Course-based Science Research Promotes Learning in Diverse Students at Diverse Institutions

Course-based research experiences (CREs) are powerful strategies for spreading learning and improving persistence for all students, both science majors and nonscience majors. Here we address the crucial components of CREs (context, discovery, ownership, iteration, communication, presentation) found across a broad range of such courses at a variety of academic institutions. We also address how the design of a CRE should vary according to the background of student participants; no single CRE format is perfect. We provide a framework for implementing CREs across multiple institutional types and several disciplines throughout the typical four years of undergraduate work, designed to a variety of student backgrounds. Our experiences implementing CREs also provide guidance on overcoming barriers to their implementation

Adverse Health Outcomes among U.S. Testicular Cancer Survivors after Cisplatin-Based Chemotherapy vs. Surgical Management

We evaluated for the first time adverse health outcomes (AHOs) among U.S. testicular cancer survivors (TCS) given chemotherapy (n = 381) vs. surgery-only patients (n = 98) managed at a single institution, accounting for non-treatment-related risk factors to delineate chemotherapy’s impact. Chemotherapy consisted largely of bleomycin-etoposide-cisplatin (BEP) administered in 3 or 4 cycles (BEPX3, n = 235; BEPX4, n = 82). Incidence of ≥ 3 AHOs was lowest in surgery-only TCS and increased with BEPX3, BEPX4 and other cisplatin-based regimens (12.2%, 40.8%, 52.5%, 54.8%; P<0.0001). Multivariate modeling assessed associations of risk factors and treatment with hearing impairment, tinnitus, peripheral neuropathy, and Raynaud phenomenon. Risk for each AHO significantly increased with both increasing chemotherapy burden (P < 0.0001) and selected modifiable risk factors (P < 0.05): hypertension (OR = 2.40) and noise exposure (OR ≥ 2.3) for hearing impairment; noise exposure for tinnitus (OR ≥ 1.69); peripheral vascular disease for neuropathy (OR = 8.72), and current smoking for Raynaud phenomenon (OR = 2.41). Clinicians should manage modifiable risk factors for AHOs among TCS

A Sedimentological Record of Early Miocene Ice Advance and Retreat, AND-2A drill hole, McMurdo Sound, Antarctica

The lowest 501 m (∼1139–638 m) of the AND-2A core from southern McMurdo Sound is the most detailed and complete record of early Miocene sediments in Antarctica and indicates substantial variability in Antarctic ice sheet activity during early Miocene time. There are two main pulses of diamictite accumulation recorded in the core, and three significant intervals with almost no coarse clasts. Each diamictite package comprises several sequences consistent with ice advance-retreat episodes. The oldest phase of diamictite deposition, Composite Sequence 1 (CS1), has evidence for grounded ice at the drill site and has been dated around 20.2–20.1 Ma. It likely coincides with cooling associated with isotope event Mi1aa. This is overlain by a diamictite-free, sandstone-dominated interval, CS2 that includes three coarsening-upward deltaic cycles, is inferred to mark substantial warming, and has an inferred age range between 20.1 and 20.05 Ma. Above this is an interval with variable amounts of diamictite (CS3), with indicators of ice grounding, that is inferred to record ice advance relative to CS2, and is overlain by an ∼100-m-thick mud-rich interval (CS4) with no sedimentological evidence for direct glacial influence at the drill site (ca. 19.4–18.7 Ma). A third overlying diamictite-rich interval (CS5) overlies an unconformity spanning 18.7–17.8 Ma (coinciding with isotope event Mi1b), and records a return to more ice-influenced conditions at the drill site in late early Miocene time. The overall picture for the early Miocene (spanning the period 20.2–17.35 Ma) is one of ice advance alternating with periods of ice retreat and hence significant global climate fluctuations after the permanent establishment of the Antarctic ice sheet at the Eocene/Oligocene boundary, and preceding the relative warmth of the middle Miocene climatic optimum (ca. 17.5–14.5 Ma). Sedimentary cyclicity in CS1 and CS2 is consistent with ∼21 k.y. precession but in CS3 the frequency is closer to 100 k.y. (consistent with eccentricity), with a possible change to 20 k.y. precession in CS4. CS5 cyclicity is consistent with obliquity forcing. Provenance data are consistent with local Transantarctic Mountains glacial activity under precessional control in CS1 and more southerly ice-cap build up under 100 k.y. eccentricity and obliquity control during CS3 and CS5, respectively

Test of an interprofessional collaborative practice model to improve obesity-related health outcomes in Michigan

The purpose of the study was to test the effectiveness of an interprofessional collaborative practice (IPCP) education program on clinicians\u27 and students\u27 knowledge and attitudes toward IPCP and to determine the effectiveness of an IPCP weight loss program in two nurse-managed centers. The study team used the Midwest Interprofessional Practice, Education, and Research Center (MIPERC) collaborative practice education program that consists of online learning modules followed by daily huddles and collaborative care planning. The obesity intervention program was implemented by faculty and staff practitioners and students in two clinics with very different patient populations (community residents and college students). Staff/faculty practitioners and students demonstrated statistically significant knowledge gains as a result of online learning modules (Introduction to IPE p \u3c .05; Motivational Interviewing p \u3c .001; Safety Behaviors p \u3c .001; Team Dynamics p \u3c .001). Small, but not statistically significant changes in attitudes toward IPCP were seen with both groups. At program completion, enrolled patients showed statistical significant (p \u3c .001) weight losses and decreases in body mass indices. Other health outcomes showed no significant changes (blood pressure, prevalence of smoking, exercise frequency or duration p \u3e .05). The study demonstrated the potential of an IPCP program to affect weight loss in two populations

An Active Learning Approach for Rapid Characterization of Endothelial Cells in Human Tumors

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers

Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy

Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs > 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. Results Median age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P > .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P < .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P < .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P < .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking (P < .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased (P < .001). Conclusion Numbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs

Clinical and Genetic Risk Factors for Adverse Metabolic Outcomes in North American Testicular Cancer Survivors

Background: Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. Patients and Methods: TCS were aged <55 years at diagnosis and received first-line chemotherapy. Patients underwent physical examination, and had lipid panels, testosterone, and soluble cell adhesion molecule-1 (sICAM-1) evaluated. A single nucleotide polymorphism in rs523349 (5-α-reductase gene, SRD5A2), recently implicated in MetS risk, was genotyped. Using standard criteria, MetS was defined as ≥3 of the following: hypertension, abdominal obesity, hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol level, and diabetes. Matched controls were derived from the National Health and Nutrition Examination Survey. Results: We evaluated 486 TCS (median age, 38.1 years). TCS had a higher prevalence of hypertension versus controls (43.2% vs 30.7%; P<.001) but were less likely to have decreased HDL levels (23.7% vs 34.8%; P<.001) or abdominal obesity (28.2% vs 40.1%; P<.001). Overall MetS frequency was similar in TCS and controls (21.0% vs 22.4%; P=.59), did not differ by treatment (P=.20), and was not related to rs523349 (P=.61). For other CVD risk factors, TCS were significantly more likely to have elevated low-density lipoprotein (LDL) cholesterol levels (17.7% vs 9.3%; P<.001), total cholesterol levels (26.3% vs 11.1%; P<.001), and body mass index ≥25 kg/m2 (75.1% vs 69.1%; P=.04). On multivariate analysis, age at evaluation (P<.001), testosterone level ≤3.0 ng/mL (odds ratio [OR], 2.06; P=.005), and elevated sICAM-1 level (ORhighest vs lowest quartile, 3.58; P=.001) were significantly associated with MetS. Conclusions and Recommendations: Metabolic abnormalities in TCS are characterized by hypertension and increased LDL and total cholesterol levels but lower rates of decreased HDL levels and abdominal obesity, signifying possible shifts in fat distribution and fat metabolism. These changes are accompanied by hypogonadism and inflammation. TCS have a high prevalence of CVD risk factors that may not be entirely captured by standard MetS criteria. Cancer treatment–associated MetS requires further characterization

Computed Tomography With Intravenous Contrast Alone: The Role of Intra‐abdominal Fat on the Ability to Visualize the Normal Appendix in Children

Background Computed tomography ( CT ) with enteric contrast is frequently used to evaluate children with suspected appendicitis. The use of CT with intravenous ( IV ) contrast alone ( CT IV ) may be sufficient, however, particularly in patients with adequate intra‐abdominal fat ( IAF ). Objectives The authors aimed 1) to determine the ability of radiologists to visualize the normal (nondiseased) appendix with CT IV in children and to assess whether IAF adequacy affects this ability and 2) to assess the association between IAF adequacy and patient characteristics. Methods This was a retrospective 16‐center study using a preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV scan and measured weights and for whom appendectomy history was known from medical record review were included. The sample was chosen based on age to yield a sample with and without adequate IAF . Radiologists at each center reread their site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was categorized as “adequate” if there was any amount of fat completely surrounding the cecum and “inadequate” if otherwise. Results A total of 280 patients were included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no history of prior appendectomy; therefore, each patient had a presumed normal appendix. A total of 102 patients (36.4%) had adequate IAF . The proportion of normal appendices visualized with CT IV was 72.9% (95% confidence interval [ CI ] = 67.2% to 78.0%); the proportions were 89% (95% CI  = 81.5% to 94.5%) and 63% (95% CI  = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for difference of proportions = 16% to 36%). Greater weight and older age were strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a stronger predictor, particularly in females. Although statistically associated, there was noted overlap in the weights and ages of those with and without adequate IAF . Conclusions Protocols using CT with IV contrast alone to visualize the appendix can reasonably include weight, age, or both as considerations for determining when this approach is appropriate. However, although IAF will more frequently be adequate in older, heavier patients, highly accurate prediction of IAF adequacy appears challenging solely based on age and weight. Resumen Tomografía Computarizada Únicamente con Contraste Intravenoso: El Papel de la Grasa Intrabadominal en la Capacidad para Visualizar el Apéndice Normal en los Niños Introduction La tomografía computarizada ( TC ) con contraste entérico es usada frecuentemente para evaluar a los niños con sospecha de apendicitis. El uso de la TC únicamente con contraste intravenoso ( TC IV ) puede ser suficiente, especialmente en pacientes con adecuada grasa intrabdominal ( GIA ). Objetivos 1) Determinar la capacidad de los radiólogos para visualizar el apéndice normal (sin enfermedad) con TC IV en niños, y valorar si la cantidad de GIA afecta a esta capacidad; y 2) valorar la asociación entre la idoneidad de la GIA y las características del paciente. Metodología Estudio retrospectivo de 16 hospitales que utilizó una base de datos prexistente de TC abdominales. Se incluyó a los niños entre 3 y 18 años que tenían una TC IV , una medida del peso e historia de apendectomía conocida por la revisión de la historia clínica. La muestra se eligió en base a la edad con el fin de conseguir una muestra con y sin GIA adecuada. Los radiólogos de cada centro releyeron las TC IV de sus centros para valorar la visualización del apéndice y la adecuación de la GIA . La GIA se clasificó como “adecuada” si había cualquier cantidad de grasa completamente alrededor del ciego e “inadecuada” si era de otra manera. Resultados Se incluyeron 280 pacientes, con una media de edad de 10,6 años (rango 3,1 a 17,9 años). Ninguno tenía historia previa de apendectomía; por lo tanto todos los pacientes tuvieron un apéndice presumiblemente normal. Ciento dos pacientes (36,4%) tuvieron GIA adecuada. El porcentaje de apéndices normales visualizados con TC IV fue de 72,9% ( IC 95% = 67,2% a 78,0%); la proporción fue 89% ( IC 95% = 81,5% a 94,5%), y 63% ( IC 95% = 56,0% a 70,6%) en aquéllos con y sin GIA adecuada ( IC 95% para la diferencia de proporciones = 16% a 36%). El mayor peso y la mayor edad se asociaron fuertemente con la adecuación de la GIA (p < 0,001), y el peso resultó ser el mayor factor predictivo, especialmente en mujeres. Aunque se asoció estadísticamente, se vio un solapamiento en los pesos y edades de aquéllos con y sin GIA adecuada. Conclusiones Los protocolos que usan la TC IV para visualizar el apéndice pueden razonablemente incluir el peso, la edad, o ambas como consideraciones para determinar cuándo esta aproximación es apropiada. Sin embargo, aunque la cantidad de GIA será frecuentemente más apropiada en los pacientes más mayores y de mayor peso, la predicción certera de adecuación de GIA es altamente desafiante si se basa sólo en la edad y el peso.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99695/1/acem12185.pd

Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors

Background: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. Patients and Methods: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone-binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. Results: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7–68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P=.006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P=.011) or ≥30 kg/m2 (OR, 2.36; P=.005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P=.09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P=.07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P=.003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P=.013), and to report erectile dysfunction (19.6% vs 11.9%; P=.018) or peripheral neuropathy (30.7% vs 22.5%; P=.041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P=.07) or anxiety/depression (14.8% vs 9.3%; P=.06) was observed. Conclusions: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients

nnResting state fMRI scanner instabilities revealed by longitud inal phantom scans in a multi-center study

Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to four years at 13 sites across Canada with 3T research MRI scanners. QA parameters were calculated for each scan using the functional Biomarker Imaging Research Network\u27s (fBIRN) QA phantom and pipeline to capture between- and within-scanner variability. We also describe a QA protocol to measure the full-width-at-half-maximum (FWHM) of slice-wise point spread functions (PSF), used in conjunction with the fBIRN QA parameters. Variations in image resolution measured by the FWHM are a primary source of variance over time for many sites, as well as between sites and between manufacturers. We also identify an unexpected range of instabilities affecting individual slices in a number of scanners, which may amount to a substantial contribution of unexplained signal variance to their data. Finally, we identify a preliminary preprocessing approach to reduce this variance and/or alleviate the slice anomalies, and in a small human data set show that this change in preprocessing can have a significant impact on seed-based connectivity measurements for some individual subjects. We expect that other fMRI centres will find this approach to identifying and controlling scanner instabilities useful in similar studies