Arctos: Community-driven innovations for managing natural and cultural history collections.

More than tools for managing physical and digital objects, museum collection management systems (CMS) serve as platforms for structuring, integrating, and making accessible the rich data embodied by natural history collections. Here we describe Arctos, a scalable community solution for managing and publishing global biological, geological, and cultural collections data for research and education. Specific goals are to: (1) Describe the core features and implementation of Arctos for a broad audience with respect to the biodiversity informatics principles that enable high quality research; (2) Highlight the unique aspects of Arctos; (3) Illustrate Arctos as a model for supporting and enhancing the Digital Extended Specimen concept; and (4) Emphasize the role of the Arctos community for improving data discovery and enabling cross-disciplinary, integrative studies within a sustainable governance model. In addition to detailing Arctos as both a community of museum professionals and a collection database platform, we discuss how Arctos achieves its richly annotated data by creating a web of knowledge with deep connections between catalog records and derived or associated data. We also highlight the value of Arctos as an educational resource. Finally, we present the financial model of fiscal sponsorship by a nonprofit organization, implemented in 2022, to ensure the long-term success and sustainability of Arctos.

Extralimital terrestrials: A reassessment of range limits in Alaska's land mammals.

Understanding and mitigating the effects of anthropogenic climate change on species distributions requires the ability to track range shifts over time. This is particularly true for species occupying high-latitude regions, which are experiencing more extreme climate change than the rest of the world. In North America, the geographic ranges of many mammals reach their northernmost extent in Alaska, positioning this region at the leading edge of climate-induced distribution change. Over a decade has elapsed since the publication of the last spatial assessments of terrestrial mammals in the state. We compared public occurrence records against commonly referenced range maps to evaluate potential extralimital records and develop repeatable baseline range maps. We compared occurrence records from the Global Biodiversity Information Facility for 61 terrestrial mammal species native to mainland Alaska against a variety of range estimates (International Union for Conservation of Nature, Alaska Gap Analysis Project, and the published literature). We mapped extralimital records and calculated proportions of occurrences encompassed by range extents, measured mean direction and distance to prior range margins, evaluated predictive accuracy of published species models, and highlighted observations on federal lands in Alaska. Range comparisons identified 6,848 extralimital records for 39 of 61 (63.9%) terrestrial mainland Alaskan species. On average, 95.5% of Alaska Gap Analysis Project occurrence records and ranges were deemed accurate (i.e., > 90.0% correct) for 31 of 37 species, but overestimated extents for 13 species. The International Union for Conservation of Nature range maps encompassed 68.1% of occurrence records and were > 90% accurate for 17 of 39 species. Extralimital records represent either improved sampling and digitization or actual geographic range expansions. Here we provide new data-driven range maps, update standards for the archiving of museum-quality locational records and offer recommendations for mapping range changes for monitoring and conservation.

Ancient DNA indicates a century of overhunting did not reduce genetic diversity in Pacific Walruses (Odobenus rosmarus divergens).

Pacific Walruses (Odobenus rosmarus divergens [Illiger 1815]) are gregarious marine mammals considered to be sentinels of the Arctic because of their dependence on sea ice for feeding, molting, and parturition. Like many other marine mammal species, their population sizes were decimated by historical overhunting in the nineteenth and twentieth centuries. Although they have since been protected from nearly all commercial hunting pressure, they now face rapidly accelerating habitat loss as global warming reduces the extent of summer sea ice in the Arctic. To investigate how genetic variation was impacted by overhunting, we obtained mitochondrial DNA sequences from historic Pacific Walrus samples in Alaska that predate the period of overhunting, as well as from extant populations. We found that genetic variation was unchanged over this period, suggesting Pacific Walruses are resilient to genetic attrition in response to reduced population size, and that this may be related to their high vagility and lack of population structure. Although Pacific Walruses will almost certainly continue to decline in number as the planet warms and summer sea ice is further reduced, they may be less susceptible to the ratcheting effects of inbreeding that typically accompany shrinking populations.

A re-assessment of diversity among Philippine gymnures (Mammalia: Erinaceidae: Podogymnura), with a new species from eastern Mindanao.

Podogymnura, a Philippine endemic genus of gymnures ("soft-furred hedgehogs"), has been known previously only from the highlands of central Mindanao (P. truei truei and P. t. minima) and from two small islands off the northeast tip of Mindanao (P. aureospinula). Based on a combination of mitochondrial genetic and qualitative and quantitative morphological data, we recognize P. minima, formerly considered a subspecies of P. truei, as a distinct species. We also recognize specimens from two little-studied montane regions of southeastern Mindanao, Mt. Hamiguitan and Mt. Kampalili, as a distinctive new species, P. intermedia n. sp. We estimate that dispersal of a common ancestor from Borneo to Mindanao ca. 1.9 to 3.5 Ma gave rise to Podogymnura, followed by speciation within Mindanao beginning 0.53 to 0.97 Ma. These results further increase the rich diversity of mammals on Mindanao, and underscore the importance of the eastern Mindanao highlands as a likely important but little-studied center of Philippine mammalian diversity.

Ultraconserved elements improve resolution of marmot phylogeny and offer insights into biogeographic history.

Marmots (Marmota spp.) comprise a lineage of large-bodied ground squirrels that diversified rapidly in the Pleistocene, when the planet quickly transitioned to a drier, colder, and highly seasonal climate-particularly at high latitudes. Fossil evidence indicates the genus spread from North America, across Beringia, and into the European Alps over the course of only a few million years, beginning in the late Pliocene. Marmots are highly adapted to survive long and severely cold winters, and this likely favored their expansion and diversification over this time period. Previous phylogenetic studies have identified two major subgenera of marmots, but the timing of important speciation events and some species relationships have been difficult to resolve. Here we use ultraconserved elements and mitogenomes, with samples from all 15 extant species, to more precisely retrace how and when marmots came to inhabit a vast Holarctic range. Our results indicate marmots arose in North America in the Early Miocene (∼16.3 Ma) and dispersed across the Bering Land Bridge in the Pliocene (∼3-4 Ma); in addition, our fossil-calibrated timeline is suggestive of the rise and spread of open grasslands as being particularly important to marmot diversification. The woodchuck (M. monax) and the Alaska marmot (M. broweri) are found to be more closely related to the Eurasian species than to the other North American species. Paraphyly is evident in the bobak marmot (M. bobak) and the hoary marmot (M. caligata), and in the case of the latter the data are highly suggestive of a second, cryptic species in the Cascade Mountains of Washington.

Recent and rapid ecogeographical rule reversals in Northern Treeshrews.

Two of the most-studied ecogeographical rules describe patterns of body size variation within species. Bergmann's rule predicts that individuals have larger body sizes in colder climates (typically at higher latitudes), and the island rule predicts that island populations of small-bodied species average larger in size than their mainland counterparts (insular gigantism). These rules are rarely tested in conjunction or assessed across space and time simultaneously. We investigated these patterns in the Northern Treeshrew (Tupaia belangeri) using museum specimens collected across a wide spatial and temporal range. Contrary to Bergmann's rule, size increases with temperature in T. belangeri, a signal that is highly consistent across space and time. We also show that these rules are intertwined: Bergmann's rule is reversed on the mainland but holds on islands, and therefore the island rule is upheld at higher, but not lower, latitudes. Moreover, we demonstrate a rapid reversal of both rules over time. The mechanism behind these inversions remains unclear, though temperature and precipitation are significant predictors of body size. Ecogeographical rules rely on the assumption of a constant relationship between size and the factors driving its variation. Our results highlight the need to question this assumption and reevaluate these rules in the context of accelerating and uneven climate change.

Speciation and gene flow in two sympatric small mammals from Madagascar, Microgale fotsifotsy and M. soricoides (Mammalia: Tenrecidae).

Madagascar's shrew tenrecs (Mammalia: Tenrecidae; Microgale, Nesogale) represent an excellent system for studying speciation. Most species are endemic to the island's eastern humid forests, a region renowned for high levels of biodiversity and a high rate of in situ diversification. We set out to understand the speciation dynamics in a clade of recently described taxa: Microgale fotsifotsy and M. soricoides, which have nearly identical distributions in the moist evergreen forest, and M. nasoloi, which occurs in the western dry deciduous forest. A phylogenetic analysis using mitochondrial DNA data recovered two distinct clades of M. fotsifotsy: a south clade that is sister to, and broadly sympatric with, M. soricoides, and a north clade that is sister to the dry-forest and distantly allopatric species M. nasoloi. To better understand this result, we analysed cranioskeletal measurements and performed demographic analyses using nuclear sequence data from ultraconserved elements. Nuclear data did not support a sister relationship between M. soricoides and the south clade of M. fotsifotsy but did demonstrate introgression between these clades, which probably explains the discordance between nuclear and mitochondrial phylogenies. Demographic analyses also revealed the absence of gene flow between the north and south clades of M. fotsifotsy. Morphometric data revealed several major differences between M. soricoides and M. fotsifotsy, as well as more subtle differences between the two clades of M. fotsifotsy. In light of these results, we treat the south clade of M. fotsifotsy as a new candidate species. Our findings demonstrate the utility of integrating multiple data types to understand complex speciation histories, and contribute to a growing body of evidence that species diversity on Madagascar is underestimated.

Utility of routine oral contrast study for detecting postesophagectomy anastomotic leak - a systematic review and meta-analysis.

Oral contrast studies are used to detect anastomotic leak (AL) postesophagectomy. However, recent evidence suggests oral contrast studies have low sensitivity in detecting ALs, and their false positive results can lead to unnecessary prolonged hospital stay. The objective of this study was to determine if oral contrast studies should be used routinely post-esophagectomy for cancer. A systematic literature search was conducted for studies published between January 1990 and June 2018. Data extracted for analyses included type of esophagectomy, operative morbidity (such as AL and pneumonia), mortality rates, timing of contrast study, and type of oral contrast used. The sensitivity, specificity, and positive and negative predictive values of routine oral contrast studies to detect AL were calculated using the aforementioned variables. Two hundred and forty-seven studies were reviewed with 16 studies included in the meta-analysis. Postoperative oral contrast study was performed in 94.0% of cases between day 5 and 7. The rates of early and delayed leaks were 2.4% (1.8%-3.3%) and 2.8% (1.8%-4.4%), respectively. Routine contrast studies have a sensitivity and specificity of 0.44 (0.32-0.57) and 0.98 (0.95-0.99), respectively. Analysis of covariates revealed that sensitivity is reduced in centers with a higher volume of cases (greater than 15 per year: 0.50 [0.34-0.75; p = 0.0008]) and specificity was higher in centers with a lower leak rate. Given its poor sensitivity and inability to detect early/delayed AL, oral contrast study should be used selectively with endoscopy and/or computerized tomography scan to assess surgical anastomoses following esophagectomy.

Caught in the act: Incipient speciation across a latitudinal gradient in a semifossorial mammal from Madagascar, the mole tenrec Oryzorictes hova (Tenrecidae).

Madagascar is one of the world's foremost biodiversity hotspots, yet a large portion of its flora and fauna remains undescribed and the driving forces of in situ diversification are not well understood. Recent studies have identified a widespread, latitudinally structured phylogeographic pattern in Madagascar's humid-forest mammals, amphibians, reptiles, and insects. Several factors may be driving this pattern, namely biogeographic barriers (i.e., rivers or valleys) or past episodes of forest contraction and expansion. In this study, we describe the phylogeographic structure of the small, semifossorial mammal Oryzorictes hova, one of Madagascar's two species of mole tenrec, found throughout Madagascar's eastern humid forest belt, from high-elevation montane forest to low-elevation forests, as well as disturbed habitat such as rice fields. Using one mitochondrial locus, four nuclear loci, and 31 craniomandibular measurements, we identified three distinct populations of O. hova associated with the northern, central, and southern regions of the island. We found little evidence of gene flow among these populations, so we treated each population as a potential species. We validated species limits using two Bayesian methods: BP&P, employing only DNA sequence data, and iBPP using both DNA and morphological data, and we assessed whether these methods are susceptible to producing false positive errors. Molecular and morphological data support the recognition of each of the three populations of O. hova as distinct species, but formal species descriptions will require additional data from type specimens. This study illustrates the importance of using integrative datasets, multiple methodological approaches, and extensive geographic sampling for species delimitation and adds evidence for a widespread phylogeographic pattern in Madagascar's humid forest taxa.

Rule reversal: Ecogeographical patterns of body size variation in the common treeshrew (Mammalia, Scandentia).

There are a number of ecogeographical "rules" that describe patterns of geographical variation among organisms. The island rule predicts that populations of larger mammals on islands evolve smaller mean body size than their mainland counterparts, whereas smaller-bodied mammals evolve larger size. Bergmann's rule predicts that populations of a species in colder climates (generally at higher latitudes) have larger mean body sizes than conspecifics in warmer climates (at lower latitudes). These two rules are rarely tested together and neither has been rigorously tested in treeshrews, a clade of small-bodied mammals in their own order (Scandentia) broadly distributed in mainland Southeast Asia and on islands throughout much of the Sunda Shelf. The common treeshrew, Tupaia glis, is an excellent candidate for study and was used to test these two rules simultaneously for the first time in treeshrews. This species is distributed on the Malay Peninsula and several offshore islands east, west, and south of the mainland. Using craniodental dimensions as a proxy for body size, we investigated how island size, distance from the mainland, and maximum sea depth between the mainland and the islands relate to body size of 13 insular T. glis populations while also controlling for latitude and correlation among variables. We found a strong negative effect of latitude on body size in the common treeshrew, indicating the inverse of Bergmann's rule. We did not detect any overall difference in body size between the island and mainland populations. However, there was an effect of island area and maximum sea depth on body size among island populations. Although there is a strong latitudinal effect on body size, neither Bergmann's rule nor the island rule applies to the common treeshrew. The results of our analyses demonstrate the necessity of assessing multiple variables simultaneously in studies of ecogeographical rules.

Reconstructing the molecular phylogeny of giant sengis (Macroscelidea; Macroscelididae; Rhynchocyon).

Giant sengis (Macroscelidea; Macroscelididae; Rhynchocyon), also known as giant elephant-shrews, are small-bodied mammals that range from central through eastern Africa. Previous research on giant sengi systematics has relied primarily on pelage color and geographic distribution. Because some species have complex phenotypic variation and large geographic ranges, we used molecular markers to evaluate the phylogeny and taxonomy of the genus, which currently includes four species: R. chrysopygus, R. cirnei (six subspecies), R. petersi (two subspecies), and R. udzungwensis. We extracted DNA from fresh and historical museum samples from all taxa except one R. cirnei subspecies, and we generated and analyzed approximately 4700 aligned nucleotides (2685 bases of mitochondrial DNA and 2019 bases of nuclear DNA) to reconstruct a molecular phylogeny. We genetically evaluate Rhynchocyon spp. sequences previously published on GenBank, propose that the captive R. petersi population in North American zoos is likely R. p. adersi, and suggest that hybridization among taxa is not widespread in Rhynchocyon. The DNA sample we have from the distinctive but undescribed giant sengi from the Boni forest of northern coastal Kenya is unexpectedly nearly identical to R. chrysopygus, which will require further study. Our analyses support the current morphology-based taxonomy, with each recognized species forming a monophyletic clade, but we propose elevating R. c. stuhlmanni to a full species.

Novel Orthopoxvirus Infection in an Alaska Resident.

BACKGROUND.: Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of population-level immunity. In July 2015, a female resident of interior Alaska presented to an urgent care clinic with a dermal lesion consistent with poxvirus infection. Laboratory testing of a virus isolated from the lesion confirmed infection by an Orthopoxvirus. METHODS.: The virus isolate was characterized by using electron microscopy and nucleic acid sequencing. An epidemiologic investigation that included patient interviews, contact tracing, and serum testing, as well as environmental and small-mammal sampling, was conducted to identify the infection source and possible additional cases. RESULTS.: Neither signs of active infection nor evidence of recent prior infection were observed in any of the 4 patient contacts identified. The patient's infection source was not definitively identified. Potential routes of exposure included imported fomites from Azerbaijan via the patient's cohabiting partner or wild small mammals in or around the patient's residence. Phylogenetic analyses demonstrated that the virus represents a distinct and previously undescribed genetic lineage of Orthopoxvirus, which is most closely related to the Old World orthopoxviruses. CONCLUSIONS.: Investigation findings point to infection of the patient after exposure in or near Fairbanks. This conclusion raises questions about the geographic origins (Old World vs North American) of the genus Orthopoxvirus. Clinicians should remain vigilant for signs of poxvirus infection and alert public health officials when cases are suspected.

The German Infant Nutritional Intervention Study (GINI) for the preventive effect of hydrolyzed infant formulas in infants at high risk for allergic diseases. Design and selected results.

In the complex interaction between certain environmental factors and genetic disposition, the early allergen exposure plays a major role in the development of allergic diseases. In aiming to reduce the allergen burden for the infant at risk during early infancy, cow's milk protein hydrolysate infant formulas (hypoallergenic infant formulas) are appropriate alternatives to breastfeeding for primary allergy prevention. The German Infant Nutritional Intervention-Program (GINI) was supported for the first 3 years by the German Ministry for Education and Research (BMBF) (FKZ 01 EE 9401-4). It is a birth cohort which was primarily scheduled until the children were 3 years old. The aim of the prospective, randomized, double-blind intervention study was to investigate the impact of different cow's milk protein hydrolysate infant formulas in the first 4 - 6 months on the development of allergic diseases in children at risk due to at least one parent or biological sibling with a history of allergic disease. The allocation to one of the 4 intervention formulas (partial whey hydrolysate, extensive whey hydrolysate, extensive casein hydrolysate or standard cow's milk formula) was randomised and stratified by family history (single/biparental) and the respective obstetric clinic. Recruitment was carried out by the three clinical centers (Research Institute Marien-Hospital Wesel, Children's Department, Ludwigs-Maximilians-University Munich and Children's Department Technical University Munich) in 18 obstetric clinics between 01.09.1995 and 30.06.1998. Along with the intervention study a non-interventional, complementary observational cohort of children with or without allergy risk was recruited and followed by annual self-reporting parental questionnaires. The GINI intervention study (GINI-I, N = 2.252) and the non-interventional observation study (GINI-NI, N = 3.739) are combined in the population-based GINIplus study (see article J. Heinrich et al. in this journal). The results of the GINI intervention study confirm that, cow's milk protein hydrolysate infant formulas have a preventive effect on allergic manifestation compared with a standard cow's milk formula, until school age. However, the dimension of the effect is different between the formulas. This effect, which is mainly driven by the effect on atopic eczema, develops in the first months of life and persists without rebound. In the formula groups the cumulative incidence of atopic eczema until school age is reduced between 26% and 45% compared with standard cow's milk formula. A beneficial effect of the hydrolysate formulas on the respiratory manifestations asthma and rhinoconjunctivitis, however, could not be shown. By comparing the GINI intervention and non-intervention arm of the GINIplus study it was demonstrated, that a family history for allergy doubles the risk for eczema in the offspring. Early intervention with cow's milk protein hydrolysate infant formulas is able to substantially compensate this risk for eczema until the age of 6 years. In contrast, by randomization to standard cow's milk formula this risk showed a trend towards a higher incidence compared with children at risk from the non-intervention group. Thus, the results of the GINIplus study have contributed to answer some of the controversially discussed questions.

Multiple Loci and Complete Taxonomic Sampling Resolve the Phylogeny and Biogeographic History of Tenrecs (Mammalia: Tenrecidae) and Reveal Higher Speciation Rates in Madagascar's Humid Forests.

The family Tenrecidae (tenrecs) is one of only four extant terrestrial mammal lineages to have colonized and diversified on Madagascar. Over the last 15 years, several studies have disagreed on relationships among major tenrec lineages, resulting in multiple reinterpretations of the number and timing of historical transoceanic dispersal events between Africa and Madagascar. We reconstructed the phylogeny of Tenrecidae using multiple loci from all recognized extant species and estimated divergence timing using six fossil calibrations within Afrotheria. All phylogenetic analyses strongly support monophyly of the Malagasy tenrecs, and our divergence timing analysis places their colonization of the island at 30-56 Ma. Our comprehensive phylogeny supports three important taxonomic revisions that reflect the evolutionary history of tenrecs: (1) we formally elevate the African otter shrews to their own family Potamogalidae, thereby rendering extant Tenrecidae entirely endemic to Madagascar; (2) we subsume the semiaquatic genus Limnogale within the shrew tenrec genus Microgale; and (3) we re-elevate the two largest-bodied shrew tenrecs, Microgale dobsoni and Microgale talazaci, to the genus Nesogale Thomas (1918) Finally, we use recently summarized habitat data to test the hypothesis that diversification rates differ between humid and arid habitats on Madagascar, and we compare three common methods for ancestral biogeographic reconstruction. These analyses suggest higher speciation rates in humid habitats and reveal a minimum of three and more likely five independent transitions to arid habitats. Our results resolve the relationships among previously recalcitrant taxa, illuminate the timing and mechanisms of major biogeographic patterns in an extraordinary example of an island radiation, and permit the first comprehensive, phylogenetically consistent taxonomy of Madagascar's tenrecs.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

Colonization from divergent ancestors: glaciation signatures on contemporary patterns of genomic variation in Collared Pikas (Ochotona collaris).

Identifying the genetic structure of a species and the factors that drive it is an important first step in modern population management, in part because populations evolving from separate ancestral sources may possess potentially different characteristics. This is especially true for climate-sensitive species such as pikas, where the delimitation of distinct genetic units and the characterization of population responses to contemporary and historical environmental pressures are of particular interest. We combined a restriction site-associated DNA sequencing (RADSeq) data set containing 4156 single nucleotide polymorphisms with ecological niche models (ENMs) of present and past habitat suitability to characterize population composition and evaluate the effects of historical range shifts, contemporary climates and landscape factors on gene flow in Collared Pikas, which are found in Alaska and adjacent regions of northwestern Canada and are the lesser-studied of North America's two pika species. The results suggest that contemporary environmental factors contribute little to current population connectivity. Instead, genetic diversity is strongly shaped by the presence of three ancestral lineages isolated during the Pleistocene (~148 and 52 kya). Based on ENMs and genetic data, populations originating from a northern refugium experienced longer-term stability, whereas both southern lineages underwent population expansion - contradicting the southern stability and northern expansion patterns seen in many other taxa. Current populations are comparable with respect to generally low diversity within populations and little-to-no recent admixture. The predominance of divergent histories structuring populations implies that if we are to understand and manage pika populations, we must specifically assess and accurately account for the forces underlying genetic similarity.

Comparative phylogeography highlights the double-edged sword of climate change faced by arctic- and alpine-adapted mammals.

Recent studies suggest that alpine and arctic organisms may have distinctly different phylogeographic histories from temperate or tropical taxa, with recent range contraction into interglacial refugia as opposed to post-glacial expansion out of refugia. We use a combination of phylogeographic inference, demographic reconstructions, and hierarchical Approximate Bayesian Computation to test for phylodemographic concordance among five species of alpine-adapted small mammals in eastern Beringia. These species (Collared Pikas, Hoary Marmots, Brown Lemmings, Arctic Ground Squirrels, and Singing Voles) vary in specificity to alpine and boreal-tundra habitat but share commonalities (e.g., cold tolerance and nunatak survival) that might result in concordant responses to Pleistocene glaciations. All five species contain a similar phylogeographic disjunction separating eastern and Beringian lineages, which we show to be the result of simultaneous divergence. Genetic diversity is similar within each haplogroup for each species, and there is no support for a post-Pleistocene population expansion in eastern lineages relative to those from Beringia. Bayesian skyline plots for four of the five species do not support Pleistocene population contraction. Brown Lemmings show evidence of late Quaternary demographic expansion without subsequent population decline. The Wrangell-St. Elias region of eastern Alaska appears to be an important zone of recent secondary contact for nearctic alpine mammals. Despite differences in natural history and ecology, similar phylogeographic histories are supported for all species, suggesting that these, and likely other, alpine- and arctic-adapted taxa are already experiencing population and/or range declines that are likely to synergistically accelerate in the face of rapid climate change. Climate change may therefore be acting as a double-edged sword that erodes genetic diversity within populations but promotes divergence and the generation of biodiversity.

Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial.

The safety, kinetics and efficacy of plerixafor+pegfilgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization are poorly understood. We treated 12 study patients (SP; lymphoma n=10 or myeloma n=2) with pegfilgrastim (6 mg SC stat D1) and plerixafor (0.24 mg/kg SC nocte from D3). Six SP were 'predicted poor-mobilizers' and six were 'predicted adequate-mobilizers'. Peripheral blood (PB) CD34(+) monitoring commenced on D3. Apheresis commenced on D4. Comparison was with 22 historical controls (HC; lymphoma n=18, myeloma n=4; poor mobilizers n=4), mobilized with pegfilgrastim alone. Eight (67%) SP had PB CD34(+) count ⩽5 × 10(6)/L D3 post pegfilgrastim; all SP surpassed this threshold the morning after plerixafor. In SP, PBCD34(+) counts peaked D4 6/12 (50%), remaining ⩾5 × 10(6)/L for 4 days in 8/12 (67%). All SP successfully yielded target cell numbers (⩾2 × 10(6)/kg) within four aphereses. After maximum four aphereses, median total CD34+ yield was higher in SP than HC; 8.0 (range 2.4-12.9) vs 4.8 (0.4-14.0) × 10(6)/kg (P=0.04). Seven of twelve (58%) SP achieved target yield after one apheresis. Flow cytometry revealed no tumor cells in PB or apheresis product of SP. Plerixafor+pegfilgrastim was well tolerated with bone pain (n=2), diarrhoea (n=2) and facial paraesthesiae (n=3). Plerixafor+pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers, and is superior to pegfilgrastim alone.

Perioperative epidural analgesia reduces cancer recurrence after gastro-oesophageal surgery.

BACKGROUND: Recent interest has focused on the role of perioperative epidural analgesia in improving cancer outcomes. The heterogeneity of studies (tumour type, stage and outcome endpoints) has produced inconsistent results. Clinical practice also highlights the variability in epidural effectiveness. We considered the novel hypothesis that effective epidural analgesia improves cancer outcomes following gastro-oesophageal cancer surgery in patients with grouped pathological staging. METHODS: Following institutional approval, a database analysis identified 140 patients, with 2-year minimum follow-up after gastro-oesophageal cancer surgery. All patients were operated on by a single surgeon (2005-2010). Information pertaining to cancer and survival outcomes was extracted. RESULTS: Univariate analysis demonstrated a 1-year 14% vs. 33% (P = 0.01) and 2-year 27% vs. 40% [hazard ratio (HR)=0.59; 95% CI, 0.32-1.09, P = 0.087] incidence of cancer recurrence in patients with (vs. without) effective (> 36 h duration) epidural analgesia, respectively. Multivariate analysis demonstrated increased time to cancer recurrence (HR = 0.33; 95% CI: 0.17-0.63, P < 0.0001) and overall survival benefit (HR = 0.42; 95% CI: 0.21-0.83, P < 0.0001) at 2-year follow-up following effective epidural analgesia. Subgroup analysis identified epidural-related cancer recurrence benefit in patients with oesophageal cancer (HR = 0.34; 95% CI: 0.16-0.75, P = 0.005) and in patients with tumour lymphovascular space infiltration (LVSI), (HR = 0.49; 95% CI: 0.26-0.94, P = 0.03). Effective epidural analgesia improved estimated median time to death (2.9 vs. 1.8 years, P = 0.029) in patients with tumour LVSI. CONCLUSIONS: This study found an association between effective post-operative epidural analgesia and medium-term benefit on cancer recurrence and survival following oesophageal surgery. A prospective study that controls for disease type, stage and epidural effectiveness is warranted.