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We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which [approximately] 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an "idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in "ADNP," "CHD8," and "DYRK1A," prominent sensory sensitivities in "SCN2A," and fewer sensation avoidance behaviors in "GRIN2B" (relative to the idiopathic ASD comparison group).

The social movement toward cultural relativism has led to a growing distrust and even disbelief in the value of scientific inquiry regarding the effects of, or the need for, special education for students with disabilities. The authors examine the basic underpinnings of scientific methodology and its fundamental role in establishing best practice in the field. We also address contrary views and their risks and weaknesses. Scientific methodology is foundational to effective programs and services to marginalized students, including those with disabilities.

Abstract Background Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses. Results The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation. Conclusions The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus.

Abstract Background Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD – ADNP, CHD8, and DYRK1A – with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. Methods Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. Results Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. Conclusions Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.

Abstract Background : Veterinary knowledge regarding feline heartworm has been increasing significantly over the past two decades. Necropsy surveys of shelter cats have shown feline adult heartworm infection prevalence to be 5–20% of the rate in unprotected dogs; however, other studies have shown feline heartworm antibody prevalence up to 33%, reflecting higher exposure rates and potential immature adult infections. Thus, the true prevalence of feline heartworm infection is likely underestimated due to the limitations of current diagnostic techniques, inadequate testing protocols, and the high likelihood of cats exhibiting transient clinical signs or dying without confirmation of infection. Diagnosing Feline Heartworm Disease (FHWD), also referred to as Heartworm Associated Respiratory Disease (HARD), is one of the conundrums of veterinary medicine. The purpose of this study was to evaluate and characterize the occurrence of Heartworm Associated Respiratory Disease [HARD] in shelter cats, naturally-infected with D.immitis. Methods Fifty shelter cats slated for euthanasia between December 2009 and June 2010 were investigated by gross necropsy, radiography, serology, and lung histopathology using techniques that have been established in experimental models of cat heartworm infection. The relationship between pulmonary vascular disease and serological markers for heartworm was also examined using correlations and statistical modeling. Serology included standard heartworm antigen test and a commonly used heartworm antibody test. Also included were heat-treated heartworm antigen test and two additional heartworm antibody tests previously evaluated on experimentally-infected cats. Results None of the cats were heartworm antibody (HW Ab) positive on a commonly used HW Ab test used by many reference laboratories even though 20% of the study cats were heartworm antigen (HW Ag) positive on heat-treated samples. Two additional HW Ab test were positive on 26% and 22% of the study cats. The combination of heat-treated HW Ag, HW Ab tests, and histopathology indicated 34% of the study cats had HARD. Conclusions Utilizing both, the above tests, and thoracic radiographs, enhanced the ability to predict vascular disease, possibly caused by infection with immature and adult heartworms and supported the premise that cats develop heartworm disease at the same rate as dogs. Graphical Abstract

Abstract The American chestnut (Castanea dentata, 2n = 2x = 24), once known as the “King of the Appalachian Forest”, was decimated by chestnut blight during the first half of the twentieth century by an invasive fungus (Cryphonectria parasitica). The Chinese chestnut (C. mollissima, 2n = 2x = 24), in contrast to American chestnut, is resistant to this blight. Efforts are being made to transfer this resistance to American chestnut through backcross breeding and genetic engineering. Both chestnut genomes have been genetically mapped and recently sequenced to facilitate gene discovery efforts aimed at assisting molecular breeding and genetic engineering. To complement and extend this genomic work, we analyzed the distribution and organization of their ribosomal DNAs (35S and 5S rDNA), and the chromatin composition of the nucleolus organizing region (NOR)-associated satellites. Using fluorescent in situ hybridization (FISH), we have identified two 35S (one major and one minor) and one 5S rDNA sites. The major 35S rDNA sites are terminal and sub-terminal in American and Chinese chestnuts, respectively, originating at the end of the short arm of the chromosome, extending through the secondary constriction and into the satellites. An additional 5S locus was identified in certain Chinese chestnut accessions, and it was linked distally to the major 35S site. The NOR-associated satellite in Chinese chestnut was found to comprise a proximal region packed with 35S rDNA and a distinct distal heterochromatic region. In contrast, the American chestnut satellite was relatively small and devoid of the distal heterochromatic region.

Chestnut blight (caused by Cryphonectria parasitica), together with Phytophthora root rot (caused by Phytophthora cinnamomi), has nearly extirpated American chestnut (Castanea dentata) from its native range. In contrast to the susceptibility of American chestnut, many Chinese chestnut (C. mollissima) genotypes are resistant to blight. In this research, we performed a series of genome-wide association studies for blight resistance originating from three unrelated Chinese chestnut trees (Mahogany, Nanking and M16) and a Quantitative Trait Locus (QTL) study on a Mahogany-derived inter-species F2 family. We evaluated trees for resistance to blight after artificial inoculation with two fungal strains and scored nine morpho-phenological traits that are the hallmarks of species differentiation between American and Chinese chestnuts. Results support a moderately complex genetic architecture for blight resistance, as 31 QTLs were found on 12 chromosomes across all studies. Additionally, although most morpho-phenological trait QTLs overlap or are adjacent to blight resistance QTLs, they tend to aggregate in a few genomic regions. Finally, comparison between QTL intervals for blight resistance and those previously published for Phytophthora root rot resistance, revealed five common disease resistance regions on chromosomes 1, 5, and 11. Our results suggest that it will be difficult, but still possible to eliminate Chinese chestnut alleles for the morpho-phenological traits while achieving relatively high blight resistance in a backcross hybrid tree. We see potential for a breeding scheme that utilizes marker-assisted selection early for relatively large effect QTLs followed by genome selection in later generations for smaller effect genomic regions.

Abstract Background The American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated metabolites, which are known to be a leading cause of pulmonary pathology. Studies have determined that doxycycline administered at 10 mg/kg BID for 28 days is an effective dose for eliminating Wolbachia, but what has not been determined is the clinical relevance of this elimination. The current guidelines also recommend a 30-day wait period following administration of doxycycline to allow for clearance of metabolites, such as Wolbachia surface protein, and for further reduction in heartworm biomass before administration of adulticide. Reducing the doxycycline dose and eliminating the wait period may carry practical benefits for the animal, client, and practitioner. Methods To investigate these treatment practices, Dirofilaria immitis adults were surgically transplanted into each of 45 dogs, which were divided into nine study groups of five dogs each. Seventy-five days after transplantation, two groups each were administered 5, 7.5, or 10 mg/kg BID doxycycline orally for 28 days and 6 µg/kg ivermectin monthly, with three untreated groups serving as controls. Study animals were necropsied and examined prior to treatment as well as 30 and 60 days post-treatment. Results Mean worm weight was unaffected by dosage but exhibited a significant increase at 30 days and significant decrease at 60 days post-treatment, including in control groups. Histopathology lesion scores did not significantly differ among groups, with the exception of the lung composite score for one untreated group. Liver enzymes, the levels of which are a concern in doxycycline treatment, were also examined, with no abnormalities in alanine aminotransferase or alkaline phosphatase observed. Conclusions No consistent worsening of tissue lesions was observed with or without the AHS-recommended 30-day wait period, nor did reduced dosages of doxycycline lead to worsening of pathology or any change in efficacy in depleting worm weight. Mean worm weight did significantly increase prior to, and decrease following, the wait period. Future work that also includes adulticide treatment (i.e. melarsomine) will study treatment recommendations that may improve both animal health and owner compliance. Graphical abstract

People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases Elimination Act (IDEA) Syringe Services Program (SSP). Unexpectedly, Flu vaccination-induced antibody responses in groups with OUD were superior to PWH without OUD. Here, we investigated the profile of 48 plasma biomarkers comprised of TNF and Ig superfamily (SF) molecules known to impact interactions between T and B cells in 209 participants divided into four groups: (1) HIV+OP+, (2) HIV−OP+, (3) HIV+OP−, and (4) HIV−OP−. The differential expression of the top eight molecules ranked by median values in individual Groups 1–3 in comparison to Group 4 was highly significant. Both OP+ groups 1 and 2 had higher co-stimulatory TNF SF molecules, including 4-1BB, OX-40, CD40, CD30, and 4-1BBL, which were found to positively correlate with Flu Ab titers. In contrast, HIV+OP− exhibited a profile dominant in Ig SF molecules, including PDL-2, CTLA-4, and Perforin, with PDL-2 showing a negative correlation with Flu vaccine titers. These findings are relevant to vaccine development in the fields of HIV and OUD.

IntroductionPeople with HIV (PWH) are known to have underlying inflammation and immune activation despite virologic control. Substance use including opioid dependence is common in this population and is associated with increased morbidity and reduced lifespan. The primary objective of the present study termed opioid immunity study (OPIS), was to investigate the impact of chronic opioids in PWH.MethodsThe study recruited people with and without HIV who had opioid use disorder (OUD). Study participants (n=221) were categorized into four groups: HIV+OP+, n=34; HIV-OP+, n=66; HIV+OP-, n=55 and HIV-OP-, n=62 as controls. PWH were virally suppressed on ART and those with OUD were followed in a syringe exchange program with confirmation of OP use by urine drug screening. A composite cytokine score was developed for 20 plasma cytokines that are linked to inflammation. Cellular markers of immune activation (IA), exhaustion, and senescence were determined in CD4 and CD8 T cells. Regression models were constructed to examine the relationships of HIV status and opioid use, controlling for other confounding factors.ResultsHIV+OP+ participants exhibited highest inflammatory cytokines and cellular IA, followed by HIV-OP+ for inflammation and HIV+OP- for IA. Inflammation was found to be driven more by opioid use than HIV positivity while IA was driven more by HIV than opioid use. In people with OUD, expression of CD38 on CD28-CD57+ senescent-like T cells was elevated and correlated positively with inflammation.DiscussionGiven the association of inflammation with a multitude of adverse health outcomes, our findings merit further investigations to understand the mechanistic pathways involved.

The nature of unconventional charge density wave in kagome metals is currently under intense debate. Here the authors report the coexistence of the 2 × 2 × 1 charge density wave in the kagome sublattice and the Sb 5p-electron assisted 2 × 2 × 2 charge density waves in CsV3Sb5.

Abstract The Mediterranean Sea hosts two subduction systems along the convergent Africa-Eurasia plate boundary that have produced strong ground shaking and generated tsunamis. Based on historical descriptions and sedimentary records, one of these events, in 365 CE, impacted a broad geographical area, including tsunami evidence for distances of 700–800 km from the source event, qualifying it as a ‘megatsunami’. Understanding how megatsunamis are produced, and where they are more likely, requires a better understanding of the different secondary processes linked to these events such as massive slope failures, multiple turbidity current generation, and basin seiching. Our sedimentary records from an extensive collection of cores located in distal and disconnected basins, identify turbidites which are analyzed using granulometry, elemental (XRF), micropaleontological, and geochemical data in order to reconstruct their coastal or marine source. The results show that the 365 CE basin floor sediments are a mixture of inner shelf and slope materials. The tsunami wave produced multiple far-field slope failures that resulted in stacked basal turbidites. It also caused transport of continent-derived organic carbon and deposition over basal turbidites and into isolated basins of the deep ocean. The composition of sediment in isolated basins suggests their deposition by large-scale sheet like flows similar to what has been caused by the Tohoku earthquake associated tsunamis. This is significant for rectifying and resolving where risk is greatest and how cross-basin tsunamis are generated. Based on these results, estimates of the underlying deposits from the same locations were interpreted as possible older megatsunamis.

Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high–confidence risk genes. We investigated the inheritance of 46 GIGYF1 LGD variants, including the highly recurrent mutation c.333del:p.L111Rfs*234. Inherited GIGYF1 heterozygous LGD variants were 1.8 times more common than de novo mutations. Among individuals with ASD, cognitive impairments were less likely in those with GIGYF1 LGD variants relative to those with other high-confidence gene mutations. Using a Gigyf1 conditional KO mouse model, we showed that haploinsufficiency in the developing brain led to social impairments without significant cognitive impairments. In contrast, homozygous mice showed more severe social disability as well as cognitive impairments. Gigyf1 deficiency in mice led to a reduction in the number of upper-layer cortical neurons, accompanied by a decrease in proliferation and increase in differentiation of neural progenitor cells. We showed that GIGYF1 regulated the recycling of IGF-1R to the cell surface. KO of GIGYF1 led to a decreased level of IGF-1R on the cell surface, disrupting the IGF-1R/ERK signaling pathway. In summary, our findings show that GIGYF1 is a regulator of IGF-1R recycling. Haploinsufficiency of GIGYF1 was associated with autistic behavior, likely through interference with IGF-1R/ERK signaling pathway.

Racial and ethnic minority communities have been disproportionately affected by COVID-19, but the uptake of COVID-19 mitigation strategies like vaccination and testing have been slower in these populations. With the continued spread of COVID-19 while in-person learning is a priority, school-aged youth and their caregivers must make health-related decisions daily to ensure health at school. It is critical to understand factors associated with COVID-related health decisions such as vaccination, testing, and other health behaviors (e.g., wearing masks, hand washing). Community-engaged campaigns are necessary to overcome barriers to these health behaviors and promote health equity. The aim of this study was to examine COVID-19-related concerns and influences on health decisions in middle and high schools serving primarily racial and ethnic minority, low-income families. Seven focus groups were conducted with school staff, parents, and students (aged 16 years and older). Qualitative data were analyzed using a general inductive approach. Factors related to COVID-19 concerns and health decisions centered on (1) vaccine hesitancy, (2) testing hesitancy, (3) developmental stage (i.e., ability to engage in health behaviors based on developmental factors like age), (4) cultural and family traditions and beliefs, (5) compatibility of policies and places with recommended health behaviors, (6) reliability of information, and (7) perceived risk. We explore sub-themes in further detail. It is important to understand the community's level of concern and identify factors that influence COVID-19 medical decision making to better address disparities in COVID-19 testing and vaccination uptake.

Abstract The unconventional normal-state properties of the cuprates are often discussed in terms of emergent electronic order that onsets below a putative critical doping of x c ≈ 0.19. Charge density wave (CDW) correlations represent one such order; however, experimental evidence for such order generally spans a limited range of doping that falls short of the critical value x c, leading to questions regarding its essential relevance. Here, we use X-ray diffraction to demonstrate that CDW correlations in La2−x Sr x CuO4 persist up to a doping of at least x = 0.21. The correlations show strong changes through the superconducting transition, but no obvious discontinuity through x c ≈ 0.19, despite changes in Fermi surface topology and electronic transport at this doping. These results demonstrate the interaction between CDWs and superconductivity even in overdoped cuprates and prompt a reconsideration of the role of CDW correlations in the high-temperature cuprate phase diagram.

Oak decline is a general term used for the progressive dieback and eventual mortality of oak trees due to many compounding stressors, typically a combination of predisposing, inciting, and contributing factors. While pinpointing individual causes of decline in oak trees is a challenge, past studies have identified site and stand characteristics associated with oak decline. In this study, we developed a risk map of oak decline for the Daniel Boone National Forest (DBNF), combining GIS, remote sensing (RS), and public reporting (citizen science, CS). Starting with ground reports of decline (CS), we developed a site-scale model (GIS and RS) for oak decline based on four previously identified predisposing factors: elevation, slope, solar radiation, and topographic wetness. We found that areas identified in the model as having a high oak decline risk also reflected areas of observed oak decline (CS). We then optimized and expanded this risk model to the entire range of the DBNF, based on both site characteristics (as piloted for the case study site) and stand inventory data. The stand inventory data (including species composition and age) further improved the model, resulting in a risk map at the landscape level. This case study can serve as a planning tool and highlights the potential usefulness of integrating GIS, remote sensing, and citizen science.

Societal Impact Statement The scientists that study and work to improve forest health need information on where pests and diseases are spreading, as well as where healthy, resilient trees remain. TreeSnap is a citizen science project and mobile app created to meet this need by enabling citizens to easily submit global positioning system (GPS) locations, photos, and observational information about trees of interest to scientists. The app was designed and built to ensure that the data being collected directly helps scientists engaged in a number of forest health research activities, including studying the genetic diversity of tree species, breeding trees, and monitoring tree health.

A 55-year old male, a patient with established glaucoma, presented with worsening of visual complaints. Field analysis revealed an apparent progression of the pre-existing field changes. A possible overlap of a neurological field defect was however suspected. Computerised tomogram (CT) revealed an acute vascular event in the territory of the middle cerebral artery. Mistaking the new field defect as a sign of glaucoma progression, would have resulted in missing the cerebrovascular accident, with a possible ominous outcome. Careful interpretation of visual fields (especially in those with pre-existing field defects), is therefore, a must in every given clinical scenario.

Abstract Identification of catastrophic events recorded as resedimented deep marine deposits can be challenging because of multiple possible triggering mechanisms. This study investigates seismo‐turbidites (STs) deposited in the Ionian Sea as a consequence of major historical earthquakes related to the Calabrian Arc subduction system. Taking advantage of the available sedimentological reconstructions, we focused our analysis on high‐resolution X‐ray fluorescence core scanner (XRF‐CS), organic carbon and isotopic data to define geochemical signatures characterizing the ST units. The relationships between geochemical and sedimentological proxies were statistically tested using Pearson correlation and principal component analysis (PCA). Up to ∼78% of the total variance in the data set can be reduced to three principal components which identified four elemental ratio groups associated to the degree of terrestrial/coastal influence in each major depositional unit (i.e., pelagic, ST sandy stacked units, homogenites, tsunamite‐seiche laminites, and tsunamite backwash). The sample score results were evaluated together with organic carbon data in order to assess geochemical variability throughout the composite turbidite structure in different basins settings. The basal parts of the ST contain coarse‐grained sediment stacks whose sources can be traced back and sedimentary processes (surficial sediment erosion/massive slope failures) can be defined using geochemical data. The topmost parts of the STs exhibit a mixed compositional character suggesting basin‐wide processes such as seiche oscillations and tsunami wave erosion/backwashing. The application of selected XRF‐CS based elemental ratios as proxies in paleoseismological studies can help reconstruct the seismic history of a continental margin.

Purpose: To describe the influence of corrected refractive error on measured torsional fusional amplitudes (TA) by comparing the TA between emmetropes and spectacle corrected myopes, using the after-image slides of the synoptophore, as targets. Methods: Fifty emmetropes (Group I) and 50 myopes (Group II) with best-corrected acuity of 6/6 in each eye were included in the study. Near point of convergence (NPC), near point of accommodation (NPA), and horizontal fusional amplitudes (HFA) were assessed in all the subjects. After-image slides, both horizontally aligned, were used as targets (without the bright flashes). One of the slides was rotated inwards, till cyclo-diplopia was reported by the subject; the procedure was repeated with the slide rotated outwards. The sum of the two readings was taken as TA. NPC, NPA, HFA, and TA were analyzed. Results: There was no significant difference in the NPC, NPA, and HFA between the two groups. The emmetropic subjects had significantly better torsional amplitude (8.4 ± 1.4 degrees) compared to myopes (7.7 ± 1.5 degrees, P = 0.03). We postulate that this difference may be due to perceived image minification, which brings the edges of retinal image of the targets closer to the fovea, thus rendering the myopes lesser tolerant to cyclodiplopia than emmetropes. Conclusion: Refractive error, corrected with spectacles, influences the measured TA. Myopic subjects have lesser torsional fusional amplitude than emmetropes.

An interdisciplinary group from two higher-education institutions in Philadelphia developed a novel framework for interprofessional education. This framework was applied to two different scenarios disease outbreak and natural disaster, which were used in simulations in 2018 and 2020. By design, these simulations included students from a broad range of disciplines, beyond the typical healthcare fields. Students were first grouped by discipline and were then placed in interdisciplinary teams for the rest of the scenario. Students were administered four surveys throughout which included 10 point-Likert scale and free response items. A statistically significant post-simulation increase in student interest and confidence was found. Survey analysis also revealed higher scores of positive group behaviors among interdisciplinary teams when compared to discipline groups. Importantly, students realized the importance of broad representation of disciplines for disaster preparedness. The PennDemic framework may be helpful for teams looking to develop simulations to build interest and confidence in disaster preparedness/response and interdisciplinary teamwork.

The root rot causing oomycete, Phytophthora agathidicida, threatens the long-term survival of the iconic New Zealand kauri. Currently, testing for this pathogen involves an extended soil bioassay that takes 14-20 days and requires specialised staff, consumables, and infrastructure. Here we describe a loop-mediated isothermal amplification (LAMP) assay for the detection of P. agathidicida that targets a portion of the mitochondrial apocytochrome b coding sequence. This assay has high specificity and sensitivity; it did not cross react with a range of other Phytophthora isolates and detected as little as 1 fg of total P. agathidicida DNA or 116 copies of the target locus. Assay performance was further investigated by testing plant tissue baits from flooded soil samples using both the extended soil bioassay and LAMP testing of DNA extracted from baits. In these comparisons, P. agathidicida was detected more frequently using the LAMP test. In addition to greater sensitivity, by removing the need for culturing, the hybrid baiting plus LAMP approach is more cost effective than the extended soil bioassay and, importantly, does not require a centralised laboratory facility with specialised staff, consumables, and equipment. Such testing will allow us to address outstanding questions about P. agathidicida. For example, the hybrid approach could enable monitoring of the pathogen beyond areas with visible disease symptoms, allow direct evaluation of rates and patterns of spread, and allow the effectiveness of disease control to be evaluated. The hybrid LAMP bioassay also has the potential to empower local communities to evaluate the pathogen status of local kauri stands, providing information for disease management and conservation initiatives.

Sustainable intensification (SI) of low input farming systems is promoted as a strategy to improve smallholder farmer food security in southern Africa. Using the Limpopo province South Africa as a case study (four villages across a climate gradient), we combined survey data (140 households) and quantitative agronomic observations to understand climate-induced limitations for SI of maize-based smallholder systems. Insights were used to benchmark the agroecosystem model Agricultural Production System sIMulator, which was setup to ex ante evaluate technology packages (TPs) over 21-seasons (1998–2019): TP0 status quo (no input, broadcast sowing), TP1 fertiliser (micro dosing), TP2 planting density (recommended), TP3 weeding (all removed), TP4 irrigation, TP5 planting date (early, recommended), and TP6 all combined (TPs 1–5). An additional TP7 (forecasting) investigated varying planting density and fertiliser in line with weather forecasts. Input intensity levels were low and villages expressed similar challenges to climate risk adaptation, with strategies mostly limited to adjusted planting dates and densities, with less than 2% of farmers having access to water for irrigation. Simulations showed that combining all management interventions would be expected to lead to the highest mean maize grain yields (3200 kg ha ^−1 across villages) and the lowest harvest failure risk compared to individual interventions. Likewise, simulations suggested that irrigation alone would not result in yield gains and simple agronomic adjustments in line with weather forecasts indicated that farmers could expect to turn rainfall variability into an opportunity well worth taking advantage of. Our study emphasises the need for a cropping systems approach that addresses multiple crop stresses simultaneously.

Antarctic ice sheet and Southern Ocean paleoceanographic configurations during the late Oligocene are not well resolved. They are however important to understand the influence of high-latitude Southern Hemisphere feedbacks on global climate under CO2 scenarios (between 400 and 750 ppm) projected by the IPCC for this century, assuming unabated CO2 emissions. Sediments recovered by the Integrated Ocean Drilling Program (IODP) at Site U1356, offshore of the Wilkes Land margin in East Antarctica, provide an opportunity to study ice sheet and paleoceanographic configurations during the late Oligocene (26–25 Ma). Our study, based on a combination of sediment facies analysis, magnetic susceptibility, density, and X-ray fluorescence geochemical data, shows that glacial and interglacial sediments are continuously reworked by bottom currents, with maximum velocities occurring during the interglacial periods. Glacial sediments record poorly ventilated, low-oxygenation bottom water conditions, interpreted as resulting from a northward shift of westerly winds and surface oceanic fronts. Interglacial sediments record more oxygenated and ventilated bottom water conditions and strong current velocities, which suggests enhanced mixing of the water masses as a result of a southward shift of the polar front. Intervals with preserved carbonated nannofossils within some of the interglacial facies are interpreted as forming under warmer paleoclimatic conditions when less corrosive warmer northern component water (e.g., North Atlantic sourced deep water) had a greater influence on the site. Spectral analysis on the late Oligocene sediment interval shows that the glacial–interglacial cyclicity and related displacements of the Southern Ocean frontal systems between 26 and 25 Ma were forced mainly by obliquity. The paucity of iceberg-rafted debris (IRD) throughout the studied interval contrasts with earlier Oligocene and post-Miocene Climate Optimum sections from Site U1356 and with late Oligocene strata from the Ross Sea, which contain IRD and evidence for coastal glaciers and sea ice. These observations, supported by elevated sea surface paleotemperatures, the absence of sea ice, and reconstructions of fossil pollen between 26 and 25 Ma at Site U1356, suggest that open-ocean water conditions prevailed. Combined, this evidence suggests that glaciers or ice caps likely occupied the topographic highs and lowlands of the now marine Wilkes Subglacial Basin (WSB). Unlike today, the continental shelf was not overdeepened and thus ice sheets in the WSB were likely land-based, and marine-based ice sheet expansion was likely limited to coastal regions.

Abstract Background Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. Methods REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and β-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. Discussion MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. Trial registration Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482. Date of registration - 21/06/2016.

The combination of nontrivial band topology and symmetry-breaking phases gives rise to novel quantum states and phenomena such as topological superconductivity, quantum anomalous Hall effect, and axion electrodynamics. Evidence of intertwined charge density wave (CDW) and superconducting order parameters has recently been observed in a novel kagome material AV_{3}Sb_{5} (A=K, Rb, Cs) that features a Z_{2} topological invariant in the electronic structure. However, the origin of the CDW and its intricate interplay with the topological state has yet to be determined. Here, using hard-x-ray scattering, we demonstrate a three-dimensional CDW with 2×2×2 superstructure in (Rb,Cs)V_{3}Sb_{5}. Unexpectedly, we find that the CDW fails to induce acoustic phonon anomalies at the CDW wave vector but yields a novel Raman mode that quickly damps into a broad continuum below the CDW transition temperature. Our observations exclude strong electron-phonon-coupling-driven CDW in AV_{3}Sb_{5} and support an unconventional CDW that was proposed in the kagome lattice at van Hove filling.

Flexoelectric coupling between strain gradients and polarization influences the physics of ferroelectric devices but it is difficult to directly probe its effects. Here, Li et al. use principal component analysis to compare STEM images with phase-field modeling and extract the flexoelectric contributions.

Abstract Background The objective of heartworm treatment is to improve the clinical condition of the patient and to eliminate pre-cardiac, juvenile, and adult worm stages with minimal complications. Pulmonary thromboembolisms are an inevitable consequence of worm death and can result in severe pulmonary reactions and even death of the patient. To minimize these reactions, various treatment protocols involving melarsomine, the only adulticidal drug approved by the US Food and Drug Administrations (FDA), in conjunction with macrocyclic lactone heartworm preventives and glucocorticosteroids have been advocated. The discovery of the bacterial endosymbiont Wolbachia in Dirofilaria immitis has led to several experimental studies examining the effects of administering doxycycline to reduce or eliminate Wolbachia organism. These studies have shown a decrease in gross and microscopic pathology of pulmonary parenchyma in experimental heartworm infections pretreated with doxycycline before melarsomine administration. Methods Electronic medical records from a large veterinary practice in northeast Alabama were searched to identify dogs treated for heartworms with melarsomine from January 2005 through December 2012. The search was refined further to select for dogs that met the following criteria: 1) received two or three doses of ivermectin heartworm preventive prior to melarsomine injections, 2) received one injection of melarsomine followed by two injections 4 to 8 weeks later, and 3) were treated with prednisone following melarsomine injections. The dogs were then divided into those that also were treated with doxycycline 10 mg/kg BID for 4 weeks (Group A, n = 47) and those that did not receive doxycycline (Group B, n = 47). The medical notes of all 94 cases were then reviewed for comments concerning coughing, dyspnea, or hemoptysis in the history, physical exam template, or from telephone conversations with clients the week following each visit. Any dog that died within one year of treatment from either cardiovascular or pulmonary problems was noted. Results Dogs from Group A receiving doxycycline had fewer respiratory complications (6.52%) and heartworm disease-related deaths (0%) than Group B (19.14% and 4.25%, respectively). Conclusions Although there are not enough cases to indicate statistical significance, the results strongly suggest that including doxycycline into canine heartworm treatment protocols decreases post-treatment complications and mortality in naturally infected clinical cases.

Metallic oxide SrNbO3has been identified as an efficient hydrogen evolution photocatalyst. Here, Venkatesan and co-workers show that its visible light absorption stems from plasmon resonance, thanks to its large carrier density (despite a large 4.1 eV bandgap), as opposed to from an interband transition.