Spatial prioritization for widespread invasive species control: Trade-offs between current impact and future spread.

Spatially explicit prioritization of invasive species control is a complex issue, requiring consideration of trade-offs between immediate and future benefits. This study aimed to prioritize management efforts to account for current and future threats from widespread invasions and examine the strength of the trade-off between these different management goals. As a case study, we identified spatially explicit management priorities for the widespread invasion of introduced willow into riparian and wetland habitats across a 102,145-km2 region in eastern Australia. In addition to targeting places where willow threatens biodiversity now, a second set of management goals was to limit reinfestation and further spread that could occur via two different mechanisms (downstream and by wind). A model of likely willow distribution across the region was combined with spatial data for biodiversity (native vegetation, threatened species and communities), ecological conditions, management costs, and two potential dispersal layers. We used systematic conservation planning software (Zonation) to prioritize where willow management should be focussed across more than 100,000 catchments for a range of different scenarios that reflected different weights between management goals. For willow invasion, we found that we could prioritize willow management to reduce the future threat of dispersal downstream with little reduction in the protection of biodiversity. However, accounting for future threats from wind dispersal resulted in a stronger trade-off with protection of threatened biodiversity. The strongest trade-off was observed when both dispersal mechanisms were considered together. This study shows that considering current and future goals together offers the potential to substantially improve conservation outcomes for invasive species management. Our approach also informs land managers about the relative trade-offs among different management goals under different control scenarios, helping to make management decisions more transparent. This approach can be used for other widespread invasive species to help improve invasive species management decisions.

A Rapid Access Brief Psychotherapy Intervention to Respond to Healthcare Workers in Ontario Whose Mental Health was Negatively Impacted During the COVID-19 Pandemic.

OBJECTIVE: Although the coronavirus disease 2019 (COVID-19) pandemic has had widespread negative impacts on the mental health of healthcare workers (HCWs), there has been little research on psychological interventions during the pandemic for this population. The current study examines whether a brief coping-focused treatment intervention delivered in a virtual individual format would be associated with positive changes in Canadian HCWs' mental health during the pandemic. METHOD: Three hundred and thirty-three HCWs receiving the intervention at 3 large specialty tertiary care hospitals in Ontario, Canada, completed measures of anxiety, depression, perceived stress, work/social impairment, insomnia and fear of COVID-19. After completing treatment, HCWs rated their satisfaction with the treatment. RESULTS: The intervention was associated with large effect size improvements in anxiety, depression, perceived stress, insomnia and fear of COVID-19, and moderate effect size improvements in work/social impairment. At treatment session 1, prior mental health diagnosis and treatment were both significantly correlated with depression, anxiety, and work/social impairment scores. Secondary analyses of data from one of the sites revealed that treatment-related changes in anxiety, depression, perceived stress and work/social impairment were independent of age, gender, occupational setting, profession and the presence of a previous mental health diagnosis or treatment, with the exception that nurses improved at a slightly greater rate than other professions in terms of work/social impairment. HCWs were highly satisfied with the treatment. CONCLUSIONS: A large number of HCWs experiencing significant distress at baseline self-referred for assistance. Timely and flexible access to a brief virtual coping-focused intervention was associated with improvements in symptoms and impairment, and treatment response was largely unrelated to demographic or professional characteristics. Short-term psychological interventions for HCWs during a pandemic may have a highly positive impact given their association with improvement in various aspects of HCWs' mental health improvement.

Can the AUDIT consumption items distinguish lower severity from high severity patients seeking treatment for alcohol use disorder?

Brief screening tools based on the Alcohol Use Disorders Identification Test (AUDIT) consumption items (e.g., AUDIT-C and AUDIT-3) are commonly used in general medical settings to identify at-risk drinkers who may benefit from alcohol interventions. Conversely, in specialty alcohol treatment settings with a high volume of self-referrals, there may be a need for brief screening tools that can help to identify patients who are unlikely to require intensive treatments, but there has been little research on the use of AUDIT-C or AUDIT-3 in this context. The current study examined the utility of brief screeners comprised of the AUDIT consumption items for distinguishing lower-severity patients from high severity patients in a cohort of individuals self-referring to specialty alcohol treatment. Participants were adults seeking treatment for alcohol problems (N = 853) at a large public psychiatric hospital in Toronto, Canada, who completed the full 10-item AUDIT as part of an initial telephone screening with hospital staff. Results of receiver operating characteristic curve analyses showed that both the AUDIT-C and the AUDIT-3 demonstrated adequate accuracy (area under the curve; AUC > 0.85) for distinguishing lower-severity patients (defined as those in AUDIT zones I, II, and III) from high-severity patients (defined as those in AUDIT zone IV). Exploratory analyses showed that the addition of AUDIT item 4 (impaired control) to the AUDIT-C and AUDIT-3 significantly improved classification accuracy (AUCs = 0.95; ps < .001), and the resulting brief screeners had cut-points with good sensitivity and specificity (i.e., >80%). Results support the potential utility of brief screeners comprised of the AUDIT consumption items for distinguishing lower-severity from high severity individuals seeking specialty alcohol treatment services, which may assist with the initial screening and triage process. The addition of AUDIT item 4 improved the performance of the AUDIT-C and AUDIT-3 in this context. Future research validating these findings against external criteria, including comprehensive diagnostic information, is required.

Sexual Health Behavior and Mental Health Among Older African American Women: The Sistahs, Sexuality, and Mental Health Well-Being Project.

BACKGROUND: In Los Angeles County, the rates of sexually transmitted infections and diseases among African Americans represent a significant public health disparity. Older African American women are at particular risk as they are more likely to engage in high-risk sexual behaviors and report social isolation and loneliness than their younger counterparts. However, the literature on the relationship between sexual health and mental health in this group is limited. The purpose of this study was to use a community-based participatory research (CBPR) approach to better understand sexual health behaviors and mental health among African American women over 50 years of age who reside in South Los Angeles. MATERIALS AND METHODS: This project was divided into two phases. Phase I (January-March 2017) of the project consisted of four dialog/focus groups (N = 45) (ages: 50-80; Mage = 67). The purpose of Phase II (April 2017) was to present study results from Phase I to the community via a community-based conference, as well as gather feedback and generate discussion about the next steps for community prevention/intervention. RESULTS: Women reported that they did not feel comfortable discussing sexual practices with their physician, partners, and friends. Most women identified depression, loneliness, and self-esteem issues as reasons for engaging in high-risk sexual behaviors. During Phase II, potential intervention avenues emerged to address issues such as lack of physician-patient communication, lack of community support, and dialogs about sex. CONCLUSIONS: The use of CBPR greatly enhanced our knowledge of the core issues surrounding sexual health and mental health among older African American women.

Excess EDTA interferes with cortisol measurement using a solid-phase, chemiluminescent enzyme immunoassay.

Hormone assays that use a solid-phase, automated, chemiluminescent enzyme immunoassay (CEIA) with an alkaline phosphatase-tagged hormone or antibody as a reporter are performed on serum or EDTA plasma in our laboratory. CEIA cortisol results appeared to increase in the presence of excess EDTA. We investigated the effect of the addition of different amounts of EDTA on cortisol concentrations in pooled canine serum samples. The recommended EDTA plasma concentration of 4.1 mmol/L (1.8 mg/mL) did not alter cortisol concentrations when added to serum pools; however, the addition of ≥5.1 mmol/L (2.25 mg/mL) of EDTA increased apparent concentrations of cortisol. Supplementation of serum samples with MgCl2 to 5 mmol/L reversed the effect of EDTA up to a concentration of ~8.1 mmol/L (3.6 mg/mL). Our findings show that CEIA cortisol results on EDTA plasma can be artificially increased if the EDTA concentration exceeds 5.1 mmol/L.

Quantitation of aldosterone in human plasma by ultra high performance liquid chromatography tandem mass spectrometry.

Aldosterone is a mineralocorticoid steroid hormone whose measurement in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Traditionally measurement of aldosterone has been performed by radioimmunoassay, however these assays lack specificity as they are prone to interference from structurally related steroid hormones. Herein, we have developed a novel, sensitive and specific method utilising solid phase extraction and quantitation of aldosterone from human plasma by UPLC-MS/MS. Standards, quality controls and samples (250µL) were extracted using Oasis(®) HLB 96-well plates. Extract (30µL) was injected onto a Krudcatcher UPLC In-Line Filter, 0.5µm guard column, coupled to a Kinetex PFP, 100mm×2.1mm, 2.6µm column with methanolic mobile phase gradient elution. Eluant was connected to a Waters(®) Xevo TQS tandem mass spectrometer operating in electrospray negative mode. We detected multiple reaction monitoring (MRM) transitions of m/z 359.0>189.1 for aldosterone and 366.0>194.1 for d7-aldosterone respectively, which co-eluted at 2.65min. Ion suppression was negligible. Mean recovery was 89.6%, limit of detection and lower limit of quantitation were 26pmol/L and 30pmol/L respectively. The assay was linear up to 3200pmol/L (r(2)=0.9999). Mean intra- and inter-assay imprecision and bias were all <10%. Comparison of the UPLC-MS/MS method with an immunoassay in routine clinical use in the UK yielded the equation UPLC-MS/MS=0.789(RIA)-41.7, linear regression r(2)=0.88, n=54. We have developed a sensitive and specific method for the extraction and measurement of aldosterone from human plasma. The method features a simple 96-well plate solid phase extraction procedure, highly selective column chemistry and short chromatographic run times.

Standardization developments for large scale biobanks in smoking related diseases - a model system for blood sample processing and storage.

BACKGROUND: Biobank samples stored in biobanks give researchers and respiratory healthcare institutions access to datasets of analytes valuable for both diagnostic and research practices. The usefulness of these samples in clinical decision-making is highly dependent on their quality and integrity. New procedures that better preserve sample integrity and reduce degradation are being developed to meet the needs of both present and future biobanking. Hereby we present an automatic sample workflow scheme that is designed to handle high numbers of blood samples. METHODS: Blood fractions are aliquoted, heat sealed using novel technology, and stored in 384 tube high-density sample arrays. RESULTS: The newly developed 384 biobank rack system is especially suited for preserving identical small aliquots. We provide data on robotic processing of clinical samples at -80°C, following initial processing, analysis and shipping between laboratories throughout Europe. Subsequent to unpacking, re-sorting, and storage at these sites, the samples have been returned for analysis. Biomarker analysis of 13 common tests in the clinical chemistry unit of the hospital provides evidence of qualitative and stable logistics using the 384-sample tube system. CONCLUSIONS: This technology development allows rapid access to a given sample in the frozen archive while maintaining individual sample integrity with sample tube confinement and quality management.

Cytogenetics caseload survey summary 2012.

In 2004 a cytogenetics caseload and FTE survey was conducted to evaluate cytogenetic laboratory caseload and full-time employee equivalent (FTE) statistics. A similar survey was recently conducted to re-evaluate data. Information gathered by the survey included classification of laboratory type, number of employees according to title, and annual caseload volumes by sample or test type. Workload was evaluated by assigning weighted values to test types based on complexity. Compared with the data from 2004, the current data suggestsgreater complexity in cytogenetics lab testing as well as greater efficiency and productivity.

A high-throughput computational framework for identifying significant copy number aberrations from array comparative genomic hybridisation data.

Reliable identification of copy number aberrations (CNA) from comparative genomic hybridization data would be improved by the availability of a generalised method for processing large datasets. To this end, we developed swatCGH, a data analysis framework and region detection heuristic for computational grids. swatCGH analyses sequentially displaced (sliding) windows of neighbouring probes and applies adaptive thresholds of varying stringency to identify the 10% of each chromosome that contains the most frequently occurring CNAs. We used the method to analyse a published dataset, comparing data preprocessed using four different DNA segmentation algorithms, and two methods for prioritising the detected CNAs. The consolidated list of the most commonly detected aberrations confirmed the value of swatCGH as a simplified high-throughput method for identifying biologically significant CNA regions of interest.

Distinct activities of the anaphase-promoting complex/cyclosome (APC/C) in mouse embryonic cells.

The first differentiation event in mammalian development gives rise to the blastocyst, consisting of two cell lineages that have also segregated in how the cell cycle is structured. Pluripotent cells of the inner cell mass divide mitotically to retain a diploid DNA content, but the outer trophoblast cells can amplify their genomes more than 500-fold by undergoing multiple rounds of DNA replication, completely bypassing mitosis. Central to this striking divergence in cell cycle control is the E3 ubiquitin-ligase activity of the anaphase-promoting complex or cyclosome (APC/C). Extended suppression of APC/C activity during interphase of mouse pluripotent cells promotes rapid cell cycle progression by allowing stabilization of cyclins, whereas unopposed APC/C activity during S phase of mouse trophoblast cells triggers proteasomal-mediated degradation of geminin and giant cell formation. While differential APC/C activity might govern the atypical cell cycles observed in pre-implantation mouse embryos, geminin is a critical APC/C substrate that: (1) escapes degradation in pluripotent cells to maintain expression of Oct4, Sox2 and Nanog; and (2) mediates specification and endoreduplication when targeted for ectopic destruction in trophoblast. Thus, in contrast to trophoblast giant cells that lack geminin, geminin is preserved in both mouse pluripotent cells and non-endoreduplicating human cytotrophoblast cells.

Regulation of p53 stability and function by the deubiquitinating enzyme USP42.

The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by the ubiquitin ligase MDM2. In this study, we have identified USP42 as a DUB that interacts with and deubiquitinates p53. USP42 forms a direct complex with p53 and controls level of ubiquitination during the early phase of the response to a range of stress signals. Although we do not find a clear role for USP42 in controlling either the basal or fully activated levels of p53, the function of USP42 is required to allow the rapid activation of p53-dependent transcription and a p53-dependent cell-cycle arrest in response to stress. These functions of USP42 are likely to contribute to the repair and recovery of cells from mild or transient damage.

MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity.

The tumor suppressor p53 is extensively regulated by post-translational modification, including modification by the small ubiquitin-related modifier SUMO. We show here that MDM2, previously shown to promote ubiquitin, Nedd8 and SUMO-1 modification of p53, can also enhance conjugation of endogenous SUMO-2/3 to p53. Sumoylation activity requires p53-MDM2 binding but does not depend on an intact RING finger. Both ARF and L11 can promote SUMO-2/3 conjugation of p53. However, unlike the previously described SUMO-1 conjugation of p53 by an MDM2-ARF complex, this activity does not depend on the ability of MDM2 to relocalize to the nucleolus. Interestingly, the SUMO consensus is not conserved in mouse p53, which is therefore not modified by SUMO-2/3. Finally, we show that conjugation of SUMO-2/3 to p53 correlates with a reduction of both activation and repression of a subset of p53-target genes.

Geminin escapes degradation in G1 of mouse pluripotent cells and mediates the expression of Oct4, Sox2, and Nanog.

Geminin is an essential cell-cycle protein that is only present from S phase to early mitosis in metazoan somatic cells. Genetic ablation of geminin in the mouse results in preimplantation embryonic lethality because pluripotent cells fail to form and all cells differentiate to trophoblast. Here we show that geminin is present in G1 phase of mouse pluripotent cells in contrast to somatic cells, where anaphase-promoting complex/cyclosome (APC/C)-mediated proteasomal destruction removes geminin in G1. Silencing geminin directly or by depleting the APC/C inhibitor Emi1 causes loss of stem cell identity and trophoblast differentiation of mouse embryonal carcinoma and embryonic stem cells. Depletion of cyclins A2 or B1 does not induce this effect, even though both of these APC/C substrates are also present during G1 of pluripotent cells. Crucially, geminin antagonizes the chromatin-remodeling protein Brg1 to maintain expression of Oct4, Sox2, and Nanog. Our results define a pluripotency pathway by which suppressed APC/C activity protects geminin from degradation in G1, allowing sustained expression of core pluripotency factors. Collectively, these findings link the cell cycle to the pluripotent state but also raise an unexplained paradox: How is cell-cycle progression possible in pluripotent cells when oscillations of key regulatory proteins are lost?

Relationship between Mediterranean Diet Score and atherothrombotic risk: findings from the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994.

BACKGROUND: Mediterranean diet has been promoted as the preferred dietary model for cardiovascular disease prevention in the United States. OBJECTIVE: We sought to evaluate the degree to which the Mediterranean diet is associated with reduced levels of atherothrombotic biomarkers in a population-based sample in the U.S. DESIGN: Data from 13,197 adults between the ages of 18 and 90 were collected and atherothrombotic risk factors assessed as part of the NHANES III, 1988-1994. Adherence to the Mediterranean diet was evaluated using food frequency questionnaires, supplemented by the 24-h dietary recall data, to develop Mediterranean Diet Scores (MedDietScore) that were analyzed in tertiles. The cross-sectional relationship of MedDietScore to atherothrombotic factors were analyzed using multiple variable regression analysis adjusted for complex sampling design using SUDAAN. RESULTS: The components of the Mediterranean diet and the dietary pattern's associations with atherothrombotic risk factors differed by age and gender. For men <45 years of age as MedDietScore increased: total cholesterol/HDL cholesterol (TC/HDL) ratio (p=0.0390), serum insulin (p=0.0414), and white blood cell (WBC) (p=0.0246) decreased. For men>or=45 years as MedDietScore increased: TC/HDL ratio (p=0.0008), Hemoglobin A1c (HgbA1c) (p=0.0001), HOMA index (p=0.0486), C-reactive protein (p=0.0034), fibrinogen (p=0.0028) decreased and HDL cholesterol (HDL-c) levels (p<0.0001) increased. For pre-menopausal women, as MedDietScore increased: TC/HDL ratio (p<0.0001), non-HDL cholesterol (p=0.0012), apolipoprotein B (p=0.0112), HgbA1c (p=0.0001), decreased and HDL-c levels (p<0.0001) increased. For post-menopausal women, as MedDietScore increased: TC/HDL ratio (p=0.0005), Triglycerides (p<0.0001), serum insulin (p=0.0062), HOMA index (p=0.0063) and Homocysteine (Hcy) (0.0046) levels decreased and HDL-c levels (p=0.0005) increased. CONCLUSIONS: Mediterranean diet appears to be associated with selective measures of cardioprotective lipid profiles, glucose metabolism, and inflammation and coagulation levels.

Drosophila morgue influences cell numbers and positions in the embryonic nervous system.

Morgue is a unique multi-domain protein that contains a zinc finger motif, an F box, and a variant E2 conjugase domain. The presence of these domains suggests potentially complex and novel functions for Morgue in ubiquitination pathways. Morgue was originally identified via its gain-of-function enhancement of eye cell death phenotypes in Drosophila and ectopic expression of Morgue also influences circadian rhythms. However, there is as yet little known about Morgues normal developmental or physiological functions. To address this issue, we generated several morgue loss-of-function mutants via P element excision mutagenesis and analyzed the mutant phenotypes during the fly life cycle. These studies revealed that morgue null mutants are viable, though approximately 10% of the mutants exhibit defects in pupal spiracle eversion and malformations in the adult abdominal cuticle. In addition, a similar subset of morgue mutant embryos exhibited alterations in the normal number, position, or morphology of specific neurons and glia. Analysis of Morgue protein localization was addressed through generation of a transgenic fly strain that expresses a GFP::Morgue fusion protein. Use of this strain revealed Morgue protein localization in multiple cellular compartments, including nuclei, cytoplasm and membranes. Taken together, these diverse phenotypes and distribution patterns suggest pleiotropic functions for Morgue.

Isolation of stool-derived mucus provides a high yield of colonocytes suitable for early detection of colorectal carcinoma.

BACKGROUND: Promising stool-based screening tests for colorectal carcinoma (CRC) rely on detection of exfoliated colonocytes or their contents. However, methods of colonocyte retrieval have not been studied systematically and current approaches are restricted by low yields. We examined colonocyte numbers in stool wash fractions and assessed the suitability of retrieved cells for immunocytochemistry for minichromosome maintenance protein 2 (MCM2), a marker of the proliferative deregulation that characterizes malignancy. METHODS: Colonocyte numbers were accurately quantified in 129 wash fractions derived from 18 stools, comparing the mucus retained by a 125-microm filter (F fraction) with the fine and coarse content in the filtrate (S and P fractions, respectively). MCM2 immunocytochemistry was done on sections of fibrin clot containing filter-derived mucus, obtained from stools of eight independent subjects. RESULTS: Total colonocyte yield in the F fraction (mean, 433.8 per 100 microL) was higher than in the S (140.3) and P (204.6) fractions (P = 0.004 and 0.03, respectively) due to increased numbers of morphologically abnormal cells, which predominantly represented malignant cells in samples from CRC patients. Several thousand abnormal cells could be obtained from stool-derived mucus in all CRC patients, an order of magnitude greater than numbers in subjects without CRC. Median MCM2 labeling index in abnormal cells was 50% (range, 30-60%) in CRC patients and 0% in subjects without CRC. Cells in clot sections were well preserved and not obscured by fecal debris. CONCLUSIONS: Isolation of stool-derived mucus is technically straightforward and can improve the performance of protein-based and/or nucleic acid-based approaches to CRC screening.

Modifications of p53: competing for the lysines.

The p53 tumour suppressor protein is subject to numerous post-translational modifications, which coalesce in various combinations and patterns to regulate its activity. In addition to a multitude of phosphorylated serines and threonines, many of the lysine residues in p53 can be modified to regulate activity, stability and subcellular localization of the protein. This complexity is amplified by the variety of modifications that can target the same lysine residue - often with opposing effects on p53 function.

p53-Ubl fusions as models of ubiquitination, sumoylation and neddylation of p53.

The tumour suppressor p53 has been shown to be modified at its C-terminus with ubiquitin and the ubiquitin-like proteins SUMO and NEDD8. Whereas monoubiquitination of p53 is strongly associated with nuclear export, the effects of sumoylation and neddylation remain unclear. In this study we have generated p53-Ub, p53-SUMO-1 and p53-NEDD8 fusion proteins as models for the effect of these modifications on the localization and function of p53. As shown before, the ubiquitin fusion clearly drives nuclear export of p53 and we now find that this is also partially the case for a SUMO-1 fusion, which does not localise to PML bodies. In contrast a NEDD8 fusion has little effect on nuclear export, and mutating NEDD8 to more closely resemble ubiquitin did not restore nuclear export. Despite their differing subcellular localization, we find that both p53-ubiquitin and p53-NEDD8 retain similar transcriptional activity and both induce apoptosis at a similar level to unfused p53. The p53-ubiquitin fusion protein is potentially a good model for studying the role of p53 outside the nucleus. However, in our experiments we find that the export of p53 from the nucleus is not sufficient to activate its cytoplasmic apoptotic function which may depend on the ability to deubiquitinate cytoplasmic p53.

A role for Numb in p53 stabilization.

The cell-fate determinant Numb has recently been shown to help activate the tumor suppressor protein p53. Loss of Numb in breast cancers would result, therefore, in both the activation of the potential oncogene Notch and the diminution of tumor suppression by p53.