At the Foot of Prince George Street: The Burtis House, Hell Point, and Climate Change

This studio project includes a final report and abridged report that was submitted to Preservation Maryland.Annapolis is redeveloping its City Dock area into an elevated green space. The city will create preventative measures that protect the downtown area from rising sea levels. These measures include reconfiguring the stormwater system, elevating sea-level walls, and building storm surge gates. This redevelopment plan is a multi-phase initiative that provides for preserving and adapting for future use of the historic Burtis House, located at 69 Prince George Street. The Captain William Burtis House is ideally located to share the story of the history of Annapolis. As the sole surviving historic waterman’s home situated on City Dock, this property can assist visitors in understanding the Chesapeake way of life’s past, present, and future. With the redevelopment of the City Dock area, the Burtis House and site can become a welcoming and attractive place to learn about the region’s history. Due to its location, Burtis House has endured intermittent flooding, and it is vulnerable to sea level rise, subsidence, and tidal surges. Therefore, the building must be safeguarded against coastal flooding and stabilized until its use is determined. Preservation Maryland is leading the Burtis House initiative in partnership with the City of Annapolis and the National Park Service Chesapeake office. In 2021 Preservation Maryland issued a request for proposal for Phase 1 of this project. This first phase prioritizes the stabilization of the structure and preservation of the existing historic fabric from the effects of climate change for future adaptive reuse. Preventative measures against the impacts of climate change include raising Burtis house by four feet, water infiltration measures, and other defenses. As part of this phase, Preservation Maryland was looking for professional consultant services to conduct historical research on the context of the Burtis House and the neighborhood around it. The study would be utilized in interpretive panels placed around the house as work was being done. The University of Maryland’s Historic Preservation Studio class (HISP 650) responded to Preservation Maryland’s request for proposal for consultant services and was accepted. This report is the result.Nicholas Redding, Preservation Maryland Laura Houston, Preservation Marylan

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

National Register Nomination for Captain William Henry Burtis House, Annapolis, Maryland

The Burtis House, at 69 Prince George Street Annapolis, Maryland, is located within the Annapolis Historic District and is the last waterman’s house directly on the city waterfront. Burtis House was constructed circa 1882 and its period of significance spans from ca. 1882 to 1910, the years William Burtis, the house’s original owner, resided there. The property has a Maryland Inventory of Historic Properties (MIHP) number, AA-1152, although the nomination form, which was written in 1983, contains only cursory information about the house. The form has no information about who William Burtis was, why Burtis or the house is significant, or even context about its location. Recent research illuminates the history of the Burtis family, Burtis House, and the working-class Annapolis neighborhood it was once a part of, known as Hell Point. This study examines the historical context of Burtis House to create a new understanding of the property, which will emphasize the importance of William Burtis in Annapolis’s history, tell the story of the Burtis family, reveal the largely forgotten history of Hell Point and nineteenth century Annapolis, and illustrate the significance of Burtis House’s survival to the present day

Measuring the Frequency of Inner-Experience Characteristics by Self-Report: The Nevada Inner Experience Questionnaire

Descriptive experience sampling has suggested that there are five frequently occurring phenomena of inner experience: inner speaking, inner seeing, unsymbolized thinking, feelings, and sensory awareness. Descriptive experience sampling is a labor- and skill-intensive procedure, so it would be desirable to estimate the frequency of these phenomena by questionnaire. However, appropriate questionnaires either do not exist or have substantial limitations. We therefore created the Nevada Inner Experience Questionnaire (NIEQ), with five subscales estimating the frequency of each of the frequent phenomena, and examine here its psychometric adequacy. Exploratory factor analysis produced four of the expected factors (inner speaking, inner seeing, unsymbolized thinking, feelings) but did not produce a sensory awareness factor. Confirmatory factor analysis validated the five-factor model. The correlation between an existing self-talk questionnaire (Brinthaupt’s Self-Talk Scale) and the NIEQ inner speaking subscale provides one piece of concurrent validation