Shifts in learning assistants' self-determination due to COVID-19 disruptions in Calculus II course delivery.

BACKGROUND: The Learning Assistant (LA) model with its subsequent support and training has evidenced significant gains for undergraduate STEM learning and persistence, especially in high-stakes courses like Calculus. Yet, when a swift and unexpected transition occurs from face-to-face to online, remote learning of the LA environment, it is unknown how LAs are able to maintain their motivation (competence, autonomy, and relatedness), adapt to these new challenges, and sustain their student-centered efforts. This study used Self-Determination Theory (SDT) to model theoretical aspects of LAs' motivations (persistence and performance) both before and after changes were made in delivery of a Calculus II course at Texas Tech University due to COVID-19 interruptions. RESULTS: Analysis of weekly written reflections, a focus group session, and a post-course questionnaire of 13 Calculus II LAs throughout Spring semester of 2020 showed that LAs' reports of competence proportionally decreased when they transitioned online, which was followed by a moderate proportional increase in reports of autonomy (actions they took to adapt to distance instruction) and a dramatic proportional increase in reports of relatedness (to build structures for maintaining communication and building community with undergraduate students). CONCLUSIONS: Relatedness emerged as the most salient factor from SDT to maintain LA self-determination due to the COVID-19 facilitated interruption to course delivery in a high-stakes undergraduate STEM course. Given that online learning continues during the pandemic and is likely to continue after, this research provides an understanding to how LAs responded to this event and the mounting importance of relatedness when LAs are working with undergraduate STEM learners. Programmatic recommendations are given for enhancing LA preparation including selecting LAs for autonomy and relatedness factors (in addition to competence), modeling mentoring for remote learners, and coaching in best practices for online instruction.

IL-6 and Soluble Receptors in Overweight and Obese African American Women With and Without Breast Cancer.

Interleukin 6 (IL-6) and its receptors are expressed in approximately half of breast cancer (BC) tissues, and high serum IL-6 levels are associated with poor prognosis. African American (AA) patients with BC have higher serum IL-6 levels compared to Caucasians, suggesting additional risk of disease-related complications in AAs. The purpose of this study was to compare IL-6 complex biomarkers in AA women with and without a history of BC. We conducted a secondary analysis of phenotypic data from two studies of weight loss in AA women with and without a history of BC who had similar age and adiposity. Biomarkers analyzed included tumor necrosis factor alpha (TNF-α), IL-6, IL-6 soluble receptor (IL6sr), and soluble glycoprotein 130 (GP130); IL6sr and GP130 were newly analyzed for this study. TNF-α levels were 1.86 times higher in the BC group (N = 7) compared to those without BC (N = 10; p < 0.001) despite similar age, weight, and body mass index. GP130 levels tended to be higher in women with BC; IL-6 and Il-6 sr were not different between groups. There was a strong correlation between GP130 and TNF-α (r = .638; p = .006) in the group overall. High TNF-α levels in the BC group and a strong correlation between GP130 and TNF-α in the overall group suggest the presence of IL-6 complex initiated TNF-α production. Further study is needed to evaluate IL-6 reduction through a variety of approaches, including weight loss and anti-IL-6 therapies, which may ultimately implicate the reduction of IL-6 complex associated BC-specific recurrence and mortality.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

Progesterone signaling during pregnancy in the lab opossum, Monodelphis domestica.

To investigate subtle pregnancy-associated changes in the lab opossum, Monodelphis domestica, an induced ovulator, we compared pregnant with non-pregnant and pseudopregnant animals with regard to serum P4 levels and progesterone receptor (PR) expression. Using video-verified, time-mated lab opossums as sources of biological material, we compared ovaries, uteri and sera obtained on odd-numbered days of the 14.5-day pregnancy in this animal. Females that mated successfully but did not produce embryos were classified as pseudopregnant. P4 levels differed significantly between pregnant (N = 21) and either non-pregnant (N = 3) or pseudopregnant (N = 3) opossums, but not between the non-pregnant and pseudopregnant groups. A significant decline in serum P4 occurred between pregnancy days 3 and 5, coinciding with an elevated probability of pregnancy failure between days 5 and 9. PR was detected in the nuclei of uterine-gland epithelial cells on pregnancy days 5 and 7 as well as variably in the corpora lutea (CL) of animals on pregnancy days 3-11. PR expression in the CL suggests that P4 may be autostimulatory in lab opossums and that certain levels of this steroid are required during normal pregnancy. The significant day-3 drop in P4 may explain why pregnancy failure in this polyovular metatherian is likeliest to occur between days 5 and 9, an interval during which the extended period of blastocyst morphogenesis and expansion occurs. Taken together, these results suggest that P4 may have unrecognized signaling roles not only in pregnancy but perhaps embryonic development as well in the lab opossum.

Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

BACKGROUND: Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. METHODS: We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. RESULTS: Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. CONCLUSION: A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping.

Will Culling White-Tailed Deer Prevent Lyme Disease?

White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances.

Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model.

BACKGROUND: Insulin-like growth factor receptor (IGF-1R) has been studied as an oncologic target in soft tissue sarcoma (STS), but its role in sarcoma biology is unclear. Anti-IGF-1R antibody cixutumumab demonstrated acceptable toxicity but limited activity as a single agent in STS. We carried out a dose-escalation study of cixutumumab with doxorubicin to evaluate safety and dosing of the combination. PATIENTS AND METHODS: Eligible patients with advanced STS were treated with cixutumumab intravenously on days 1/8/15 at one of three dose levels (A: 1 mg/kg, B: 3 mg/kg, C: 6 mg/kg) with doxorubicin at 75 mg/m(2) as a 48 h infusion on day 1 of a 21 day cycle. After six cycles of the combination, patients could receive cixutumumab alone. The Time-to-Event Continual Reassessment Method was used to estimate the probability of dose-limiting toxicity (DLT) and to assign patients to the dose with an estimated probability of DLT≤20%. RESULTS: Between September 2008 and January 2012, 30 patients with advanced STS received a median of six cycles of therapy (range <1-22). Two DLTs were observed, grade 3 mucositis (dose level B) and grade 4 hyperglycemia (dose level C). Grade 2 and 3 reduced left ventricular ejection fraction was seen in three and two patients, respectively. Five partial responses were observed, and estimated progression-free survival was 5.3 months (95% confidence interval 3.0-6.3) in 26 response-assessable patients. Immunohistochemical staining of 11 available tumor samples for IGF-1R and phospho-IGF-1R was not significantly different among responders and non-responders, and serum analysis of select single-nucleotide polymorphisms did not predict for cardiotoxicity. CONCLUSION: The maximum tolerated dose was doxorubicin 75 mg/m(2) on day 1 and cixitumumab 6 mg/kg on days 1/8/15 of a 21 day cycle. Cardiac toxicity was observed and should be monitored in subsequent studies, which should be considered in STS only if a predictive biomarker of benefit to anti-IGF-1R therapy is identified. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00720174.

Assessing the influence of topography and canopy structure on Douglas fir throughfall with LiDAR and empirical data in the Santa Cruz mountains, USA.

Atmospheric inputs to forest ecosystems vary considerably over small spatial scales due to subtle changes in relief and vegetation structure. Relationships between throughfall fluxes (ions that pass through the canopy in water), topographic and canopy characteristics derived from sub-meter resolution light detection and ranging (LiDAR), and field measurements were compared to test the potential utility of LiDAR in empirical models of atmospheric deposition. From October 2012 to May 2013, we measured bulk (primarily wet) deposition and sulfate-S, chloride (Cl(-)), and nitrate-N fluxes beneath eight clusters of Douglas fir trees differing in size and canopy exposure in the Santa Cruz Mountains, California. For all trees sampled, LiDAR data were used to derive canopy surface height, tree height, slope, and canopy curvature, while tree height, diameter (DBH), and leaf area index were measured in the field. Wet season throughfall fluxes to Douglas fir clusters ranged from 1.4 to 3.8 kg S ha(-1), 17-54 kg Cl(-) ha(-1), and 0.2-4 kg N ha(-1). Throughfall S and Cl(-) fluxes were highest under clusters with large trees at topographically exposed sites; net fluxes were 2-18-fold greater underneath exposed/large clusters than all other clusters. LiDAR indices of canopy curvature and height were positively correlated with net sulfate-S fluxes, indicating that small-scale canopy surface features captured by LiDAR influence fog and dry deposition. Although tree diameter was more strongly correlated with net sulfate-S throughfall flux, our data suggest that LiDAR data can be related to empirical measurements of throughfall fluxes to generate robust high-resolution models of atmospheric deposition.

Perfusionist techniques of reducing acute kidney injury following cardiopulmonary bypass: an evidence-based review.

Cardiac surgery utilizing cardiopulmonary bypass has come a long way since its introduction nearly 60 years ago. In the early days, end-organ damage was linked to contact of the blood with the extracorporeal circuit. One potential cardiac surgery complication known to result in significant morbidity and mortality is acute kidney injury (AKI). Causes of AKI are multifaceted, but most of them are associated with techniques that perfusionists employ during extracorporeal circuit management. These can cause patients to either go on dialysis or renal replacement therapy. Patients with AKI have longer lengths of stay and consume significant resources beyond those with normal kidney function. Few current evidence-based markers determine if the kidneys are adequately protected during surgery. Most relevant literature does not address perfusion-specific techniques that reduce the incidence of AKI. This paper reviews the pathophysiology of the kidney and focuses on perfusion techniques that may reduce the incidence of AKI.

Transmission dynamics of primary pneumonic plague in the USA.

Plague is thought to have killed millions during three catastrophic pandemics. Primary pneumonic plague, the most severe form of the disease, is transmissible from person-to-person and has the potential for propagating epidemics. Efforts to quantify its transmission potential have relied on published data from large outbreaks, an approach that artificially inflates the basic reproductive number (R(0)) and skews the distribution of individual infectiousness. Using data for all primary pneumonic plague cases reported in the USA from 1900 to 2009, we determined that the majority of cases will fail to transmit, even in the absence of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained outbreaks still exists due to superspreading events. These findings challenge current concepts regarding primary pneumonic plague transmission.

Long-term use of the CentriMag® Ventricular Assist System as a right ventricular assist device: a case report.

Right ventricular failure (RVF) following implantation of a left ventricular assist system (LVAS) is associated with high morbidity and mortality.( 1-4 ) Numerous centers have reported short-term use of the CentriMag (®) Ventricular Assist System (CVAS) (Levitronix LLC, Waltham, MA) for treatment of cardiogenic shock, decompensated heart failure and right ventricular failure (RVF) following LVAS implantation.( 5-9 ) The present report reviews the clinical course of a patient requiring long-term right ventricular support utilizing the CVAS, following a HeartMate (®) II LVAS (Thoratec Corp. Pleasanton, CA) implantation. Elevated cytotoxic antibody levels complicated the patient's treatment plan by precluding orthotropic heart transplantation. The CVAS operated for 304 days without mechanical difficulty until replaced with the HeartWare (®) Ventricular Assist System (HeartWare Inc. Miramar, FL).

Anesthetic management for resection of cor triatriatum during the second trimester of pregnancy.

Hemodynamic changes during pregnancy can result in cardiovascular decompensation in women with pre-existing cardiac diseases. Despite optimized medical treatment, some patients with severe structural cardiac abnormalities may need surgical intervention during pregnancy. We describe a woman who presented at 20 weeks of gestation with acute heart failure due to cor triatriatum, a rare form of congenital heart disease. This condition is characterized by a perforated fibromuscular membrane dividing the left atrium into two chambers. The clinical presentation varies from asymptomatic to acute heart failure depending on the size of the fenestrations in the membrane and the presence of associated cardiac malformations. In our patient, two severely restrictive orifices in a membrane within the left atrium, moderate to severe pulmonary hypertension and good biventricular function were demonstrated by transthoracic echocardiography. Without surgical resection, the increased blood volume and cardiac output associated with pregnancy could have resulted in cardiovascular decompensation. She underwent urgent corrective open heart surgery with cardiopulmonary bypass. Perioperative anesthetic management included prevention of tachycardia, atrial dysrhythmias and pulmonary hypertension, close monitoring for and prompt treatment of maternal hypotension, maintaining euvolemia and good cardiac contractility and avoiding hemodilution and hypothermia. These approaches, together with minimizing bypass time, resulted in successful maternal and fetal outcome.

First American experience with the Terumo DuraHeart left ventricular assist system.

Since the first implantation of a left ventricular assist system (LVAS) 45 years ago, LVAS therapy has emerged as a viable option for the treatment of advanced heart failure. The current generation of LVASs in clinical evaluation has design features enabling longer and more reliable support durations. We describe the operating characteristics of the DuraHeart LVAS (Terumo Heart, Inc., Ann Arbor, MI). The DuraHeart LVAS is a magnetically-levitated centrifugal pump that began a FDA-approved clinical trial for evaluation of bridge to transplant indication in July of 2008. Magnetic levitation of the spinning-pump impeller is hypothesized to improve long-term mechanical reliability and biological compatibility of the pump. Other design features make the DuraHeart LVAS particularly suited for implantation without cardiopulmonary bypass (CPB). A description of the implant procedure for the first six American implants of the DuraHeart LVAS both on-CPB and off-CPB, including CPB techniques employed, are discussed. While it is still very early in the DuraHeart LVAS experience, the initial outcomes of the first six patient implants would suggest that the device is a safe and effective LVAS.