Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

A Formative Evaluation of the Family Strengthening Program in the Treasure Valley

Family Advocates, a nonprofit organization serving families in the Treasure Valley in Idaho, offers the Family Strengthening Program. This is a 20-week program providing weekly meetings for families who need to develop strong family cohesion, resilience, and parenting skills to maintain healthy families. The program uses the Strengthening Families’ approach with an emphasis on the protective factors framework and provides incentives to participants for participation. A third-party evaluation team from a local university conducted a formative evaluation of the program to help improve its quality. The evaluation team used both goal-based and goal-free, needs-based evaluation approaches, and analyzed quantitative and qualitative data. This included survey data from past weekly sessions, Facebook alumni group communications, and group interviews and surveys with participants, graduates, volunteers, and staff. The triangulated data indicated that program participants were highly satisfied with the program and felt the program helped improve their protective factors. The data also revealed the parents’ perceptions regarding program incentives as well as their preference for learning in socialized contexts. Based on the formative evaluation results and considering the participants’ perceptions and experiences, the program amended their curriculum and incentive plans to better accommodate the participants’ needs

Expressions 2013

https://openspace.dmacc.edu/expressions/1027/thumbnail.jp

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Topoisomerase Inhibitors Addressing Fluoroquinolone Resistance in Gram-Negative Bacteria.

Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resistance determining region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1H)-ones, exemplified by 34, that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gram-negative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex but does not form significant contacts with residues in the quinolone resistance determining region

The New Lighthouse Keepers: A Comparative Analysis of Ownership Structures Under the National Historic Lighthouse Preservation Act Program

With the automation of lights and rapid advances in navigational technology in the twentieth century, lighthouses became obsolete and fell into deterioration. With a large push by a lighthouse preservation movement in the 1990s, Congress passed the National Historic Lighthouse Preservation Act of 2000 (NHLPA), an amendment to the National Historic Preservation Act (NHPA). This legislation allowed the U.S. Coast Guard, which holds jurisdiction over lighthouse administration, to declare their lighthouses excess and transfer or sell them through a process administered by the National Park Service and General Services Administration. Through an application process, federal agencies, local and state governments, or nonprofit organizations can apply for a no-cost transfer of a lighthouse. If no suitable applicant is found, the lighthouse goes to auction where it is sold to the highest bidder, or a private owner. Between passage of the National Historic Lighthouse Preservation Act in 2000 and the present day, the U.S. Coast Guard transferred ownership of 120 historic lighthouses to governmental, nonprofit, or private owners. This thesis assesses this program by ascertaining, first, which category of ownership participates most actively in the program, and, second, how new owners have resolved the significant responsibilities that come with ownership of a large, complicated historic structure. Evaluation of the results of questionaires revealed that new owners have met their obligations for repair and maintenance and express satisfaction with their efforts to preserve one of the nation\u27s most popular building types. By studying the different ownership structures and day-to-day management of the lighthouses, a better understanding was gained of the challenges and rewards of our present day keepers, and what needs to be done now and by future generations to preserve these important iconic structures

LpxD project

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Lasker Foundation Newsletter

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Queer Cryptographers: Jane Austen, Charlotte Brontë, and Sarah Orne Jewett

This dissertation coins the term “queer cryptography” to discuss the creation of multiple perceived realities as a means to undermine heteronormative sanctions for female writers in the nineteenth-century. I use the term “queer cryptographer” to discuss a uniquely feminine literary tradition of constructing coded, subversive, narratives within the seemingly benign genre of the domestic fiction. My dissertation is a chronological study of how three queer cryptographers discuss same-sex desire in their nineteenth-century works of domestic fiction. I begin my study with Jane Austen, following Austen with Charlotte Brontë, and finishing with Sarah Orne Jewett. Interestingly, not only did each successive queer cryptographer in my dissertation read the former’s work, establishing a very real female literary community, but they also each participate within a conversation concerning same-sex relationships and their permanence in societies that criminalize homosexuality. I look at Austen’s Pride and Prejudice, Emma, and Persuasion, Brontë’s Jane Eyre, and Jewett’s Deephaven to demonstrate a progression of the depictions of same-sex relationships from simply understanding same-sex desire as a state between erotic innocence and heterosexual marriage to portraying same-sex relationships as of equal importance as heterosexual marriages. Thus, I understand these coded discussions of same-sex desire as having a positive role in the very fabric of heteronormativity. By understanding this progressive commentary, we must reconsider what we think we know about works of domestic fiction in the nineteenth century and the female writers behind them

Jane Austen's open secret same-sex love in Pride and prejudice, Emma, and Persuasion

I argue that Austen's famously heteronormative novels do not actually begin with compulsory heterosexuality: they arrive there gradually, contingently, and only by first carving out an authorized space in which queer relations may, or indeed must, take hold. Engaging intimacies between both men and women within Pride and Prejudice, Persuasion, and Emma, I explore how Austen constructs a heteronormativity that is itself premised upon queer desire and the progressive implications this casts upon Austen as a female writer within Regency England. In each of my three chapters, I look at how samesex intimacies are cultivated in the following social spheres: the realm of illness within Persuasion, the realm of Regency courtship within Pride and Prejudice, and the realm of domesticity within Emma. I argue that Austen conforms to patriarchal sanctions for female authorship while simultaneously undermining this sanction by depicting same-sex desire. Through depicting a same-sex desire that lays the very foundation of each novel's culminated heteronormativity, Austen redefines desire and, in the process, redefines herself as a progressive author. I suggest that Austen follows the lead of famous romantics such as Percy Shelley and Lord Byron, and promotes the progressive notion of homosexuality as a universal state through her subtle depictions of same-sex intimacies in her famously heteronormative novels. I engage D.A. Miller's theory of open secrets, Steven Cohan's analysis of helper figures, Eve Sedgwick's logic of closeted homosexuality, Freud's theory of jealousy, Michael Warner and Lauren Berlant's engagement of public and private, and Judith Butler's theory of gender performativity