Putting zoo animal cancer into perspective.

As part of a comparative research agenda that promises insights that help extend the human lifespan and combat cancer, cancer prevalence in zoo animals has received recent attention. Here, we want to draw attention to a principle of cancer research that was introduced into the zoo world as early on as 1933, but that seems to have gone somewhat forgotten: Cancer is mainly a disease of old age, and therefore studies aiming at identifying taxa that are particularly susceptible or resistant to cancer must control for whether the respective zoo populations are 'old.' In a comparative context, 'old age' cannot be measured in absolute terms (e.g., years), but only in relation to a species' maximum lifespan: Species that achieve, across zoos, a higher mean lifespan as a percent of their maximum lifespan are 'older.' When applying this metric to former as well as more recently published data on cancer prevalence, it appears that those species that become relatively old in zoos-in particular, the carnivores-have a relatively high cancer prevalence. Any improvement in animal husbandry-which reduces premature deaths-should, by default, lead to more cancer. Cancer in zoo animals, like any other old-age condition, might therefore be embraced as a proxy for good husbandry. Rather than following a sensationalist approach that dramatizes disease and death per se, zoos should be clear about what their husbandry goals are, what relative longevities they want to achieve for which species, and what old-age diseases they should therefore expect: in the end, one has to die of something.

The historical development of zoo elephant survivorship.

In the discussion about zoo elephant husbandry, the report of Clubb et al. (2008, Science 322: 1649) that zoo elephants had a "compromised survivorship" compared to certain non-zoo populations is a grave argument, and was possibly one of the triggers of a large variety of investigations into zoo elephant welfare, and changes in zoo elephant management. A side observation of that report was that whereas survivorship in African elephants (Loxodonta africana) improved since 1960, this was not the case in Asian elephants (Elephas maximus). We used historical data (based on the Species360 database) to revisit this aspect, including recent developments since 2008. Assessing the North American and European populations from 1910 until today, there were significant improvements of adult (≥10 years) survivorship in both species. For the period from 1960 until today, survivorship improvement was significant for African elephants and close to a significant improvement in Asian elephants; Asian elephants generally had a higher survivorship than Africans. Juvenile (<10 years) survivorship did not change significantly since 1960 and was higher in African elephants, most likely due to the effect of elephant herpes virus on Asian elephants. Current zoo elephant survivorship is higher than some, and lower than some other non-zoo populations. We discuss that in our view, the shape of the survivorship curve, and its change over time, are more relevant than comparisons with specific populations. Zoo elephant survivorship should be monitored continuously, and the expectation of a continuous trend towards improvement should be met.

Historical development of the survivorship of zoo rhinoceroses-A comparative historical analysis.

Zoo animal husbandry is a skill that should be developing constantly. In theory, this should lead to an improvement of zoo animal survivorship over time. Additionally, it has been suggested that species that are at a comparatively higher risk of extinction in their natural habitats (in situ) might also be more difficult to keep under zoo conditions (ex situ). Here, we assessed these questions for three zoo-managed rhinoceros species with different extinction risk status allocated by the IUCN: the "critically endangered" black rhino (Diceros bicornis), the "vulnerable" greater one-horned (GOH) rhino (Rhinoceros unicornis), and the "near threatened" white rhino (Ceratotherium simum). Comparing zoo animals ≥1 year of age, the black rhino had the lowest and the white rhino the highest survivorship, in congruence with their extinction risk status. Historically, the survivorship of both black and white rhino in zoos improved significantly over time, whereas that of GOH rhino stagnated. Juvenile mortality was generally low and decreased even further in black and white rhinos over time. Together with the development of population pyramids, this shows increasing competence of the global zoo community to sustain all three species. Compared to the continuously expanding zoo population of GOH and white rhinos, the zoo-managed black rhino population has stagnated in numbers in recent years. Zoos do not only contribute to conservation by propagating ex situ populations, but also by increasing species-specific husbandry skills. We recommend detailed research to understand specific factors responsible for the stagnation but also the general improvement of survivorship of zoo-managed rhinos.

A Hippocratic Oath for Mathematicians? Mapping the Landscape of Ethics in Mathematics.

While the consequences of mathematically-based software, algorithms and strategies have become ever wider and better appreciated, ethical reflection on mathematics has remained primitive. We review the somewhat disconnected suggestions of commentators in recent decades with a view to piecing together a coherent approach to ethics in mathematics. Calls for a Hippocratic Oath for mathematicians are examined and it is concluded that while lessons can be learned from the medical profession, the relation of mathematicians to those affected by their work is significantly different. There is something to be learned also from the codes of conduct of cognate but professionalised quantitative disciplines such as engineering and accountancy, as well as from legal principles bearing on professional work. We conclude with recommendations that professional societies in mathematics should sponsor an (international) code of ethics, institutional mission statements for mathematicians and syllabuses of ethics courses for incorporation into mathematics degrees.

Cryoaerogels and Cryohydrogels as Efficient Electrocatalysts.

Additive-free cryoaerogel coatings from noble metal nanoparticles are prepared and electrochemically investigated. By using liquid nitrogen or isopentane as cooling medium, two different superstructures are created for each type of noble metal nanoparticle. These materials (made from the same amount of particles) have superior morphological and catalytic properties as compared to simply immobilized, densely packed nanoparticles. The morphology of all materials is investigated with scanning electron microscopy (SEM). Electrochemically active surface areas (ECSAs) are calculated from cyclic voltammetry measurements. The catalytic activity is studied for the ethanol oxidation reaction (EOR). Both are found to be increased for superstructured materials prepared by cryoaerogelation. Furthermore, cryoaerogels with cellular to dendritic structure that arise from freezing with isopentane show the best catalytic performance and highest ECSA. Moreover, as a new class of materials, cryohydrogels are created for the first time by thawing flash-frozen nanoparticle solutions. Structure and morphology of these materials match with the corresponding types of cryoaerogels and are confirmed via SEM. Even the catalytic activity in EOR is in accordance with the results from cryoaerogel coatings. As a proof of concept, this approach offers a novel platform towards the easier and faster production of cryogelated materials for wet-chemical applications.

Validation of Ab-Initio-Predicted Magnetic Anisotropies and Magneto-structural Correlations in Linear Hetero-trinuclear DyIII -NiII 2 Compounds.

Reported are single crystal SQUID and single crystal high-frequency/high-field EPR data of a trinuclear complex with a rare six-coordinate coordination sphere of a DyIII center coupled to two terminal six-coordinate NiII ions. The analysis of the single crystal spectroscopic parameters allows for an accurate description of the ground state wavefunction. The experimental analysis is supplemented by the analysis of the paramagnetic NMR spectra, allowing for a thorough description of the DyIII center. The experimental data are interpreted on the basis of an ab initio ligand field analysis, and the computed parameters are in good agreement with the experimental observations. This supports the quality of the theoretical approach based on a pseudo-spin Hamiltonian for the electronic ground state. Further support emerges from the ab initio ligand field theory based analysis of a structurally very similar system that, in contrast to the complex reported here, shows single molecule magnetic properties, and this is in agreement with the quantum-chemical prediction and analysis.

Structural Diversity in Cryoaerogel Synthesis.

Different techniques that enable the selective microstructure design of aerogels without the use of additives are presented. For this, aerogels were prepared from platinum nanoparticle solutions using the cryoaerogelation method, and respective impacts of different freezing times, freezing media, and freezing temperatures were investigated with electron microscopy as well as inductively coupled plasma optical emission spectroscopy. The use of lower freezing temperatures, freezing media with higher heat conductivities, and longer freezing periods led to extremely different network structures with enhanced stability. In detail, materials were created in the shape of lamellar, cellular, and dendritic networks. So far, without changing the building blocks, it was not possible to create the selective morphologies of resulting aerogels in cryoaerogelation. Now, these additive-free approaches enable targeted structuring and will open up new opportunities in the future cryoaerogel design.

Robotic-Assisted Versus Conventional Open Partial Nephrectomy (Robocop): A Propensity Score-Matched Analysis of 249 Patients.

OBJECTIVES: The objective of this study was to compare open partial nephrectomy (OPN) and robotic-assisted PN (RAPN) based on a propensity score-matched sample and to test the Comprehensive Complication Index (CCI) as an end point for complications. METHODS: Patients undergoing PN from 2010 to 2018 at a university care center were included. OPN and RAPN cases were matched in a 2:1 ratio using propensity score-matching with age, gender, BMI, RENAL score, and tumor size as confounders. The primary end point was complications measured with the CCI as continuous score (0-100, 100 indicating death). RESULTS: Data of 570 patients were available. After matching, both cohorts (OPN = 166; RAPN = 83) showed no baseline differences. For the primary end point, CCI, RAPN was superior (RAPN 2.6 ± 7.9 vs. OPN 8.7 ± 13.9; p < 0.001). Additionally, RAPN was superior for length of stay (RAPN 6.5 ± 4.0 vs. OPN 7.4 ± 3.5 days; p < 0.001), hemoglobin drop (RAPN 2.8 ± 1.4 vs. OPN 3.8 ± 1.6 g/dL; p < 0.001), and drop of glomerular filtration rate (RAPN 11.4 ± 14.2 vs. OPN 19.5 ± 14.3 mL/min; p < 0.001). OPN had shorter operating times (RAPN 157 ± 43 vs. OPN 143 ± 45 min; p = 0.014) and less ischemia (RAPN 13% vs. OPN 28%; p = 0.016). CONCLUSIONS: RAPN provides superior short-term results regarding overall complications without compromising renal function for small and less complex tumors. However, OPN remains an important option for more complex and larger tumors.

The historical development of juvenile mortality and adult longevity in zoo-kept carnivores.

Zoos need to evaluate their aim of high husbandry standards. One way of approaching this is to use the demographic data that has been collected by participating zoos for decades, assessing historical change over time to identify the presence or absence of progress. Using the example of carnivores, with data covering seven decades (1950-2019), 13 carnivore families, and 95 species, we show that juvenile mortality has decreased, and adult longevity increased, over this interval. While no reason for complacency, the results indicate that the commitment of zoos to continuously improve is having measurable consequences.

Massive Conformal Symmetry and Integrability for Feynman Integrals.

In the context of planar holography, integrability plays an important role for solving certain massless quantum field theories such as N=4 super Yang-Mills theory. In this Letter, we show that integrability also features in the building blocks of massive quantum field theories. At one-loop order we prove that all massive n-gon Feynman integrals in generic spacetime dimensions are invariant under a massive Yangian symmetry. At two loops similar statements can be proven for graphs built from two n-gons. At generic loop order we conjecture that all graphs cut from regular tilings of the plane with massive propagators on the boundary are invariant. We support this conjecture by a number of numerical tests for higher loops and legs. The observed Yangian extends the bosonic part of the massive dual conformal symmetry that was found a decade ago on the Coulomb branch of N=4 super Yang-Mills theory. By translating the Yangian level-one generators from dual to original momentum space, we introduce a massive generalization of momentum space conformal symmetry. Even for non-dual-conformal integrals this novel symmetry persists. The Yangian can thus be understood as the closure of massive dual conformal symmetry and this new massive momentum space conformal symmetry, which suggests an interpretation via AdS/CFT. As an application of our findings, we bootstrap the hypergeometric building blocks for examples of massive Feynman integrals.

The uneven weight distribution between predators and prey: Comparing gut fill between terrestrial herbivores and carnivores.

The general observation that secondary consumers ingest highly digestible food and have simple short guts and small abdominal cavities intuitively results in the assumption that mammalian carnivores carry less digesta in their gut compared to herbivores. Due to logistic constraints, this assumption has not been tested quantitatively so far. In this contribution, we estimated the dry matter gut contents (DMC) for 25 species of the order Carnivora (including two strictly herbivorous ones, the giant and the red panda) using the physical 'Occupancy Principle', based on a literature data collection on dry matter intake (DMI), apparent dry matter digestibility (aD DM) and retention time (RT), and compared the results to an existing collection for herbivores. Scaling exponents with body mass (BM) for both carnivores and herbivores were in the same range with DMI ~ BM0.75; aD DM ~ BM0; RT ~ BM0.11 and DMC ~ BM0.88. The trophic level (carnivore vs herbivore) significantly affected all digestive physiology parameters except for RT. Numerically, the carnivore DMI level reached 77%, the RT 32% and DMC only 29% of the corresponding herbivore values, whereas the herbivore aD DM only reached 82% of that of carnivores. Thus, we quantitatively show that carnivores carry less inert mass or gut content compared to herbivores, which putatively benefits them in predator-prey interactions and might have contributed to the evolution towards unguligradism in herbivores. As expected, the two panda species appeared as outliers in the dataset with low aD DM and RT for a herbivore but extremely high DMI values, resulting in DMC in the lower part of the herbivore range. Whereas the difference in DMI and DMC scaling in herbivores might allow larger herbivores to compensate for lower diet quality by ingesting more, this difference may allow larger carnivores not to go for less digestible prey parts, but mainly to increase meal intervals, i.e. not having to hunt on a daily basis.

Introduction of Noninvasive Prenatal Testing for Blood Group and Platelet Antigens from Cell-Free Plasma DNA Using Digital PCR.

BACKGROUND: Noninvasive prenatal testing (NIPT) for fetal antigens is a common standard for targeted immune prophylaxis in RhD-mediated hemolytic disease of the fetus and newborn, and is most frequently done by quantitative PCR (qPCR). A similar approach is considered for other blood group and human platelet alloantigens (HPA). Because of a higher sensitivity compared to qPCR for rare molecule detection, we established and validated digital PCR (dPCR) assays for the detection of RHD exons 3, 5 and 7, KEL1, HPA-1a, and HPA-5b from cell-free DNA (cfDNA) in plasma. The dPCR assays for the Y-chromosomal marker amelogenin and autosomal SNPs were implemented as controls for the proof of fetal DNA. METHODS: Validation was performed on dilution series of mixed plasma samples from volunteer donors with known genotypes. After preamplification of the target loci, two-color (FAM and VIC) TaqManTM probe chemistry and chip-based dPCR were applied. The assays for RHD included GAPDH as an internal control. For the diallelic markers KEL1/2, HPA-1a/b, HPA-5a/b, and AMEL-X/Y and 3 autosomal SNPs, the probes enabled allelic discrimination in the two fluorescence channels. The dPCR protocol for NIPT was applied to plasma samples from pregnant women. RESULTS: The RHD exon 5 assay allowed the detection of a 0.05% RHD target in an RhD-negative background, whereas the exon 7 assay required at least a 0.25% target. The exon 3 assay showed the highest background and required at least a 2.5% RHD target for reliable detection. The dPCR assays for the diallelic markers revealed similar sensitivity and enabled the detection of at least a 0.5% target allele. The HPA-1a assay was the most sensitive and allowed target detection in plasma mixtures containing only 0.05% HPA-1a. The plasma samples from 13 pregnant women at different gestational ages showed unambiguous positive and negative results for the analyzed targets. CONCLUSION: Analysis of cfDNA from maternal plasma using dPCR is suitable for the detection of fetal alleles. Because of the high sensitivity of the assays, the NIPT protocol for RhD, KEL1, and HPA can also be applied to earlier stages of pregnancy.

Application of Mie theory for enhanced size determination of microparticles using optical particle counters.

The approach to particle sizing with optical particle counters is often simple interpolation of calibration data. A method is presented that uses the results of Mie-theory-based simulations to describe the signal between calibration points, thus reducing the number of necessary calibration points or increasing the sizing accuracy significantly. Through the use of Mie theory, particles with a refractive index differing from the calibration particles can be measured without an individual calibration. The method can be used with custom research setups or commercially available optical particle counters with various detector designs. If needed, the method can be applied to particle counters for which only the light wavelength used is known. The method is tested using a commercially available optical particle counter with a polystyrene microsphere calibration, measuring polystyrene microspheres as well as THP-1 cells, Chinese hamster ovary cells, and yeast cells. Without material specific calibration, simple interpolation results in about half the actual particle sizes for these biological samples, whereas the presented method yields accurate results.

Controlled feeding experiments with diets of different abrasiveness reveal slow development of mesowear signal in goats (Capra aegagrus hircus).

Dental mesowear is applied as a proxy to determine the general diet of mammalian herbivores based on tooth-cusp shape and occlusal relief. Low, blunt cusps are considered typical of grazers and high, sharp cusps typical of browsers. However, how internal or external abrasives impact mesowear, and the time frame the wear signature takes to develop, still need to be explored. Four different pelleted diets of increasing abrasiveness (lucerne, grass, grass and rice husks, and grass, rice husks and sand) were fed to four groups of a total of 28 adult goats in a controlled feeding experiment over a 6-month period. Tooth morphology was captured by medical CT scans at the beginning and end of the experiment. These scans, as well as the crania obtained post mortem, were scored using the mesowear method. Comparisons between diet groups showed few significant differences after 6 months, irrespective of whether CT scans or the real teeth were scored. Only when assessing the difference in signal between the beginning and the end of the experiment did relevant, significant diet-specific effects emerge. Diets containing lower phytolith content caused a more pronounced change in mesowear towards sharper cusps/higher reliefs, while the feed containing sand did not result in more extreme changes in mesowear when compared with the same feed without sand. Our experiment suggests that the formation of a stable and hence reliable mesowear signal requires more time to develop than 6 months.

Influence of testosterone on phase II metabolism and availability of soy isoflavones in male Wistar rats.

Genistein and daidzein are the main isoflavones in soy. Their potential beneficial or adverse effects in males like the prevention of prostate cancer or the impact on reproductive functions are controversially discussed. Major determinants of their bioactivity are the absorption and biotransformation of isoflavones. In this study, we focused on the influence of testosterone on plasma availability and phase II metabolism of isoflavones. Male Wistar rats, receiving an isoflavones rich diet, were randomized into three groups: Two groups were orchiectomized (ORX) at postnatal day (PND) 80 and treated for 11 days with testosterone propionate (TP) (ORX TP group) or a vehicle (ORX group) after a 7 days lasting hormonal decline. The third group served as control and remained intact. Rats were sacrificed at PND 98. ORX rats had reduced isoflavones plasma levels. Differently regulated mRNA expressions of transporters relevant for transport of phase II metabolites in liver and kidney may be responsible for this reduction, more precisely Slc10a1 and Slc21a1 in kidney as well as Slc22a8 in liver. While main phase II metabolites in intact rats were disulfates and sulfoglucuronides, the amount of sulfate conjugates was significantly diminished by ORX. In accordance with that, mRNA expression of different sulfotransferases was reduced in liver by ORX. The observed effects could be almost restored by TP treatment. In conclusion, testosterone, and likely further androgens, has a huge impact on phase II metabolism and availability of isoflavones by influencing the expression of different sulfotransferases and transporters.

Seasonal mortality in zoo ruminants.

While seasonality has often been investigated with respect to reproduction, seasonality of mortality has received less attention. We investigated whether a seasonal signal of mortality exists in wild ruminants kept in zoos, using data from 60,591 individuals of 88 species. We quantified the mortality in the 3 consecutive months with the highest above-baseline mortality (3 MM). 3 MM was not related to relative life expectancy of species, indicating that seasonal mortality does not necessarily impact husbandry success. Although 3 MM was mainly observed in autumn/winter months, there was no evidence for an expected negative relationship with the latitude of the species' natural habitat and no positive relationship between 3 MM and the mean temperature in that habitat, indicating no evidence for species from lower latitudes/warmer climates being more susceptible to seasonal mortality under zoo conditions. 3 MM was related to reproductive biology, with seasonally reproducing species also displaying more seasonal mortality. This pattern differed between groups: In cervids, the onset of seasonal mortality appeared linked to the onset of rut in both sexes. This was less evident in bovids, where in a number of species (especially caprids), the onset of female seasonal mortality was linked to the lambing period. While showing that the origin of a species from warmer climate zones does not constrain husbandry success in ruminants in terms of an increased seasonal mortality, the results suggest that husbandry measures aimed at protecting females from rutting males are important, especially in cervids. Zoo Biol. 36:74-86, 2017. © 2016 Wiley Periodicals, Inc.

Phase II metabolism of the soy isoflavones genistein and daidzein in humans, rats and mice: a cross-species and sex comparison.

Soy isoflavones (IF) are in the focus of biomedical research since more than two decades. To assess their bioactivity, IF are investigated in rats and mice as a model. As the biological activity of IF is affected by their biotransformation, our aim was to comprehensively compare the conjugative and microbial metabolism of daidzein and genistein in adult humans, rats and mice of both sexes. One identical soy extract and a validated LC-MS method were used for all studies. We detected considerable differences between the three species. In rats and mice, sex-specific differences were observed in addition. The major plasma phase II metabolites in humans were the 7-sulfo-4'-glucuronides (39-49 %) and, in case of genistein, also the diglucuronide (34 %), whereas in mice monosulfates (33-41 %) and monoglucuronides (30-40 %) predominated. In male rats the disulfates (23-62 %) and 7-sulfo-4'-glucuronides (19-54 %) were predominant, while in female rats the 7-glucuronides (81-93 %) exhibited highest concentrations. The portion of aglycones was low in humans (0.5-1.3 %) and rats (0.5-3.1 %) but comparatively high in mice (3.1-26.0 %), especially in the case of daidzein. Furthermore, substantial differences were observed between daidzein and genistein metabolism. In contrast to humans, all rats and mice were equol producer, independent of their sex. In conclusion, there are marked differences between humans, rats and mice in the profile of major metabolites following IF phase II metabolism. These differences may contribute to resolve inconsistencies in results concerning the bioactivity of IF and should be considered when applying findings of animal studies to humans, e.g., for risk assessment.

A Thermally Populated, Perpendicularly Twisted Alkene Triplet Diradical.

Variable-temperature NMR and ESR spectroscopic studies reveal that bis(dibenzo[a,i]fluorenylidene) 1 possesses a singlet ground state, 1(S0 ), while the 90° twisted triplet 1(T1 ) is populated to a small extent already at room temperature. Analysis of the increasing amount of paramagnetic 1(T1 ) at temperatures between 300 and 500 K yields the exchange interaction Jex /h c=3351 cm-1 and a singlet-triplet energy splitting of 9.6 kcal mol-1 , which is in excellent agreement with calculations (9.3 kcal mol-1 at the UKS BP86/B3LYP/revPBE level of theory). In contrast, the zero-field splitting parameter D is very small (calculated value -0.018 cm-1 ) and unmeasurable.

Magnetic Interactions in a Series of Homodinuclear Lanthanide Complexes.

A series of seven isostructural homodinuclear lanthanide complexes are reported. The magnetic properties (ac and dc SQUID measurements) are discussed on the basis of the X-ray structural properties which show that the two lanthanide sites are structurally different. MCD spectroscopy of the dysprosium(III) and neodymium(III) complexes ([Dy(III)2(L)(OAc)4](+) and [Nd(III)2(L)(OAc)4](+)) allowed us to thoroughly analyze the ligand field, and high-frequency EPR spectroscopy of the gadolinium(III) species ([Gd(III)2(L)(OAc)4](+)) showed the importance of dipolar coupling in these systems. An extensive quantum-chemical analysis of the dysprosium(III) complex ([Dy(III)2(L)(OAc)4](+)), involving an ab initio (CASSCF) wave function, explicit spin-orbit coupling (RASSI-SO), and a ligand field analysis (Lines model and Stevens operators), is in full agreement with all experimental data (SQUID, HF-EPR, MCD) and specifically allowed us to accurately simulate the experimental χT versus T data, which therefore allowed us to establish a qualitative model for all relaxation pathways.

Digesta kinetics in gazelles in comparison to other ruminants: Evidence for taxon-specific rumen fluid throughput to adjust digesta washing to the natural diet.

Digesta flow plays an important role in ruminant digestive physiology. We measured the mean retention time (MRT) of a solute and a particle marker in the gastrointestinal tract (GIT) and the reticulorumen (RR) of five gazelles and one dikdik species. Species-specific differences were independent from body mass (BM) or food intake. Comparative evaluations (including up to 31 other ruminant species) indicate that MRT GIT relate positively to BM, and are less related to feeding type (the percentage of grass in the natural diet, %grass) than MRT RR. The MRTparticleRR is related to BM and (as a trend) %grass, matching a higher RR capacity with increasing BM in grazers compared to browsers. MRTsoluteRR is neither linked to BM nor to %grass but shows a consistent phylogenetic signal. Selectivity factors (SF; MRTparticle/MRTsolute, proxies for the degree of digesta washing) are positively related to %grass, with a threshold effect, where species with >20% grass have higher SF. These findings suggest that in different ruminant taxa, morphophysiological adaptations controlling MRTsoluteRR evolved to achieve a similar SF RR in relation to a %grass threshold. A high SF could facilitate an increased microbial yield from the forestomach. Reasons for variation in SF above the %grass threshold might represent important drivers of ruminant diversification and await closer investigation.