Forecasting potential invaders to prevent future biological invasions worldwide.

The ever-increasing and expanding globalisation of trade and transport underpins the escalating global problem of biological invasions. Developing biosecurity infrastructures is crucial to anticipate and prevent the transport and introduction of invasive alien species. Still, robust and defensible forecasts of potential invaders are rare, especially for species without known invasion history. Here, we aim to support decision-making by developing a quantitative invasion risk assessment tool based on invasion syndromes (i.e., generalising typical attributes of invasive alien species). We implemented a workflow based on 'Multiple Imputation with Chain Equation' to estimate invasion syndromes from imputed datasets of species' life-history and ecological traits and macroecological patterns. Importantly, our models disentangle the factors explaining (i) transport and introduction and (ii) establishment. We showcase our tool by modelling the invasion syndromes of 466 amphibians and reptile species with invasion history. Then, we project these models to amphibians and reptiles worldwide (16,236 species [c.76% global coverage]) to identify species with a risk of being unintentionally transported and introduced, and risk of establishing alien populations. Our invasion syndrome models showed high predictive accuracy with a good balance between specificity and generality. Unintentionally transported and introduced species tend to be common and thrive well in human-disturbed habitats. In contrast, those with established alien populations tend to be large-sized, are habitat generalists, thrive well in human-disturbed habitats, and have large native geographic ranges. We forecast that 160 amphibians and reptiles without known invasion history could be unintentionally transported and introduced in the future. Among them, 57 species have a high risk of establishing alien populations. Our reliable, reproducible, transferable, statistically robust and scientifically defensible quantitative invasion risk assessment tool is a significant new addition to the suite of decision-support tools needed for developing a future-proof preventative biosecurity globally.

Association of glucose metabolism and blood pressure during pregnancy with subsequent maternal blood pressure.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow-up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks' gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10-14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (SBP ≥ 140 and/or DBP ≥ 90 or treatment for hypertension) at follow-up. Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68-0.92; SBP beta -0.91, 95% CI -1.34 to -0.49; DBP beta -0.50, 95% CI -0.81 to -0.19). In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10-14 years postpartum; however, insulin sensitivity during pregnancy was associated independently of blood pressure, BMI, and other covariates measured during pregnancy.

Superfluid liquid helium control for the primordial inflation polarization explorer balloon payload.

The Primordial Inflation Polarization Explorer (PIPER) is a stratospheric balloon payload to measure the polarization of the cosmic microwave background. Twin telescopes mounted within an open-aperture bucket dewar couple the sky to bolometric detector arrays. We reduce detector loading and photon noise by cooling the entire optical chain to 1.7 K or colder. A set of fountain-effect pumps sprays superfluid liquid helium onto each optical surface, producing helium flows of 50-100 cm3 s-1 at heights up to 200 cm above the liquid level. We describe the fountain-effect pumps and the cryogenic performance of the PIPER payload during two flights in 2017 and 2019.

The balloon-borne cryogenic telescope testbed mission: Bulk cryogen transfer at 40 km altitude.

The balloon-borne cryogenic telescope testbed is a stratospheric balloon payload intended to develop technology for a future cryogenic suborbital observatory. A series of flights are intended to establish ultra-light dewar performance and open-aperture observing techniques for large (3 m-5 m diameter) cryogenic telescopes at infrared wavelengths. An initial flight in 2019 demonstrated bulk transfer of liquid nitrogen and liquid helium at stratospheric altitudes. An 827 kg payload carried 14 l of liquid nitrogen (LN2) and 268 l of liquid helium (LHe) in pressurized storage dewars to an altitude of 39.7 km. Once at float altitude, liquid nitrogen transfer cooled a separate, unpressurized bucket dewar to a temperature of 65 K, followed by the transfer of 32 l of liquid helium from the storage dewar into the bucket dewar. Calorimetric tests measured the total heat leak to the LHe bath within the bucket dewar. A subsequent flight will replace the receiving bucket dewar with an ultra-light dewar of similar size to compare the performance of an ultra-light design dewar to that of conventional superinsulated dewars.

Niche shifts and environmental non-equilibrium undermine the usefulness of ecological niche models for invasion risk assessments.

Niche shifts and environmental non-equilibrium in invading alien species undermine niche-based predictions of alien species' potential distributions and, consequently, their usefulness for invasion risk assessments. Here, we compared the realized climatic niches of four alien amphibian species (Hylarana erythraea, Rhinella marina, Hoplobatrachus rugulosus, and Kaloula pulchra) in their native and Philippine-invaded ranges to investigate niche changes that have unfolded during their invasion and, with this, assessed the extent of niche conservatism and environmental equilibrium. We investigated how niche changes affected reciprocal transferability of ecological niche models (ENMs) calibrated using data from the species' native and Philippine-invaded ranges, and both ranges combined. We found varying levels of niche change across the species' realized climatic niches in the Philippines: climatic niche shift for H. rugulosus; niche conservatism for R. marina and K. pulchra; environmental non-equilibrium in the Philippine-invaded range for all species; and environmental non-equilibrium in the native range or adaptive changes post-introduction for all species except H. erythraea. Niche changes undermined the reciprocal transferability of ENMs calibrated using native and Philippine-invaded range data. Our paper highlights the difficulty of predicting potential distributions given niche shifts and environmental non-equilibrium; we suggest calibrating ENMs with data from species' combined native and invaded ranges, and to regularly reassess niche changes and recalibrate ENMs as species' invasions progress.

Sub-Kelvin cooling for two kilopixel bolometer arrays in the PIPER receiver.

The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne telescope mission to search for inflationary gravitational waves from the early universe. PIPER employs two 32 × 40 arrays of superconducting transition-edge sensors, which operate at 100 mK. An open bucket Dewar of liquid helium maintains the receiver and telescope optics at 1.7 K. We describe the thermal design of the receiver and sub-Kelvin cooling with a continuous adiabatic demagnetization refrigerator (CADR). The CADR operates between 70 and 130 mK and provides ≈10 µW cooling power at 100 mK, nearly five times the loading of the two detector assemblies. We describe electronics and software to robustly control the CADR, overall CADR performance in flightlike integrated receiver testing, and practical considerations for implementation in the balloon float environment.

The curious case of the endemic freshwater crocodile Crocodylus mindorensis as incidental host of marine fish acanthocephalan.

We performed the first host-parasite survey of the Philippine crocodile, Crocodylus mindorensis, a critically endangered species for which ecological information is lacking. We collected by gastric lavage samples of the stomach contents of crocodiles (n = 10) residing at the Palawan Wildlife Rescue and Conservation Center in Puerto Princesa, Palawan, Philippines. The only parasite detected was an acanthocephalan, which was identified as Neorhadinorhynchus nudus (n = 68), a parasite typically found in the marine fish species consumed by three crocodile individuals. Given the known hosts of N. nudus, its parasitism of C. mindorensis in captivity is likely established by consumption of marine fish. Our findings have implications for the conservation management of C. mindorensis, particularly in terms of preventing introduction of parasites that could lead to development of infectious disease or alter the fitness of captive animals.

A new species of limestone karst inhabiting forest frog, genus Platymantis (Amphibia: Anura: Ceratobatrachidae: subgenus Lupacolus) from southern Luzon Island, Philippines.

We describe a new species of limestone karst dwelling forest frog of the genus Platymantis from the Quezon Protected Landscape in southeastern Luzon Island, Philippines. We assign Platymantis quezoni, sp. nov., to the diverse assemblage of terrestrial species in the Platymantis dorsalis Group, subgenus Lupacolus on the basis of its body size and proportions, only slightly expanded terminal discs of the fingers and toes, and its terrestrial microhabitat. The new species is distinguished from these and all other Philippine congeners by features of its external morphology, its restriction to a distinctive limestone karst microhabitat, and its advertisement call, which is unique among frogs of the family Ceratobatrachidae. Several distinguishing morphological characters include its moderate body size (22.1-33.9 mm SVL for 16 adult males and 32.4-39.7 mm SVL for five adult females), slightly expanded terminal discs of the fingers and toes, smooth skin with limited dermal tuberculation, and a dorsal color pattern of mottled tan to dark brown with black blotches. The new species is the sixth Philippine Platymantis known to occur exclusively on limestone karst substrates (previously known karst-obligate species include: P. bayani, P. biak, P. insulatus, P. paengi, and P. speleaus). Recently accelerated discovery of limestone karst anurans across the Philippines suggests that numerous additional species may await discovery on the hundreds of scattered karst formations throughout the archipelago. This possibility suggests that a major conservation priority in coming years will be to study, characterize, describe, and preserve the endemic species supported by this patchy, unique and imperiled type of forest ecosystem in the Philippines.

Should HLA mismatch acceptability for sensitized transplant candidates be determined at the high-resolution rather than the antigen level?

Defining HLA mismatch acceptability of organ transplant donors for sensitized recipients has traditionally been based on serologically defined HLA antigens. Now, however, it is well accepted that HLA antibodies specifically recognize a wide range of epitopes present on HLA antigens and that molecularly defined high resolution alleles corresponding to the same low resolution antigen can possess different epitope repertoires. Hence, determination of HLA compatibility at the allele level represents a more accurate approach to identify suitable donors for sensitized patients. This approach would offer opportunities for increased transplant rates and improved long term graft survivals.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity.

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), ß=0.026 and P=4.8 × 10(-4), ß=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; ß =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; ß=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

Conservation genetics of the Philippine tarsier: cryptic genetic variation restructures conservation priorities for an island archipelago primate.

Establishment of conservation priorities for primates is a particular concern in the island archipelagos of Southeast Asia, where rates of habitat destruction are among the highest in the world. Conservation programs require knowledge of taxonomic diversity to ensure success. The Philippine tarsier is a flagship species that promotes environmental awareness and a thriving ecotourism economy in the Philippines. However, assessment of its conservation status has been impeded by taxonomic uncertainty, a paucity of field studies, and a lack of vouchered specimens and genetic samples available for study in biodiversity repositories. Consequently, conservation priorities are unclear. In this study we use mitochondrial and nuclear DNA to empirically infer geographic partitioning of genetic variation and to identify evolutionarily distinct lineages for conservation action. The distribution of Philippine tarsier genetic diversity is neither congruent with expectations based on biogeographical patterns documented in other Philippine vertebrates, nor does it agree with the most recent Philippine tarsier taxonomic arrangement. We identify three principal evolutionary lineages that do not correspond to the currently recognized subspecies, highlight the discovery of a novel cryptic and range-restricted subcenter of genetic variation in an unanticipated part of the archipelago, and identify additional geographically structured genetic variation that should be the focus of future studies and conservation action. Conservation of this flagship species necessitates establishment of protected areas and targeted conservation programs within the range of each genetically distinct variant of the Philippine tarsier.

Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1.

HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.

Center-defined unacceptable HLA antigens facilitate transplants for sensitized patients in a multi-center kidney exchange program.

Multi-center kidney paired donation (KPD) is an exciting new transplant option that has not yet approached its full potential. One barrier to progress is accurate virtual crossmatching for KPD waitlists with many highly sensitized patients. Virtual crossmatch results from a large multi-center consortium, the National Kidney Registry (NKR), were analyzed to determine the effectiveness of flexible center-specific criteria for virtual crossmatching. Approximately two-thirds of the patients on the NKR waitlist are highly sensitized (>80% CPRA). These patients have antibodies against HLA-A (63%), HLA-B (66%), HLA-C (41%), HLA-DRB1 (60%), HLA-DRB3/4/5 (18-22%), HLA-DQB1 (54%) and HLA-DPB1 (26%). With donors typed for these loci before activation, 91% of virtual crossmatches accurately predicted an acceptable cell-based donor crossmatch. Failed virtual crossmatches were attributed to equivocal virtual crossmatches (46%), changes in HLA antibodies (21%), antibodies against HLA-DQA (6%), transcription errors (6%), suspected non-HLA antibodies (5%), allele-specific antibodies (1%) and unknown causes (15%). Some failed crossmatches could be prevented by modifiable factors such as more frequent assessment of HLA antibodies, DQA1 typing of donors and auditing data entry. Importantly, when transplant centers have flexibility to define crossmatch criteria, it is currently feasible to use virtual crossmatching for highly sensitized patients to reliably predict acceptable cell-based crossmatches.

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease.

BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m(2), alemtuzumab 54 mg/m(2) (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.

Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort.

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 µg/l higher for TT higher by 1 SD, p=0.001) and 1-h C-peptide (0.79 µg/l higher for TT higher by 1 SD, p<0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 µg/l higher for FT higher by 1 SD, p<0.001), and 1-h C-peptide (0.83 µg/l higher for FT higher by 1 SD, p<0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

Dynamic challenges inhibiting optimal adoption of kidney paired donation: findings of a consensus conference.

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.