Recent Expansion Research Articles

What happens in ice age, does not stay in ice age: Phylogeography of Bombus terrestris revealed a low genetic diversity amongst the Eurasian populations

The objective of this research was to assess the genetic diversity and phylogeography of Bombus terrestris and examine the historical events that shaped its contemporary genetic structures using the COI mitochondrial marker. Specimens of the species were collected from its distribution range alongside the Alborz Mountain range, and GenBank sequences from the Eurasian distribution range were incorporated into the dataset. The COI sequences were employed in Bayesian and Maximum Likelihood analyses to generate phylogenetic trees for the species populations and to investigate the evolutionary history of the species. Additionally, species occurrence points and climate data were utilized in Species Distribution Modeling (SDM) analyses to reconstruct the species range under past, present, and future climate conditions. The ML and BI trees yielded similar topologies, indicating extremely low genetic diversity and a homogeneous structure in the species population distribution range in Eurasia. Demographic analyses suggested that the species may have experienced a bottleneck during the last glacial maximum in Eurasia, followed by a recent expansion. The SDM analyses revealed significant fluctuations in the species range in the past and expansion under present conditions. Given the high dispersal ability of the species, the population expansion rate has surpassed the rate of developing new genetic diversity, and the estimated polymorphic sites for the species are likely relatively recent. This low level of genetic variation can also be attributed to the absence of geographical barriers and the excellent flying ability of the queen bee, leading to sustained gene flow throughout the entire continent. Despite the general correlation between larger populations and higher genetic diversity, bumblebees can expand their population size without increasing genetic diversity when residing in resourceful habitats.

HIt Discovery using docking ENriched by GEnerative Modeling (HIDDEN GEM): A novel computational workflow for accelerated virtual screening of ultra-large chemical libraries.

Recent rapid expansion of make-on-demand, purchasable, chemical libraries comprising dozens of billions or even trillions of molecules has challenged the efficient application of traditional structure-based virtual screening methods that rely on molecular docking. We present a novel computational methodology termed HIDDEN GEM (HIt Discovery using Docking ENriched by GEnerative Modeling) that greatly accelerates virtual screening. This workflow uniquely integrates machine learning, generative chemistry, massive chemical similarity searching and molecular docking of small, selected libraries in the beginning and the end of the workflow. For each target, HIDDEN GEM nominates a small number of top-scoring virtual hits prioritized from ultra-large chemical libraries. We have benchmarked HIDDEN GEM by conducting virtual screening campaigns for 16 diverse protein targets using Enamine REAL Space library comprising 37 billion molecules. We show that HIDDEN GEM yields the highest enrichment factors as compared to state of the art accelerated virtual screening methods, while requiring the least computational resources. HIDDEN GEM can be executed with any docking software and employed by users with limited computational resources.

A Review on Approval and Registration Process of Medical Devices in Canada and India

A medical device is any device or material used to promote human health. Due to an increase in the prevalence of chronic diseases, irregular health examinations, and sedentary lifestyles, as well as an increase in cases of obesity, diabetes, neuro-based disorders, heart diseases, and chronic diseases linked to lifestyle disorders, the use of medical devices is increasing. There are many medical devices in use today, and different rules and regulations apply to their marketing in various nations. To be sold on the market, a medical device needs to have its marketing authorization granted by the appropriate country's regulatory organization. Medical device-based therapeutic therapy is offering technologically sophisticated alternatives for the management of a number of ailments. The ministry of health and family welfare as well as science and technology in India rely heavily on the CDSCO as their primary medical regulating body. This article has been produced to discuss how medical devices are approved and registered, as well as the recent market expansion. Medical equipment sales are strong but profitable in Canada. It has one-fifth the population of Brazil, yet spends nearly as much on healthcare every year. As a result, rules and regulations must be in place to oversee the sale of such products. standardized medical equipment in order to facilitate their swift approval as well as the registration of medical devices, registration across all markets is crucial.

Interrogatives, inquiries, and exam questions

AbstractThe speech act of inquiry is generally treated as a default kind of asking questions. The widespread norm states that one inquires whether p only if one does not know that p. However, the fact that inquiring is just one kind of asking questions has received little to no attention. Just as in the declarative mood we can perform not only assertions, but various other speech acts, like guesses or predictions, so in the interrogative mood we can also make various speech act types. I propose a speech-act-theoretic account of a distinct kind of question that I label exam questions. According to the proposed account, one performs an exam question p only if (i) one has access to the answer to p, and (ii) one does not officially know whether the hearer knows the answer to p. Exam questions satisfy all the necessary requirements of being a distinct kind of speech act. Additionally, my proposal contributes to the recent expansion of the normative approach to a variety of speech acts.

Combined Edge Loss UNet for Optimized Segmentation in Total Knee Arthroplasty Preoperative Planning.

Bone segmentation and 3D reconstruction are crucial for total knee arthroplasty (TKA) surgical planning with Personalized Surgical Instruments (PSIs). Traditional semi-automatic approaches are time-consuming and operator-dependent, although they provide reliable outcomes. Moreover, the recent expansion of artificial intelligence (AI) tools towards various medical domains is transforming modern healthcare. Accordingly, this study introduces an automated AI-based pipeline to replace the current operator-based tibia and femur 3D reconstruction procedure enhancing TKA preoperative planning. Leveraging an 822 CT image dataset, a novel patch-based method and an improved segmentation label generation algorithm were coupled to a Combined Edge Loss UNet (CEL-UNet), a novel CNN architecture featuring an additional decoding branch to boost the bone boundary segmentation. Root Mean Squared Errors and Hausdorff distances compared the predicted surfaces to the reference bones showing median and interquartile values of 0.26 (0.19-0.36) mm and 0.24 (0.18-0.32) mm, and of 1.06 (0.73-2.15) mm and 1.43 (0.82-2.86) mm for the tibia and femur, respectively, outperforming previous results of our group, state-of-the-art, and UNet models. A feasibility analysis for a PSI-based surgical plan revealed sub-millimetric distance errors and sub-angular alignment uncertainties in the PSI contact areas and the two cutting planes. Finally, operational environment testing underscored the pipeline's efficiency. More than half of the processed cases complied with the PSI prototyping requirements, reducing the overall time from 35 min to 13.1 s, while the remaining ones underwent a manual refinement step to achieve such PSI requirements, performing the procedure four to eleven times faster than the manufacturer standards. To conclude, this research advocates the need for real-world applicability and optimization of AI solutions in orthopedic surgical practice.

Can the Seed Trade Provide a Potential Pathway for the Global Distribution of Foliar Pathogens? An Investigation into the Use of Heat Treatments to Reduce Risk of Dothistroma septosporum Transmission via Seed Stock.

The international plant trade results in the accidental movement of invasive pests and pathogens, and has contributed significantly to recent range expansion of pathogens including Dothistroma septosporum. Seeds are usually thought to present a lower biosecurity risk than plants, but the importation of Pinus contorta seeds from North America to Britain in the mid-1900s, and similarities between British and Canadian D. septosporum populations suggests seeds could be a pathway. Dothistroma septosporum has not been isolated from seeds, but inadequately cleaned seed material could contain infected needle fragments. This case study investigated whether cone kilning, and wet and dry heat treatments could reduce D. septosporum transmission without damaging seed viability. Pinus needles infected with D. septosporum were incubated alongside cones undergoing three commercial seed extraction processes. Additional needles were exposed to temperatures ranging from 10 to 67 °C dry heat for up to 48 h, or incubated in water heated to between 20 and 60 °C for up to one hour. Pinus sylvestris seeds were exposed to 60 and 65 dry heat °C for 48 h, and further seed samples incubated in water heated to between 20 and 60 °C for up to one hour. Dothistroma septosporum survived the three kilning processes and while seeds were not damaged by dry heat exceeding 63.5 °C, at this temperature no D. septosporum survived. Wet heat treatments resulted in less than 10% pathogen survival following incubation at 40 °C, while at this temperature the seeds suffered no significant impacts, even when submerged for one hour. Thus, commercial seed kilning could allow D. septosporum transmission, but elevated wet and dry heat treatments could be applied to seed stock to minimise pathogen risk without significantly damaging seed viability.

A Conversation on Feminism, Ableism, and Medical Assistance in Dying

This article explores the recent expansion of Medical Assistance in Dying (MAiD) in Canada and its negative implications for women with disabilities. In 2021, the government extended MAiD to people with disabilities who are not dying, which the authors contend is a modern form of eugenics. Structured as a conversation and deploying a systemic, equality-based feminist analysis, the article tracks the shifts in scope and justification for MAiD through judicial and legislative developments, the overwhelming opposition by organizations representing people with disabilities, and the failure of feminist organizations to support their disabled sisters. The authors articulate a feminist response to the expansion of MAiD to address this troubling silence. After Isabel Grant sets out the foundations of Track 2 MAiD, Janine Benedet develops a critique of the concepts of autonomy, choice, and privacy as used by MAiD expansionists to justify these premature deaths. Elizabeth Sheehy explores some of the structural issues that affect the impetus for MAiD: women’s poverty, the medical profession, the gendered nature of caregiving, and men’s violence. Isabel Grant demonstrates the particular dangers for women of the extension of MAiD on the basis of mental illness, as evidenced by data from other countries. Catherine Frazee describes what a truly intersectional feminist approach to MAiD demands of more privileged feminists and concludes the conversation with a call for feminist solidarity.

How Veeries vary: Whole genome sequencing resolves genetic structure in a long-distance migratory bird

Abstract In high-latitude species with high dispersal ability, such as long-distance migratory birds, populations are often assumed to exhibit little genetic structure due to high gene flow or recent postglacial expansion. We sequenced over 120 low-coverage whole genomes from across the breeding range of a long-distance migratory bird, the Veery (Catharus fuscescens), revealing strong evidence for isolation by distance. Additionally, we found distinct genetic structure between boreal, western montane U.S., and southern Appalachian sampling regions. We suggest that population genetic structure in this highly migratory species is detectable with the high resolution afforded by whole-genomic data because, similar to many migratory birds, the Veery exhibits high breeding-site fidelity, which likely limits gene flow. Resolution of isolation by distance across the breeding range was sufficient to assign likely breeding origins of individuals sampled in this species’ poorly understood South American nonbreeding range, demonstrating the potential to assess migratory connectivity in this species using genomic data. As the Veery’s breeding range extends across both historically glaciated and unglaciated regions in North America, we also evaluated whether contemporary patterns of structure and genetic diversity are consistent with historical population isolation in glacial refugia. We found that patterns of genetic diversity did not support southern montane regions (southern Appalachians or western U.S. mountains) as glacial refugia. Overall, our findings suggest that isolation by distance yields subtle associations between genetic structure and geography across the breeding range of this highly vagile species even in the absence of obvious historical vicariance or contemporary barriers to dispersal.

Assessment of genetic diversity of Trypanosoma evansi in the domestic animal populations through ITS-1 gene sequence analysis.

Trypanosoma evansi infects domestic animals, causing a debilitating and occasionally fatal disease. The disease leads to significant economic losses to farmers and poses a substantial impediment to the growth of livestock production in developing nations, including India. Considering the challenges associated with managing this infection, there is an urgent need to enhance our understanding of the molecular and genetic diversity of T. evansi. Therefore, this study was planned to analyze the genetic diversity of T. evansi using available internal transcribed spacer-1 (ITS-1) gene sequences from India and compare them with sequences from around the globe. Blood samples used in this study were collected from naturally infected animals including dogs, cattle, and buffaloes in the Indian state of Madhya Pradesh. Using the ITS-1 gene, we amplified a 540 base pairs (bp) segment using polymerase chain reaction (PCR), sequenced it, and identified intra-specific variations. Phylogenetic analysis of 90 sequences, including 27 from India, revealed three distinct clusters with high bootstrap support values. A haplotype network analysis identified 34 haplotypes, with H7 being the most prevalent, indicating a complex evolutionary history involving multiple countries. The genetic analysis of the Indian population revealed distinct characteristics. Despite low nucleotide diversity, there was high haplotype diversity in comparison to other populations. Tajima's D, Fu and Li's D, and Fu and Li's F exhibited non-significant negative values, indicating potential stability. Additionally, the slightly positive values in Fu's Fs, Raggedness (r), and Ramos-Onsins and Rozas (R2) statistics suggested a lack of recent significant selective pressures or population expansions. Furthermore, the presence of genetic differentiation and gene flow among T. evansi populations highlighted ongoing evolutionary processes. These findings collectively depicted a complex genetic landscape, suggesting both stability and ongoing evolutionary dynamics within the Indian population of T. evansi. The findings of this study are important for understanding the evolutionary history and population dynamics of T. evansi, and they may help us develop effective control strategies.

Factors Influencing Prospective Students to Join Higher Learning Institutions: Insights from Mbeya University of Science and Technology

The recent expansion of educational boundaries has created a competitive market, and higher learning institutions are resorting to digital marketing to reach out to prospective students. This study investigated the factors that affect potential students’ enrollment in Higher Learning Institutions (HLIs). A sample size of 384 was used in the explanatory cross-sectional study design. We used both descriptive and inferential analyses. The results showed that students' education level and entry credentials were statistically significant at p<0.05 and p<0.01, respectively, while income level was statistically significant at p<0.01. It was also discovered that the National Council for Technical and Vocational Education (NACTE), alumnae, the Tanzania Commission for Universities (TCU), and university websites were trustworthy sources of information. Therefore, academic level, entry qualification of the respective institution, NACTE, alumnae, TCU, and university website influence information search on HLI opportunities. It is suggested that HLIs make admission qualifications available to prospective candidates and commit to quality programmes and excellent services.

Taking It to the Limit: Effects of Increased Student Loan Availability on Attainment, Earnings, and Financial Well-Being

Growing reliance on student loans and repayment difficulties have raised concerns of a student debt crisis in the United States, but little is known about the effects of student borrowing on human capital and long-run financial well-being. We use variation induced by recent expansions in federal loan limits combined with administrative data-sets to identify the effects of increased access to student loans on credit-constrained students’ educational attainment, earnings, debt, and loan repayment. Increased student loan availability raises student debt and improves degree completion, later-life earnings, and student loan repayment, while having no effect on homeownership or other types of debt. (JEL G51, I22, I23, I26, J24)

Pathways linking educational attainment to cognitive functioning among older Brazilians

AbstractBackgroundCognitive impairment in Brazil is a growing population health concern. Studies suggest that Brazil may have one of the highest age‐standardized prevalence of Alzheimer’s disease and related dementias (ADRD) in the world. However, improving education attainment among older adults may lead to a decline in cognitive impairment across the population in the coming years. The purpose of this study is to examine the pathways that link educational attainment to cognitive functioning in Brazil, a highly unequal, resource rich society.MethodI use the 2016 Brazilian Longitudinal Study of Aging, a nationally representative study of Brazilian older adults 50+, to predicting cognitive functioning at first interview. I use structural equation modeling to predict direct and indirect effects of education via childhood socioeconomic characteristics, adulthood socioeconomic conditions, health behaviors and health conditions on overall cognitive functioning as well as specific domains of cognition (memory vs. non‐memory).ResultFindings provide evidence of both indirect and direct pathways from education to cognitive functioning. The indirect pathways were mainly found through adulthood SES achievement (although health conditions had their own association with cognitive functioning). Additionally, indirect effects were limited among adults with 8+ years of education, suggesting that prior to 8 years of education the impact of education on cognitive functioning may be through cognitive development that is carried forward into older adulthood.ConclusionThis study shows the importance of early childhood education and the potential benefits for later life cognitive functioning, which has broad implications for cognitive health in rapidly aging countries with more recent early childhood educational expansion.

The absence of disturbances promoted Late Holocene expansion of silver fir (Abies alba) in the Bohemian Forest

Temperate forests in the Northern Hemisphere are strongly affected by increasing annual temperatures and natural disturbances such as droughts, fires, and pest outbreaks. In many regions, alternatives are explored by the forestry industry for previously commercialized tree species which are rapidly declining in areas outside their optimal climatic niches. However, as the current ranges of tree species have been mainly constrained by human activity, their true climatic and ecological niches are likely different from our observations. For example, little is known about environmental niches and population dynamics of tree species with limited dispersal ability, such as silver fir (Abies alba). Long-term (paleo) records of past landscape composition, past climate, and past disturbances can help to reveal the natural environmental niches of tree species. This study focuses on the Bohemian Forest (Šumava) in Czechia, where the human alteration of forests in higher elevations (>1000 m asl) has only been demonstrated from Medieval times onward. We present an interdisciplinary approach of geochemistry, pollen, charcoal, botanical and insect macro remains from a high-elevation peat record for the last seven millennia. Our multi-proxy study aimed to identify episodes of increased fire and other disturbances such as insect outbreaks, which could have influenced forest dynamics and vegetation succession in this montane region. However, the charcoal and macro-fossil records do not indicate any large local fires, insect outbreaks, browsing, or other disturbances (e.g., anthropogenic) for a major part of the record, suggesting that changes in the vegetation after 6500 cal yr BP were mainly caused by climatic fluctuations. Silver fir (Abies alba) expanded from 4300 cal yr BP, and likely became the dominant tree species at this locality for the next 2000 years, with extremely high pollen values up to 60%. During the establishment of silver fir around the peat bog around 5600 cal yr BP and its expansion around 4300 cal yr BP, the geochemical record and low counts of the testate amoeba Archerella flavum indicate drier conditions on the peat bog. Comparison with climatic simulations on a 1 × 1-km scale from the CHELSA database suggests that the local expansion of silver fir possibly coincided with a decrease in precipitation during both the wettest and warmest quarter of the year, related to a decreasing trend in seasonality of annual precipitation; this might confirm the species' higher tolerance to drought. Although silver fir is currently extremely rare in the Bohemian Forest, it has the potential for local expansion if logging, fire, and game browsing are kept to a minimum.

Genetic structure and demographic history of whiting Merlangius merlangus (Linnaeus, 1758) populations distributed in Turkey inferred from variation in mitochondrial DNA sequences

The genetic diversity, structure, and demographic history of the economically important and overfished Gadidae species Merlangius merlangus were investigated using the non-coding mitochondrial Control Region (CR) from five different sites in the Sea of Marmara and the Black Sea in Turkey. The populations of M. merlangus were found to be genetically diverse, with 14 haplotypes and 15 polymorphic regions. The overall haploid diversity was 0.910 ± 0.024, and the nucleotide diversity was 0.003± 0.0003. Genetic distances between populations varied between 0.13% and 8.02%, while genetic distances within M. merlangus populations varied between 0.09% and 0.42%. Principle Coordinates Analysis showed that Marmara, Black Sea, and Karadeniz Ereğli populations were clearly separated. Pairwise FST values varied from 0.12 to 0.69, highlighting high genetic variation among populations. The Black Sea and Marmara lineages of M. merlangus diverged from the North Sea lineage 1.65 (1.08-2.29) mya, whereas the separation between the Atlantic lineage occurred about 0.84 (0.51-1.2) mya. The recent expansion of the whiting population was identified through neutrality tests and mismatch distribution analyses. This study provides important insight into the genetic structure, conservation, and management of this species.

Ouverture de ‘New Horizons in Global Management’

The Russian-Ukrainian War introduced new elements into the strategic assessments of large global corporations, changing competitive horizons and developing new models of competition. The impact of the recent BRICS expansion on the global corporations management and on the growth of sustainability goals reflects a growing global new competitive landscape that places global corporations in a delicate position as a possible counterweight to the EU, to the U.S and to the Asian World.

Subalpine ”pinification”: Early signs of a pending and distinct biogeographic shift in the Swedish Scandes: Review and updates

This study focuses, by in situ records and long-term observations, on recent (post-Litte Ice Age), arboreal change in a mountain birch dominated (Betula pubescens ssp. czerepanovii) valley in the Swedish Scandes. During the early Holocene thermal optimum and up to the onset of the mid-Holocene Neoglaciation, Scots pine (Pinus sylvestris) dominated the tree cover of this valley and formed the treeline ecotone adjacent to the early alpine tundra. Subsequently, and consistent with progressive cooling until the late 19th century, prevailing pine stands demised and opened for landscape-level expansion of birch and spruce (Picea abies). A short and distinct break in that process took place by the Medieval Climate warming phase, about 1000-800 years before present. Subsequently, during pre-industrial time, temperatures reached their lowest levels of the entire post-glacial period. This was the so-called Little Ice Age, which ended the long-term Holocene cooling. That cold-climate epoque was broken by the late-19th and early 20th century. Thereafter and up to the present-day, temperatures in the study region (summer and winter) have increased by slightly less than 2 °C. As a consequence, treelines of all species have advanced by a maximum of more than 200 altitudinal meters. Pine displays the most persistent expansion, particularly over the past few decades. “Falangist” occurrences appear in the pure birch forest, tens of kilometers and hundreds of meters, respectively, beyond and above the outposts by the early 20th century. Occasionally, scattered young pine trees now grow close to the birch forest limit and somewhat above. In particular, at sites where pine stands demised during the Little Ice Age, c. AD. 1300-1850, prolific regeneration and insignificant winter mortality are recorded over the past 15 years. In comparison, birch and spruce provide no analogous signs of recent expansion. It may be hypothesized that unabated climate warming and corresponding arboreal progression will profoundly transform the plant cover of this valley, and others alike, into the same pine-dominated state that prevailed during the early Holocene. In other words, a new biogeographic zonation pattern may be on the rise, with pine back as the dominant subalpine species. This option is focused by continued monitoring.

Single Cell Whole Genome Measurement of Genomic Heterogeneity and Clonal Evolution in Multiple Myeloma

Background: Sequencing studies have advanced our understanding of the genomic underpinnings of Multiple Myeloma (MM). While whole genome sequencing (WGS) has emerged as a comprehensive approach for profiling the genomic landscape of MM, WGS has limited sensitivity in defining the intrapatient genomic heterogeneity. Single cell RNA approaches can capture phenotypic heterogeneity but fail to recover most of the key genomic drivers. To overcome these historical limitations, we utilized a newer single cell whole genome direct library preparation (scWGS DLP+; Lacks et al. Cell 2019) sequencing technology able to detect early changes and study clonal population dynamics, providing a more precise understanding of the emergence and clinical impact of genomic events during MM evolution. Methods: scWGS DLP+ was applied to CD138 + Plasma Cells (PC) isolated from bone marrow samples of MM patients. Using newly developed computational approaches, we characterized the Single Nucleotide Variants (SNVs), copy number changes and complex Structural Variants (SVs) at a single cell level and use this information to reconstruct the evolutionary histories of each patient's myeloma. Results: We applied DLP to 7 MM patients obtaining 800-1600 single cell whole genomes per patient. All canonical IgH translocations identified by FISH were recovered in the scWGS data. Single cell copy number heterogeneity was observed in all but 1 patient, including heterogeneity affecting known drivers. The number of subclones ranged from 1 to 15, with an average of 6 subclones detected per patient (≥10 cells, ≥5MB distinct segmental difference). This is in striking contrast with bulk WGS where we are usually able to define no more than one or two subclones. Gain of 1q (3 copies) was observed in all patients but was either rare (1-3%, 3 patients) or clonal (>99%, 4 patients), with two clonal 1q patients exhibiting convergent subclonal 1q amplification (>3 copies). Loss of previously gained chromosomes was observed including loss of ancestrally gained chromosome 15 in hypodiploid Patient 2, and sporadic loss of 1q in patients with ubiquitous 1q gain. For 3 of 7 patients, hypodiploidy (HRD) had arisen before the most recent clonal expansion. HRD clones continued to diversify, accruing multiple additional events on HRD chromosomes including large or focal gains, or deletions subsequent to a gain. Interestingly, one case had 1 small hypodiploid clone co-existing with a completely different major clone with 1q and t(14;20) IgH translocation, suggesting the existence of two distinct clonal plasma cell populations (one malignant and one likely bening). Two of the 7 patients harbored both small (<20 cells) whole genome doubled (WGD) subclones, and small numbers of highly aneuploid likely produced by multi-polar cell division post WGD. We explored two patient's evolutionary histories in detail, highlighting the unique resolution of scWGS DLP+ to detect CNV but also SNV, mutational signatures and SVs. Patient 3 exhibited 4 distinct subclones with distant evolutionary origin as evidenced by the relatively small number of shared SNV. APOBEC signature mutations were detected in all 4 subclones suggesting APOBEC mutagenesis was still ongoing across the cell populations in this patient. In Patient 1, a complex SV on chromosome 17 resulted in loss of most of 17q and an amplification of 17q segments. The heterogeneous structure of chromosome 17 across clones suggests a late onset of this complex event and ongoing instability. Chromosome 16 exhibited a pattern of cell specific arm loss likely resulting from telomere loss. Interestingly, a minor clone showed complex amplification of 16p affecting TNFRSF17, suggesting that chromosome 16 is at an earlier stage of a process of instability that starts with cell specific arm loss, and ends with clonal expansion of a complex amplification SV targeting a gene with fitness benefit. Discussion: Applied to Multiple Myeloma, scWGS shows higher clonal heterogeneity than previously described with multiple clones exhibiting diverse genetic alterations. The findings underscore the genomic complexity and dynamic nature of MM, highlighting the need for sensitive techniques like scWGS to capture the full spectrum and chronological order of genomic events.

Habitat specialization predicts demographic response and vulnerability of floodplain birds in Amazonia.

The annual flooding cycle of Amazonian rivers sustains the largest floodplains on Earth, which harbour a unique bird community. Recent studies suggest that habitat specialization drove different patterns of population structure and gene flow in floodplain birds. However, the lack of a direct estimate of habitat affinity prevents a proper test of its effects on population histories. In this work, we used occurrence data, satellite images and genomic data (ultra-conserved elements) from 24 bird species specialized on a variety of seasonally flooded environments to classify habitat affinities and test its influence on evolutionary histories of Amazonian floodplain birds. We demonstrate that birds with higher specialization in river islands and dynamic environments have gone through more recent demographic expansion and currently have less genetic diversity than floodplain generalist birds. Our results indicate that there is an intrinsic relationship between habitat affinity and environmental dynamics, influencing patterns of population structure, demographic history and genetic diversity. Within the floodplains, historical landscape changes have had more severe impacts on island specialists, making them more vulnerable to current and future anthropogenic changes, as those imposed by hydroelectric dams in the Amazon Basin.

Comparison of Myeloablative Conditioning with Cyclophosphamide and Total-Body Irradiation (Cy/TBI) Vs. Fludarabine, Melphalan, and Total-Body Irradiation (Flu/Mel/TBI) in Patients Undergoing Allogeneic Stem Cell Transplant for AML/ALL

Background: Cyclophosphamide combined with total-body irradiation (Cy/TBI) has been widely used worldwide as the standard myeloablative conditioning (MAC) for allogeneic stem cell transplantation (allo-HCT), but there are concerns about the antitumor effects of CY, as well as side effects, including cardiotoxicity and mucosal toxicity. A few studies suggest that the addition of an anticancer agent to a Cy/TBI regimen may reduce recurrence rates, but comparative studies of Cy/TBI regimens versus other TBI regimens are scarce. Furthermore, the recent expansion of post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis has increased its utility for cyclophosphamide-free conditioning regimens. Our institution has extensive experience with cord blood transplantation for relatively elderly patients with high-risk leukemia and has worked to develop safer and more effective MAC regimens other than Cy/TBI. The purpose of this study is to examine the safety and efficacy of fludarabine and melphalan combined with total-body irradiation (Flu/Mel/TBI) regimen, which is widely used at our institution, compared to Cy/TBI. Methods: We retrospectively analyzed adult acute leukemia patients who underwent allo-HCT between August 1994 to February 2023 at Toranomon Hospital. The inclusion criteria were as follows: a diagnosis of acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), the first allo-HCT, and Cy (120mg/kg) /TBI (8-12Gy) or Flu (180mg/m 2) /Mel (80-120mg/m 2) /TBI (8-12Gy) as MAC regimen. We excluded patients who underwent haploidentical transplantation with post-transplant cyclophosphamide. The primary endpoint was the 5-year cumulative incidence of relapse, and the secondary endpoints were the 5-year cumulative incidence of non-relapse mortality (NRM), 5-year overall survival (OS), and relapse-free survival (RFS). OS and RFS were estimated by the Kaplan-Meier method and multivariate Cox proportional hazard models. The cumulative incidence of relapse and NRM were investigated with a competing risk analysis using Gray's test and multivariable Fine and Gray competing risk regression. Results: A total of 198 patients were included in this study, comprising 101 patients treated with Cy/TBI and 97 treated with Flu/Mel/TBI. Patients who received Flu/Mel/TBI were of higher age (Median age: Cy/TBI 36 years vs. Flu/Mel/TBI 53 years, p<0.01), higher ECOG PS score (PS≥1: 51.5% vs. 66.0%, p=0.044), fewer AML (49.5% vs. 22.7%, p<0.01), and more frequent CBT (45.5% vs. 76.3%, p<0.01). Disease status at HCT (CR1: 53.5% vs. 43.3%, p=0.154) and HCT-CI scores (HCT-CI≥1: 35.6% vs. 44.3%, p=0.214) were not different between the two regimen groups. Regarding the primary endpoint, the 5-year cumulative incidence of relapse was significantly lower in Flu/Mel/TBI group (36.8% vs. 24.9%, p= 0.035). The cumulative incidence of NRM was not significantly different between the two groups (19.1% vs. 25.2%, p=0.345). In the multivariate analysis, conditioning with Flu/Mel/TBI was significantly associated only with a lower risk of relapse (HR: 2.817; 95%CI: 1.183-6.712; p=0.019). Regarding NRM, only disease status not in CR1 was associated with a higher risk (CR1 vs. non-CR1 HR: 2.21; 95%CI: 1.095-4.468; p=0.027). There was no significant difference in 5-year OS (Cy/TBI 48.1% vs. Flu/Mel/TBI 51.4%, p=0.604) and RFS (44.2% vs. 49.9%, p=0.24). Conclusion: Despite older age and worse PS in the Flu/Mel/TBI group, Flu/Mel/TBI had a significantly lower 5-year cumulative relapse rate than Cy/TBI, with no significant difference in NRM. Our results suggest that Flu/Mel/TBI is a reasonable alternative to CY/TBI and may be a superior TBI-containing MAC regimen.

Computation of parabolic cylinder functions having complex argument

Numerical methods for the computation of the parabolic cylinder function U(a,z) for real a and complex z are presented. The main tools are recent asymptotic expansions involving exponential and Airy functions, with slowly varying analytic coefficient functions involving simple coefficients, and stable integral representations; these two main methods can be complemented with Maclaurin series and a Poincaré asymptotic expansion. We provide numerical evidence showing that the combination of these methods is enough for computing the function with 5×10−13 relative accuracy in double precision floating point arithmetic.