Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age

Background: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10–100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and in vitro proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients. Objectives: To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs. Study Design: In vitro study. Methods: BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15–17 months), adult (5–8 years), middle-aged (12–18 years), and geriatric (≥ 22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers. Results: The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types. Main Limitations: Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated. Conclusions: The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of in vitro proliferation were observed in both MSC types from horses in the age groups below 18 years of age

Optimum sample size to estimate mean parasite abundance in fi sh parasite surveys

[EN] To reach ethically and scientifically valid mean abundance values in parasitological and epidemiological studies this paper considers analytic and simulation approaches for sample size determination. The sample size estimation was carried out by applying mathematical formula with predetermined precision level and parameter of the negative binomial distribution estimated from the empirical data. A simulation approach to optimum sample size determination aimed at the estimation of true value of the mean abundance and its confidence interval (CI) was based on the Bag of Little Bootstraps (BLB). The abundance of two species of monogenean parasites Ligophorus cephali and L. mediterraneus from Mugil cephalus across the Azov-Black Seas localities were subjected to the analysis. The dispersion pattern of both helminth species could be characterized as a highly aggregated distribution with the variance being substantially larger than the mean abundance. The holistic approach applied here offers a wide range of appropriate methods in searching for the optimum sample size and the understanding about the expected precision level of the mean. Given the superior performance of the BLB relative to formulae with its few assumptions, the bootstrap procedure is the preferred method. Two important assessments were performed in the present study: i) based on CIs width a reasonable precision level for the mean abundance in parasitological surveys of Ligophorus spp. could be chosen between 0.8 and 0.5 with 1.6 and 1x mean of the CIs width, and ii) the sample size equal 80 or more host individuals allows accurate and precise estimation of mean abundance. Meanwhile for the host sample size in range between 25 and 40 individuals, the median estimates showed minimal bias but the sampling distribution skewed to the low values; a sample size of 10 host individuals yielded to unreliable estimates.SS and VS were supported by MEDEA project fellowships, Erasmus Mundus Action 2. CC-S was funded by project #MTM2014-52975-C2-1-R:" Inference in Structured Additive Regression (STAR) Models with Extensions to Multivariate Responses. Applications in Biomedicine", cofinanced by the Ministry of Economy and Competitiveness (SPAIN) and by the European Regional Development Fund (FEDER). This study is partially supported by Ministry of Education and Science of Ukraine, project #1/17.Shvydka, S.; Sarabeev, V.; Estruch, VD.; Cadarso-Suarez, C. (2018). Optimum sample size to estimate mean parasite abundance in fi sh parasite surveys. Helminthologia. 55(1):52-59. https://doi.org/10.1515/helm-2017-0054S5259551Rohde, K., Hayward, C., & Heap, M. (1995). Aspects of the ecology of metazoan ectoparasites of marine fishes. International Journal for Parasitology, 25(8), 945-970. doi:10.1016/0020-7519(95)00015-tAnderson, R. M., & Gordon, D. M. (1982). Processes influencing the distribution of parasite numbers within host populations with special emphasis on parasite-induced host mortalities. Parasitology, 85(2), 373-398. doi:10.1017/s0031182000055347Poiani, A. (1992). Ectoparasitism as a possible cost of social life: a comparative analysis using Australian passerines (Passeriformes). Oecologia, 92(3), 429-441. doi:10.1007/bf00317470Kleiner, A., Talwalkar, A., Sarkar, P., & Jordan, M. I. (2014). A scalable bootstrap for massive data. Journal of the Royal Statistical Society: Series B (Statistical Methodology), 76(4), 795-816. doi:10.1111/rssb.12050Jovani, R., & Tella, J. L. (2006). Parasite prevalence and sample size: misconceptions and solutions. Trends in Parasitology, 22(5), 214-218. doi:10.1016/j.pt.2006.02.011BAGGE, A. M., SASAL, P., VALTONEN, E. T., & KARVONEN, A. (2005). Infracommunity level aggregation in the monogenean communities of crucian carp (Carassius carassius). Parasitology, 131(3), 367-372. doi:10.1017/s0031182005007626Belghyti, D., Berrada-rkhami, O., Boy, V., Aguesse, P., & Gabrion, C. (1994). Population biology of two helminth parasites of flatfishes from the Atlantic coast of Morocco. Journal of Fish Biology, 44(6), 1005-1021. doi:10.1111/j.1095-8649.1994.tb01272.xTAYLOR, L. R. (1961). Aggregation, Variance and the Mean. Nature, 189(4766), 732-735. doi:10.1038/189732a

Mood instability, mental illness and suicidal ideas : results from a household survey

Purpose: There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. Methods: We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. Results: There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95 % confidence interval (CI) 7.51–15.13] and PTSD by 8.69 (95 % CI 5.90–12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95 % CI 3.39–6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. Conclusions: MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required

Detection and identification by PCR of Clostridium chauvoei in clinical isolates, bovine faeces and substrates from biogas plant

<p>Abstract</p> <p>Background</p> <p><it>Clostridium chauvoei </it>causes blackleg, an acute disease associated with high mortality in ruminants. The apparent primary port of entry is oral, during grazing on pasture contaminated by spores. Cases of blackleg can occur year after year on contaminated pastures. A method to determine the prevalence of <it>C. chauvoei </it>spores on pasture would be useful.</p> <p>The standard method for <it>C. chauvoei </it>detection is culture and biochemical identification, which requires a pure culture. In most muscle samples from cattle dead from blackleg the amount of <it>C. chauvoei </it>in samples is high and the bacterium can easily be cultured, although some samples may be contaminated. Detection by PCR would be faster and independent of contaminating flora.</p> <p>Digested residues from biogas plants provide an excellent fertiliser, but it is known that spore-forming baeria such as <it>Clostridium </it>spp. are not reduced by pasteurisation. The use of digested residues as fertiliser may contribute to the spread of <it>C. chauvoei</it>. Soil, manure and substrate from biogas plants are contaminated with other anaerobic bacteria which outgrow <it>C. chauvoei</it>. Therefore, detection by PCR is would be useful. This study applied a PCR-based method to detect of <it>C. chauvoei </it>in 25 muscle and blood samples, 114 manure samples, 84 soil samples and 33 samples from the biogas process.</p> <p>Methods</p> <p>Muscle tissues from suspected cases of blackleg were analysed both by the standard culture method followed by biochemical identification and by PCR, with and without preculture. To investigate whether muscle tissue samples are necessary, samples taken by swabs were also investigated. Samples from a biogas plant and manure and soil from farms were analysed by culture followed by PCR. The farms had proven cases of blackleg. For detection of <it>C. chauvoei </it>in the samples, a specific PCR primer pair complementary to the spacer region of the 16S-23S rRNA gene was used.</p> <p>Results</p> <p><it>Clostridium chauvoei </it>was detected in 32% of muscle samples analysed by culture with identification by biochemical methods and in 56% of cases by culture in combination with PCR. <it>Clostridium chauvoei </it>was detected in 3 (out of 11) samples from the biogas plants collected before pasteurisation, but samples taken after pasteurisation and after digestion all tested negative. <it>Clostridium chauvoei </it>was not detected in any soil or silage samples and only one manure samples tested positive.</p> <p>Conclusion</p> <p>The diagnostic method used for <it>C. chauvoei </it>was not applicable in estimating the risk of blackleg on particular pastures from manure or soil samples, but found to be highly useful for clinical samples.</p

Bridging the domestic building fabric performance gap

It is recognized that there is often a discrepancy between the measured fabric thermal performance of dwellings as built and the predicted performance of the same dwellings and that the magnitude of this difference in performance can be quite large. This paper presents the results of a number of in-depth building fabric thermal performance tests undertaken on three case study dwellings located on two separate Passivhaus developments in the UK: one masonry cavity and the other two timber-frame. The results from the tests revealed that all the case study dwellings performed very close to that predicted. This is in contrast with other work that has been undertaken regarding the performance of the building fabric, which indicates that a very wide range of performance exists in new-build dwellings in the UK, and that the difference between the measured and predicted fabric performance can be greater than 100%. Despite the small non-random size of the sample, the results suggest that careful design coupled with the implementation of appropriate quality control systems, such as those required to attain Passivhaus Certification, may be conducive to delivering dwellings that begin to ‘bridge the gap’ between measured and predicted fabric performance

High performance aluminum–cerium alloys for high-temperature applications

Light-weight high-temperature alloys are important to the transportation industry where weight, cost, and operating temperature are major factors in the design of energy efficient vehicles. Aluminum alloys fill this gap economically but lack high-temperature mechanical performance. Alloying aluminum with cerium creates a highly castable alloy, compatible with traditional aluminum alloy additions, that exhibits dramatically improved high-temperature performance. These compositions display a room temperature ultimate tensile strength of 400 MPa and yield strength of 320 MPa, with 80% mechanical property retention at 240 °C. A mechanism is identified that addresses the mechanical property stability of the Al-alloys to at least 300 °C and their microstructural stability to above 500 °C which may enable applications without the need for heat treatment. Finally, neutron diffraction under load provides insight into the unusual mechanisms driving the mechanical strength

A novel length back-calculation approach accounting for ontogenetic changes in the fish length – otolith size relationship during the early life of sprat (Sprattus sprattus)

(Sprattus sprattus), accounting for ontogenetic changes in the relationship between fish length and otolith length. In sprat, metamorphosis from larvae to juveniles is characterized by the coincidence of low length growth, strong growth in body height, and maximal otolith growth. Consequently, the method identifies a point of metamorphosis for an individual as the otolith radius at maximum increment widths. By incorporating this information in our back-calculation method, estimated length growth for the early larval stage was more than 60% higher compared with the result of the biological intercept model. After minimal length growth during metamorphosis, we found the highest increase in length during the early juvenile stage. We thus located the strongest growth potential in the early juvenile stage, which is supposed to be critical in determining recruitment strength in Baltic sprat

The MAGPI Survey: Drivers of kinematic asymmetries in the ionised gas of z∼0.3z\sim0.3 star-forming galaxies

Galaxy gas kinematics are sensitive to the physical processes that contribute to a galaxy's evolution. It is expected that external processes will cause more significant kinematic disturbances in the outer regions, while internal processes will cause more disturbances for the inner regions. Using a subsample of 47 galaxies ($0.27<z<0.36$) from the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, we conduct a study into the source of kinematic disturbances by measuring the asymmetry present in the ionised gas line-of-sight velocity maps at the $0.5R_e$ (inner regions) and $1.5R_e$ (outer regions) elliptical annuli. By comparing the inner and outer kinematic asymmetries, we aim to better understand what physical processes are driving the asymmetries in galaxies. We find the local environment plays a role in kinematic disturbance, in agreement with other integral field spectroscopy studies of the local universe, with most asymmetric systems being in close proximity to a more massive neighbour. We do not find evidence suggesting that hosting an Active Galactic Nucleus (AGN) contributes to asymmetry within the inner regions, with some caveats due to emission line modelling. In contrast to previous studies, we do not find evidence that processes leading to asymmetry also enhance star formation in MAGPI galaxies. Finally, we find a weak anti-correlation between stellar mass and asymmetry (ie. high stellar mass galaxies are less asymmetric). We conclude by discussing possible sources driving the asymmetry in the ionised gas, such as disturbances being present in the colder gas phase (either molecular or atomic) prior to the gas being ionised, and non-axisymmetric features (e.g., a bar) being present in the galactic disk. Our results highlight the complex interplay between ionised gas kinematic disturbances and physical processes involved in galaxy evolution.Comment: e.g., 20 pages, 19 figure

1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

Abstract Background There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma &gt; 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma &gt; 1 mm in BT. Methods This phase III, multicentre trial [NCT02385214] administered by the Australia &amp; New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma &gt; 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation. Results Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p &lt; 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months’ follow-up, no differences were noted in QoL between groups. Discussion This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma. </jats:sec