Pre-Ride Biomarkers and Endurance Horse Welfare: Analyzing the Impact of the Elimination of Superoxide Dismutase, δ-Aminolevulinic-Dehydratase, Thiobarbituric Acid Reactive Substances, Iron, and Serum Amyloid A Levels in Elite 160 km Endurance Rides

High elimination rates and concerns for horse welfare are important issues in endurance riding. Improved understanding of the causes of elimination could increase completion rates in this sport. We have identified pre-ride laboratory risk factors that enable an assessment of potential elimination before the ride. A longitudinal cohort study was performed among 49 healthy horses competing in the 160 km endurance ride at the 2016 World Championship of Endurance Riding in Samorin/Slovakia. Blood samples were taken before the event. For statistical evaluation, horses were categorized into three groups: finishers, lame horses, and metabolically eliminated horses. Risk factors were calculated for each group using multinominal logistic regression. δ-Aminolevulinic-dehydratase (ALAD), thiobarbituric acid reactive substances (TBARSs), iron, and serum amyloid A (SAA) were measured and did not show an impact on the race outcome, but elevated pre-ride superoxide dismutase (SOD) was shown to have an effect on lameness elimination (p = 0.011). It might serve as an indicator for withdrawing horses at risk of later elimination before endurance rides, ultimately resulting in lower elimination rates and an increase in overall horse welfare

Robustness of the projected squeezed state protocol

Projected squeezed (PS) states are multipartite entangled states generated by unitary spin squeezing, followed by a collective quantum measurement and post-selection. They can lead to an appreciable decrease in the state preparation time of the maximally entangled N-qubit Greenberger-Horne-Zeilinger (GHZ) state when compared to deterministic preparation by unitary transformations in physical systems where spin squeezing can be realized, such as ion, neutral atom, and superconducting qubits. Here we simulate the generation of PS states in non-ideal experimental conditions with relevant decoherence channels. By employing the Kraus operator method, and quantum trajectory method to reduce the computational complexity, we assess the quantum Fisher information and overlap fidelity with an ideal GHZ state. Our findings highlight PS states as useful metrological resources, demonstrating a robustness against environmental effects with increasing qubit number N.Comment: 19 pages, 12 figures, appendi

Age and Hydration of Competing Horses Influence the Outcome of Elite 160 km Endurance Rides

High elimination rates and the concern for horse welfare are important issues in endurance riding. An improved understanding of the causes of elimination could increase completion rates in this sport. We have identified pre-ride risk factors that allow an assessment of potential elimination before the ride. A longitudinal cohort study was performed among 49 healthy horses competing in the 160 km endurance ride at the 2016 World Championship of Endurance Riding in Samorin/Slovakia. Blood samples were drawn before the ride. For statistical evaluation, horses were categorized in three groups: finishers, lame and metabolically eliminated horses. Risk factors were calculated for each group using multinomial logistic regression. A 1% increase in hematocrit levels was associated with a higher OR for elimination (lameness: OR 1.26, p = 0.017; metabolic: OR 1.34, p = 0.010). Furthermore, increased potassium values correlated negatively with the race outcome. For a 1 mmol/l increase in potassium, the lameness OR was 4.21, p = 0.039 and metabolic OR was 1.15, p = 0.848. Eight-year-old horses had a 100% elimination rate and survival analyses showed a significantly higher hazard for elimination (p = 0.025). We thus conclude that age and hydration affect the outcome of elite endurance rides. Further investigation of age as a risk factor seems to be clinically relevant and adjustments of FEI qualification modes may be appropriate

Relationships between Substrate Promiscuity and Chiral Selectivity of Esterases from Phylogenetically and Environmentally Diverse Microorganisms

Substrate specificity and selectivity of a biocatalyst are determined by the protein sequence and structure of its active site. Finding versatile biocatalysts acting against multiple substrates while at the same time being chiral selective is of interest for the pharmaceutical and chemical industry. However, the relationships between these two properties in natural microbial enzymes remain underexplored. Here, we performed an experimental analysis of substrate promiscuity and chiral selectivity in a set of 145 purified esterases from phylogenetically and environmentally diverse microorganisms, which were assayed against 96 diverse esters, 20 of which were enantiomers. Our results revealed a negative correlation between substrate promiscuity and chiral selectivity in the evaluated enzymes. Esterases displaying prominent substrate promiscuity and large catalytic environments are characterized by low chiral selectivity, a feature that has limited commercial value. Although a low level of substrate promiscuity does not guarantee high chiral selectivity, the probability that esterases with smaller active sites possess chiral selectivity factors of interest for industry (>25) is significantly higher than for promiscuous enzymes. Together, the present study unambiguously demonstrates that promiscuous and selective esterases appear to be rare in nature and that substrate promiscuity can be used as an indicator of the chiral selectivity level of esterases, and vice versa

Bioprospecting reveals class III ω-transaminases converting bulky ketones and environmentally relevant polyamines

Amination of bulky ketones, particularly in (R) configuration, is an attractive chemical conversion; however, known ω-transaminases (ω-TAs) show insufficient levels of performance. By applying two screening methods, we discovered 10 amine transaminases from the class III ω-TA family that were 38% to 76% identical to homologues. We present examples of such enzymes preferring bulky ketones over keto acids and aldehydes with stringent (S) selectivity. We also report representatives from the class III ω-TAs capable of converting (R) and (S) amines and bulky ketones and one that can convert amines with longer alkyl substituents. The preference for bulky ketones was associated with the presence of a hairpin region proximal to the conserved Arg414 and residues conforming and close to it. The outward orientation of Arg414 additionally favored the conversion of (R) amines. This configuration was also found to favor the utilization of putrescine as an amine donor, so that class III ω-TAs with Arg414 in outward orientation may participate in vivo in the catabolism of putrescine. The positioning of the conserved Ser231 also contributes to the preference for amines with longer alkyl substituents. Optimal temperatures for activity ranged from 45 to 65°C, and a few enzymes retained ≥50% of their activity in water-soluble solvents (up to 50% [vol/vol]). Hence, our results will pave the way to design, in the future, new class III ω-TAs converting bulky ketones and (R) amines for the production of high-value products and to screen for those converting putrescine

Moving away from the "unit cost". Predicting country-specific average cost curves of VMMC services accounting for variations in service delivery platforms in sub-Saharan Africa.

BACKGROUND: One critical element to optimize funding decisions involves the cost and efficiency implications of implementing alternative program components and configurations. Program planners, policy makers and funders alike are in need of relevant, strategic data and analyses to help them plan and implement effective and efficient programs. Contrary to widely accepted conceptions in both policy and academic arenas, average costs per service (so-called "unit costs") vary considerably across implementation settings and facilities. The objective of this work is twofold: 1) to estimate the variation of VMMC unit costs across service delivery platforms (SDP) in Sub-Saharan countries, and 2) to develop and validate a strategy to extrapolate unit costs to settings for which no data exists. METHODS: We identified high-quality VMMC cost studies through a literature review. Authors were contacted to request the facility-level datasets (primary data) underlying their results. We standardized the disparate datasets into an aggregated database which included 228 facilities in eight countries. We estimated multivariate models to assess the correlation between VMMC unit costs and scale, while simultaneously accounting for the influence of the SDP (which we defined as all possible combinations of type of facility, ownership, urbanicity, and country), on the unit cost variation. We defined SDP as any combination of such four characteristics. Finally, we extrapolated VMMC unit costs for all SDPs in 13 countries, including those not contained in our dataset. RESULTS: The average unit cost was 73 USD (IQR: 28.3, 100.7). South Africa showed the highest within-country cost variation, as well as the highest mean unit cost (135 USD). Uganda and Namibia had minimal within-country cost variation, and Uganda had the lowest mean VMMC unit cost (22 USD). Our results showed evidence consistent with economies of scale. Private ownership and Hospitals were significant determinants of higher unit costs. By identifying key cost drivers, including country- and facility-level characteristics, as well as the effects of scale we developed econometric models to estimate unit cost curves for VMMC services in a variety of clinical and geographical settings. CONCLUSION: While our study did not produce new empirical data, our results did increase by a tenfold the availability of unit costs estimates for 128 SDPs in 14 priority countries for VMMC. It is to our knowledge, the most comprehensive analysis of VMMC unit costs to date. Furthermore, we provide a proof of concept of the ability to generate predictive cost estimates for settings where empirical data does not exist

Developing the Global Health Cost Consortium Unit Cost Study Repository for HIV and TB: methodology and lessons learned.

Consistently defined, accurate, and easily accessible cost data are a valuable resource to inform efficiency analyses, budget preparation, and sustainability planning in global health. The Global Health Cost Consortium (GHCC) designed the Unit Cost Study Repository (UCSR) to be a resource for standardised HIV and TB intervention cost data displayed by key characteristics such as intervention type, country, and target population. To develop the UCSR, the GHCC defined a typology of interventions for each disease; aligned interventions according to the standardised principles, methods, and cost and activity categories from the GHCC Reference Case for Estimating the Costs of Global Health Services and Interventions; completed a systematic literature review; conducted extensive data extraction; performed quality assurance; grappled with complex methodological issues such as the proper approach to the inflation and conversion of costs; developed and implemented a study quality rating system; and designed a web-based user interface that flexibly displays large amounts of data in a user-friendly way. Key lessons learned from the extraction process include the importance of assessing the multiple uses of extracted data; the critical role of standardising definitions (particularly units of measurement); using appropriate classifications of interventions and components of costs; the efficiency derived from programming data checks; and the necessity of extraction quality monitoring by senior analysts. For the web interface, lessons were: understanding the target audiences, including consulting them regarding critical characteristics; designing the display of data in "levels"; and incorporating alert and unique trait descriptions to further clarify differences in the data

Reconciling Himalayan midcrustal discontinuities: The Main Central thrust system

The occurrence of thrust-sense tectonometamorphic discontinuities within the exhumed Himalayan metamorphic core can be explained as part of the Main Central thrust system. This imbricate thrust structure, which significantly thickened the orogenic midcrustal core, comprises a series of thrust-sense faults that all merge into a single detachment. The existence of these various structures, and their potential for complex overprinting along the main detachment, may help explain the contention surrounding the definition, mapping, and interpretation of the Main Central thrust. The unique evolution of specific segments of the Main Central thrust system along the orogen is interpreted to be a reflection of the inherent basement structure and ramp position, and structural level of exposure of the mid-crust. This helps explain the variation in the timing and structural position of tectonometamorphic discontinuities along the length of the mountain belt