The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica).

The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51 kya, into the Americas, from where a relatively recent (<20 kya) back migration to Asia took place. The exception to the haplogroup subspecies specificity is represented by the sedentary Levantine H. r. transitiva that extensively shares haplogroup A with the migratory European H. r. rustica and, to a lesser extent, haplogroup B with the Egyptian H. r. savignii. Our data indicate that rustica and transitiva most likely derive from a sedentary Levantine population source that split at the end of the Younger Dryas (YD) (11.7 kya). Since then, however, transitiva received genetic inputs from and admixed with both the closely related rustica and the adjacent savignii. Demographic analyses confirm this species' strong link with climate fluctuations and human activities making it an excellent indicator for monitoring and assessing the impact of current global changes on wildlife.

The Limiting Dynamics of SGD: Modified Loss, Phase-Space Oscillations, and Anomalous Diffusion.

In this work, we explore the limiting dynamics of deep neural networks trained with stochastic gradient descent (SGD). As observed previously, long after performance has converged, networks continue to move through parameter space by a process of anomalous diffusion in which distance traveled grows as a power law in the number of gradient updates with a nontrivial exponent. We reveal an intricate interaction among the hyperparameters of optimization, the structure in the gradient noise, and the Hessian matrix at the end of training that explains this anomalous diffusion. To build this understanding, we first derive a continuous-time model for SGD with finite learning rates and batch sizes as an underdamped Langevin equation. We study this equation in the setting of linear regression, where we can derive exact, analytic expressions for the phase-space dynamics of the parameters and their instantaneous velocities from initialization to stationarity. Using the Fokker-Planck equation, we show that the key ingredient driving these dynamics is not the original training loss but rather the combination of a modified loss, which implicitly regularizes the velocity, and probability currents that cause oscillations in phase space. We identify qualitative and quantitative predictions of this theory in the dynamics of a ResNet-18 model trained on ImageNet. Through the lens of statistical physics, we uncover a mechanistic origin for the anomalous limiting dynamics of deep neural networks trained with SGD. Understanding the limiting dynamics of SGD, and its dependence on various important hyperparameters like batch size, learning rate, and momentum, can serve as a basis for future work that can turn these insights into algorithmic gains.

Iterative Development of the Caregiver Wellness After Traumatic Brain Injury Program (CG-Well).

OBJECTIVES: (1) To iteratively design a web/phone-based intervention to support caregivers of adults acutely following traumatic brain injury (TBI), Caregiver Wellness (CG-Well), and (2) to obtain qualitative and quantitative feedback on CG-Well from experts and caregivers to refine the intervention. SETTING: A level I trauma and tertiary medical center. PARTICIPANTS: Convenience sample of a total of 19 caregivers and 25 experts. DESIGN: Multistep prospective study with iterative changes to CG-Well: (1) developed intervention content based on qualitative feedback from a prior study and literature review; (2) obtained qualitative feedback from 10 experts; (3) refined content using a modified Delphi approach involving 4 caregivers and 6 experts followed by qualitative interviews with 9 caregivers; (4) designed CG-Well website and videos; and (5) obtained feedback on program acceptability, appropriateness, and feasibility from 6 caregivers and 9 experts. INTERVENTIONS: CG-Well included content on TBI, self-care and support, and skill-building strategies delivered through a website and telephone calls. MAIN OUTCOME MEASURES: Qualitative data were analyzed using content analysis. Caregivers and experts completed Likert-type scales to rate module relevance, clarity, accuracy, utility and website acceptability, appropriateness, and feasibility (1 = strongly disagree to 5 = strongly agree). Means and standard deviations (SD) characterized ratings. RESULTS: Qualitative findings were instrumental in designing and refining CG-Well. Ratings were positive for modules (means and SD for relevant [4.9, 0.33], clear [4.6, 0.53], accurate [4.9, 0.33], and useful [5, 0]) and the website (means and SD for acceptable [4.8, 0.36], appropriate [4.8, 0.35], and feasible [4.8, 0.36]). CONCLUSIONS: The iterative design process for CG-Well resulted in a highly acceptable program. An early-stage randomized controlled trial is underway to estimate treatment effects for a future well-powered clinical trial.

The Successful Rotor Wing Transport of 2 Patients Requiring Biventricular Impella Support: A Case Series and Review.

Despite many advances in care, the mortality rate for cardiogenic shock remains high. Because the medical management of patients with cardiogenic shock is limited, many patients often require mechanical circulatory support. As such, cardiogenic shock patients requiring percutaneous ventricular support devices such as the Impella (Abiomed, Danvers, MA) may be encountered by critical care transport crews with increasing frequency. Recently, biventricular Impella support has been described as a mechanical support strategy for biventricular failure. This case series describes the successful rotor wing transport of 2 patients with severe cardiogenic shock requiring biventricular Impella support and presents a review of Impella RP (Abiomed) and biventricular Impella support devices for the critical care transport medicine clinician.

Relative importance of tree species richness, tree functional type, and microenvironment for soil macrofauna communities in European forests.

Soil fauna communities are major drivers of many forest ecosystem processes. Tree species diversity and composition shape soil fauna communities, but their relationships are poorly understood, notably whether or not soil fauna diversity depends on tree species diversity. Here, we characterized soil macrofauna communities from forests composed of either one or three tree species, located in four different climate zones and growing on different soil types. Using multivariate analysis and model averaging we investigated the relative importance of tree species richness, tree functional type (deciduous vs. evergreen), litter quality, microhabitat and microclimatic characteristics as drivers of soil macrofauna community composition and structure. We found that macrofauna communities in mixed forest stands were represented by a higher number of broad taxonomic groups that were more diverse and more evenly represented. We also observed a switch from earthworm-dominated to predator-dominated communities with increasing evergreen proportion in forest stands, which we interpreted as a result of a lower litter quality and a higher forest floor mass. Finally, canopy openness was positively related to detritivore abundance and biomass, leading to higher predator species richness and diversity probably through trophic cascade effects. Interestingly, considering different levels of taxonomic resolution in the analyses highlighted different facets of macrofauna response to tree species richness, likely a result of both different ecological niche range and methodological constraints. Overall, our study supports the positive effects of tree species richness on macrofauna diversity and abundance through multiple changes in resource quality and availability, microhabitat, and microclimate modifications.

Are winter and summer dormancy symmetrical seasonal adaptive strategies? The case of temperate herbaceous perennials.

BACKGROUND: Dormancy in higher plants is an adaptive response enabling plant survival during the harshest seasons and has been more explored in woody species than in herbaceous species. Nevertheless, winter and summer shoot meristem dormancy are adaptive strategies that could play a major role in enhancing seasonal stress tolerance and resilience of widespread herbaceous plant communities. SCOPE: This review outlines the symmetrical aspects of winter and summer dormancy in order to better understand plant adaptation to severe stress, and highlight research priorities in a changing climate. Seasonal dormancy is a good model to explore the growth-stress survival trade-off and unravel the relationships between growth potential and stress hardiness. Although photoperiod and temperature are known to play a crucial, though reversed, role in the induction and release of both types of dormancy, the thresholds and combined effects of these environmental factors remain to be identified. The biochemical compounds involved in induction or release in winter dormancy (abscisic acid, ethylene, sugars, cytokinins and gibberellins) could be a priority research focus for summer dormancy. To address these research priorities, herbaceous species, being more tractable than woody species, are excellent model plants for which both summer and winter dormancy have been clearly identified. CONCLUSIONS: Summer and winter dormancy, although responding to inverse conditions, share many characteristics. This analogous nature can facilitate research as well as lead to insight into plant adaptations to extreme conditions and the evolution of phenological patterns of species and communities under climate change. The development of phenotypes showing reduced winter and/or enhanced summer dormancy may be expected and could improve adaptation to less predictable environmental stresses correlated with future climates. To this end, it is suggested to explore the inter- and intraspecific genotypic variability of dormancy and its plasticity according to environmental conditions to contribute to predicting and mitigating global warming.

T24 HRAS transformed NIH/3T3 mouse cells (GhrasT-NIH/3T3) in serial tumorigenic in vitro/in vivo passages give rise to increasingly aggressive tumorigenic cell lines T1-A and T2-A and metastatic cell lines T3-HA and T4-PA.

Cancer cells often arise progressively from "normal" to "pre-cancer" to "transformed" to "local metastasis" to "metastatic disease" to "aggressive metastatic disease". Recent whole genome sequencing (WGS) and spectral karyotyping (SKY) of cancer cells and tumorigenic models have shown this progression involves three major types of genome rearrangements: ordered small step-wise changes, more dramatic "punctuated evolution" (chromoplexy), and large catastrophic steps (chromothripsis) which all occur in random combinations to generate near infinite numbers of stochastically rearranged metastatic cancer cell genomes. This paper describes a series of mouse cell lines developed sequentially to mimic this type of progression. This starts with the new GhrasT-NIH/Swiss cell line that was produced from the NIH/3T3 cell line that had been transformed by transfection with HRAS oncogene DNA from the T24 human bladder carcinoma. These GhrasT-NIH/Swiss cells were injected s.c. into NIH/Swiss mice to produce primary tumors from which one was used to establish the T1-A cell line. T1-A cells injected i.v. into the tail vein of a NIH/Swiss mouse produced a local metastatic tumor near the base of the tail from which the T2-A cell line was established. T2-A cells injected i.v. into the tail vein of a nude NIH/Swiss mouse produced metastases in the liver and one lung from which the T3-HA (H=hepatic) and T3-PA (P=pulmonary) cell lines were developed, respectively. T3-HA cells injected i.v. into a nude mouse produced a metastasis in the lung from which the T4-PA cell line was established. PCR analysis indicated the human T24 HRAS oncogene was carried along with each in vitro/in vivo transfer step and found in the T2-A and T4-PA cell lines. Light photomicrographs indicate that all transformed cells are morphologically similar. GhrasT-NIH/Swiss cells injected s.c. produced tumors in 4% of NIH/Swiss mice in 6-10 weeks; T1-A cells injected s.c. produced tumors in 100% of NIH/Swiss mice in 7-10 days. T1-A, T-2A, T3-HA and T4-PA cells when injected i.v. into the tail produced local metastasis in non-nude or nude NIH/Swiss mice. T4-PA cells were more widely metastatic than T3-HA cells when injected i.v. into nude mice. Evaluation of the injected mice indicated a general increase in metastatic potential of each cell line in the progression as compared to the GhrasT-NIH/3T3 transformed cells. A new photomicrographic technique to follow growth rates within six preselected 2×2mm(2) grids per plate is described. Average doubling times of the transformed cells GhrasT-NIH/3T3 (17h), T1A (17.5h), T2A (15.5h), T3-HA (17.5h) and T4-PA (18.5h) (average 17.2h) were significantly faster (P=0.006) than NIH Swiss primary embryonic cells and NIH/3T3 cells (22 h each). This cell series is currently used in this lab for studies of cancer cell inhibitors, mitochondrial biogenesis and gene expression and is available for further study by other investigators for intra- and inter-laboratory comparisons of WGS, transcriptome sequencing, SKY and other analyses. The genome rearrangements in these cells together with their phenotypic properties may help provide more insights into how one tumorigenic progression occurred to produce the various cell lines that led to the highly metastatic T4-PA cell line.

Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests that while TPP1 protein delivered via the CSF may protect these cells, preservation of the remainder of the retina will require delivery of normal TPP1 more directly to the retina, probably via the vitreous body.

Intravitreal implantation of TPP1-transduced stem cells delays retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis.

The CLN2 form of neuronal ceroid lipofuscinosis is a neurodegenerative disease that results from mutations in the TPP1 gene. Affected children exhibit progressive declines in most neurological functions including vision. Functional declines are accompanied by progressive brain and retinal atrophy. TPP1 encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Dachshunds with a TPP1 null mutation exhibit a disorder very similar to human CLN2 disease. Periodic infusion of recombinant TPP1 protein or a single injection of a TPP1 gene therapy vector into the cerebrospinal fluid of affected dogs significantly delays the onset and progression of neurological signs but does not slow vision loss or retinal degeneration. Studies were conducted to determine whether intravitreal implantation of autologous bone marrow derived stem cells transduced with a TPP1 expression construct would inhibit retinal degeneration in the canine model. A single injection of the transduced cells at an early stage in the disease progression substantially inhibited the development of disease-related retinal function deficits and structural changes. No adverse effects of the treatment were detected. These findings indicate that ex vivo gene therapy using autologous stem cells is an effective means of achieving sustained delivery of therapeutic compounds to tissues such as the retina for which systemic administration would be ineffective.

Emergency department management of infective endocarditis-associated stroke.

Stroke in patients with endocarditis is a unique, highly morbid condition requiring a high index of suspicion for diagnosis. This issue reviews the historical and physical examination factors that can provide clues to the etiology. The workup of these patients, involving both infection-focused and stroke-focused laboratory testing and neuroimaging, is discussed. The mainstay of treatment is empiric antibiotics, as thrombolytics are contraindicated. Recent evidence regarding the use of mechanical thrombectomy in largevessel occlusion strokes is discussed, as well as surgical options and consultation strategies with stroke, neurocritical care, infectious disease, and neurosurgery teams.

The United Nations Convention on the Rights of Persons with Disabilities and Social Work: Evidence for Impact?

The United Nations Convention on the Rights of Persons with Disabilities (hereafter CRPD) has provided a radical imperative for the reform of mental health and capacity legislation around the world. The interpretation of the CRPD has been controversial, ranging from the complete abolition of detention, forcible treatment, and substitute decision-making to accepting that elements of these measures need to be retained based on non-discriminatory criteria, additional safeguards, and a comprehensive shift towards supported decision-making. While the potential effects of the CRPD on mental health social work and social work generally are considerable given their shared commitment towards social justice, to date there has been no review of research evidence exploring their relationship. In addressing this knowledge gap, this study held a preliminary discussion with practitioners and academics at the European Association of Social Work Mental Health Special Interest Group in Amsterdam 2022, followed by a scoping literature review on the question: What impact, if any, has the CRPD had on social work practice? The review produced four main findings: impact on legislation; positive impact on practice; limited impact on practice; and impact on social work education and research. In sum, while there were some positive indications of social work and mental health social work practice being influenced by the CRPD, these were scant. Barriers to change included tendencies among some social workers to practise substitute decision-making, in part related to resourcing and policy contexts, and understandings of disability aligned to individualised/medical rather than social perspectives. The results indicate that legal reform on its own is insufficient to impact social work practice, and that realising the potential of the CRPD will necessitate good quality training, as well as improving social workers' knowledge of the human rights of people with mental impairment.

Leveraging research infrastructure co-location to evaluate constraints on terrestrial carbon cycling in northern European forests.

Integrated long-term, in-situ observations are needed to document ongoing environmental change, to "ground-truth" remote sensing and model outputs and to predict future Earth system behaviour. The scientific and societal value of in-situ observations increases with site representativeness, temporal duration, number of parameters measured and comparability within and across sites. Research Infrastructures (RIs) can support harmonised, cross-site data collection, curation and publication. Integrating RI networks through site co-location and standardised observation methods can help answers three questions about the terrestrial carbon sink: (i) What are present and future carbon sequestration rates in northern European forests? (ii) How are these rates controlled? (iii) Why do the observed patterns exist? Here, we present a conceptual model for RI co-location and highlight potential insights into the terrestrial carbon sink achievable when long-term in-situ Earth observation sites participate in multiple RI networks (e.g., ICOS and eLTER). Finally, we offer recommendations to promote RI co-location.

A Perspective on Plant Phenomics: Coupling Deep Learning and Near-Infrared Spectroscopy.

The trait-based approach in plant ecology aims at understanding and classifying the diversity of ecological strategies by comparing plant morphology and physiology across organisms. The major drawback of the approach is that the time and financial cost of measuring the traits on many individuals and environments can be prohibitive. We show that combining near-infrared spectroscopy (NIRS) with deep learning resolves this limitation by quickly, non-destructively, and accurately measuring a suite of traits, including plant morphology, chemistry, and metabolism. Such an approach also allows to position plants within the well-known CSR triangle that depicts the diversity of plant ecological strategies. The processing of NIRS through deep learning identifies the effect of growth conditions on trait values, an issue that plagues traditional statistical approaches. Together, the coupling of NIRS and deep learning is a promising high-throughput approach to capture a range of ecological information on plant diversity and functioning and can accelerate the creation of extensive trait databases.

Genetic diversity loss in the Anthropocene.

Anthropogenic habitat loss and climate change are reducing species' geographic ranges, increasing extinction risk and losses of species' genetic diversity. Although preserving genetic diversity is key to maintaining species' adaptability, we lack predictive tools and global estimates of genetic diversity loss across ecosystems. We introduce a mathematical framework that bridges biodiversity theory and population genetics to understand the loss of naturally occurring DNA mutations with decreasing habitat. By analyzing genomic variation of 10,095 georeferenced individuals from 20 plant and animal species, we show that genome-wide diversity follows a mutations-area relationship power law with geographic area, which can predict genetic diversity loss from local population extinctions. We estimate that more than 10% of genetic diversity may already be lost for many threatened and nonthreatened species, surpassing the United Nations' post-2020 targets for genetic preservation.

A Tale of Two Brothers: Familial Voltage-Gated Potassium Channel Autoimmune Encephalitis.

This is the first reported case of familial voltage-gated potassium channel (VGKC) autoimmune encephalitis. The symptoms of autoimmune encephalitis can mimic infectious encephalitis with headache, fatigue, and neuropsychiatric symptoms. Autoimmunity is emerging as a distinct cause of encephalitis in the children. Prompt recognition, diagnosis, and treatment are important to prevent brain damage. Two brothers presented two years apart with different symptoms. The explanation for their distinct symptoms lies in the multifactorial development of autoimmunity. The presentation of autoimmune encephalitis can depend on the offending antibodies. The most common are antibodies against the N-methyl-D-aspartic acid (NMDA) receptor and the VGKC complex. Antibodies to the VGKC complex are divided into three different groups depending on their antigenic target: leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), or neither. Anti-VGKC antibodies in children are associated with neuroinflammation and encephalitis. Autoimmunity to LGI1 and CASPR2 antigens is associated with distinct human leukocyte antigen (HLA) alleles. Different HLA isotypes are involved in antigen processing and presentation and can lead to a genetic predisposition to autoimmunity. VGKC autoimmune encephalitis can present with memory changes, psychiatric symptoms, and motor abnormalities. Both brothers presented with these symptoms in their own unique way. Efficient diagnosis and immunosuppression helped improve their outcomes.

Higher tree diversity increases soil microbial resistance to drought.

Predicted increases in drought frequency and severity may change soil microbial functioning. Microbial resistance and recovery to drought depend on plant community characteristics, among other factors, yet how changes in plant diversity modify microbial drought responses is uncertain. Here, we assessed how repeated drying-rewetting cycles affect soil microbial functioning and whether tree species diversity modifies these effects with a microcosm experiment using soils from different European forests. Our results show that microbial aerobic respiration and denitrification decline under drought but are similar in single and mixed tree species forests. However, microbial communities from mixed forests resist drought better than those from mono-specific forests. This positive tree species mixture effect is robust across forests differing in environmental conditions and species composition. Our data show that mixed forests mitigate drought effects on soil microbial processes, suggesting greater stability of biogeochemical cycling in mixed forests should drought frequency increase in the future.

Invasion of the Fungal Pathogen Batrachochytrium dendrobatidis on California Islands.

Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen, has infected >500 species and caused extinctions or declines in >200 species worldwide. Despite over a decade of research, little is known about its invasion biology. To better understand this, we conducted a museum specimen survey (1910-1997) of Bd in amphibians on 11 California islands and found a pattern consistent with the emergence of Bd epizootics on the mainland, suggesting that geographic isolation did not prevent Bd invasion. We propose that suitable habitat, host diversity, and human visitation overcome isolation from the mainland and play a role in Bd invasion.