Development of LIME-NZ: a generic tool for prompt estimation of economic impacts of disease for New Zealand livestock.

AIMS: To develop a simple and robust generic tool to measure the impacts of livestock diseases on New Zealand dairy, beef and sheep farms using enterprise gross margin models. METHODS: The most recent (2018-2020) livestock production benchmarking data was extracted from industry-led economic surveys. Gross margin models were built for each enterprise type, accounting for 11 dairy farm types and 16 farm types for beef and sheep. Disease parameters, including changes in mortality, reproduction performance, milk yield, price of animals and culling rate, as well as additional expenses for veterinary intervention, were applied to the infected compartment of the herd/flock using the assumed annual within-herd disease incidence. Farm-level disease impacts were estimated as the difference in annual profit between the baseline and infected farm. The baseline gross margin models were validated against the industry data. The disease impact models were validated using a recently published study on bovine viral diarrhoea (BVD). The impact assessment tool, LIME-NZ, was developed using the statistical software R and implemented in the web-based R package Shiny. The input parameters can be varied interactively to obtain a range of disease impacts for uncertain disease parameters. RESULTS: The baseline gross margin models demonstrated reasonable accuracy with a mean percentage error of <14% when compared with the industry reports. The estimated annual impacts of BVD were comparable to those reported in the BVD study, NZ$38.5-140.4 thousand and $0.9-32.6 thousand per farm per year for dairy and beef enterprises, respectively. CONCLUSIONS: LIME-NZ can be used to rapidly obtain the likely economic impacts of diseases that are endemic, recently introduced or at increased risk of introduction in the New Zealand context. This will aid communication and decision-making among government agencies and the livestock industry, including veterinarians and livestock producers, about the management of diseases, until refined information becomes available to improve decision-making.

Discovery of New Isotope

The new isotope ^{241}U was synthesized and systematic atomic mass measurements of nineteen neutron-rich Pa-Pu isotopes were performed in the multinucleon transfer reactions of the ^{238}U+^{198}Pt system at the KISS facility. The present experimental results demonstrate the crucial role of the multinucleon transfer reactions for accessing unexplored neutron-rich actinide isotopes toward the N=152 shell gap in this region of nuclides.

Study of the N=32 and N=34 Shell Gap for Ti and V by the First High-Precision Multireflection Time-of-Flight Mass Measurements at BigRIPS-SLOWRI.

The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.

Livestock movement patterns in the main livestock production provinces of Lao PDR.

Foot-and-mouth disease (FMD) is a highly infectious transboundary disease that is endemic and affects the livelihood of smallholder farmers in Lao People's Democratic Republic (PDR). Knowledge about livestock movement patterns is important for preventing the spread of FMD between villages. This study describes the livestock movement patterns in Champasak, Savannakhet and Xiangkhouang provinces of Lao PDR. Face-to-face interviews were conducted with randomly selected villagers (n = 195) and traders (n = 169) in 115 villages between February and March 2019. Livestock owners commonly purchased (mainly breeding) animals from other smallholders (81%) and sold (mainly slaughter) animals to traders (76%) or other smallholders (16%), typically within the same district and province. The median inter-village trade distance was 20-30 km, with an average frequency of 4 trades per village per month. Traders purchased animals from smallholders (71%) and middlemen (25%) located within their district. It was common for many traders (74%) to retain animals at their property before selling, typically a median of 4 beef cattle per trader. Local trades within the district were far more common (72%) than distant trades. The movements of grazing/fattening large ruminants between villages were reported in 30% of the villages in all three provinces and occurred mostly within the same district or province in short distance (6 km). Social Network Analysis has identified animal movement hubs in the three provinces which could be targeted for FMD control and surveillance. Movements of animals for further use (fattening/ reproduction), long-distance movements and frequent local movements described in this area have important implications for FMD circulation. The findings from the study will inform FMD spread simulation models for Lao PDR. The knowledge gained from these data will also help the Lao PDR authorities understand the patterns of animal movements associated with disease spread.

Properties of

Mass-separated ^{187}Ta_{114} in a high-spin isomeric state has been produced for the first time by multinucleon transfer reactions, employing an argon gas-stopping cell and laser ionization. Internal γ rays revealed a T_{1/2}=7.3±0.9 s isomer at 1778±1 keV, which decays through a rotational band with perturbations associated with the approach to a prolate-oblate shape transition. Model calculations show less influence from triaxiality compared to heavier elements in the same mass region. The isomer-decay reduced E2 hindrance factor f_{ν}=27±1 supports the interpretation that axial symmetry is approximately conserved.

Measurement of a time dependent spatial beam profile of an RF-driven H- ion source.

The AC component of a beam current extracted from a negative hydrogen (H-) ion source was detected through a 0.1 mm wide, 66.5 mm long entrance slit to observe the spatial distribution. An internal antenna type multicusp source driven by a 2 MHz radio frequency (RF) power delivered beams to an electrostatic accelerator coupled to a pair of magnetic lenses. The local beam intensity measured by a Faraday cup after the entrance slit exhibited an oscillation showing two main frequency components: the RF power supply frequency and the frequency two times the driving RF. The frequency spectrum of the detected signal showed sharp peaks at 2 MHz, 4 MHz, and 6 MHz as well as at 3 MHz and 5 MHz. A 1 mm displacement of the Faraday cup slit position from the center of the beam axis increased the oscillation amplitude, corresponding to a larger amplitude of the AC component at the beam edge.

Development of a magnetic quadrupole lens for low energy heavy ion beam transport.

A magnetic quadrupole lens system coupled to a 30° bending deflection magnet was designed and constructed to realize a beam focusing of Xe+ ions with the energy less than 200 eV. Compared to a triplet electrostatic quadrupole lens system, the quadrupole doublet magnetic lens system showed a larger beam transmission, indicating the mitigation of the space charge in the beam transport region free of the electrostatic field. The misalignment of the magnetic field axis was observed probably due to a slow change in magnetization of magnetic materials to construct the magnetic circuit of the quadrupole lens. A countermeasure to realign the beam axis by coupling the permanent magnets to trim coil electromagnets is proposed.

High-stability, high-voltage power supplies for use with multi-reflection time-of-flight mass spectrographs.

Achieving the highest possible mass resolving power in a multireflection time-of-flight mass spectrometer requires very high-stability power supplies. To this end, we have developed a programmable high-voltage power supply that can achieve long-term stability in the order of parts-per-million. Herein, we present the design of a stable high-voltage system and bench-top stability measurements up to 1 kV; a stabilization technique can, in principle, be applied up to 15 kV or more. We demonstrate that in the ≤1 Hz band, the output stability is at the level of 1 part per million (ppm) for 1 h, with only slightly more output variation across 3 days. We further demonstrate that the output is largely free of noise in the 1 Hz-200 Hz band. We also demonstrate settling to the ppm level within 1 min following a 100 V step transition. Finally, we demonstrate that when these power supplies are used to bias the electrodes of a multireflection time-of-flight mass spectrograph, the measured time-of-flight is stable at the ppm-level for at least 1 h.

Efficient two-color two-step laser ionization schemes of λ1∼ 250 nm and λ2 = 307.9 nm for heavy refractory elements-Measurements of ionization cross-sections and hyperfine spectra of tantalum and tungsten.

We demonstrated efficient two-color two-step laser ionization schemes in the combined use of λ1 ∼ 250 nm and λ2 = 307.9 nm, which are applicable to heavy refractory elements with an atomic number in the wide range of Z = 69-78. We investigated newly observed ionization schemes of tantalum and tungsten atoms in an argon-gas-cell-based laser ion source for the efficient ionization of atoms of unstable nuclei through the two-color two-step laser resonance ionization technique. We experimentally determined the ionization cross sections from the measured saturation curves by solving the rate equations for the ground, intermediate, and ionization continuum populations. Hyperfine structures of these elements were also studied to deduce the isotope-shift, pressure-shift, and pressure-broadening in the resonance spectra of the excitation transitions in the argon gas cell. The electronic factor F255 of the excitation transition λ1 = 255.2115 nm between the ground and intermediate states was deduced from the measured isotope shifts of stable 182,183,184,186W isotopes. The ionization schemes investigated here are applicable to extract any isotopes of these elements by considering the measured pressure shift and nuclear isotope shift in optimizing the wavelength λ1.

Prevalence of lameness in sheep transported to meat processing plants in New Zealand and associated risk factors.

Aims: To estimate the prevalence of lameness in sheep transported to meat processing plants in New Zealand, and to identify factors associated with the prevalence of lameness. Methods: The survey was conducted over the main meat processing season, running from October 2012 to the end of May 2013, at 10 sheep processing premises (five North Island and five South Island). A sample of 50 sheep selected from approximately six sheep consignments per week from each of the processing plants were scored for lameness, using a scale from Grade 1 (mild) to 3 (severe, non-weight-bearing). For each consignment the breed, age class and mean carcass weight were recorded. A multivariable regression model was fitted to identify the risk factors for prevalence of lame sheep (Grade 1-3) within a consignment. Results: In total, 1,854/78,833 (2.4 (95% CI = 2.2-2.5)%) sheep were diagnosed with lameness. Of the 1,854 lame sheep, lameness severity was Grade 1 in 1,349 (72.8%), Grade 2 in 450 (24.3%) and Grade 3 in 55 (3.0%) sheep. Within consignments ≥1 lame sheep was observed in 600/1,682 (35.7 (95% CI = 33.4-38.0)%) consignments. In Merino lambs and ewes the prevalence of lameness was greater than that of other breeds (p < 0.001), but in rams/wethers, the prevalence of lameness was lower in Merino than other breeds (p < 0.05). In sheep originating from the North Island, increasing mean carcass weight was associated with an increase in the prevalence of lameness (p < 0.001), but in the South Island prevalence was similar for different carcass weights (p = 0.5). In the North Island increasing yarding time was associated with an increase in the lameness prevalence (p < 0.01), but not in the South Island (p = 0.7). Sheep from the South Island generally had a higher prevalence of lameness than the North Island and the prevalence of lameness was lower over summer and autumn relative to the previous spring (p < 0.01). Conclusion: The results from this survey provided a measure of the prevalence of lameness in a section of the New Zealand sheep population, namely those animals sent for slaughter; as well as identification of several risk factors associated with lameness.

Impact of Donor Age on Outcome of Intestinal Transplantation in Japan.

BACKGROUND: Donor age for intestinal transplantation (ITx) is somewhat younger than that for other solid organs. Clear criteria for adequate donors have not been established. There is a donor scarcity for ITx in Japan due to the shortage of young donors. METHODS: We reviewed outcomes associated with ITx in Japan based on donor age for cadaveric and living donation. RESULTS: Standardized report forms were sent to all known ITx programs, asking for information on ITxs performed between 1996 and 2016. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method. Five institutions provided data on 27 grafts in 24 patients. There were 14 cadaveric and 13 living donor transplants. Median donor age for ITxs was 40 (range, 17-60) years. Graft survival at 5 years was 66% for patients >40 years old (n = 18) and 47% for those <40 years old (n = 9), not a statistically significant difference (P = .49). Graft survival at 5 years was 60% in those >50 years old (n = 5) and 57% for those <50 years old (n = 22), again not a significant difference (P = .27). CONCLUSION: There is no difference in survival between for those with donor age <40 vs >40 years. Donor age for ITx can be extended from >40 to up to 50 years, which may help to mitigate the donor shortage. It will be necessary to clarify the donor criteria for ITx through accumulation of further data on ITx.

Three-Year Prospective Follow-up of Potential Pediatric Candidate for Intestinal Transplantation.

Intestinal transplantation (ITx) is a treatment for refractory intestinal failure (IF). However, the indications for and timing of ITx are still controversial because the course of IF is unknown. We performed a prospective multi-institutional cohort study to identify the prognostic factors for referral to an ITx facility. Patients under 18 years of age in Japan who suffered from IF and had received parenteral nutrition for longer than 6 months were enrolled in this study. They were followed up for 3 years. Seventy-two patients were followed. The mean age at the beginning of the study was 7.0 years. Diagnoses were short gut syndrome (n = 25), motility disorder (n = 45), and other (n = 2). The overall 3-year survival rate was 95%. The 3-year survival rate was 86% in patients with intestinal-failure-associated liver disease (IFALD) (n = 6) compared to 97% in those without IFALD (n = 66) (P = .0003). Furthermore, the 3-year survival rates of patients who did and did not meet the criteria for ITx were 82% (n = 11) and 97% (n = 62), respectively (P = .034). Six (44%) of 14 patients whose performance status (PS) was ≥3 at enrollment were dead or still had a PS ≥ 3 at 3 years. This study indicates that IFALD is a poor prognostic factor in pediatric patients with IF. Our indication for ITx, namely the presence of IFALD or loss of more than 2 parenteral nutrition access sites, seems to be applicable.

First Direct Mass Measurements of Nuclides around Z=100 with a Multireflection Time-of-Flight Mass Spectrograph.

The masses of ^{246}Es, ^{251}Fm, and the transfermium nuclei ^{249-252}Md and ^{254}No, produced by hot- and cold-fusion reactions, in the vicinity of the deformed N=152 neutron shell closure, have been directly measured using a multireflection time-of-flight mass spectrograph. The masses of ^{246}Es and ^{249,250,252}Md were measured for the first time. Using the masses of ^{249,250}Md as anchor points for α decay chains, the masses of heavier nuclei, up to ^{261}Bh and ^{266}Mt, were determined. These new masses were compared with theoretical global mass models and demonstrated to be in good agreement with macroscopic-microscopic models in this region. The empirical shell gap parameter δ_{2n} derived from three isotopic masses was updated with the new masses and corroborates the existence of the deformed N=152 neutron shell closure for Md and Lr.

A compound chimeric antigen receptor strategy for targeting multiple myeloma.

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ-/-) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

Disulfide bond formation of thiols by using carbon nanotubes.

Clarification of the interactions between carbon nanotubes (CNTs) and proteinogenic amino acids is a key approach to understanding CNT-protein interactions. Previous studies have addressed the mechanism of the physical adsorption of amino acids onto CNTs. However, little is known about their chemical reactions in aqueous solutions. Here, we established dispersant-free systems to clarify intrinsic CNT-thiol interactions. We demonstrated that the redox reaction of CNTs with cysteine, containing a thiol group, leads to disulfide bond formation between cysteine molecules, even under acidic conditions. The generality of the redox reaction is validated using other thiols such as dithiothreitol and glutathione. The present results suggest that structures of proteins and peptides containing free thiol groups are chemically modified and misfolded on CNT surfaces by this disulfide bond formation in biological systems.

Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor.

The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs). Here, we report a robust anti-CD5 CAR (CD5CAR) transduced into a human NK cell line NK-92 that can undergo stable expansion ex vivo. We found that CD5CAR NK-92 cells possessed consistent, specific, and potent anti-tumor activity against a variety of T-cell leukemia and lymphoma cell lines as well as primary tumor cells. Furthermore, we were able to demonstrate significant inhibition and control of disease progression in xenograft mouse models of T-ALL. The data suggest that CAR redirected targeting for T-cell malignancies using NK cells may be a viable method for new and complementary therapeutic approaches that could improve the current outcome for patients.

Evaluation of the Control Strategy for the 2010 Foot-and-Mouth Disease Outbreak in Japan Using Disease Simulation.

In 2010, Japan experienced a foot-and-mouth disease (FMD) epidemic where 292 premises were infected over a period of 75 days. The epidemic was controlled by stamping-out and vaccination, applied 5 weeks after the first confirmation of disease within a 10 km radius of identified infected places. This study aimed at identifying the role of emergency vaccination to epidemic control while adjusting for the dynamic pattern of local spread, and assessing alternative vaccination strategies, using a disease simulation model. Our results indicate that the overall hazard of local spread remained high throughout the silent spread phase and the first two weeks post-detection, with significant reduction occurring from week 3 onwards. The estimated effectiveness of emergency vaccination quantified as reduction in the hazard of infection was at most 81% and 44% for cattle and pig farms, respectively. The vaccination strategy reduced the simulated median number of IPs by 22%, epidemic duration by 64% and culling duration by 52%, but increased the total number of infected or vaccinated premises subject to culling by 144% compared with no vaccination. The simulation indicated that vaccination starting 2 weeks earlier (3 weeks post-first detection) with a smaller vaccination radius (3 km) was more effective for eradication of the epidemic compared with the actually implemented strategy.

Malignant Oestrogen-producing Teratoma in a Cat.

A 5-year-old female domestic shorthair cat was presented with abdominal distension and serum biochemical evaluation indicated a high concentration of oestradiol (32.81 pg/ml). Exploratory laparotomy revealed a large cystic mass in the right ovary with cystic fluid containing a high level of oestradiol (18.80 pg/ml). The tumour was composed of immature neuroectodermal tissue, mature cartilage, smooth muscle, adipose tissue and aggregated, poorly differentiated mesenchymal cells. It contained cysts of various sizes that were lined by epithelium of different types. The basal layer of the lining epithelium was shown to express aromatase by immunohistochemistry. The findings suggest that this was a novel, malignant, oestrogen-secreting teratoma and that the aromatase-positive, neoplastic cells may have been the source of elevated levels of serum oestrogen.

A gas circulation and purification system for gas-cell-based low-energy RI-beam production.

A gas circulation and purification system was developed at the RIKEN Radioactive Isotope Beam Factory that can be used for gas-cell-based low-energy RI-beam production. A high-flow-rate gas cell filled with one atmosphere of buffer gas (argon or helium) is used for the deceleration and thermalization of high-energy RI-beams. The exhausted buffer gas is efficiently collected using a compact dry pump and returned to the gas cell with a recovery efficiency of >97%. The buffer gas is efficiently purified using two gas purifiers as well as collision cleaning, which eliminates impurities in the gas. An impurity level of one part per billion is achieved with this method.