Disciplinary Learning From an Authentic Engineering Context

This small-scale design study describes disciplinary learning in mathematical modeling and science from an authentic engineeringthemed module. Current research in tissue engineering served as source material for the module, including science content for readings and a mathematical modeling activity in which students work in small teams to design a model in response to a problem from a client. The design of the module was guided by well-established principles of model-eliciting activities (a special class of problem-solving activities deeply studied in mathematics education) and recently published implementation design principles, which emphasize the portability of model-eliciting activities to many classroom settings. Two mathematical modeling research questions were addressed: 1. What mathematical approaches did student-teams take when they designed mathematical models to evaluate the quality of blood vessel networks? and 2. What attributes of mature mathematical models were captured in the mathematical models that the student-teams designed? One science content research question was addressed: 1. Before and after the module, what aspects of angiogenesis did students describe when they were asked what they knew about the process of blood vessel growth from existing vessels? Participants who field-tested the module included high school students in a summer enrichment program and early college students enrolled in four general-studies mathematics courses. Data collected from participants included mathematical models produced by small teams of students, as well as students’ individual responses before and after the module to a prompt asking them what they knew about the process of new blood vessel growth from existing vessels. The data were analyzed for mathematical model type and science content by adopting methods of grounded theory, in which researchers suspend expectations about what should be in the data and, instead, allow for the emergence of patterns and trends. The mathematical models were further analyzed for mathematical maturity using an a priori coding scheme of attributes of a mathematical model. Analyses showed that student-teams created mathematical models of varying maturity using four different mathematical approaches, and comparisons of students’ responses to the science prompt showed students knew essentially nothing about angiogenesis before the module but described important aspects of angiogenesis after the module. These findings were used to set up an agenda for future research about the design of the module and the relationship between disciplinary learning and authentic engineering problems

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Institutionalizing the founder\u27s charism: An inquiry into the exercise of leadership by principals of American Dominican schools

The purpose of this study was to identify and describe whether and how selected Dominican secondary school principals communicate the Dominican charism through their leadership vision and empower the faculty to integrate this charism into their professional activity. The study examined the leadership beliefs and behavior of five Dominican Sisters who serve as principals in secondary schools owned by their respective Dominican congregations and compared the leadership of these principals to discover similarities in the articulation of the charism. The examination of the Dominican charism was limited to three components: an orientation to study, a contemplative attitude and prayer, and collaboration based on mutual respect. Non-participant observation and semi-structured interviews were the methods used to assess the principals\u27 influence on the expression of these components in the beliefs and activities of selected faculty, the staff development program, the academic tone, the fine arts curriculum, the religious practices, and governance structures within the school. The study found that (a) there was some diversity among the principals in relationship to their understanding of the charism, (b) there were common elements and values, communicated by four of the five principals and empowered in four of the five faculties, which illustrated the presence of the three components of the charism within the life of the school, and (c) the basic difference within the leadership of the principals was in the degree of communication and empowerment across the five principals and faculties. It concluded that these commonalities and differences speak to the issue of future leadership of Dominican secondary schools. The study recommended that a task force of experienced Dominican principals develop a leadership renewal program which allows current principals to generate discussion on the charism with implications for educational leadership. It further recommended that models be developed which orient future principals to Dominican leadership from both a theoretical and practical perspective. This study is significant because it seeks to initiate a discussion on the complex issue of institutionalizing the charism within Dominican secondary schools and points out that the role of leadership is crucial to this institutionalization

An assessment of perceptions of urban parents and school personnel toward bilingual bicultural education

Purpose The purpose of this study was to assess the relationships between and among the perceptions of parents, teachers, principals, and bilingual administrators toward three aspects of bilingual education: language, culture, and instruction. Procedures A survey instrument consisting of forty-two items was administered to thirty-five parents, one hundred thirty-one teachers, thirty-seven principals, and twenty-three bilingual administrators in two urban settings to assess their perceptions toward linguistic, cultural, and instructional aspects of bilingual education. It was hypothesized, in null form, that persons involved in bilingual bicultural education programs would have perceptions which were congruent in relation to each of these aspects. Information was gathered and analyzed to determine the congruence or distance of incongruence of these perceptions by specific populations. Analysis of variance and discriminant function analysis were used to determine the presence of differences which were statistically significant at the . 05 level of confidence. Findings Statistically significant differences were found in the perceptions of parents and school personnel in regard to bilingual education. Relative to the three areas examined--language, culture, and instruction--statistically significant differences existed between the groups' perceptions toward instruction, but no statistically significant perceptual differences were indicated toward culture and language. Significant differences were also found when perceptions of culture and instruction were compared by ethnicity. When responses to selected pluralist and assimilationist items in the survey instrument were examined, the populations tended toward the pluralistic viewpoint. Recommendations The findings of this study suggest the following recommendations: 1. Communication channels should be established or redesigned in ways which insure greater understanding and congruence of perceptions regarding bilingual bicultural education. 2. Because parents showed the greatest distance of incongruence in regard to instruction, it is essential that they become a part of the total instructional process. 3. Teachers showed greater variation of perceptions than any other group in all three areas of bilingual bicultural education, and this finding indicates the need for a program which provides consistent philosophical and pedagogical approaches.Education, College o

DNA Sequence of the Gene Encoding the E_ɑ Ia Polypeptide of the BALB/c Mouse

A 3.4-kilobase DNA fragment containing the gene coding for the Eɑ chain of an Ia (I region-associated) antigen from the BALB/c mouse has been sequenced. It contains at least three exons, which correlate with the major structural domains of the Eɑ chain-the two external domains al and ɑ2, and the transmembrane-cytoplasmic domain. The coding sequence of the mouse Eɑ gene shows striking homology to its human counterpart at the DNA and protein levels. The translated ɑ2 exon demonstrates significant similarity to β_2-microglohulin, to immunoglobulin constant region domains, and to certain domains of transplantation antigens. These observations and those of others suggest that the Ia antigen, transplantation antigen, and immunoglohulin gene families share a common ancestor

SleepMinder : an innovative contact-free device for the estimation of the apnoea-hypopnoea index

We describe an innovative sensor technology (SleepMinder™) for contact-less and convenient measurement of sleep and breathing in the home. The system is based on a novel non-contact biomotion sensor and proprietary automated analysis software. The biomotion sensor uses an ultra low-power radio-frequency transceiver to sense the movement and respiration of a subject. Proprietary software performs a variety of signal analysis tasks including respiration analysis, sleep quality measurement and sleep apnea assessment. This paper measures the performance of SleepMinder as a device for the monitoring of sleep-disordered breathing (SDB) and the provision of an estimate of the apnoea-hypopnoea index (AHI). The SleepMinder was tested against expert manually scored PSG data of patients gathered in an accredited sleep laboratory. The comparison of SleepMinder to this gold standard was performed across overnight recordings of 129 subjects with suspected SDB. The dataset had a wide demographic profile with the age ranging between 20 and 81 years. Body weight included subjects with normal weight through to the very obese (Body Mass Index: 21-44 kg/m2). SDB severity ranged from subjects free of SDB to those with severe SDB (AHI: 0.8-96 events/hours). SleepMinder's AHI estimation has a correlation of 91% and can detect clinically significant SDB (AHI>15) with a sensitivity of 89% and a specificity of 92%