Massachusetts Offshore Wind Future Cost Study

The Special Initiative on Offshore Wind is an independent project at the University of Delaware's College of Earth, Ocean and Environment that supports the advancement of offshore wind as part of a comprehensive solution to the most pressing energy problems facing the United States.  The Special Initiative on Offshore Wind provides expertise, analysis, information sharing, and strategic partnership with industry, advocacy and government stakeholders to build understanding and drive the deployment of offshore wind

A study of rural high school principals’ perceptions as social justice leaders

This multisite case study explores how rural principals in high poverty schools in a Southern state that had identified themselves as social justice leaders perceived student diversity, specifically LGBTQ students, and how they sustained a socially-just school climate for all students. Using a qualitative approach lent itself to understanding the principals’ descriptions of themselves as social justice leaders in their respective school and community contexts through their conversations (Creswell, 2007; Marshall & Rossman, 2016). The investigators drew from Theoharis’ (2007, 2009) and Bishop’s (2012) studies to serve as the theoretical framework guiding this study. The results indicated that the principals in this case study struggled with recognizing LGBTQ students’ needs and well-being. The findings in this study contain implications for pre-service preparation and in-service professional development programs to draw upon social justice leadership theory and research to inform leadership practices when addressing external and internal resistance. Moreover, this study recognizes the need for leadership preparation programs to integrate critical self-consciousness (Freire, 2000) with purposeful reflection (Webster-Smith, 2011) as essential to the development of the social justice leader

Kinship Diversion in the District of Columbia: A Review of Local Practice to Inform National Policy

This article addresses a practice commonly known in the child welfare community as “kinship diversion,” where a child welfare agency informally places children with relatives as an alternative to foster care. While evidence predominantly shows that abused and neglected children have better outcomes when they are placed with relatives when they cannot remain safely at home, serious concerns about these children’s safety and well-being arise when the placement with relatives is informal. Indeed, it is often not understood that these same relatives can be approved as foster parents and can receive essential financial assistance and supportive services to help safely raise these children, who often have significant needs. By contrast, kinship diversion does not protect abused and neglected children from harm nor does it help stabilize the family unit financially or emotionally. As such, the safety of diverted abused and neglected children is imperiled because child protection agencies do not oversee or manage what happens to them. Using the practices of the District of Columbia child protection agency as an example of how kinship diversion is implemented by child welfare agencies nationally, this article provides recommendations for identifying and implementing best practices in this area to protect diverted children

Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

The budding yeast heat shock protein Hsp42 coaggregates with misfolded proteins and may link those aggregates to further sorting factors

The Use of Preoperative Prophylactic Systemic Antibiotics for the Prevention of Endopthalmitis in Open Globe Injuries:A Meta-Analysis

Topic:This study reports the effect of systemic prophylactic antibiotics (and their route) on the risk of endophthalmitis after open globe injury. Clinical relevance:Endophthalmitis is a major complication of open globe injury, it can lead to rapid sight loss in the affected eye. The administration of systemic antibiotic prophylaxis is common practice in some health care systems, although there is no consensus on their use. PubMed, CENTRAL, Web of Science, CINAHL and Embase were searched. This was completed 6th July 2021 and updated 10th Dec 2022. We included randomised and non-randomised prospective studies which reported the rate of post-open globe injury endophthalmitis, when systemic pre-operative antibiotic prophylaxis (via the oral or intravenous route) was given. The Cochrane Risk of Bias tool and ROBINS-I tool were used for assessing the risk of bias. Where meta-analysis was performed results were reported as odds ratio. PROSPERO registration: CRD42021271271. Three studies were included. One prospective observational study compared outcomes of patients who had received systemic or no systemic pre-operative antibiotics. The endophthalmitis rates reported were 3.75% and 4.91% in the systemic and no systemic pre-operative antibiotics groups, a non-significant difference (p = 0.68). Two randomised controlled trials were included (1,555 patients). The rates of endophthalmitis were 17 events in 751 patients (2.26%) and 17 events in 804 patients (2.11%) in the oral antibiotics and intravenous (+/- oral) antibiotics groups, respectively. Meta-analysis demonstrated no significant differences between groups (OR 1.07 [95% confidence interval 0.54 – 2.12]). The incidences of endophthalmitis after open globe injury were low with and without systemic antibiotic prophylaxis, although high risk cases were excluded in the included studies. When antibiotic prophylaxis is considered, there is moderate evidence that oral antibiotic administration is non-inferior to intravenous

The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies:A Meta-analysis

Topic: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial.Clinical Relevance: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat.Methods: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR).Results: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%–0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%–0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%–0.33%). The ARR using a random effects model was −0.0010 (in favour of eye removal; 95% CI, −0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data.Discussion: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO.Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Mapping the Hsp90 Genetic Interaction Network in Candida albicans Reveals Environmental Contingency and Rewired Circuitry

The molecular chaperone Hsp90 regulates the folding of diverse signal transducers in all eukaryotes, profoundly affecting cellular circuitry. In fungi, Hsp90 influences development, drug resistance, and evolution. Hsp90 interacts with ∼10% of the proteome in the model yeast Saccharomyces cerevisiae, while only two interactions have been identified in Candida albicans, the leading fungal pathogen of humans. Utilizing a chemical genomic approach, we mapped the C. albicans Hsp90 interaction network under diverse stress conditions. The chaperone network is environmentally contingent, and most of the 226 genetic interactors are important for growth only under specific conditions, suggesting that they operate downstream of Hsp90, as with the MAPK Hog1. Few interactors are important for growth in many environments, and these are poised to operate upstream of Hsp90, as with the protein kinase CK2 and the transcription factor Ahr1. We establish environmental contingency in the first chaperone network of a fungal pathogen, novel effectors upstream and downstream of Hsp90, and network rewiring over evolutionary time

Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential