space spraying strategies affect Aedes aegypti (L.) (Diptera: Culicidae) populations in both space and time? More specifically, how well are these mosquitoes killed, and how quickly do their populations recover and from where? Field trials were carried out with ultralow volume sprayers in Kamphaeng Phet province, Thailand, with a pyrethrin mixture that was applied 1) indoors only, 2) indoors plus outdoors, 3) indoors with a doubled spraying time, and 4) indoors with doubled spraying time plus outdoors. We found that within 7 d, Ae. aegypti populations recovered to approximately 50% of their original numbers. Spraying the outdoor area and doubling the time sprayed per room only had a significant impact on mosquito numbers 1 d after spraying. Two and 7 d after spraying, these effects were no longer detected. By investigating the spatial arrangement of Ae. aegypti numbers, we found that during the first 2 d after spraying immigration from untreated areas extended approximately 15 m into the sprayed area, whereas after 7 d this effect extended up to 50 m. Results are discussed in relation to ongoing dengue control efforts in Thailand.

Molecular heterogeneity along the dorsal-ventral axis of the murine hippocampal CA1 field: a microarray analysis of gene expression.

There has been increasing interest in functional heterogeneity along the septotemporal, dorsal-ventral (D-V) axis of the hippocampus. Although anatomical connectivity and lesion studies point to discrete roles for these sub-regions, the contribution of differential gene expression across this axis has not been systematically studied. Here we present findings from an Affymetrix microarray screen aimed at identifying genes in the CA1 region of the adult murine hippocampus that show significant differential expression along the D-V axis. Our results indicate that the vast majority of monitored genes (>90%) had tissue expression levels that differed by less than 20% between regions, while less than 0.1% of genes had expression levels that varied more than three-fold by sub-region. Only 23 probes showed a CA1 dorsoventral signal intensity ratio greater than three: 18 enriched dorsally and five enriched ventrally. Probes with the greatest difference in expression levels represent a range of genes with known functions in patterning and signaling, as well as genes without known function. Selective screening with digoxigenin-labeled in situ hybridization confirms the existence of CA1 sub-regionalized expression, with some genes exhibiting a graded expression pattern across the D-V axis, and others restricted to a discrete region. Our findings demonstrate that there are gene expression differences across the D-V axis of the adult murine hippocampus within traditionally recognized cytoarchitecturally defined boundaries. Combined with the previously recognized differences in connectivity and results from lesion studies, our data further confirm the existence of functional heterogeneity along the D-V axis.

Isolation of viruses from mosquitoes (Diptera: Culicidae) collected in the Amazon Basin region of Peru.

As part of a comprehensive study on the ecology of arthropod-borne viruses in the Amazon Basin region of Peru, we assayed 539,694 mosquitoes captured in Loreto Department, Peru, for arboviruses. Mosquitoes were captured either by dry ice-baited miniature light traps or with aspirators while mosquitoes were landing on human collectors, identified to species, and later tested on Vero cells for virus. In total, 164 virus isolations were made and included members of the Alphavirus (eastern equine encephalomyelitis, Trocara, Una, Venezuelan equine encephalomyelitis, and western equine encephalomyelitis viruses), Flavivirus (Ilheus and St. Louis encephalitis), and Orthobunyavirus (Caraparu, Itaqui, Mirim, Murutucu, and Wyeomyia viruses) genera. In addition, several viruses distinct from the above-mentioned genera were identified to the serogroup level. Eastern equine encephalomyelitis virus was associated primarily with Culex pedroi Sirivanakarn & Belkin, whereas Venezuelan equine encephalomyelitis virus was associated primarily with Culex gnomatos Sallum, Huchings & Ferreira. Most isolations of Ilheus virus were made from Psorophora ferox (Von Humboldt). Although species of the Culex subgenus Melanoconion accounted for only 45% of the mosquitoes collected, 85% of the virus isolations were made from this subgenus. Knowledge of the viruses that are being transmitted in the Amazon Basin region of Peru will enable the development of more effective diagnostic assays, more efficient and rapid diagnoses of clinical illnesses caused by these pathogens, risk analysis for military/civilian operations, and development of potential disease control measures.