Clinical Translational Research Center

Philadelphia, United States

Clinical Translational Research Center

Philadelphia, United States
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Lovera J.,Louisiana State University Health Sciences Center | Ramos A.,Louisiana State University Health Sciences Center | Devier D.,Louisiana State University Health Sciences Center | Garrison V.,Clinical Translational Research Center | And 6 more authors.
Journal of the neurological sciences | Year: 2015

OBJECTIVES: Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E.DESIGN: PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study.PARTICIPANTS: Recruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study. Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems.INTERVENTIONS: PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants.OUTCOME MEASURES: PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm×10cm×1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 16×16 resulting in 1cm(3) voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing.RESULTS: PhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint. PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (G I, and 1G III). Median time to onset of abnormal LFTs was 20 weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels. PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had similar levels of EGCG but differed in the levels of minor catechins. There were no significant differences between the lots on participants' median free EGCG plasma levels at either 3h or 8h as well as conjugated EGCG levels at 3h (all p>0.4, Wilcoxon exact test). Free EGCG levels at 8h correlated with changes in NAA adjusted by water content. A 1ng/ml higher EGCG plasma concentration correlated with a 0.9% increase in NAA[95% CI(0.5%,1.4%), visit*level interaction F=14.4, p<0.001]. However, EGCG plasma concentrations did not correlate with NAA adjusted by creatine (1ng/ml higher EGCG was associated with 0.02%,[95% CI(-0.27%,0.3%) change in NAA, p>0.5]). There was a trend towards an increase in creatine levels (referenced to water content) from baseline to exit (1 5% increase, [95% CI(-6%,17%), p=0.4]). The free EGCG levels at 8hours correlated significantly with change in creatine levels (1ng/ml higher EGCG level at 8h was associated with a 1.1% increase in creatine [95% CI(0.6%,1.6%)]). Thus it is possible that the discrepancy between the correlation of the EGCG 8h levels with NAA changes referenced to water and the 8h EGCG levels with NAA changes referenced to creatine was due to a change in creatine among the subjects with higher EGCG levels. Conjugated 3h and 8h levels and free 3h levels did not correlate with NAA changes (all p >0.5).CONCLUSIONS/CLASSIFICATION OF EVIDENCE: Class III evidence: Polyphenon E at a dose of 400mg of EGCG twice a day is not futile at increasing brain NAA levels. Class I evidence: some lots of Polyphenon E have a high risk of hepatotoxicity.FUNDING: National Center for Complementary and Alternative Medicine K23AT004433, National Multiple Sclerosis Society RG4816-A-1 and National Institute of General Medical Sciences 1 U54 GM104940. Mitsui Norin provided Polyphenon E and placebo and their representative reviewed the manuscript prior to publication. Mitsui Norin was not involved in other aspects of the study. The decision to submit the manuscript remained with the investigators.REGISTRATION: NCT00836719 and NCT01451723 Copyright © 2015. Published by Elsevier B.V.


PubMed | Clinical Translational Research Center, National Jewish Health, University of Colorado at Denver, Denver Health Medical Center and 4 more.
Type: Journal Article | Journal: Journal of clinical microbiology | Year: 2016

Blood transcriptional signatures are promising for tuberculosis (TB) diagnosis but have not been evaluated among U.S.To be used clinically, transcriptional classifiers need reproducible accuracy in diverse populations that vary in genetic composition, disease spectrum and severity, and comorbidities. In a prospective case-control study, we identified novel transcriptional classifiers for active TB among U.S. patients and systematically compared their accuracy to classifiers from published studies. Blood samples from HIV-uninfected U.S. adults with active TB, pneumonia, or latent TB infection underwent whole-transcriptome microarray. We used support vector machines to classify disease state based on transcriptional patterns. We externally validated our classifiers using data from sub-Saharan African cohorts and evaluated previously published transcriptional classifiers in our population. Our classifier distinguishing active TB from pneumonia had an area under the concentration-time curve (AUC) of 96.5% (95.4% to 97.6%) among U.S. patients, but the AUC was lower (90.6% [89.6% to 91.7%]) in HIV-uninfected Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 90.0% (87.7% to 92.3%) and 82.9% (80.8% to 85.1%) when tested in U.S.Our classifier distinguishing active TB from latent TB had AUC values of 95.9% (95.2% to 96.6%) among U.S. patients and 95.3% (94.7% to 96.0%) among Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 98.0% (97.4% to 98.7%) and 94.8% (92.9% to 96.8%) when tested in U.S.Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable across populations and can be explored as screening assays.


PubMed | Clinical Translational Research Center, University of Missouri - Kansas City, Louisiana State University Health Sciences Center and University of Oregon
Type: Clinical Trial, Phase I | Journal: Journal of the neurological sciences | Year: 2015

Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E.PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study.Recruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon for the PhII study. Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems.PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon , blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants.PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm10cm1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 1616 resulting in 1cm(3) voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing.PhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint. PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (G I, and 1G III). Median time to onset of abnormal LFTs was 20 weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels. PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had similar levels of EGCG but differed in the levels of minor catechins. There were no significant differences between the lots on participants median free EGCG plasma levels at either 3h or 8h as well as conjugated EGCG levels at 3h (all p>0.4, Wilcoxon exact test). Free EGCG levels at 8h correlated with changes in NAA adjusted by water content. A 1ng/ml higher EGCG plasma concentration correlated with a 0.9% increase in NAA[95% CI(0.5%,1.4%), visit*level interaction F=14.4, p<0.001]. However, EGCG plasma concentrations did not correlate with NAA adjusted by creatine (1ng/ml higher EGCG was associated with 0.02%,[95% CI(-0.27%,0.3%) change in NAA, p>0.5]). There was a trend towards an increase in creatine levels (referenced to water content) from baseline to exit (1 5% increase, [95% CI(-6%,17%), p=0.4]). The free EGCG levels at 8hours correlated significantly with change in creatine levels (1ng/ml higher EGCG level at 8h was associated with a 1.1% increase in creatine [95% CI(0.6%,1.6%)]). Thus it is possible that the discrepancy between the correlation of the EGCG 8h levels with NAA changes referenced to water and the 8h EGCG levels with NAA changes referenced to creatine was due to a change in creatine among the subjects with higher EGCG levels. Conjugated 3h and 8h levels and free 3h levels did not correlate with NAA changes (all p >0.5).Class III evidence: Polyphenon E at a dose of 400mg of EGCG twice a day is not futile at increasing brain NAA levels. Class I evidence: some lots of Polyphenon E have a high risk of hepatotoxicity.National Center for Complementary and Alternative Medicine K23AT004433, National Multiple Sclerosis Society RG4816-A-1 and National Institute of General Medical Sciences 1 U54 GM104940. Mitsui Norin provided Polyphenon E and placebo and their representative reviewed the manuscript prior to publication. Mitsui Norin was not involved in other aspects of the study. The decision to submit the manuscript remained with the investigators.NCT00836719 and NCT01451723


PubMed | Cincinnati Childrens Hospital Medical Center and Clinical Translational Research Center
Type: Comparative Study | Journal: Respiratory care | Year: 2014

Sleeping metabolic rate (SMR) is used as a proxy for basal metabolic rate in infants, when measurement while awake is not practical. Measuring SMR via indirect calorimetry (IC) can be useful for assessing feeding adequacy especially in compromised neonates. Standard IC equipment, including a hood placed over the head, is not designed for the smallest of patients. Our aim was to determine whether a nonstandard smaller hood measures SMR in neonates similarly compared with a standard large hood.SMR was measured in healthy neonates (controls) and those born with single-ventricle congenital heart disease (cases). Two measurements were performed: SMR using a standard large hood and SMR using a smaller hood. Time-to-steady state, minute ventilation (VE), and fraction of exhaled carbon dioxide (FCO2 ; an indicator of data quality) were also measured. Primary outcome was SMR using both hoods. Results are stated as median (interquartile range). Spearmans correlations measured association between the small and large hoods.We studied 9 controls and 7 cases. SMR in controls was not different between the small and large hoods (35.7 [15.14] vs 37.8 [7.41] kcal/kg/d, respectively). In cases, SMR with the small hood was significantly greater than that with the large hood (45.5 [4.63] vs 34.2 [8] kcal/kg/d, P < .02). FCO2 was significantly higher with the small hood versus the large hood in both groups, and VE was significantly lower with the small hood versus the large hood in controls only. The SMRs with the small and large hoods were significantly correlated in the control group (r = 0.80, P < .01). Time-to-steady state was similar in both groups regardless of hood size.SMR measured with a small hood yields results similar to those measured with a large hood in healthy neonates without affecting testing time or other aspects of the IC procedure. Furthermore, results in compromised infants suggest that a smaller hood may facilitate SMR testing in this population.


Lovera J.,Louisiana State University Health Sciences Center | Ramos A.,Louisiana State University Health Sciences Center | Devier D.,Louisiana State University Health Sciences Center | Garrison V.,Clinical Translational Research Center | And 6 more authors.
Journal of the Neurological Sciences | Year: 2015

Objectives: Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects.Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. Design: PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. Participants: Recruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study. Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. Interventions: PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200. mg of EGCG per capsule; total daily dose 800. mg) for six months.PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. Outcome measures: PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA.PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm×10cm×1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 16×16 resulting in 1cm3 voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing. Results: PhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p. <. 0.01] rejecting the futility endpoint.PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (G I, and 1. G III). Median time to onset of abnormal LFTs was 20. weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels.PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had similar levels of EGCG but differed in the levels of minor catechins. There were no significant differences between the lots on participants' median free EGCG plasma levels at either 3. h or 8. h as well as conjugated EGCG levels at 3. h (all p. >. 0.4, Wilcoxon exact test).Free EGCG levels at 8. h correlated with changes in NAA adjusted by water content. A 1. ng/ml higher EGCG plasma concentration correlated with a 0.9% increase in NAA[95% CI(0.5%,1.4%), visit*level interaction F = 14.4, p. <. 0.001]. However, EGCG plasma concentrations did not correlate with NAA adjusted by creatine (1. ng/ml higher EGCG was associated with 0.02%,[95% CI(-. 0.27%,0.3%) change in NAA, p. >. 0.5]). There was a trend towards an increase in creatine levels (referenced to water content) from baseline to exit (1 5% increase, [95% CI(-. 6%,17%), p = 0.4]). The free EGCG levels at 8. hours correlated significantly with change in creatine levels (1. ng/ml higher EGCG level at 8. h was associated with a 1.1% increase in creatine [95% CI(0.6%,1.6%)]). Thus it is possible that the discrepancy between the correlation of the EGCG 8. h levels with NAA changes referenced to water and the 8. h EGCG levels with NAA changes referenced to creatine was due to a change in creatine among the subjects with higher EGCG levels.Conjugated 3. h and 8. h levels and free 3. h levels did not correlate with NAA changes (all p >. 0.5). Conclusions/classification of evidence: Class III evidence: Polyphenon E at a dose of 400. mg of EGCG twice a day is not futile at increasing brain NAA levels. Class I evidence: some lots of Polyphenon E have a high risk of hepatotoxicity. Funding: National Center for Complementary and Alternative Medicine K23AT004433, National Multiple Sclerosis Society RG4816-A-1 and National Institute of General Medical Sciences 1 U54 GM104940. Mitsui Norin provided Polyphenon E and placebo and their representative reviewed the manuscript prior to publication. Mitsui Norin was not involved in other aspects of the study. The decision to submit the manuscript remained with the investigators. Registration: NCT00836719 and NCT01451723NCT00836719NCT01451723. © 2015.


PubMed | Clinical Translational Research Center, University of Pennsylvania and Children's Hospital of Philadelphia
Type: Journal Article | Journal: Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus | Year: 2015

This study assessed validity, reliability, and feasibility of a filter paper blood spot insulin-like growth factor 1 (IGF-1) assay for retinopathy of prematurity (ROP) research. Blood samples were collected from 45 healthy children. Half of each sample was spun to obtain serum; half was applied to filter cards and stored for varying times and at different temperatures. IGF-1 assays were performed using a commercially available kit. Intraclass correlation between blood spot and serum IGF-1 values was high (0.97) for validity, and the mean differences were low for test-retest reliability. Time (up to 25 days) and temperature (4 C to 37 C) had no significant effect on sample stability. Feasibility was further assessed in a second cohort study of 74 premature infants being screened for ROP. A total of 817 filter card samples were successfully collected and transported to a central lab, where IGF-1 assays were successfully performed.


Roelfsema F.,Leiden University | Pijl H.,Leiden University | Keenan D.M.,University of Virginia | Veldhuis J.D.,Clinical Translational Research Center
European Journal of Endocrinology | Year: 2012

Background: The ACTH-cortisol axis in women is activated and associated with decreased ACTH potency, estimated by relating ACTH and cortisol pulse masses. Recently, a new accurate method for constructing the endogenous dose-response relationship was introduced, which is based on the relation between ACTH concentrations and associated cortisol secretion rates within cortisol bursts. Hypothesis: The endogenous dose-response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness. Subjects: Twenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h. Outcomes: ACTH and cortisol secretion rates, analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were quantified. Results: The initial potency (negative logarithm) was -7.83±0.75 (mean±S.E.M.) in obese women and -10.14±1.08 in lean women (P=0.10), and the corresponding values for the recovery phase were -26.62±2.21 and -36.67±1.66 (P=0.004). The sensitivity (curve slope) amounted to 0.468±0.05 in obese women and 0.784±0.09 in normal weight women (P=0.004). The efficacy (maximal value) was 17.6±4.9 nmol/l per min in obese women and 26.3±3.8 nmol/l per min in normal weight women (P=0.009). Basal secretion rate, inflection point, and EC 50 values were not different. Bromocriptine or acipimox did not change the dose-response curve. Conclusion: The ACTH-cortisol relation in obesity in women is characterized by decreased sensitivity and efficacy, thus explaining non-elevated serum cortisol concentrations despite increased plasma ACTH levels. © 2012 European Society of Endocrinology.


PubMed | Clinical Translational Research Center, Cornell University, Mead Johnson Nutrition Company, University of Cincinnati and 4 more.
Type: Journal Article | Journal: The American journal of clinical nutrition | Year: 2016

An understudied component of the diet, branched-chain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs.We tested the hypotheses that concentrations of BCFAs in human milk differ between populations and are associated with maternal diet.We surveyed the BCFA composition of samples collected as part of a standardized, prospective study of human-milk composition. Mothers were enrolled from 3 urban populations with differing diets: Cincinnati, Ohio; Shanghai, China; and Mexico City, Mexico. Enrollment was limited to healthy mothers of term singleton infants. We undertook a cross-sectional analysis of milk from all women with samples at postpartum week 4 (n = 359; 120 women/site). Fatty acids were extracted from milk by using a modified Bligh-Dyer technique and analyzed by gas chromatography. Statistical analysis was performed by ANOVA and Tobit regression. For Cincinnati mothers, 24-h diet recalls were analyzed in relation to the individual BCFA concentrations measured in milk samples.Total BCFAs in milk differed by site, with the highest concentration in Cincinnati followed by Mexico City and Shanghai (mean SE: 7.90 0.41, 6.10 0.36, and 4.27 0.25 mg/100 mL, respectively; P < 0.001). Site differences persisted after delivery mode, maternal age, and body mass index were controlled for. The individual concentrations of iso-14:0, iso-16:0, iso-18:0, anteiso-15:0, and anteiso-17:0 also differed between sites. Milk concentrations of iso-14:0 and anteiso-15:0 were associated with maternal intake of dairy; iso-16:0 was associated with maternal intakes of dairy and beef.BCFA concentrations in milk at 4 wk postpartum differed between mothers from Cincinnati, Shanghai, and Mexico City. Variations in human-milk BCFAs are influenced by diet. The impact of BCFAs on infant health warrants investigation.


News Article | January 21, 2016
Site: www.labdesignnews.com

Projections released by the U.S. Department of Education paint a bright future for jobs in the science, technology, engineering and mathematics (STEM) fields. As populations grow, natural resources diminish, disease prevention and treatment become more complex and evolutionary and universal mysteries continue to be explored, science and technology will remain critical to expanding human knowledge and solving challenges of today and for the future. Opportunities abound for STEM graduates today, but preparing enough STEM graduates to drive the scientific breakthroughs and technological innovations of tomorrow will be a daunting task for colleges and universities across the country. The U.S. President’s Council of Advisors on Science and Technology predicts that in the next decade, we will need approximately 1 million more STEM professionals than we will produce at our current rate. Currently, about 300,000 graduates obtain Bachelor and Associate degrees in STEM fields every year. In order to create this new workforce of 1 million additional STEM experts, that number needs to increase by 100,000 annually. The challenge is clear: Universities must attract more students to STEM programs. However, once these students have enrolled, another challenge begins to unfold: Only about 40 percent of students who enroll in STEM programs graduate with STEM degrees. The remaining 60 percent switch to non-STEM fields or drop out of college entirely. To address the challenges of attraction and retention, educational institutions throughout the country are trading in traditional teaching methods for new pedagogical techniques. These new methods move beyond a model where students passively listen to lectures and cram for tests, to methods that engage students in activities, enable collaboration across STEM disciplines and encourage students to use their hands just as much as their heads. With these new approaches to learning and teaching come new approaches to designing learning environments. These new spaces are eliminating the stereotypes associated with traditional STEM classrooms and fostering the type of creative brilliance that can help us educate and prepare one million new STEM graduates. Here are three ideas every university should consider when rethinking their STEM learning spaces to better recruit and retain students for the future. Get out of the basement Traditionally, STEM teaching labs and research spaces were located in building cores or basements. These underground “lairs” were uncomfortable and uninviting to students and faculty using these facilities. They featured little to no windows, no natural light and the overall environment felt more institutional than educational. For students that didn’t have a class assigned to these spaces, the labs were relatively unknown, and were considered untouchable and intimidating. Countless studies show the design of classroom environments influence students’ motivation and learning, and universities are seeing the value in encouraging the student body to observe the scientific process to raise curiosity and interest. From a design perspective, we use the term “putting science on display” pretty regularly. The general idea is to place science classrooms and labs in public, high-traffic areas. Instead of solid walls, expansive floor-to-ceiling windows celebrate the sciences and allow passersby the opportunity to observe research and watch it unfold. This helps make science an approachable, open process, and as an added benefit, it gives universities the chance to show off their cool research equipment. The University of Buffalo has embraced this idea with its Clinical Translational Research Center (CTRC). Embedded in the same building as Kaleida Health’s Gates Vascular Institute, the CTRC uses interior glass throughout the building to show science in an open, transparent process. Embrace startup culture A key component of successful STEM programs is experimentation. For example, if you look at the most successful technology startups over the last 10 years, very few started in a formal academic settings. More often than not, they started in garages or coffee shops—places with more sofas than fixed bench space. There’s a lot STEM learning environments can learn from these spaces, specifically in how they encourage free thinking and experimentation. Taking inspiration from startups, our team at CannonDesign is seeing an increase in makerspace, hackerspace and innovation hubs within STEM buildings. These spaces serve a pretty basic purpose: nurturing creativity, encouraging experimentation and stimulating intellectual inquiry in an informal setting. They don’t act exclusively as labs, garages or workshops, but they do include many of the tools found in these space (3-D printers, welding machines, computers, building materials). The Univ. of Utah sees the value in such spaces with their new Lassonde Studios Entrepreneurial building that features a 20,000-sf making/planning/hacking space to foster interdisciplinary and cross-disciplinary “mash-ups” extending beyond STEM disciplines and including others, such as business majors. Infuse appropriate technology into S&T academic environments Millennials and Generation Z grew up in a digital world and expect to take full advantage of technology in every aspect of life, especially college. However, technology hasn’t revolutionized education the way it has other industries. STEM learning environments can be leading examples for how using technology can enhance learning by making it more engaging and accessible. The flipped classroom is a good example of an effective use of technology for enhanced learning. The flipped classroom is a pedagogical model that has students watch video lectures and complete homework prior to class. Doing this creates richer face-to-face interactions when students are actually in class; instead of listening to a lecture, they spend their time asking questions, participating in hands-on activities and even getting involved in real university research efforts. On the most dramatic end of the spectrum, some universities are using virtual reality, simulation and gaming to inspire and educate future STEM innovators. These tools allow students to quite literally take part in technology. For example, CAVE environments, which are rooms wrapped in screens that project 3D virtual environments, allow students to immerse themselves in a setting and actually interact with what they’re seeing. From an infrastructure design standpoint, these technology-rich spaces require a building that provides enhanced server space, room for complex computing platforms, and the power and cooling sources to keep everything up and running. One interesting trend our team is also seeing related to technology is a decrease in dedicated computer labs. Prior to the days of constant connectivity, computer labs acted as the hub of higher education buildings. But today, 90 percent of students own a laptop, 86 percent of students own a smartphone and 47 percent of students own a tablet. The need to access university-owned equipment is dwindling, and the need to plug in personal devices and work anywhere is the new norm. There’s no denying universities need to prove themselves up to the challenge of attracting and retaining the much needed next generation of STEM professionals. How they choose to design their STEM learning environments can play a big role in helping them meet this challenge and exceed current projections. Stephen Blair leads CannonDesign’s global science and technology practice, focused on helping academic and corporate institutions design solutions that turn challenges into opportunities for success. www.cannondesign.com


Meier J.J.,Ruhr University Bochum | Pennartz C.,Ruhr University Bochum | Schenker N.,Ruhr University Bochum | Menge B.A.,Ruhr University Bochum | And 4 more authors.
Diabetes, Obesity and Metabolism | Year: 2013

Aim: Postprandial insulin pulsatility is impaired in patients with type 2 diabetes, but the effects of exogenous insulin therapy on pulsatile insulin secretion are not known. We addressed, whether pulsatile insulin secretion is related to glycaemic control, whether basal insulin supplementation increases postprandial insulin secretion, and if so, is this accomplished by a specific improvement in pulsatile insulin secretion? Methods: Fourteen patients with type 2 diabetes underwent a mixed meal test before and after an 8-week treatment period with insulin glargine. Glucose, insulin and C-peptide levels were measured, and insulin pulsatility was determined by deconvolution analysis. Results: Insulin treatment lowered fasting glycaemia from 179.6±7.5mg/dl to 117.6±6.5mg/dl (p<0.001). Postprandial insulin and C-peptide levels increased significantly after the treatment period (p<0.0001). The total calculated insulin secretion rate increased with insulin treatment (p=0.0039), with non-significant increases in both pulsatile and non-pulsatile insulin secretion. Insulin pulse frequency was unchanged by the intervention. There was an inverse relationship between fasting and postprandial glycaemia and insulin pulse mass (r2=0.51 and 0.56, respectively), whereas non-pulsatile insulin secretion was unrelated to either fasting or postprandial glucose concentrations (r2=0.0073 and 0.031). Conclusions: Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous β-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes. © 2012 Blackwell Publishing Ltd.

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