Decision-making in musculoskeletal health care is complex, with discrepancy among clinical providers, and variation in the per cent of referrals for specialist care. To date there is an increased focus on specialist referrals, risking overuse of expensive testing and contributing to unnecessary treatment. This report will considerer the difficulties of primary care musculoskeletal decision-making using shoulder injuries as an example, presenting a solution based on multi-criteria decision-making analysis with online software. The associated issues involved in clinical decision-making are complex. Contributing to the components of complexity are; the aetiology of shoulders being multi-faceted, the experience and knowledge of providers, and the burden of patient demands. Notwithstanding, funding considerations, resource allocation availability, and other associated issues around clinical decision-making. Considering there are many facets involved in decision-making, this is an area where multi-criteria decision-making analysis (MCDM) may be appropriate. MCDM which uses mathematical analysis, is increasingly being used in health care and could be applied to the challenges of musculoskeletal care. MCDM has the potential to decrease variability in decision-making and be used as a tool to augment clinical decisions. Furthermore, the key clinical factors that decision-making is based on are to date unclear, therefore, this preliminary report offers a start towards moving to a clarification of the key factors, and an approach for implementing improved shoulder clinical care decision-making which could then be adapted and applied to other body sites.

1) The more demanding requirements of DNA preservation for genomic research can be difficult to meet when field conditions limit the methodological approaches that can be used, or cause samples to be stored in suboptimal conditions. Such limitations may increase rates of DNA degradation, potentially rendering samples unusable for applications such as genome-wide sequencing. Nonetheless, little is known about the impact of suboptimal sampling conditions. 2) We evaluated the performance of two widely used preservation solutions (1. DESS: 20% DMSO, 0.25M EDTA, NaCl saturated solution, and 2. ethanol) under a range of storage conditions over a three-month period (sampling at 1 day, 1 week, 2 weeks, 1 month, and 3 months) to provide practical guidelines for DNA preservation. DNA degradation was quantified as the reduction in average DNA fragment size over time (DNA fragmentation) because the size distribution of DNA segments plays a key role in generating genomic datasets. Tissues were collected from a marine teleost species, the Australasian snapper, Chrysophrys auratus. 3) We found that the storage solution has a dramatic effect on DNA preservation. In DESS, DNA was only moderately degraded after three months of storage while DNA stored in ethanol showed high levels of DNA degradation already within 24 hours, making samples unsuitable for next-generation-sequencing. 4) We recommend DESS as the most promising solution to improve DNA preservation. These results provide practical and economical advice to improve DNA preservation when sampling for genome-wide applications. Keywords: DMSO, DNA preservation, ethanol, fish, next-generation-sequencing, NGS, snapper

Background: Maternal levels of angiogenic factors are promising prognostic parameters in patients with suspected preeclampsia, but in women with confirmed preeclampsia this performance has been less explored. Objective: To assess in women with early-onset severe preeclampsia whether longitudinal changes in angiogenic factors improve the prediction of adverse outcome. Study design: A cohort was created of consecutive women admitted for early-onset severe preeclampsia with no indication for immediate delivery. Levels of placental growth factor [PlGF], soluble fms-like tyrosine kinase [sFlt-1] and sFlt-1/PlGF ratio were measured at admission and before delivery; and average daily change was calculated. The association of longitudinal changes of angiogenic factors with maternal complications and with the time interval to delivery was evaluated by logistic and Cox regression. Results: Sixty-three women were analyzed, of which 23 (36.5%) had a complication. Longitudinal changes of sFlt-1 were more pronounce in complicated pregnancies (median: 1079.5 vs. 343.7 pg/mL/day; p=0.04). On the multivariate analysis, the baseline model (clinical risk score and sFlt-1 at admission) explained a 6.6% of the uncertainty for complication (R2-Naegelkerke). The addition of sFlt-1 longitudinal changes improved this performance to 23.2% (p=0.004). The median time from admission to delivery was 3 days (95% confidence interval: 1.9-4.05) in those in the highest quartile of sFlt-1 longitudinal changes vs. 10 days (95% confidence interval: 8.1-11.9) in the remaining women (Log-rank test p<0.001). Conclusions: Longitudinal changes in sFlt-1 maternal levels from admission for confirmed early-onset severe preeclampsia add to baseline characteristics in the prediction of maternal complications.

The stiffness degradation represents one of the most interesting phenomena used for describing the fatigue behaviour of composites. In this regard, in literature, several works have been presented for modelling the fatigue life by studying the stiffness degradation. A critical aspect of modelling damage fatigue is represented by the difficulties in simulating the whole behaviour of material and then in describing the damage progression in all its stages. In addition, the validation of models requires the measurement of stiffness variations by means of experimental techniques. Above all for real components, the difficulties in defying proper models are accompanied by the difficulties in measuring stiffness degradation due to inapplicability of classic experimental techniques. In this work, the stiffness degradation of quasi-isotropic carbon-fibre-reinforced-polymer obtained by automated fiber placement, has been assessed by means of Thermoelastic Stress Analysis. The amplitude of temperature signal at the mechanical frequency (thermoelastic signal) was considered as an indicator of material degradation and compared to the data provided by an extensometer. The correlation between thermoelastic and mechanical data allowed to build a new experimental model for evaluating and predicting material stiffness degradation by just using thermoelastic data. The proposed approach seems to be very promising for stiffness degradation assessment of real and complex mechanical components subjected to actual loading conditions.

Environmental dating tracers (3H, 3He, 4He, CFC-12, CFC-11, SF6) and the natural response of spring (hydrochemistry, water temperature, and hydrodynamics) were jointly used to asses mixing processes and to characterize groundwater flow in a relatively small carbonate aquifer with complex geology in South Spain. Results evidence a marked karst behavior of some temporary outlets, while some perennial springs show buffer and delayed responses to recharge events. There is also a general geochemical evolution pattern, from higher to lower altitudes, in which mineralization and the relation Mg/Ca rises, evidencing longer water-rock interaction. The large SF6 concentrations in groundwater suggest terrigenic production, while CFC-11 values are affected by sorption or degradation. The groundwater age in the perennial springs deduced from CFC-12 and 3H/3He point out to mean residence times of several decades, although the difference between both methods and the large amount of radiogenic 4He in the samples indicates a contribution of old groundwater (free of 3H and CFC-12). Lumped Parameter Models and Shape-Free Models were created based on 3H, tritiogenic 3He, CFC-12, and radiogenic 4He data in order to interpret the age distribution of the samples. The resulting groundwater-age distributions evidence the existence of two mixing components, with an old fraction ranging between 160 and 220 years. Some dating parameters derived from the mixing models and their correlation to physicochemical parameters permits to explain the hydrogeochemical processes occurring within the system. All these results prove that large time residence times are possible in small alpine systems with a clear karst behavior when the geological setting is complex, and they highlight the importance of applying different approaches, including groundwater dating techniques, to completely understand the groundwater flow regime within this type of media.

In Rodriguez et al.1 an analytical expression was deduced to predict the slip ratio in dispersed oil-water flow. Although the quantitative agreement was quite good, the expression systematically underestimated the slip ratio. New experimental data of similar flows were collected in two different experimental facilities in pipes of different materials and diameters (26 mm and 82.8 mm i.d.). Oil-water flow data collected within a range of mixture Reynolds numbers from 1∙10^5 to 20∙10^6 in glass, acrylic and steel pipes with oil viscosities varying from 7 to 220 mPa.s were used to deduce a more generic correlation for slip ratio as a function of the mixture Froud number (5 < Fr < 70). The underestimation of the slip ratio was corrected. The new slip-ratio correlation can be used to significantly improve the prediction of volumetric fraction in flow situations where turbulent dispersion of oil in water occurs.

To understand the growth response to drought, we performed a proteomics study in the leaf growth zone of maize (Zea mays L.) seedlings and functionally characterized the role of starch biosynthesis in the regulation of growth, photosynthesis and antioxidant capacity, using the shrunken2 mutant (sh2), defective in ADP-glucose pyrophosphorylase. Drought induced differential expression of 284 proteins overrepresented for photosynthesis, amino acids, sugar and starch metabolism, and redox-regulation. Changes in protein levels correlated with enzyme activities (increased ATP synthase, cysteine synthase, starch synthase, RuBisCo, peroxiredoxin, glutaredoxin, thioredoxin and decreased triosephosphate isomerase, ferredoxin, cellulose synthase activities, respectively) and metabolite concentrations (increased ATP, cysteine, glycine, serine, starch, proline and decreased cellulose levels). The sh2 mutant had a reduced ability to increase starch levels under drought conditions, causing soluble sugar starvation at the end of the night and impaired leaf growth. Increased RuBisCo activity and pigment concentrations observed in WT in response to drought were lacking in the mutant, which suffered more oxidative damage and recovered more slowly after re-watering. These results demonstrate that starch biosynthesis plays a crucial role in maintaining leaf growth under drought stress and facilitates enhanced carbon acquisition upon recovery.

Objective To compare the safety and efficacy of Veregen® ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). Design A Phase II randomised control trial. Setting A tertiary gynaecological oncology referral center. Population All women diagnosed with primary and recurrence uVIN. Methods Eligible patients were randomised to receive either Veregen® or placebo ointment (applied 3 times daily for 16 weeks), and were followed up at 2, 4, 8, 16, 32 and 52 weeks. Main outcome measures Outcome measures, recorded at 16 and 32 weeks, were histological (HR) and clinical (CR) response (as measured by ≥30% reduction in the sum of the longest diameter of all lesions when compared to baseline), toxicity and changes in quality of life and pain scores. Results 26 patients were randomised and all 13 patients who received Veregen® showed either complete (n=5) or partial (n=8) CR with a trend towards an improvement in baseline symptoms. In placebo group, 3 patients had complete CR, 2 had partial CR and 6 had stable disease. Patients in the Veregen® group showed a significant improvement in CR as compared to the placebo group (P=0.0026). There was no evidence of difference in HR and toxicity reported in both groups. Conclusion Our study indicates that Veregen application is safe and leads to at least a partial clinical resolution of uVIN lesions and symptoms improvement, thus warranting a phase III multi-centre RCT.

Although cell wall polymers play important roles in the tolerance of plants to abiotic stress, the effects of salinity on cell wall composition and metabolism in grasses remain largely unexplored. Here, we conducted an in-depth study of changes in cell wall composition and phenolic metabolism induced upon salinity in maize seedlings and plants. Cell wall characterization revealed that salt stress modulated the deposition of cellulose, matrix polysaccharides and lignin. The extraction and analysis of arabinoxylans by size-exclusion chromatography, two-dimensional NMR spectroscopy and carbohydrate gel electrophoresis showed a reduction of arabinoxylan content in salt-stressed roots, with no changes in xylose/arabinose ratios. Saponification and mild acid hydrolysis followed by RP-HPLC analysis revealed that salt stress also reduced the feruloylation of arabinoxylans. Determination of lignin content and composition by nitrobenzene oxidation and two-dimensional NMR confirmed the increased incorporation of syringyl units in lignin polymer. Our data also revealed the induction of the expression of genes and enzymes enrolled in phenylpropanoid biosynthesis under salinity. The UPLC-MS-based metabolite profiling confirmed the modulation of phenolic profiling by salinity and the accumulation of ferulate and its derivatives 3- and 4-O-feruloyl quinate. In conclusion, we present a model for explaining cell wall remodeling in response to salinity.

We introduce a straightforward method for the preparation of novel starch-based ultramicroporous carbons (SCs) that demonstrate high CH4 uptake and excellent CH4/N2 selectivity. These SCs are derived from a combination of starch and 1-6 wt. % of acrylic acid, and the resulting materials are amenable to surface cation exchangeability as demonstrated by the formation of highly dispersed K+ in carbon precursors. Following activation, these SCs contain ultramicropores with narrow pore-size distributions of <0.7 nm, leading to porous carbon-rich materials that exhibit CH4 uptake values as high as 1.86 mmol/g at 100 kPa and 298 K, the highest uptake value for CH4 to date, with the IAST-predicted CH4/N2 selectivity up to 5.7. Both the potential mechanism for the formation of narrow pores and the origin of the favorable CH4 adsorption properties are discussed and examined. This work may potentially guide future designs for carbon-rich materials with excellent gas adsorption properties.

Dibutyl phthalate (DBP) is an environmental pollutant that can threaten human health. The strain Arthrobacter sp. ZJUTW, isolated from the sludge of river of Hangzhou city, can efficiently degrade DBP. Its genomic and transcriptomic differences when cultivated with DBP and with glucose revealed specific DBP metabolic pathways in the ZJUTW strain. The degrading gene clusters distribute separately on a circular chromosome and a plasmid pQL1. Genes related to the initial steps of DBP degradation from DBP to phthalic acid (PA), the pehA gene and pht gene cluster, are located on the plasmid pQL1. While pca gene cluster related to the transforming of protocatechuic acid (PCA) to acetyl-CoA, is located on the chromosome. After homologous alignment analysis with the reported gene clusters, we found that there were a series of double copies of homologous genes in pht and pca gene clusters that contribute to the efficient degradation of DBP by ZJUTW. In addition, transcriptomic analysis showed a synergistic effect between pht and pca clusters, which also favor ZJUTW allowing it to efficiently degrade DBP. Combined genomic and transcriptomic analyses affords the complete DBP metabolic pathway in Arthrobacter sp. ZJUTW that is different from that of reported other Arthrobacter strains. After necessary modification based on its metabolic characteristics, Arthrobacter sp. ZJUTW or its mutants might represent promising candidates for use in the bioremediation of DBP pollution.

Secondary contact between closely related species can lead to the formation of hybrid zones, allowing for interspecific gene flow among taxa. Species replacement can take place if one of the species possesses a competitive advantage over the other, resulting in hybrid zone movement. This displacement may leave a genomic footprint across the landscape in the form of asymmetric introgression of selectively neutral alleles from the displaced to the advancing species. Hybrid zone movement has been suggested for marbled newts in the Iberian Peninsula, supported by the presence of a Triturus marmoratus stronghold surrounded by populations of the supposedly advancing T. pygmaeus in the northwest of the Lisbon Peninsula, i.e., an enclave. Moreover, a newly constructed two-species distribution model suggests that climate conditions following the Last Glacial Maximum may have favoured T. pygmaeus over T. marmoratus along the Atlantic coast. To test for the presence of a T. marmoratus genomic footprint in the area that may have witnessed species displacement, we developed and employed 54 nuclear SNPs and one mitochondrial DNA marker. We found no additional enclaves nor genetic traces of T. marmoratus in T. pygmaeus populations. Therefore, two main hypothesis arise in the absence of a genomic footprint: i) species replacement without hybridisation, either in allopatry or in sympatry under strong reproductive isolation; or ii) displacement with hybridisation where the footprint was eroded due to strong purifying selection. We predict testing for a genomic footprint north of the reported enclave could confirm that species replacement in the marbled newts occurred with hybridisation.

The fifth order short pulse equation models the nonlinear propagation of optical pulses of a few oscillations duration in dielectric media. In particular, it models the propagation of circularly and elliptically polarized few-cycle solitons in a Kerr medium. In this paper, we prove the well-posedness of the classical solutions for the Cauchy problem associated with this equation.

Mine reclamation in the Athabasca oil sands region Canada, is required by law where companies must reconstruct disturbed landscapes into functioning ecosystems such as forests, wetlands and lakes that existed in the Boreal landscape prior to mining. Winter is a major hydrological factor in this region as snow covers the landscape for 5 to 6 months and is ~25% of the annual precipitation, yet few studies have explored the influence of winter processes on the hydrology of constructed watersheds. One year (2017-2018) of intensive snow hydrology measurements are supplemented with six years (2013-2018) of meteorological measurements from the constructed Sandhill Fen Watershed to: 1) understand snow accumulation and redistribution, snowmelt timing, rate and partitioning, 2) apply a physically-based model for simulating winter processes on hillslopes and 3) evaluate the impact of soil prescriptions and climate change projections on winter processes in reclaimed systems. The 2017-2018 snow season was between November and April and SWE ranged between 40-140 mm. Snow distribution was primarily influenced by topography with little influence of snow trapping from developing vegetation. Snow accumulation was most variable on hillslopes and redistribution was driven by slope position, with SWE greatest at the base of slopes and decreased towards crests. Snowmelt on hillslopes was controlled by slope aspect, as snow declined rapidly on west and south-facing slopes, compared to east and north-facing slopes. Unlike results previously reported on constructed uplands, snowmelt runoff from uplands was much less (~30%), highlighting the influence of different construction materials. Model simulations indicate that antecedent soil moisture and soil temperature have a large influence on partitioning snowmelt over a range of observed conditions. Under a warmer and wetter climate, average annual peak SWE and snow season duration could decline up to 52 % and up to 61 days, respectively while snowmelt runoff ceases completely under the warmest scenarios. Results suggest considerable future variability in snowmelt runoff from hillslopes, yet soil properties can be used to enhance vertical or lateral flows.

Small mammal abundances are frequently limited by resource availability but predators can exert strong lethal (direct mortality) and non-lethal limitations (e.g. depressed site-level activity). Artificially increasing resource availability for small mammals provides a unique opportunity to examine predator-prey interactions. We monitored the 3-year response of arboreal rodents and their predators at nest platforms (n = 598; 23 young forest sites), using annual inspections and remote cameras (n = 168). One year after adding nest platforms we found a 2.9 to 9.2-fold increase in red tree vole (Arborimus longicaudus) use at the site-level, but little use by potential predators. Predator use of nest platforms began in year two and increased in year three of the study. Most potential nest predators were positively correlated with tree vole presence at nest platforms but effect size and direction varied with temporal grain considered (e.g. hour vs day time-bin widths). Flying squirrels (Glaucomys humboldtensis) were positively correlated with disturbances caused by digging birds. Using a Cormack-Jolly-Seber model and encounter histories produced from visual re-captures of marked tree voles, we estimated apparent annual survival to be 0.099 ± 0.057 (x̄ ± 1 SE) for females and 0.005 ± 0.014 for males. Weasels (Mustela spp.), an active seeking predator, preyed upon tree voles most frequently with 10% of weasel detections resulting in mortality of a tree vole (n = 8) whereas owls, an ambush predator, did not prey upon tree voles at nest platforms even though they were detected at similar frequencies as weasels. Weasels also exerted potential non-lethal effects and we observed a >10-fold reduction in the number of tree vole detections per week after weasel detection. Our evidence indicates that predators exert direct and indirect effects on tree vole populations with active seeking predators being the most important predators at nest sites.

We seek to explain why the hydrogen bond possesses unusual strength in small water clusters that account for many of the complex behaviors of water. We have investigated and visualized the donation of covalent character from covalent (sigma) to hydrogen-bonds, by calculating the eigenvector coupling properties of QTAIM, stress tensor σ(r) and Ehrenfest Force F(r) on the F(r) molecular graph. The next generation 3-D bond-path framework sets are presented and only the F(r) bond-path framework sets reproduce the earlier finding on the coupling between covalent (sigma) and hydrogen-bonds that possess a degree of covalent character. The directional character of the covalent (sigma) and hydrogen-bonds 3-D bond-path framework sets for the F(r) explains differences found in the earlier results from QTAIM and the stress tensor σ(r).

Pipeline transmission is one of the most important ways of oil and gas transportation, and its safety is majorly threatened by fatigue fracture that generally occurs in heat-affected zone (HAZ) adjacent to the welded joint of the pipeline. Therefore, studying the fatigue properties of HAZ is important. In this work, the microstructure and mechanical properties in the HAZ of a X80 pipe were accurately simulated by thermal simulation. The fatigue life and crack growth rate of typical sub-HAZ were tested. Results showed that the fine grain HAZ had the lowest strength and fatigue life. By contrast, the coarse grain HAZ had the highest strength, but its fatigue life was lower than that of the intercritical HAZ. Furthermore, the microstructure of each sub-HAZ and its effect on fatigue properties were discussed in detail. The results will reveal the effects of microstructure and mechanical properties on the service safety of pipeline transportation.

Biodiversity is under threat worldwide. Over the past decade, the field of population genomics has developed across non-model organisms, and the results of this research have begun to be applied in conservation and management of wildlife species. Genomics tools can provide precise estimates of basic features of wildlife populations, such as effective population size, inbreeding, demographic history, and population structure, that are critical for conservation efforts. Moreover, population genomics studies can identify particular genetic loci and variants responsible for inbreeding depression or adaptation to changing environments, allowing for conservation efforts to estimate the capacity of populations to evolve and adapt in response to environmental change and to manage for adaptive variation. While connections from basic research to applied wildlife conservation have been slow to develop, these connections are increasingly strengthening. Here we review the primary areas in which population genomics approaches can be applied to wildlife conservation and management, highlight examples of how they have been used, and provide recommendations for building on the progress that has been made in this field.