bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxic proliferation requires EGFR-mediated ERK activation in human pulmonary microvascular endothelial cells
Authors: White Hilary A. , Jin Yi , Chicoine Louis G. , Chen Bernadette , Liu Yusen , Nelin Leif D.
Published: February 2017

We have previously shown that hypoxic proliferation of human pulmonary microvascular endothelial cells (hPMVECs) depends on epidermal growth factor receptor (EGFR) activation. To determine downstream signaling leading to proliferation, we tested the hypothesis that hypoxia-induced proliferation in hPMVECs would require EGFR-mediated activation of extracellular signal-regulated kinase (ERK) leading to arginase II induction. To test this hypothesis, hPMVECs were incubated in either normoxia (21% O2, 5% CO2) or hypoxia (1% O2, 5% CO2) and Western blotting was performed for EGFR, arginase II, phosphorylated-ERK (pERK), and total ERK (ERK). Hypoxia led to greater EGFR, pERK, and arginase II protein levels than did normoxia in hPMVECs. To examine the role of EGFR in these hypoxia-induced changes, hPMVECs were transfected with siRNA against EGFR or a scrambled siRNA and placed in hypoxia. Inhibition of EGFR using siRNA attenuated hypoxia-induced pERK and arginase II expression as well as the hypoxia-induced increase in viable cell numbers. hPMVECs were then treated with vehicle, an EGFR inhibitor (AG1478), or an ERK pathway inhibitor (U0126) and placed in hypoxia. Pharmacologic inhibition of EGFR significantly attenuated the hypoxia-induced increase in pERK level. Both AG1478 and U0126 also significantly attenuated the hypoxia-induced increase in viable hPMVECs numbers. hPMVECs were transfected with an adenoviral vector containing arginase II (AdArg2) and overexpression of arginase II rescued the U0126-mediated decrease in viable cell numbers in hypoxic hPMVECs. Our findings suggest that hypoxic activation of EGFR results in phosphorylation of ERK, which is required for hypoxic induction of arginase II and cellular proliferation.
Lung pericyte-like cells are functional interstitial immune sentinel cells
Authors: Hung Chi F. , Mittelsteadt Kristen L. , Brauer Rena , McKinney Bonnie L. , Hallstrand Teal S. , Parks William C. , Chen Peter , Schnapp Lynn M. , Liles W. Conrad , Duffield Jeremy S. , Altemeier William A.
Published: February 2017

Pericytes are perivascular PDGF receptor-β+(PDGFRβ+) stromal cells required for vasculogenesis and maintenance of microvascular homeostasis in many organs. Because of their unique juxtaposition to microvascular endothelium, lung PDGFRβ+cells are well situated to detect proinflammatory molecules released following epithelial injury and promote acute inflammatory responses. Thus we hypothesized that these cells represent an unrecognized immune surveillance or injury-sentinel interstitial cell. To evaluate this hypothesis, we isolated PDGFRβ+cells from murine lung and demonstrated that they have characteristics consistent with a pericyte population (referred to as pericyte-like cells for simplicity hereafter). We showed that pericyte-like cells expressed functional Toll-like receptors and upregulated chemokine expression following exposure to bronchoalveolar lavage fluid (BALF) collected from mice with sterile lung injury. Interestingly, BALF from mice without lung injury also induced chemokine expression in pericyte-like cells, suggesting that pericyte-like cells are primed to sense epithelial injury (permeability changes). Following LPS-induced lung inflammation, increased numbers of pericyte-like cells expressed IL-6, chemokine (C-X-C motif) ligand-1, chemokine (C-C motif) ligand 2/ monocyte chemotactic protein-1, and ICAM-1 in vivo. Sterile lung injury in pericyte-ablated mice was associated with decreased inflammation compared with normal mice. In summary, we found that pericyte-like cells are immune responsive and express diverse chemokines in response to lung injury in vitro and in vivo. Furthermore, pericyte-like cell ablation attenuated inflammation in sterile lung injury, suggesting that these cells play an important functional role in mediating lung inflammatory responses. We propose a model in which pericyte-like cells function as interstitial immune sentinels, detecting proinflammatory molecules released following epithelial barrier damage and participating in recruitment of circulating leukocytes.
Inflammation-induced caveolin-1 and BMPRII depletion promotes endothelial dysfunction and TGF-β-driven pulmonary vascular remodeling
Authors: Oliveira Suellen D. S. , Castellon Maricela , Chen Jiwang , Bonini Marcelo G. , Gu Xiaowu , Elliott Michael H. , Machado Roberto F. , Minshall Richard D.
Published: February 2017

Endothelial cell (EC) activation and vascular injury are hallmark features of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Caveolin-1 (Cav-1) is highly expressed in pulmonary microvascular ECs and plays a key role in maintaining vascular homeostasis. The aim of this study was to determine if the lung inflammatory response to Escherichia coli lipopolysaccharide (LPS) promotes priming of ECs via Cav-1 depletion and if this contributes to the onset of pulmonary vascular remodeling. To test the hypothesis that depletion of Cav-1 primes ECs to respond to profibrotic signals, C57BL6 wild-type (WT) mice ( Tie2.Cre−;Cav1fl/fl) were exposed to nebulized LPS (10 mg; 1 h daily for 4 days) and compared with EC-specific Cav1−/−( Tie2.Cre+;Cav1fl/fl). After 96 h of LPS exposure, total lung Cav-1 and bone morphogenetic protein receptor type II (BMPRII) expression were reduced in WT mice. Moreover, plasma albumin leakage, infiltration of immune cells, and levels of IL-6/IL-6R and transforming growth factor-β (TGF-β) were elevated in both LPS-treated WT and EC-Cav1−/−mice. Finally, EC-Cav1−/−mice exhibited a modest increase in microvascular thickness basally and even more so on exposure to LPS (96 h). EC-Cav1−/−mice and LPS-treated WT mice exhibited reduced BMPRII expression and endothelial nitric oxide synthase uncoupling, which along with increased TGF-β promoted TGFβRI-dependent SMAD-2/3 phosphorylation. Finally, human lung sections from patients with ARDS displayed reduced EC Cav-1 expression, elevated TGF-β levels, and severe pulmonary vascular remodeling. Thus EC Cav-1 depletion, oxidative stress-mediated reduction in BMPRII expression, and enhanced TGF-β-driven SMAD-2/3 signaling promote pulmonary vascular remodeling in inflamed lungs.
Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer
Authors: Carter Hannah , Marty Rachel , Hofree Matan , Gross Andrew M. , Jensen James , Fisch Kathleen M. , Wu Xingyu , DeBoever Christopher , Van Nostrand Eric L. , Song Yan , Wheeler Emily , Kreisberg Jason F. , Lippman Scott M. , Yeo Gene W. , Gutkind J. Silvio , Ideker Trey
Published: February 2017

Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline–somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this association, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observed that stratifying patients by germline polymorphisms exposed distinct somatic mutation landscapes, implicating new cancer genes. This study creates a validated resource of inherited variants that govern where and how cancer develops, opening avenues for prevention research.

Significance: This study systematically identifies germline variants that directly affect tumor evolution, either by dramatically increasing alteration frequency of specific cancer genes or by influencing the site where a tumor develops. Cancer Discovery; 7(4); 410–23. ©2017 AACR.

See related commentary by Geeleher and Huang, p. 354.

This article is highlighted in the In This Issue feature, p. 339
Design and Rationale of a Randomized Trial of a Care Transition Strategy in Patients With Acute Heart Failure Discharged From the Emergency Department
Authors: Fermann Gregory J. , Levy Phillip D. , Pang Peter , Butler Javed , Ayaz S. Imran , Char Douglas , Dunn Patrick , Jenkins Cathy A. , Kampe Christy , Khan Yosef , Kumar Vijaya A. , Lindenfeld JoAnn , Liu Dandan , Miller Karen , Peacock W. Frank , Rizk Samaa , Robichaux Chad , Rothman Russell L. , Schrock Jon , Singer Adam , Sterling Sarah A. , Storrow Alan B. , Walsh Cheryl , Wilburn John , Collins Sean P.
Published: February 2017

GUIDED-HF (Get With the Guidelines in Emergency Department Patients With Heart Failure) is a multicenter randomized trial of a patient-centered transitional care intervention in patients with acute heart failure (AHF) who are discharged either directly from the emergency department (ED) or after a brief period of ED-based observation. To optimize care and reduce ED and hospital revisits, there has been significant emphasis on improving transitions at the time of hospital discharge for patients with HF. Such efforts have been almost exclusively directed at hospitalized patients; individuals with AHF who are discharged from the ED or ED-based observation are not included in these transitional care initiatives. Patients with AHF discharged directly from the ED or after a brief period of ED-based observation are randomly assigned to our transition GUIDED-HF strategy or standard ED discharge. Patients in the GUIDED arm receive a tailored discharge plan via the study team, based on their identified barriers to outpatient management and associated guideline-based interventions. This plan includes conducting a home visit soon after ED discharge combined with close outpatient follow-up and subsequent coaching calls to improve postdischarge care and avoid subsequent ED revisits and inpatient admissions. Up to 700 patients at 11 sites will be enrolled over 3 years of the study. GUIDED-HF will test a novel approach to AHF management strategy that includes tailored transitional care for patients discharged from the ED or ED-based observation. If successful, this program may significantly alter the current paradigm of AHF patient care.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02519283.
Population Impact & Efficiency of Benefit‐Targeted Versus Risk‐Targeted Statin Prescribing for Primary Prevention of Cardiovascular Disease
Authors: Pletcher Mark J. , Pignone Michael , Jarmul Jamie A. , Moran Andrew E. , Vittinghoff Eric , Newman Thomas
Published: February 2017

Background

Benefit‐targeted statin prescribing may be superior to risk‐targeted statin prescribing (the current standard), but the impact and efficiency of this approach are unclear.

Methods and Results

We analyzed the National Health and Nutrition Examination Survey (
NHANES
) using an open‐source model (the Prevention Impact and Efficiency Model) to compare targeting of statin therapy according to expected benefit (benefit‐targeted) versus baseline risk (risk‐targeted) in terms of projected population‐level impact and efficiency. Impact was defined as relative % reduction in atherosclerotic cardiovascular disease in the
US
population for the given strategy compared to current statin treatment patterns; and efficiency as the number needed to treat over 10 years (
NNT
10
, average and maximum) to prevent each atherosclerotic cardiovascular disease event. Benefit‐targeted moderate‐intensity statin therapy at a treatment threshold of 2.3% expected 10‐year absolute risk reduction could produce a 5.7% impact (95% confidence interval, 4.8–6.7). This is approximately equivalent to the potential impact of risk‐targeted therapy at a treatment threshold of 5% 10‐year atherosclerotic cardiovascular disease risk (5.6% impact [4.7–6.6]). Whereas the estimated maximum
NNT
10
is much improved for benefit‐targeted versus risk‐targeted therapy at these equivalent‐impact thresholds (43.5 vs 180), the average
NNT
10
is nearly equivalent (24.2 vs 24.6). Reaching 10% impact (half the Healthy People 2020 impact objective, loosely defined) is theoretically possible with benefit‐targeted moderate‐intensity statins of persons with expected absolute risk reduction >2.3% if we expand age eligibility and account for treatment of all persons with diabetes mellitus or with low‐density lipoprotein >190 mg/dL (impact=12.4%; average
NNT
10
=23.0).

Conclusions

Benefit‐based targeting of statin therapy provides modest gains in efficiency over risk‐based prescribing and could theoretically help attain approximately half of the Healthy People 2020 impact goal with reasonable efficiency.
Long‐Term Risk of Cardiovascular Events in Patients With Chronic Kidney Disease Who Have Survived Sepsis: A Nationwide Cohort Study
Authors: Shih Chia‐Jen , Chao Pei‐Wen , Ou Shuo‐Ming , Chen Yung‐Tai
Published: February 2017

Background

Long‐term cardiovascular outcomes after sepsis in patients with chronic kidney disease are not well known. We aimed to examine the risk of subsequent cardiovascular events in patients with chronic kidney disease discharged after hospitalization for sepsis in Taiwan.

Methods and Results

Using complete claims data for patients with chronic kidney disease from Taiwan's National Health Insurance Research Database, we identified patients with sepsis who survived hospitalization between 2000 and 2010. Each sepsis survivor was propensity score–matched to one nonsepsis hospitalized control patient. Cox regression models were used to estimate the hazard ratios (
HR
s) of clinical outcomes, including major adverse cardiovascular events (myocardial infarction and ischemic stroke), hospitalization for heart failure, and all‐cause death. Among 66 961 sepsis survivors, the incidence rates of all‐cause mortality and major adverse cardiovascular events during the study period were 288.51 and 47.05 per 1000 person‐years, respectively. In comparison with matched hospitalized nonsepsis control patients, sepsis survivors had greater risks of major adverse cardiovascular events (
HR
, 1.42; 95%
CI
, 1.37–1.47), myocardial infarction (
HR
, 1.39; 95%
CI
, 1.32–1.47), ischemic stroke (
HR
, 1.46; 95%
CI
, 1.40–1.52), hospitalization for heart failure (
HR
, 1.55; 95%
CI
, 1.51–1.59), and all‐cause mortality (
HR
, 1.56; 95%
CI
, 1.54–1.58). The results remained unchanged in analyses of several subgroups of patients, and were similar in analyses accounting for the competing risk of death.

Conclusions

Our findings highlight the association of sepsis with a significantly increased long‐term risk of cardiovascular events among survivors in the chronic kidney disease population.
Role of Genetic Variation in Collateral Circulation in the Evolution of Acute Stroke
Authors: Kao Yu-Chieh Jill , Oyarzabal Esteban A. , Zhang Hua , Faber James E. , Shih Yen-Yu Ian
Published: February 2017

Background and Purpose—

No studies have determined the effect of differences in pial collateral extent (number and diameter), independent of differences in environmental factors and unknown genetic factors, on severity of stroke. We examined ischemic tissue evolution during acute stroke, as measured by magnetic resonance imaging and histology, by comparing 2 congenic mouse strains with otherwise identical genetic backgrounds but with different alleles of the
Determinant of collateral extent-1
(
Dce1
) genetic locus. We also optimized magnetic resonance perfusion and diffusion–deficit thresholds by using histological measures of ischemic tissue.

Methods—

Perfusion, diffusion, and T
2
-weighted magnetic resonance imaging were performed on collateral-poor (congenic-Bc) and collateral-rich (congenic-B6) mice at 1, 5, and 24 hours after permanent middle cerebral artery occlusion. Magnetic resonance imaging–derived penumbra and ischemic core volumes were confirmed by histology in a subset of mice at 5 and 24 hours after permanent middle cerebral artery occlusion.

Results—

Although perfusion-deficit volumes were similar between strains 1 hour after permanent middle cerebral artery occlusion, diffusion-deficit volumes were 32% smaller in collateral-rich mice. At 5 hours, collateral-rich mice had markedly restored perfusion patterns showing reduced perfusion-deficit volumes, smaller infarct volumes, and smaller perfusion–diffusion mismatch volumes compared with the collateral-poor mice (
P
<0.05). At 24 hours, collateral-rich mice had 45% smaller T
2
-weighted lesion volumes (
P
<0.005) than collateral-poor mice, with no difference in perfusion–diffusion mismatch volumes because of penumbral death occurring 5 to 24 hours after permanent middle cerebral artery occlusion in collateral-poor mice.

Conclusions—

Variation in collateral extent significantly alters infarct volume expansion, transiently affects perfusion and diffusion magnetic resonance imaging signatures, and impacts salvage of ischemic penumbra after stroke onset.
Different Views From The 606: Examining the Impacts of an Urban Greenway on Crime in Chicago
Authors: Harris Brandon , Larson Lincoln , Ogletree Scott
Published: February 2017

Parks and greenways provide many benefits to urban communities, but their relationship to crime is often debated. We examined the links between an elevated linear trail and crime within census block groups (CBGs) surrounding Chicago’s Bloomingdale Trail, colloquially known as The 606, using two different approaches: (a) a matched case-control comparison of crime trends in 606-proximate CBGs and similar socioeconomic status (SES) neighborhoods in other parts of the city and (b) spatially oriented hierarchical regression models of crime in 606-proximate CBGs before and after trail construction. Using this dichotomous approach, we detected a positive influence of The 606 on all types of crime (violent, property, and disorderly) when examined at a coarse scale, particularly in low SES neighborhoods (Study 1), and an inverse relationship between trail proximity and property crime on a spatially proximate scale (Study 2). Future research should continue to explore complex relationships between urban greenways and crime in diverse cities.
Marital Power in Inter-Hukou Families in China: An Intersectionality Approach
Authors: Lui Lake
Published: February 2017

China’s household registration system ( hukou) that assigns citizens into “rural” or “urban” status is a stratifying tool that shapes people’s social rights based on parents’ place of origin. This ethnographic research on inter- hukou couples suggests that the interlinked institutions of state and patriarchy construct differentiated and uneven marital power dynamics whereby inequalities are reproduced and/or transformed through everyday interactions. Rural wives of urban men are socially stigmatized and are treated by their husbands’ families as “unpaid reproductive workers,” depriving them of full membership in the urban family and the urban society. To resist overlapping oppression, rural women mask themselves as appropriate wives and filial daughters-in-law, achieving “urbanness” at the frontstage. At the same time, they secretly make gender alliances in both virtual and real spaces and lobby for their urban husbands’ support at the backstage, slowly eroding the dual structure of gender and hukou through family dynamics.
Effects of a Savoring Intervention on Resilience and Well-Being of Older Adults
Authors: Smith Jennifer L. , Hanni Agnieszka A.
Published: February 2017

Savoring is the ability to be mindful of positive experiences and to be aware of and regulate positive feelings about these experiences. Previous research has found that savoring interventions can be effective at improving well-being of younger adults, but findings have not been extended to older populations. This pilot study examined the effects of a 1-week savoring intervention on older adults’ psychological resilience and well-being (i.e., depressive symptoms and happiness). Participants, 111 adults ages 60 or over, completed measures of resilience, depressive symptoms, and happiness pre- and postintervention as well as 1 month and 3 months after the intervention. Analyses revealed that participants who completed the savoring intervention with high fidelity also reported improvements in resilience, depressive symptoms, and happiness over time. These findings suggest that the savoring intervention has the potential to enhance older adults’ resilience and psychological well-being.
Social Workers’ Attempts to Navigate Among the Elderly, Their Families, and Foreign Home Care Workers in the Haredi Community
Authors: Freund Anat , Band-Winterstein Tova
Published: February 2017

Background: The study’s aim is to examine social workers’ experience in facilitating the integration of foreign home care workers (FHCWs) into the ultraorthodox Jewish (UOJ) community for the purpose of treating older adults. Method: Using the qualitative-phenomenological approach, semistructured, in-depth interviews were conducted with 18 social workers in daily contact with UOJ older adult clients in the process of integrating FHCWs. Results: Data analysis revealed three central themes—integrating FHCWs into the aging UOJ family: barriers and challenges in the interaction between the two worlds; “even the rabbi has a FHCW”: changing trends in caring for older adults; and the social worker as mediator and facilitator of a successful relationship. Discussion: Social workers play a central role, serving as a cultural bridge in the process of integrating FHCWs, as a way of addressing the needs of ultraorthodox elderly and their families, while also considering the needs of the foreign workers.
The Role of Echocardiography in the Assessment of Ventricular Septal Rupture Postmyocardial Infarction
Authors: Rampoldi Michael , Kallstrom Eric
Published: February 2017

Ventricular septal rupture (VSR) is a rare life-threatening mechanical complication secondary to acute myocardial infarction that usually occurs 2 to 8 days after infarction and frequently precipitates cardiogenic shock. The mortality rate for VSR has been reported to be between 41% and 80%; therefore, immediate surgical intervention should be considered. Furthermore, VSR is a complication of 0.17% to 0.31% of patients who present with an anterior myocardial infarction. Because of the rarity of this pathology, the role of transthoracic echocardiographic investigation will help to improve what is already considered a poor prognosis for these types of patients. This case study illustrates how transthoracic echocardiography plays an essential role in the rapid assessment and diagnosis of VSR in clinical practice.
Massive Pulmonary Embolism and Thrombolytic Therapy: Case Study
Authors: Carpenter Nicole
Published: February 2017

Acute pulmonary embolism is the third most common acute cardiovascular disease, with about 600,000 cases annually in the United States. Pulmonary embolism requires a multimodality diagnosis and immediate treatment. Although computed tomography and ventilation perfusion scans are the most commonly used modalities to diagnose pulmonary embolisms, many supplemental tests are necessary. Treatment options for pulmonary embolism include anticoagulation therapy, thrombolytic therapy, or insertion of an inferior vena cava filter when anticoagulation is contraindicated. The long-term benefits of thrombolytic therapy have made it an increasingly popular option in many institutions. The following case study describes a patient who presented to the hospital with shortness of breath for five months and was found to have extensive pulmonary embolisms upon admission. The patient underwent three days of thrombolytic therapy that significantly reduced his pulmonary arterial pressures and resulted in an almost complete resolution of his pulmonary embolisms.
Small Changes: Using Assessment to Direct Instructional Practices in Large-Enrollment Biochemistry Courses
Authors: Xu Xiaoying , Lewis Jennifer E. , Loertscher Jennifer , Minderhout Vicky , Tienson Heather L.
Published: February 2017

Multiple-choice assessments provide a straightforward way for instructors of large classes to collect data related to student understanding of key concepts at the beginning and end of a course. By tracking student performance over time, instructors receive formative feedback about their teaching and can assess the impact of instructional changes. The evidence of instructional effectiveness can in turn inform future instruction, and vice versa. In this study, we analyzed student responses on an optimized pretest and posttest administered during four different quarters in a large-enrollment biochemistry course. Student performance and the effect of instructional interventions related to three fundamental concepts—hydrogen bonding, bond energy, and pKa—were analyzed. After instructional interventions, a larger proportion of students demonstrated knowledge of these concepts compared with data collected before instructional interventions. Student responses trended from inconsistent to consistent and from incorrect to correct. The instructional effect was particularly remarkable for the later three quarters related to hydrogen bonding and bond energy. This study supports the use of multiple-choice instruments to assess the effectiveness of instructional interventions, especially in large classes, by providing instructors with quick and reliable feedback on student knowledge of each specific fundamental concept.
Deaf, Hard-of-Hearing, and Hearing Signing Undergraduates’ Attitudes toward Science in Inquiry-Based Biology Laboratory Classes
Authors: Gormally Cara
Published: February 2017

For science learning to be successful, students must develop attitudes toward support future engagement with challenging social issues related to science. This is especially important for increasing participation of students from underrepresented populations. This study investigated how participation in inquiry-based biology laboratory classes affected students’ attitudes toward science, focusing on deaf, hard-of-hearing, and hearing signing students in bilingual learning environments (i.e., taught in American Sign Language and English). Analysis of reflection assignments and interviews revealed that the majority of students developed positive attitudes toward science and scientific attitudes after participating in inquiry-based biology laboratory classes. Attitudinal growth appears to be driven by student value of laboratory activities, repeated direct engagement with scientific inquiry, and peer collaboration. Students perceived that hands-on experimentation involving peer collaboration and a positive, welcoming learning environment were key features of inquiry-based laboratories, affording attitudinal growth. Students who did not perceive biology as useful for their majors, careers, or lives did not develop positive attitudes. Students highlighted the importance of the climate of the learning environment for encouraging student contribution and noted both the benefits and pitfalls of teamwork. Informed by students’ characterizations of their learning experiences, recommendations are made for inquiry-based learning in college biology.
What’s in a Name? The Importance of Students Perceiving That an Instructor Knows Their Names in a High-Enrollment Biology Classroom
Authors: Cooper Katelyn M. , Haney Brian , Krieg Anna , Brownell Sara E.
Published: February 2017

Learning student names has been promoted as an inclusive classroom practice, but it is unknown whether students value having their names known by an instructor. We explored this question in the context of a high-enrollment active-learning undergraduate biology course. Using surveys and semistructured interviews, we investigated whether students perceived that instructors know their names, the importance of instructors knowing their names, and how instructors learned their names. We found that, while only 20% of students perceived their names were known in previous high-enrollment biology classes, 78% of students perceived that an instructor of this course knew their names. However, instructors only knew 53% of names, indicating that instructors do not have to know student names in order for students to perceive that their names are known. Using grounded theory, we identified nine reasons why students feel that having their names known is important. When we asked students how they perceived instructors learned their names, the most common response was instructor use of name tents during in-class discussion. These findings suggest that students can benefit from perceiving that instructors know their names and name tents could be a relatively easy way for students to think that instructors know their names.
Novel Pump Control Technology Accelerates Drug Delivery Onset in a Model of Pediatric Drug Infusion
Authors: Parker Michael J. , Lovich Mark A. , Tsao Amy C. , Deng Hao , Houle Timothy , Peterfreund Robert A.
Published: February 2017

BACKGROUND:

Laboratory data suggest that newly initiated drug infusions reach steady-state delivery after a significant time lag. Depending on drug and carrier flow rates and the infusion system’s common volume, lag times may exceed 20 or more minutes, especially in the neonatal/pediatric critical care environment. This study tested the hypothesis that a computer-executed algorithm controlling infusion pumps in a coordinated fashion predictably hastens the achievement of the intended steady-state drug delivery in a model of neonatal/pediatric drug infusion.

METHODS:

We constructed an in vitro model of neonatal/pediatric drug infusions through a pediatric 4-Fr central venous catheter at total system flows of 2 mL/h or 12 mL/h, representing a clinically relevant infusion range. Methylene blue served as the model infused drug for quantitative analysis. A novel algorithm, based on Taylor Dispersion Theory of fluid flow through tubes and executed by a computer, generated flow patterns that controlled and coordinated drug and carrier delivery by syringe pumps. We measured the time to achieve the intended steady-state drug delivery by conventional initiation of the drug infusion (“turning on the drug pump”) and by algorithm-controlled infusion initiation.

RESULTS:

At 2 mL/h total system flow, application of the algorithm reduced the time to achieve half of the intended drug delivery rate (T50) from 17 minutes [17, 18] to 3 minutes [3, 3] (median, interquartile range). At 12 mL/h total system flow, application of the algorithm reduced T50 from 6 minutes [6, 7] to 3 minutes [3, 3] The bootstrapped median difference is −14 (95% confidence interval [CI], −16 to −12, adjusted P=.00192) for 2 mL/h flow and −3 (95% CI, −4 to −3, adjusted P=.02061) for 12 mL/h flow. Compared with conventional initiation, the additional fluid required by the algorithm-directed infusion was 0.43 and 1.03 mL for the low- and high-infusion rates, respectively.

CONCLUSIONS:

The output of infusion pumps can be predictably controlled and coordinated by a computer-executed algorithm in a model of neonatal/pediatric drug infusions. Application of an algorithm can reduce the time to achieve the intended rate of infused drug delivery with minimal incremental volume administration.
Decision Support for the Capacity Management of Bronchoscopy Devices: Optimizing the Cost-Efficient Mix of Reusable and Single-Use Devices Through Mathematical Modeling
Authors: Edenharter Günther M. , Gartner Daniel , Pförringer Dominik
Published: February 2017

BACKGROUND:

Increasing costs of material resources challenge hospitals to stay profitable. Particularly in anesthesia departments and intensive care units, bronchoscopes are used for various indications. Inefficient management of single- and multiple-use systems can influence the hospitals’ material costs substantially. Using mathematical modeling, we developed a strategic decision support tool to determine the optimum mix of disposable and reusable bronchoscopy devices in the setting of an intensive care unit.

METHODS:

A mathematical model with the objective to minimize costs in relation to demand constraints for bronchoscopy devices was formulated. The stochastic model decides whether single-use, multi-use, or a strategically chosen mix of both device types should be used. A decision support tool was developed in which parameters for uncertain demand such as mean, standard deviation, and a reliability parameter can be inserted. Furthermore, reprocessing costs per procedure, procurement, and maintenance costs for devices can be parameterized.

RESULTS:

Our experiments show for which demand pattern and reliability measure, it is efficient to only use reusable or disposable devices and under which circumstances the combination of both device types is beneficial.

CONCLUSIONS:

To determine the optimum mix of single-use and reusable bronchoscopy devices effectively and efficiently, managers can enter their hospital-specific parameters such as demand and prices into the decision support tool.

The software can be downloaded at: https://github.com/drdanielgartner/bronchomix/.
Publication Rate of Abstracts Presented at the Society for Obstetric Anesthesia and Perinatology Annual Meetings 2010–2014
Authors: Gerlach Brent , Shah Anuj M. , Lee Michael T. , Wong Cynthia A. , Sullivan John T. , Toledo Paloma
Published: February 2017

The Society for Obstetric Anesthesia and Perinatology (SOAP) annual meeting provides a forum to present new scientific work with the goal of broader dissemination of knowledge. The objective of this study was to evaluate the proportion of research abstracts presented at SOAP meetings, from 2010 to 2014, which resulted in peer-reviewed publications. The abstract-to-publication rate was compared with the percent of abstracts presented at biomedical meetings resulting in publication, as estimated by a 2007 Cochrane Review. The SOAP abstract-to-publication rate was lower than that of the Cochrane Review (26.8% vs 44.5%, P < .0001). Future work should identify barriers to publication.
Associations Between Impaired Cerebral Blood Flow Autoregulation, Cerebral Oxygenation, and Biomarkers of Brain Injury and Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery
Authors: Goettel Nicolai , Burkhart Christoph S. , Rossi Ariane , Cabella Brenno C.T. , Berres Manfred , Monsch Andreas U. , Czosnyka Marek , Steiner Luzius A.
Published: February 2017

BACKGROUND:

Increasing evidence links postoperative cognitive dysfunction (POCD) to surgery and anesthesia. POCD is recognized as an important neuropsychological adverse outcome in surgical patients, particularly the elderly. This prospective cohort study aimed to investigate whether POCD is associated with impaired intraoperative cerebral autoregulation and oxygenation, and increased levels of biomarkers of brain injury.

METHODS:

Study subjects were patients ≥65 years of age scheduled for major noncardiac surgery. Cognitive function was assessed before and 1 week after surgery. POCD was diagnosed if a decline of >1 standard deviation of z-scores was present in ≥2 variables of the test battery. The incidence of POCD 1 week after surgery was modeled as a multivariable function of the index of autoregulation (MxA) and tissue oxygenation index (TOI), adjusting for baseline neuropsychological assessment battery (Consortium to Establish a Registry for Alzheimer’s Disease-Neuropsychological Assessment Battery [CERAD-NAB]) total score and the maximum C-reactive protein (CRP) concentration. The biomarkers of brain injury neuron-specific enolase and S100β protein, age, and level of education were included in secondary multivariable logistic regression analyses.

RESULTS:

Of the 82 patients who completed the study, 38 (46%) presented with POCD 1 week after surgery. In the multivariable regression analysis, higher intraoperative MxA (odds ratio [OR; 95% confidence interval (CI)], 1.39 [1.01–1.90] for an increase of 0.1 units, P = .08 after Bonferroni adjustment), signifying less effective autoregulation, was not associated with higher odds of POCD. The univariable logistic regression model for MxA yielded an association with POCD (OR [95% CI], 1.44 [1.06–1.95], P = .020). Tissue oxygenation index (1.12 [0.41–3.01] for an increase of 10%, P = 1.0 after Bonferroni adjustment) and baseline CERAD-NAB total score (0.80 [0.45–1.42] for an increase of 10 points, P = .45) did not affect the odds of POCD. POCD was associated with elevated CRP on postoperative day 2 (median [interquartile range]; 175 [81–294] vs 112 [62–142] mg/L, P = .033); however, the maximum CRP value (OR [95% CI], 1.35 [0.97–1.87] for a 2-fold increase, P = .07) had no distinct effect on POCD.

CONCLUSIONS:

Impairment of intraoperative cerebral blood flow autoregulation is not predictive of early POCD in elderly patients, although secondary analyses indicate that an association probably exists.
The Effect of Fixation Technique on Continuous Interscalene Nerve Block Catheter Success: A Randomized, Double-Blind Trial
Authors: Auyong David B. , Cantor David Asher , Green Cynthia , Hanson Neil A.
Published: February 2017

BACKGROUND:

Continuous peripheral nerve blocks offer advantages over single-injection blocks, including extended analgesia and reduction in opioid consumption. These benefits require that the perineural catheter remain intact for the duration of the planned local anesthetic infusion. Mechanical displacement of catheters, leaking, and consequent failure are known complications. The aim of this study was to evaluate continuous perineural catheter tip-to-nerve apposition in vivo over 48 hours comparing 2 different simple fixation strategies.

METHODS:

Subjects presenting for a continuous interscalene nerve block were randomized to perineural catheter fixation with 1 of 2 types of adhesive: Dermabond (2-octylcyanoacrylate) or Mastisol (alcohol 23A, gum mastic, storax, and methyl salicylate), covered with a simple transparent dressing. The primary outcome was the evaluation of catheter-to-nerve apposition maintenance over 48 hours via both a blinded ultrasound evaluation of local anesthetic distribution and a blinded clinical assessment. Secondary outcomes included leakage at the catheter site, pain scores, opioid consumption, catheter-to-skin migration at the insertion site, and patient satisfaction.

RESULTS:

Sixty-six subjects were recruited and randomized to compare adhesive group catheter tip-to-nerve apposition on postoperative day 2 (POD 2). Within the intention-to-treat cohort, a statistically significant decrease of perineural catheter tip-to-nerve apposition in the Mastisol group (64.7%) compared with the Dermabond group (90.6%) on POD 2 (odds ratios [OR] 0.19; 95% confidence interval [CI] 0.05–0.75; P = .012) was observed. Similar results were observed on POD 1 (OR 0.19; 95% CI 0.03–1.38; P = NS) and POD 2 (OR 0.14; 95% CI 0.02–0.97; P = .008) within the as-treated cohort. Catheter leakage (OR 67; 95% CI 7.3–589) and median catheter migration difference at the skin insertion site (2.0 cm; 95% CI 0.5–2.5) were also significantly greater in the Mastisol group than in the Dermabond group from POD 0 to POD 2 (P < .001). Median postoperative opioid consumption difference in morphine equivalents (3.2 mg; 95% CI – 9.0 to 14.2) was not significantly different between the Dermabond and the Mastisol groups through POD 2 (P = .542).

CONCLUSIONS:

Perineural catheter fixation with Dermabond in continuous interscalene nerve block improves maintenance of catheter-to-nerve apposition when compared with Mastisol.
Mobile Technology in the Perioperative Arena: Rapid Evolution and Future Disruption
Authors: Rothman Brian S. , Gupta Rajnish K. , McEvoy Matthew D.
Published: February 2017

Throughout the history of medicine, physicians have relied upon disruptive innovations and technologies to improve the quality of care delivered, patient outcomes, and patient satisfaction. The implementation of mobile technology in health care is quickly becoming the next disruptive technology. We first review the history of mobile technology over the past 3 decades, discuss the impact of hardware and software, explore the rapid expansion of applications (apps), and evaluate the adoption of mobile technology in health care. Next, we discuss how technology serves as the vehicle that can transform traditional didactic learning into one that adapts to the learning behavior of the student by using concepts such as the flipped classroom, just-in-time learning, social media, and Web 2.0/3.0. The focus in this modern education paradigm is shifting from teacher-centric to learner-centric, including providers and patients, and is being delivered as context-sensitive, or semantic, learning. Finally, we present the methods by which connected health systems via mobile devices increase information collection and analysis from patients in both clinical care and research environments. This enhanced patient and provider connection has demonstrated benefits including reducing unnecessary hospital readmissions, improved perioperative health maintenance coordination, and improved care in remote and underserved areas. A significant portion of the future of health care, and specifically perioperative medicine, revolves around mobile technology, nimble learners, patient-specific information and decision-making, and continuous connectivity between patients and health care systems. As such, an understanding of developing or evaluating mobile technology likely will be important for anesthesiologists, particularly with an ever-expanding scope of practice in perioperative medicine.
Epidemiology of Cardiac Arrest During Hospitalization for Delivery in Canada: A Nationwide Study
Authors: Balki Mrinalini , Liu Shiliang , León Juan Andrés , Baghirzada Leyla
Published: February 2017

BACKGROUND:

Cardiac arrest in pregnancy is a rare and devastating condition with high mortality and morbidity. The objective of this study was to generate information about maternal cardiac arrest in Canada by examining the frequency, temporal incidence, associated conditions, potential etiologies, and survival rates.

METHODS:

This retrospective population-based study used hospitalization data from the discharge abstract database of the Canadian Institute for Health Information relating to obstetric deliveries in Canada from April 1, 2002, to March 31, 2015. The data were accessed through the Public Health Agency of Canada’s (PHAC) Canadian Perinatal Surveillance System. Cases of cardiac arrest were identified using the diagnostic and intervention codes from the International Statistical Classification of Diseases and the Canadian Classification of Health Interventions, respectively. Data on patient demographics, medical and obstetrical conditions, and potential etiologies of cardiac arrest were collected. Multivariable logistic regression analysis was used to identify conditions associated with cardiac arrest.

RESULTS:

There were 286 cases of maternal cardiac arrest among 3,568,597 hospitalizations for delivery during the 13-year period. A total of 204 (71.3%) women survived to hospital discharge (95% confidence interval, 65.7%–76.5%). There was no significant variation in the incidence of cardiac arrest or survival from arrest over time or across provinces. Among the pre-existing conditions, hypertensive disorders of pregnancy, gestational diabetes, malignancy, and diseases of the respiratory and nervous system were found to be significantly associated with cardiac arrest. Among the obstetrical conditions, placental abnormalities and polyhydramnios were associated with cardiac arrest. The common potential etiologies included postpartum hemorrhage, heart failure, amniotic fluid embolism, and complications of anesthesia.

CONCLUSIONS:

In this first Canadian study, the incidence of cardiac arrest during pregnancy was found to be 1:12,500 deliveries. The survival rate reported in our study is higher than reported previously in other countries. Our study findings contribute to better inform the development and implementation of policies and programs in an effort to prevent and manage this condition.
Study Design Rigor in Animal-Experimental Research Published in Anesthesia Journals
Authors: Hoerauf Janine M. , Moss Angela F. , Fernandez-Bustamante Ana , Bartels Karsten
Published: February 2017

BACKGROUND:

Lack of reproducibility of preclinical studies has been identified as an impediment for translation of basic mechanistic research into effective clinical therapies. Indeed, the National Institutes of Health has revised its grant application process to require more rigorous study design, including sample size calculations, blinding procedures, and randomization steps. We hypothesized that the reporting of such metrics of study design rigor has increased over time for animal-experimental research published in anesthesia journals.

METHODS:

PubMed was searched for animal-experimental studies published in 2005, 2010, and 2015 in primarily English-language anesthesia journals. A total of 1466 publications were graded on the performance of sample size estimation, randomization, and blinding. Cochran–Armitage test was used to assess linear trends over time for the primary outcome of whether or not a metric was reported. Interrater agreement for each of the 3 metrics (power, randomization, and blinding) was assessed using the weighted κ coefficient in a 10% random sample of articles rerated by a second investigator blinded to the ratings of the first investigator.

RESULTS:

A total of 1466 manuscripts were analyzed. Reporting for all 3 metrics of experimental design rigor increased over time (2005 to 2010 to 2015): for power analysis, from 5% (27/516), to 12% (59/485), to 17% (77/465); for randomization, from 41% (213/516), to 50% (243/485), to 54% (253/465); and for blinding, from 26% (135/516), to 38% (186/485), to 47% (217/465). The weighted κ coefficients and 98.3% confidence interval indicate almost perfect agreement between the 2 raters beyond that which occurs by chance alone (power, 0.93 [0.85, 1.0], randomization, 0.91 [0.85, 0.98], and blinding, 0.90 [0.84, 0.96]).

CONCLUSIONS:

Our hypothesis that reported metrics of rigor in animal-experimental studies in anesthesia journals have increased during the past decade was confirmed. More consistent reporting, or explicit justification for absence, of sample size calculations, blinding techniques, and randomization procedures could better enable readers to evaluate potential sources of bias in animal-experimental research manuscripts. Future studies should assess whether such steps lead to improved translation of animal-experimental anesthesia research into successful clinical trials.