Million-year-old DNA sheds light on the genomic history of mammoths.

Temporal genomic data hold great potential for studying evolutionary processes such as speciation. However, sampling across speciation events would, in many cases, require genomic time series that stretch well back into the Early Pleistocene subepoch. Although theoretical models suggest that DNA should survive on this timescale1, the oldest genomic data recovered so far are from a horse specimen dated to 780-560 thousand years ago2. Here we report the recovery of genome-wide data from three mammoth specimens dating to the Early and Middle Pleistocene subepochs, two of which are more than one million years old. We find that two distinct mammoth lineages were present in eastern Siberia during the Early Pleistocene. One of these lineages gave rise to the woolly mammoth and the other represents a previously unrecognized lineage that was ancestral to the first mammoths to colonize North America. Our analyses reveal that the Columbian mammoth of North America traces its ancestry to a Middle Pleistocene hybridization between these two lineages, with roughly equal admixture proportions. Finally, we show that the majority of protein-coding changes associated with cold adaptation in woolly mammoths were already present one million years ago. These findings highlight the potential of deep-time palaeogenomics to expand our understanding of speciation and long-term adaptive evolution.

The role of thriving in mental health among people with intellectual and developmental disabilities during the COVID-19 pandemic in Canada.

BACKGROUND: The COVID-19 pandemic has had a negative impact on the mental health of people with intellectual and developmental disabilities. Numerous pandemic-related stressors experienced by people with intellectual and developmental disabilities may have impacted their ability to thrive, which has been linked to mental health outcomes. The current study examined the associations among COVID-19 stressors, thriving, and mental health problems among youth and adults with intellectual and developmental disabilities. METHOD: Caregivers of 159 people with intellectual and developmental disabilities between 12 and 35 years of age from Canada completed an online questionnaire. RESULTS: A mediation analysis revealed that COVID-19 stressors were positively associated with mental health problems, and that thriving partially mediated this association. CONCLUSION: Our findings suggest that experiences of thriving may be an important target for mental health support for people with intellectual and developmental disabilities.

Peptide-polyurea hybrids: a platform for tunable, thermally-stable, and injectable hydrogels.

Drawing inspiration from natural systems, such as the highly segmented structures found in silk fibroin, is an important strategy when designing strong, yet dynamic biomaterials. Polymer-peptide hybrids aim to incorporate the benefits of hierarchical polypeptide structures into synthetic platforms that are promising materials for hydrogel systems due to aspects such as their biocompatibility and structural tunability. In this work, we demonstrated the utility of poly(ethylene glycol) (PEG) peptide-polyurea hybrids as self-assembled hydrogels. Specifically, poly(ε-carbobenzyloxy-L-lysine)-b-PEG-b-poly(ε-carbobenzyloxy-L-lysine) and poly(ß-benzyl-L-aspartate)-b-PEG-b-poly(ß-benzyl-L-aspartate) triblock copolymers were used as the soft segments in linear peptide-polyurea (PPU) hybrids. We systematically examined the effect of peptide secondary structure and peptide segment length on hydrogelation, microstructure, and rheological properties of our PPU hydrogels. Polymers containing α-helical secondary structures resulted in rapid gelation upon the addition of water, as driven by hierarchical assembly of the peptide segments. Peptide segment length dictated gel strength and resistance to deformation via complex relationships. Simulated injection experiments demonstrated that PPU hydrogels recover their original gel network within 10 s of cessation of high shear. Finally, we showed that PPU hydrogels remain solid-like within the range of 10 to 80 °C; however, a unique softening transition occurs at temperatures corresponding to slight melting of secondary structures. Overall, this bioinspired PPU hybrid platform provides opportunities to design synthetic, bioinspired polymers for hydrogels with tunable microstructure and mechanics for a wide range of thermal and injection-based applications.

Histopathological survey of putative parasites and pathogens in non-native slipper limpets Crepidula fornicata.

Two populations of the invasive slipper limpet Crepidula fornicata were sampled in Swansea Bay and Milford Haven, Wales, UK, to determine the presence of putative pathogens and parasites known to affect co-located commercially important shellfish (e.g. oysters). A multi-resource screen, including molecular and histological diagnoses, was used to assess 1800 individuals over 12 mo for microparasites, notably haplosporidians, microsporidians and paramyxids. Although initial PCR-based methods suggested the presence of these microparasites, there was no evidence of infection when assessed histologically, or when all PCR amplicons (n = 294) were sequenced. Whole tissue histology of 305 individuals revealed turbellarians in the lumen of the alimentary canal, in addition to unusual cells of unknown origin in the epithelial lining. In total, 6% of C. fornicata screened histologically harboured turbellarians, and approximately 33% contained the abnormal cells-so named due to their altered cytoplasm and condensed chromatin. A small number of limpets (~1%) also had pathologies in the digestive gland including tubule necrosis, haemocytic infiltration and sloughed cells in the tubule lumen. Overall, these data suggest that C. fornicata are not susceptible to substantive infections by microparasites outside of their native range, which may contribute in part to their invasion success.

Evaluating Social Determinants of Health in a Mobile Integrated Healthcare-Community Paramedicine Program.

In 2018, the University of Maryland Medical Center and the Baltimore City Fire Department implemented a community paramedicine program to help medically or socially complex patients transition from hospital to home and avoid hospital utilization. This study describes how patients' social determinants of health (SDoH) needs were identified, and measures the association between needs and hospital utilization. SDoH needs were categorized into ten domains. Multinomial logistic regression was used to measure association between identified SDoH domains and predicted risk of readmission. Poisson regression was used to measure association between SDoH domains and actual 30-day hospital utilization. The most frequently identified SDoH needs were in the Coordination of Healthcare (37.7%), Durable Medical Equipment (18.8%), and Medication (16.3%) domains. Compared with low-risk patients, patients with an intermediate risk of readmission were more likely to have needs within the Coordination of Healthcare (RRR [95% CI] 1.12 [1.01, 1.24], p = 0.032) and Durable Medical Equipment (RRR = 1.13 [1.00, 1.27], p = 0.046) domains. Patients with the highest risk for readmission were more likely to have needs in the Utilities domain (RRR = 1.76 [0.97, 3.19], p = 0.063). Miscellaneous domain needs, such as requiring a social security card, were associated with increased 30-day hospital utilization (IRR = 1.23 [0.96, 1.57], p = 0.095). SDoH needs within the Coordination of Healthcare, Durable Medical Equipment, and Utilities domains were associated with higher predicted 30-day readmission, while identification documentation and social services needs were associated with actual readmission. These results suggest where to allocate resources to effectively diminish hospital utilization.

Coping strategies and psychosocial resources among women living with metastatic breast cancer: A qualitative study.

Objective: Despite more women living with metastatic breast cancer (MBC), this population is underrepresented in cancer survivorship research. Few studies have assessed how women with MBC cope with their cancer experience. This qualitative study describes the coping strategies and psychosocial resources utilized by women living with MBC.Methods: Twenty-two women with MBC participated in four focus groups. Transcripts were analyzed using a general inductive approach. Codes derived from participants' responses were subsequently condensed into themes.Results: We identified 12 coping strategies and psychosocial resources and grouped them into five themes: Behavioral Coping Strategies (i.e. stress management, active coping and planning); Cognitive Coping Strategies and Psychological Resources (i.e. cognitive reappraisal, optimism, mindfulness, positive thinking, and religious coping); Existential Approach-Oriented Coping (i.e. acceptance, values-based living, and identity integration); Avoidance (i.e. avoidant coping); and Interpersonal Resources and Seeking Social Support (i.e. social support).Conclusions: Women living with MBC utilize several engagement and disengagement coping strategies, as well as intrapersonal and interpersonal resources. This study provides useful perspectives of women living with MBC that may inform the development of psychosocial interventions. Further research is needed to assess coping strategies and psychosocial resources across different subgroups of MBC patients and determine their impact on cancer outcomes.

Invasive slipper limpets Crepidula fornicata are hosts for sterilizing digenean parasites.

Invasion and spread of alien species can drive ecosystem changes, such as, the dynamics of infectious diseases. The non-native, marine gastropod Crepidula fornicata has become established across European coastlines over the last century, but there remains little insight into its disease carrying capacity and potential role as a source/sink of parasites. To address this knowledge gap, we surveyed limpets from two sites in South Wales, UK for signatures of disease/pathology using polymerase chain reaction-based methods (haemolymph) and histology (solid tissue). We encountered trematode-like parasites in ~1% individuals (5 out of 462). Three limpets displayed gross damage in the gonad, i.e. castration, and encysted metacercariae were found in the muscle of two other individuals. On the basis of 28S rDNA and internal transcribed spacer 2 genomic targets, we identified the gonad-infecting trematodes as members of the family Microphallidae ­ putative novel species related to the genus Longiductotrema. Earlier reports suggest that C. fornicata is not a host for trematode parasites in either its native or alien range but may act as a sink due to its filter feeding lifestyle. We provide clear evidence that C. fornicata is parasitized by at least one trematode species at two sites in Wales, UK, and likely act as a spillback or accidental host among native littorinids.

Place of alcohol in the 'wellness toolkits' of midlife women in different social classes: A qualitative study in South Australia.

In this article, we explore how women in different social classes had differential access to resources and services to enhance their 'wellness'-resulting in classed roles in alcohol consumption. We analyse data from a qualitative study on alcohol by midlife women in South Australia and employ the analogy of a 'toolkit' in order to understand the structural patterning of 'wellness tools'. Bourdieu's relational model of class guides our exploration of women's inequitable opportunities for wellness. Higher social class women had 'choices' facilitated by bulging wellness toolkits, such as yoga, exercise and healthy eating regimens-alcohol consumption was not essential to promoting 'wellness' and did not have an important place in their toolkits. Middle-class women had less well-stocked toolkits and consumed alcohol in a 'compensation approach' with other wellness tools. Alcohol consumption received positive recognition and was a legitimised form of enjoyment, fun and socialising, which needed counterbalancing with healthy activities. Working-class women had sparse toolkits-other than alcohol-which was a tool for dealing with life's difficulties. Their focus was less on 'promoting wellness' and more on 'managing challenging circumstances'. Our social class-based analysis is nestled within the sociology of consumption and sociological critiques of the wellness industry.

Exploring the potential of citizen science for public health through an alcohol advertising case study.

Citizen science connects academic researchers with the public through combined efforts in scientific inquiry. The importance of involving impacted populations in health research is well established. However, how to achieve meaningful participation and the methodological impact of citizen science needs further examination. We examined the feasibility of using citizen science to understand the impact of alcohol advertising on Australian women through a breast cancer prevention project. Two hundred and eighty-two ('participants') citizen scientists completed demographic and behavioural questions via an online survey. The research participants moved into the role of citizen scientists by completing the data collection tasks of capturing and classifying images of alcohol advertising they saw online. Interrater reliability tests found high levels of agreement between citizen scientists and academic researchers with the classification of alcohol advertising brand (Kappa = 0.964, p < 0.001) and image type (Kappa = 0.936, p < 0.000). The citizen scientists were women aged 18 and over, with 62% between 35 and 55 years old. The majority were from major cities (78%), had attained a bachelor's degree or higher-level education (62%) and were recruited via email or Facebook (86%). The use of citizen science provided methodological gains through the creation of a unique dataset with higher levels of validity than the existing literature, which employed traditional investigator-driven research methodologies. Citizen science enriched the dataset and provided a powerful methodological vehicle to understand an environmental determinant of health. The study illuminates how public participation benefitted the research process, the challenges and the potential for citizen science to improve public health.

'I have a healthy relationship with alcohol': Australian midlife women, alcohol consumption and social class.

Alcohol consumption by Australian women during midlife has been increasing. Health promotion efforts to reduce alcohol consumption in order to reduce alcohol-related disease risk compete with the social contexts and value of alcohol in women's lives. This paper draws on 50 qualitative interviews with midlife women (45-64 years of age) from different social classes living in South Australia in order to gain an understanding of how and why women might justify their relationships with alcohol. Social class shaped and characterized the different types of relationships with alcohol available to women, structuring their logic for consuming alcohol and their ability to consider reducing (or 'breaking up with') alcohol. We identified more agentic relationships with alcohol in the narratives of affluent women. We identified a tendency for less control over alcohol-related decisions in the narratives of women with less privileged life chances, suggesting greater challenges in changing drinking patterns. If classed differences are not attended to in health promotion efforts, this might mitigate the effectiveness of alcohol risk messaging to women.

Fifteen-minute consultation: An approach to the management of PIMS-TS in a district general hospital.

The COVID-19 pandemic has caused significant disease across the globe but children seem to be much less affected than adults. Coincidentally with the first wave of the pandemic, a cluster of children with fever, hyperinflammation and shock were identified, and this was first described as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) by the Royal College of Paediatrics and Child Health. Patients with this novel condition were transferred to tertiary centres for management, increasing the pressure in these hospitals that were already extremely busy. There are multiple challenges related to the identification of patients presenting with PIMS-TS given that they mimic multiple other well-known paediatric conditions, like Kawasaki disease and toxic shock syndrome. Investigations and admission criteria to a district general hospital (DGH) need to be well established, and clear guidance should be available for easy decision making in a busy paediatric emergency department. Furthermore, these children can deteriorate suddenly and rapidly; close monitoring is vital, and any deterioration must be taken seriously and addressed immediately. All children who present severely ill, with shock and multiorgan failure, should be retrieved to a paediatric intensive care unit. As our knowledge of the condition has developed, more patients are now managed in a DGH, with virtual multidisciplinary team involvement. This paper outlines a structured approach to management of children presenting with suspected PIMS-TS in a DGH.

Combating ecosystem collapse from the tropics to the Antarctic.

Globally, collapse of ecosystems-potentially irreversible change to ecosystem structure, composition and function-imperils biodiversity, human health and well-being. We examine the current state and recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2 , from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic 'presses' and/or acute 'pulses', drive ecosystem collapse. Ecosystem responses to 5-17 pressures were categorised as four collapse profiles-abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three-step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.

Ancient proteins resolve the evolutionary history of Darwin's South American ungulates.

No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as 'South American native ungulates'. To Charles Darwin, who first collected their remains, they included perhaps the 'strangest animal[s] ever discovered'. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago, or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria. Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen α1- and α2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies. Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed, but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates from 'condylarths', a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.

Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Integrated assessment of the spatial distribution and structural dynamics of deep benthic marine communities.

Characterizing the spatial distribution and variation of species communities and validating these characteristics with data from the field are key elements for an ecosystem-based approach to management. However, models of species distributions that yield community structure are usually not linked to models of community dynamics, constraining understanding and management of the ecosystem, particularly in data-poor regions. Here we use a qualitative network model to predict changes in Antarctic benthic community structure between major marine habitats characterized largely by seafloor depth and slope, and use multivariate mixture models of species distributions to validate the community dynamics. We then assess how future increases in primary production associated with anticipated loss of sea-ice may affect the ecosystem. Our study shows how both spatial and structural features of ecosystems in data-poor regions can be analyzed and possible futures assessed, with direct relevance for ecosystem-based management.

Diagnosis and prevalence of two new species of haplosporidians infecting shore crabs Carcinus maenas: Haplosporidium carcini n. sp., and H. cranc n. sp.

This study provides a morphological and phylogenetic characterization of two novel species of the order Haplosporida (Haplosporidium carcini n. sp., and H. cranc n. sp.) infecting the common shore crab Carcinus maenas collected at one location in Swansea Bay, South Wales, UK. Both parasites were observed in the haemolymph, gills and hepatopancreas. The prevalence of clinical infections (i.e. parasites seen directly in fresh haemolymph preparations) was low, at ~1%, whereas subclinical levels, detected by polymerase chain reaction, were slightly higher at ~2%. Although no spores were found in any of the infected crabs examined histologically (n = 334), the morphology of monokaryotic and dikaryotic unicellular stages of the parasites enabled differentiation between the two new species. Phylogenetic analyses of the new species based on the small subunit (SSU) rDNA gene placed H. cranc in a clade of otherwise uncharacterized environmental sequences from marine samples, and H. carcini in a clade with other crustacean-associated lineages.

Prevalence and histopathology of the parasitic barnacle, Sacculina carcini in shore crabs, Carcinus maenas.

Sacculina carcini is a common parasite of the European shore crab, Carcinus maenas. Following successful penetration of the host, numerous rootlets are formed that permeate through the hosts' tissues. Ultimately, these form an externa that houses the developing nauplii larvae of the parasite. Most studies have quantified levels of infection by counting the presence of reproductive externae and their breakdown structures, called scars. However, the diagnosis of the disease based only on external features may lead to underreporting the prevalence of the parasite. In the current study, we examined the presence and severity of S. carcini in C. maenas (n = 221) in the Prince of Wales Dock, South Wales, U.K. using a range of diagnostic approaches to give an accurate representation of temporal dynamics of infection. Parasitized crabs were found with a mean prevalence of 24% as determined by histological examination of the hepatopancreas. However, the prevalence of S. carcini based on the presence of externae and scars was only 6.3% and 1.8%, respectively. Overall, parasitism was associated with smaller crabs, crabs later in the moulting cycle that were orange in colour (as opposed to green or yellow), and those with a higher number of bacteria in the haemolymph. Interestingly, only 7.5% of infected crabs showed evidence of distinct host (cellular) response to the presence of rootlets in the hepatopancreas.

Using a think-aloud methodology to understand online physical activity information search experiences and preferences of parents of children and youth with disabilities.

BACKGROUND: The Internet is a preferred source of physical activity (PA) information. However, limited research exists regarding the experiences of parents of children and youth with disabilities (CYWD) in searching for PA programme information online. This research examined the experiences and preferences of parents of CYWD in searching for PA programme information online. METHOD: Parents of CYWD (n = 10) participated in a think-aloud exercise while searching for PA programme information online. Following the think-aloud exercise, semi-structured interviews were used to further understand parents' experiences and preferences in searching for PA programme information online. RESULTS: Parents identified key features that contributed to a positive online search experience. Additionally, parents noted challenges and resulting negative affect that was experienced. CONCLUSIONS: This research can inform the development and dissemination of online PA programme information that is accessible and relevant to the preferences of parents of CYWD and can facilitate positive search experiences.

Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection.

BACKGROUND: The association between respiratory syncytial virus (RSV) loads and clinical outcomes in children remains to be defined. In most studies, viral loads (VL) were evaluated in hospitalized children and at a single time-point. We investigated the relationship between VLs and disease severity in both outpatients and inpatients with RSV infection. METHODS: We enrolled previously healthy children with RSV infection. Disease severity was defined by level of care (outpatients vs ward vs pediatric intensive care unit [PICU]), and a clinical disease severity score (CDSS). Nasopharyngeal VLs by polymerase chain reaction and CDSS were measured at enrollment and daily in inpatients. VL decay according to disease severity was analyzed using linear mixed modeling. RESULTS: From February 2015 to March 2017, we enrolled 150 infants: 39 outpatients and 111 inpatients. VLs were higher in outpatients than in age-matched inpatients. Among inpatients, initial VLs were comparable in ward and PICU patients, and preceded the peak CDSS. However, after excluding infants treated with steroids, those hospitalized in the ward had higher VLs than infants requiring PICU care (P < .001). Dynamic analyses showed that VL decay was delayed in PICU patients, especially in those treated with steroids. CONCLUSIONS: Higher VLs at presentation and a faster and consistent VL decline were both associated with less severe RSV disease in children. SUMMARY: Infants with less severe respiratory syncytial virus (RSV) disease had higher viral loads (VL) at presentation, and faster and consistent VL decline. Conversely, VL decay and overall viral exposure were prolonged and higher in infants severe RSV disease receiving steroids.

Mitogenomic evidence of close relationships between New Zealand's extinct giant raptors and small-sized Australian sister-taxa.

Prior to human arrival in the 13th century, two large birds of prey were the top predators in New Zealand. In the absence of non-volant mammals, the extinct Haast's eagle (Hieraaetus moorei), the largest eagle in the world, and the extinct Eyles' harrier (Circus teauteensis) the largest harrier in the world, had filled ecological niches that are on other landmasses occupied by animals such as large cats or canines. The evolutionary and biogeographic history of these island giants has long been a mystery. Here we reconstruct the origin and evolution of New Zealand's giant raptors using complete mitochondrial genome data. We show that both Eyles' harrier and Haast's eagle diverged from much smaller, open land adapted Australasian relatives in the late Pliocene to early Pleistocene. These events coincided with the development of open habitat in the previously densely forested islands of New Zealand. Our study provides evidence of rapid evolution of island gigantism in New Zealand's extinct birds of prey. Early Pleistocene climate and environmental changes were likely to have triggered the establishment of Australian raptors into New Zealand. Our results shed light on the evolution of two of the most impressive cases of island gigantism in the world.