Overlooked Assets: Body Size, Body Image, and Sexual Minority Women.

While public health literature indicates sexual minority women (SMW) are at risk for obesity, psychological literature suggests SMW possess the health advantage of positive body image. In this dissertation, I bring these two lines of research together to create a more complete picture of SMW’s health. First, I conducted a purposeful literature review to identify influential papers in the health sciences that focus on SMW, body size, and health status. Articles in the final analytic sample contained key gaps in the operationalization of body size and its relationship to health. The majority demonstrated a bias towards understanding body size as a marker of disease, ignoring scholarship questioning the link between body size and health. Body image was missing from half the articles, suggesting a privileging of medical metrics like BMI over SMW’s beliefs about the status of their bodies. Then, using quantitative survey data from the Michigan Smoking and Sexuality Survey (M-SASS), a cross-sectional study of SMW between the ages of 18 and 24, I conducted two sets of analyses. (1) I evaluated whether aspects of SMW’s identities where they departed from heteronormative social roles (i.e., non-traditional gender roles, sexual identity, connection to LGBTQ community) were associated with dimensions of body esteem (i.e., body weight, body attribution, and body shame). The results indicated that connection to the LGBTQ community increased positive feelings about body weight and reduced feelings of body shame. These relationships were amplified among masculine-identified SMW. (2) I assessed whether positive body image can be understood as a psychological asset available to SMW facing size discrimination. I tested three theoretically informed resilience models of body size, size discrimination, body image, and mental health (i.e., depressive symptoms, self-esteem) and found that SMW who experienced more size discrimination reported more depressive symptoms. Conversely, positive body image was associated with fewer depressive symptoms and more self-esteem. By examining body size and body image in relationship to each other and to mental health, this dissertation underscores that viewing the health of SMW solely through the lens of obesity is limiting and that SMW may have access to unique processes of resilience.PhDHealth Behavior and Health EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113430/1/johnsmm_1.pd

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

LGBT community, social network characteristics, and smoking behaviors in young sexual minority women.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106605/1/LGBT community, social network characteristics, and smoking behaviors in young sexual minority women.pd

Sexual attraction, sexual identity, and psychosocial well-being in a national sample of young women during emerging adulthood.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106627/1/Sexual attraction, sexual identity, and psychosocial well-being in a national sample of young women during emerging adulthood.pd

The Plankton Lifeform Extraction Tool: a digital tool to increase the discoverability and usability of plankton time-series data

Publication history: Accepted - 25 October 2021; Published online - 6 December 2021.Plankton form the base of the marine food web and are sensitive indicators of environmental change. Plankton time series are therefore an essential part of monitoring progress towards global biodiversity goals, such as the Convention on Biological Diversity Aichi Targets, and for informing ecosystem-based policy, such as the EU Marine Strategy Framework Directive. Multiple plankton monitoring programmes exist in Europe, but differences in sampling and analysis methods prevent the integration of their data, constraining their utility over large spatio-temporal scales. The Plankton Lifeform Extraction Tool brings together disparate European plankton datasets into a central database from which it extracts abundance time series of plankton functional groups, called “lifeforms”, according to shared biological traits. This tool has been designed to make complex plankton datasets accessible and meaningful for policy, public interest, and scientific discovery. It allows examination of large-scale shifts in lifeform abundance or distribution (for example, holoplankton being partially replaced by meroplankton), providing clues to how the marine environment is changing. The lifeform method enables datasets with different plankton sampling and taxonomic analysis methodologies to be used together to provide insights into the response to multiple stressors and robust policy evidence for decision making. Lifeform time series generated with the Plankton Lifeform Extraction Tool currently inform plankton and food web indicators for the UK's Marine Strategy, the EU's Marine Strategy Framework Directive, and for the Convention for the Protection of the Marine Environment of the North-East Atlantic (OSPAR) biodiversity assessments. The Plankton Lifeform Extraction Tool currently integrates 155 000 samples, containing over 44 million plankton records, from nine different plankton datasets within UK and European seas, collected between 1924 and 2017. Additional datasets can be added, and time series can be updated. The Plankton Lifeform Extraction Tool is hosted by The Archive for Marine Species and Habitats Data (DASSH) at https://www.dassh.ac.uk/lifeforms/ (last access: 22 November 2021, Ostle et al., 2021). The lifeform outputs are linked to specific, DOI-ed, versions of the Plankton Lifeform Traits Master List and each underlying dataset.Funding that supports this work and the data collected has come from the European Commission, European Union (EU) grant no. 11.0661/2015/712630/SUB/ENVC.2 OSPAR; UK Natural Environment Research Council (grant nos. NE/R002738/1 and NE/M007855/1); EMFF, Climate Linked Atlantic Sector Science (grant no. NE/R015953/1), Department for Environment, Food and Rural Affairs, UK Government (grant nos. ME-5308 and ME-414135), NSF USA OCE-1657887, DFO CA F5955150026/001/HAL, Natural Environment Research Council UK (grant no. NC-R8/H12/100); Horizon 2020 (MISSION ATLANTIC (grant no. 862428)); iCPR (grant no. SBFF-2019-36526), IMR Norway; DTU Aqua Denmark; and the French Ministry of Environment, Energy, and the Sea (MEEM). Recent funding for the development of PLET and the Pelagic Habitats Indicator has been provided by HBDSEG/Defra and MMO/EMFF. The MSS Scottish Coastal Observatory data and analyses are funded and maintained by the Scottish Government Schedules of Service (grant nos. ST05a and ST02H), MSS Stonehaven Samplers, North Atlantic Fisheries College, Shetland, Orkney Islands Harbour Council, and Isle Ewe Shellfish

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

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