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Biological invasions are a form of global change threatening biodiversity, ecosystem stability, and human health, and cost government agencies billions of dollars in remediation and eradication programs. Attempts to eradicate introduced species are most successful when detection of newly established populations occurs early in the invasion process. We review existing and emerging tools – specifically environmental DNA (eDNA), chemical approaches, remote sensing, citizen science, and agency-based monitoring – for surveillance and monitoring of invasive species. For each tool, we consider the benefits provided, examine challenges and limitations, discuss data sharing and integration, and suggest best practice implementations for the early detection of invasive species. Programs that promote public participation in large-scale biodiversity identification and monitoring (such as iNaturalist and eBird) may be the best resources for early detection. However, data from these platforms must be monitored and used by agencies that can mount appropriate response efforts. Control efforts are more likely to succeed when they are focused on early detection and prevention, thereby saving considerable time and resources.

Giving land managers the ability to predict invasion patterns can provide planning tools for acquisition and management of protected areas. We compared the effects of roads and streams, two substantial pathways for delivery of invasive plant propagules and sources of disturbance that may facilitate invasions, on the abundance of non-native invasive plants in 27 protected areas in the Appalachian Mountains of the eastern United States. As an extension of our road analysis, we also evaluated specific road type as a predictor of protected area invadedness. We found that road and stream predictors did not improve on a model that included only other covariates (e.g., distance to an urban area, average canopy cover, average slope, edge-to-interior ratio, percent agricultural land, and percent developed land). In this model, only percent agricultural land was marginally significant in predicting parcel invadedness. However, we found that four-wheel drive (4WD) roads did predict protected area invadedness well relative to other road types (primary, secondary, and local) and better than a covariates-only model. The role of 4WD road density in predicting protected area invadedness may be explained by their relation to recreation, the unmaintained nature of 4WD roads, or the accumulation of mud and plant materials on 4WD vehicles. Although we found overall streams and roads in general to be poor predictors of invadedness of protected areas by invasive plants, we do propose that our finding of a relationship between plant invasions and density of 4WD roads merits further investigation in the future.

Significance Sea stars inhabiting the Northeast Pacific Coast have recently experienced an extensive outbreak of wasting disease, leading to their degradation and disappearance from many coastal areas. In this paper, we present evidence that the cause of the disease is transmissible from disease-affected animals to apparently healthy individuals, that the disease-causing agent is a virus-sized microorganism, and that the best candidate viral taxon, the sea star-associated densovirus (SSaDV), is in greater abundance in diseased than in healthy sea stars. Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation (“melting”). Here, we present evidence from experimental challenge studies and field observations that link the mass mortalities to a densovirus ( Parvoviridae ). Virus-sized material (i.e., <0.2 μm) from symptomatic tissues that was inoculated into asymptomatic asteroids consistently resulted in SSWD signs whereas animals receiving heat-killed (i.e., control) virus-sized inoculum remained asymptomatic. Viral metagenomic investigations revealed the sea star-associated densovirus (SSaDV) as the most likely candidate virus associated with tissues from symptomatic asteroids. Quantification of SSaDV during transmission trials indicated that progression of SSWD paralleled increased SSaDV load. In field surveys, SSaDV loads were more abundant in symptomatic than in asymptomatic asteroids. SSaDV could be detected in plankton, sediments and in nonasteroid echinoderms, providing a possible mechanism for viral spread. SSaDV was detected in museum specimens of asteroids from 1942, suggesting that it has been present on the North American Pacific Coast for at least 72 y. SSaDV is therefore the most promising candidate disease agent responsible for asteroid mass mortality.

The impact of the 2019 coronavirus pandemic (COVID-19) in the United States is unprecedented, with unknown implications for the autism community. We surveyed 3502 parents/caregivers of individuals with an autism spectrum disorder (ASD) enrolled in Simons Powering Autism Research for Knowledge (SPARK) and found that most individuals with ASD experienced significant, ongoing disruptions to therapies. While some services were adapted to telehealth format, most participants were not receiving such services at follow-up, and those who were reported minimal benefit. Children under age five had the most severely disrupted services and lowest reported benefit of telehealth adaptation. Caregivers also reported worsening ASD symptoms and moderate family distress. Strategies to support the ASD community should be immediately developed and implemented.

Generation of cultured human cells stably expressing one or more recombinant gene sequences is a widely used approach in biomedical research, biotechnology, and drug development. Conventional methods are not efficient and have severe limitations especially when engineering cells to coexpress multiple transgenes or multiprotein complexes. In this report, we harnessed the highly efficient, nonviral, and plasmid-based piggyBac transposon system to enable concurrent genomic integration of multiple independent transposons harboring distinct protein-coding DNA sequences. Flow cytometry of cell clones derived from a single multiplexed transfection demonstrated approximately 60% (three transposons) or approximately 30% (four transposons) stable coexpression of all delivered transgenes with selection for a single marker transposon. We validated multiplexed piggyBac transposon delivery by coexpressing large transgenes encoding a multisubunit neuronal voltage-gated sodium channel (SCN1A) containing a pore-forming subunit and two accessory subunits while using two additional genes for selection. Previously unobtainable robust sodium current was demonstrated through 38 passages, suitable for use on an automated high-throughput electrophysiology platform. Cotransfection of three large (up to 10.8 kb) piggyBac transposons generated a heterozygous SCN1A stable cell line expressing two separate alleles of the pore-forming subunit and two accessory subunits (total of four sodium channel subunits) with robust functional expression. We conclude that the piggyBac transposon system can be used to perform multiplexed stable gene transfer in cultured human cells, and this technology may be valuable for applications requiring concurrent expression of multiprotein complexes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Small molecule selectin ligand inhibition improves outcome in ischemic acute renal failure. The pathophysiologic and potential therapeutic role of selectins in renal ischemia-reperfusion injury (IRI) is not fully understood, due in part to redundancy in the roles of individual selectins. We hypothesized that blockade of ligands for all three selectins using a novel small molecule (TBC-1269) would improve the course of renal IRI by overcoming redundancy issues. This was investigated in a rat model of renal IRI. Rats were treated with TBC-1269 either during or post-IRI. The effects of TBC-1269 were investigated in two models of renal IRI: moderate IRI (30 minutes bilateral renal artery clamping) and severe IRI (45 minutes clamping). The combination of anti-E- and anti-P-selectin antibodies also was investigated in rats subjected to moderate IRI. Renal function, histological injury and mortality were assessed. Rats treated with TBC-1269 during moderate IRI showed significantly reduced serum creatinine (SCr) and tubular necrosis post-ischemia compared to control animals. By contrast, delayed treatment (post-IRI) did not show a reduction in SCr. In rats with severe IRI, TBC-1269 treatment during IRI significantly reduced mortality at 48 hours post-ischemia. Rats with moderate IRI and treated with the combination of anti-E- and anti-P-selectin antibodies showed significantly reduced SCr compared to control rats at 24 hours post-ischemia. Small molecule selectin ligand inhibition provides a novel and effective approach to attenuate ischemic acute renal failure. Timing of treatment is crucial to success.

Risk Factors for Frequent and Severe Hypoglycemia in Type 1 Diabetes Catherine Allen , PHD 1 , Tamara LeCaire , MS 1 , Mari Palta , PHD 1 , Kathleen Daniels , MS 1 , Melissa Meredith , MD 2 , Donn J. D’Alessio , MD 1 and for the Wisconsin Diabetes Registry Project 1 Preventive Medicine and 2 Medicine, University of Wisconsin Medical School, Madison, Wisconsin Abstract OBJECTIVE —To determine the risk of frequent and severe hypoglycemia and the associated demographic and clinical risk factors. RESEARCH DESIGN AND METHODS —Demographic and diabetes self-management factors were measured in 415 subjects followed prospectively for 4–6.5 years of type 1 diabetes duration as participants in a population-based incident cohort. Blood samples were collected up to three times yearly to test glycosylated hemoglobin (GHb) levels. Reports of frequent (2–4 times/week) and severe (lost consciousness) hypoglycemia as well as other diabetes self-management data were collected by questionnaires. RESULTS —Frequent hypoglycemia was common (33 and 35% of participants reported this on the 4- and 6.5-year questionnaires, respectively), whereas severe hypoglycemia occurred much less often. Better glycemic control (odds ratio [OR] 1.3 per 2% decrease in GHb, 95% CI 1.1–1.5) and more frequent self-monitored blood glucose (1.5 per blood glucose check, 1.3–1.7) were independently related to frequent hypoglycemia. The association of frequent hypoglycemia with intensive insulin therapy increased with age. Better glycemic control (1.5 per 2% decrease in GHb, 1.2–2.0) and older age were related to severe hypoglycemic reactions. No sociodemographic factors other than age increased the risk of hypoglycemia. CONCLUSIONS —Frequent hypoglycemia was common in a population representing the full range of glycemic control in the community. Intensive insulin management and blood glucose monitoring independently predicted frequent but not severe hypoglycemia. This information may be useful for updating patients such that minor changes in diabetes management might decrease the daily burden of this condition while maintaining intensive insulin therapy. DCCT, Diabetes Control and Complications Trial GHb, glycosylated hemoglobin OR, odds ratio SMBG, self-monitored blood glucose Footnotes Address correspondence and reprint requests to Catherine Allen, PhD, University of Wisconsin Medical School, Department of Preventive Medicine, 610 N. Walnut St., Room 6601, Madison, WI 53705. E-mail: ciallen{at}facstaff.wisc.edu . Received for publication 30 January 2001 and accepted in revised form 20 July 2001. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Neuroblastoma is the most common neoplasm in children under 1 year of age. We examined the relation between residential exposure to pesticides and neuroblastoma, using data from a case-control study of risk factors for neuroblastoma. Incident cases of neuroblastoma (N = 538) were identified through the Pediatric Oncology Group and the Children's Cancer Group. One age-matched control was identified for each case by random digit dialing. Telephone interviews with each parent collected information on residential exposure to pesticides. Pesticide use in both the home and garden were modestly associated with neuroblastoma [odds ratio (OR) = 1.6 (95% confidence interval [95% CI] = 1.0-2.3, and OR = 1.7 (95% CI = 0.9-2.1), respectively]. Compared with infants [OR = 1.0 (95% CI = 0.6-2.0)], stronger associations were found for garden pesticides in children diagnosed after 1 year of age [OR = 2.2 (95% CI = 1.3-3.6)], which suggests that pesticides may act through a mechanism more common for neuroblastomas in older children. There was no evidence of differential pesticide effects in subgroups of neuroblastoma defined by MYCN oncogene amplification or tumor stage.

Objective: The objective of this study was to evaluate the effectiveness, safety, and tolerability of the anticonvulsant agent, topiramate, as adjunctive treatment for children and adolescents with bipolar disorders. Methods: The outpatient medical charts of children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of bipolar disorder, type I or II, and who were treated with topiramate were retrospectively reviewed by two child and adolescent psychiatrists using the Clinical Global Impression (CGI) scale and the Clinical Global Assessment Scale (CGAS). Separate CGI ratings were made for mania and overall bipolar illness. Results: Twenty-six patients (mean age 14 ± 3.5 years) with bipolar disorder, type I (n = 23) or II (n = 3), who had been treated (mean duration 4.1 ± 6.1 months) with topiramate (mean dose 104 ± 77 mg/day) were identified. Response rate (defined by a CGI-Improvement score of ≤ 2 at endpoint) was 73% for mania and 62% for overall illness. CGAS scores significantly improved from baseline to endpoint. No serious adverse events were reported. Conclusions: Although controlled trials are necessary, this retrospective study suggests that topiramate is effective and well tolerated as an adjunctive treatment for children and adolescents with bipolar disorder.