bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety envelope for load tolerance of structural element design based on multi-stage testing
Authors: Park Chanyoung , Kim Nam H
Published: September 2016

Structural elements, such as stiffened panels and lap joints, are basic components of aircraft structures. For aircraft structural design, designers select predesigned elements satisfying the design load requirement based on their load-carrying capabilities. Therefore, estimation of safety envelope of structural elements for load tolerances would be a good investment for design purpose. In this article, a method of estimating safety envelope is presented using probabilistic classification, which can estimate a specific level of failure probability under both aleatory and epistemic uncertainties. An important contribution of this article is that the calculation uncertainty is reflected in building a safety envelope using Gaussian process, and the effect of element test data on reducing the calculation uncertainty is incorporated by updating the Gaussian process model with the element test data. It is shown that even one element test can significantly reduce the calculation uncertainty due to lacking knowledge of actual physics, so that conservativeness in a safety envelope is significantly reduced. The proposed approach was demonstrated with a cantilever beam example, which represents a structural element. The example shows that calculation uncertainty provides about 93% conservativeness against the uncertainty due to a few element tests. It is shown that even a single element test can increase the load tolerance modeled with the safety envelope by 20%.
Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ
Authors: Hu Xue-Ming , Cao Shou-Bin , Zhang Hai-Long , Lyu Dong-Mei , Chen Li-Ping , Xu Heng , Pan Zhi-Qiang , Shen Wen
Published: September 2016

Background

Increasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ). However, whether miR-219 regulates CaMKIIγ expression in the dorsal root ganglia to mediate morphine tolerance remains unclear.

Results

MiR-219 expression was downregulated and CaMKIIγ expression was upregulated in mouse dorsal root ganglia following chronic morphine treatment. The changes in miR-219 and CaMKIIγ expression closely correlated with the development of morphine tolerance, which was measured using the reduction of percentage of maximum potential efficiency to thermal stimuli. Morphine tolerance was markedly delayed by upregulating miR-219 expression using miR-219 mimics or downregulating CaMKIIγ expression using CaMKIIγ small interfering RNA. The protein and mRNA expression of brain-derived neurotrophic factor were also induced in dorsal root ganglia by prolonged morphine exposure in a time-dependent manner, which were transcriptionally regulated by miR-219 and CaMKIIγ. Scavenging brain-derived neurotrophic factor via tyrosine receptor kinase B-Fc partially attenuated morphine tolerance. Moreover, functional inhibition of miR-219 via miR-219-sponge in naive mice elicited thermal hyperalgesia and spinal neuronal sensitization, which were both suppressed by CaMKIIγ small interfering RNA or tyrosine receptor kinase B-Fc.

Conclusions

These results demonstrate that miR-219 contributes to the development of chronic tolerance to morphine analgesia in mouse dorsal root ganglia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression.
Computational methods for investigation of surface curvature effects on airfoil boundary layer behavior
Authors: Shen Xiang , Avital Eldad , Rezaienia Mohammad Amin , Paul Gordon , Korakianitis Theodosios
Published: September 2016

This article presents computational algorithms for the design, analysis, and optimization of airfoil aerodynamic performance. The prescribed surface curvature distribution blade design (CIRCLE) method is applied to a symmetrical airfoil NACA0012 and a non-symmetrical airfoil E387 to remove their surface curvature and slope-of-curvature discontinuities. Computational fluid dynamics analysis is used to investigate the effects of curvature distribution on aerodynamic performance of the original and modified airfoils. An inviscid–viscid interaction scheme is introduced to predict the positions of laminar separation bubbles. The results are compared with experimental data obtained from tests on the original airfoil geometry. The computed aerodynamic advantages of the modified airfoils are analyzed in different operating conditions. The leading edge singularity of NACA0012 is removed and it is shown that the surface curvature discontinuity affects aerodynamic performance near the stalling angle of attack. The discontinuous slope-of-curvature distribution of E387 results in a larger laminar separation bubble at lower angles of attack and lower Reynolds numbers. It also affects the inherent performance of the airfoil at higher Reynolds numbers. It is shown that at relatively high angles of attack, a continuous slope-of-curvature distribution reduces the skin friction by suppressing both laminar and turbulent separation, and by delaying laminar-turbulent transition. It is concluded that the surface curvature distribution has significant effects on the boundary layer behavior and consequently an improved curvature distribution will lead to higher aerodynamic efficiency.
Managing cardiovascular risk in patients with inflammatory arthritis: practical considerations
Authors: Tournadre Anne , Mathieu Sylvain , Soubrier Martin
Published: September 2016

Patients with inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, have higher rates of cardiovascular mortality. While the increased cardiovascular risk is only explained to some extent, a lot of research is currently conducted to improve our understanding of its pathogenesis, risk stratification, and optimal cardiovascular risk management. This review sought to report epidemiological data pertaining to the cardiovascular disease burden in patients with inflammatory arthritis, underlying mechanisms accounting for excessive cardiovascular risk, along with recommendations regarding risk assessment and management in this patient population.
Rotating Squares Look Like Pincushions
Authors: Anstis Stuart , Kaneko Sae
Published: September 2016

Rotating squares appeared to be distorted into pincushions with concave sides. These illusory shape changes were caused by a perceived compression along the curved path of motion.
Postoperative use of hypnotics is associated with increased length of stay after uncomplicated surgery for colorectal cancer
Authors: Noack Morten Westergaard , Bisgård Anne Sofie , Klein Mads , Rosenberg Jacob , Gögenur Ismail
Published: September 2016

Background/Aims:

Hypnotics are used to treat perioperative sleep disorders. These drugs are associated with a higher risk of adverse effects among patients undergoing surgery. This study aims to quantify the use of hypnotics and factors influencing the administration of hypnotics in relation to colorectal cancer surgery.

Method:

A retrospective cohort study of 1979 patients undergoing colorectal cancer surgery.

Results:

In all, 381 patients (19%) received new treatment with hypnotics. Two of the six surgical centres used hypnotics less often (odds ratio (95% confidence interval), 0.24 (0.16–0.38) and 0.20 (0.12–0.35)). Active smokers (odds ratio (95% confidence interval), 1.57 (1.11–2.24)) and patients receiving perioperative blood transfusion (odds ratio (95% confidence interval), 1.58 (1.10–2.26)) had increased likelihood of receiving hypnotics. In the uncomplicated cases, a multivariable linear regression analysis showed that consumption of hypnotics postoperatively was significantly associated with increased length of stay (1.5 (0.9–2.2) days).

Conclusion:

One in five patients began treatment with hypnotics after colorectal cancer surgery. Postoperative use of hypnotics was associated with an increased length of stay for uncomplicated cases of colorectal cancer surgery.
Of Echo Chambers and Contrarian Clubs: Exposure to Political Disagreement Among German and Italian Users of Twitter
Authors: Vaccari Cristian , Valeriani Augusto , Barberá Pablo , Jost John T. , Nagler Jonathan , Tucker Joshua A.
Published: September 2016

Scholars have debated whether social media platforms, by allowing users to select the information to which they are exposed, may lead people to isolate themselves from viewpoints with which they disagree, thereby serving as political “echo chambers.” We investigate hypotheses concerning the circumstances under which Twitter users who communicate about elections would engage with (a) supportive, (b) oppositional, and (c) mixed political networks. Based on online surveys of representative samples of Italian and German individuals who posted at least one Twitter message about elections in 2013, we find substantial differences in the extent to which social media facilitates exposure to similar versus dissimilar political views. Our results suggest that exposure to supportive, oppositional, or mixed political networks on social media can be explained by broader patterns of political conversation (i.e., structure of offline networks) and specific habits in the political use of social media (i.e., the intensity of political discussion). These findings suggest that disagreement persists on social media even when ideological homophily is the modal outcome, and that scholars should pay more attention to specific situational and dispositional factors when evaluating the implications of social media for political communication.
The Oral Paradigm and Snapchat
Authors: Soffer Oren
Published: September 2016

In this short essay, I argue that the ephemeral nature of emerging instant-messaging applications, such as Snapchat, applies an oral paradigm. While online discourse of computer-mediated communication shares many qualities with oral communication, the case of ephemeral applications is unique, as the oral features are already integrated in the application technology design and as orality is often implemented on highly visual products. Snapchat applies technology that fades visual contents as if they were spoken words fading in the air after utterance. Moreover, Snapchat’s promise to delete all messages from its database after they are viewed echoes a key characteristic of primary oral culture: that is, the inability (and in our case, the obligation not) to store knowledge. In this, Snapchat demonstrates counter-logic to the contemporary grammar of new media, which is based on information aggregation.
The Risk of Transphyseal Drilling in Skeletally Immature Patients With Anterior Cruciate Ligament Injury
Authors: Faunø Peter , Rømer Lone , Nielsen Torsten , Lind Martin
Published: September 2016

Background:

Anterior cruciate ligament reconstruction (ACLR) in skeletally immature patients can result in growth plate injury, which can cause growth disturbances.

Purpose:

To evaluate radiological tibial and femoral length and axis growth disturbances as well as clinical outcomes in skeletally immature ACLR patients treated with a transphyseal drilling technique.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

A total of 39 pediatric patients with ACL injury and open physes at time of surgery, as diagnosed clinically and with magnetic resonance imaging (MRI), were treated using transphyseal ACLR using hamstring graft. Mean patient age was 11.7 years (range, 9.0-14.0 years). Patients were evaluated with full extremity radiographs measuring leg length discrepancy and malalignment, as well as clinical evaluation with KT-1000 arthrometer measurements and Tegner activity scale and Knee injury and Osteoarthritis Outcome Score (KOOS) outcomes after follow-up of 68 months (range, 29-148 months).

Results:

Of the 39 initial patients, 33 were evaluated both clinically and radiographically. We found a mean femoral length shortening of 3.5 mm ( P = .01) on the operated leg. Eight patients (24%) had a more than 10-mm shortening of the operated leg, whereas only 1 patient (3%) had a 10-mm shortening of the nonoperated leg. In 27 of 33 patients (82%; P < .001), the anatomic femoral axes of the operated leg were found to be more than 2° of valgus compared with the nonoperated leg. The tibial anatomic axes changed into a less pronounced varus angulation ( P = .02). The femoral-tibial anatomic axes were not significantly different when comparing the 2 legs. We did not find any statistical difference in growth arrest comparing patients treated surgically at the ages of 13 to 14 years to patients younger than 13 years. Tegner and KOOS scores were significantly lower among girls compared with boys. Side-to-side KT-1000 arthrometer difference improved from 5.2 mm preoperatively to 1.6 mm at follow-up.

Conclusion:

This study shows that transphyseal ACLR in children results in minor length growth disturbances in 24% of patients. The surgically induced distal femoral valgus angulation is counterbalanced by a proximal tibial varus angulation. Growth disturbance after surgery is not associated with a certain pediatric age group. Otherwise, transphyseal ACLR has satisfactory clinical outcomes, with good subjective outcomes, function level, and knee stability.
Temporal Fine-Structure Coding and Lateralized Speech Perception in Normal-Hearing and Hearing-Impaired Listeners
Authors: Lőcsei Gusztáv , Pedersen Julie H. , Laugesen Søren , Santurette Sébastien , Dau Torsten , MacDonald Ewen N.
Published: September 2016

This study investigated the relationship between speech perception performance in spatially complex, lateralized listening scenarios and temporal fine-structure (TFS) coding at low frequencies. Young normal-hearing (NH) and two groups of elderly hearing-impaired (HI) listeners with mild or moderate hearing loss above 1.5 kHz participated in the study. Speech reception thresholds (SRTs) were estimated in the presence of either speech-shaped noise, two-, four-, or eight-talker babble played reversed, or a nonreversed two-talker masker. Target audibility was ensured by applying individualized linear gains to the stimuli, which were presented over headphones. The target and masker streams were lateralized to the same or to opposite sides of the head by introducing 0.7-ms interaural time differences between the ears. TFS coding was assessed by measuring frequency discrimination thresholds and interaural phase difference thresholds at 250 Hz. NH listeners had clearly better SRTs than the HI listeners. However, when maskers were spatially separated from the target, the amount of SRT benefit due to binaural unmasking differed only slightly between the groups. Neither the frequency discrimination threshold nor the interaural phase difference threshold tasks showed a correlation with the SRTs or with the amount of masking release due to binaural unmasking, respectively. The results suggest that, although HI listeners with normal hearing thresholds below 1.5 kHz experienced difficulties with speech understanding in spatially complex environments, these limitations were unrelated to TFS coding abilities and were only weakly associated with a reduction in binaural-unmasking benefit for spatially separated competing sources.
Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection
Authors: Arcaini Luca , Besson Caroline , Frigeni Marco , Fontaine Hélène , Goldaniga Maria , Casato Milvia , Visentini Marcella , Torres Harrys A. , Loustaud-Ratti Veronique , Peveling-Oberhag Jan , Fabris Paolo , Rossotti Roberto , Zaja Francesco , Rigacci Luigi , Rattotti Sara , Bruno Raffaele , Merli Michele , Dorival Céline , Alric Laurent , Jaccard Arnaud , Pol Stanislas , Carrat Fabrice , Ferretti Virginia Valeria , Visco Carlo , Hermine Olivier
Published: September 2016

Key Points

Direct-acting antiviral agents are able to induce lymphoma response in patients with HCV-associated indolent non-Hodgkin lymphoma. The highest rate of lymphoma response (73%) was observed in patients with marginal zone lymphoma.
Draft genome sequence of Lampropedia cohaerens strain CT6T isolated from arsenic rich microbial mats of a Himalayan hot water spring
Authors: Tripathi Charu , Mahato Nitish K. , Rani Pooja , Singh Yogendra , Kamra Komal , Lal Rup
Published: September 2016

Lampropedia cohaerens strain CT6T, a non-motile, aerobic and coccoid strain was isolated from arsenic rich microbial mats (temperature ~45 °C) of a hot water spring located atop the Himalayan ranges at Manikaran, India. The present study reports the first genome sequence of type strain CT6T of genus Lampropedia cohaerens. Sequencing data was generated using the Illumina HiSeq 2000 platform and assembled with ABySS v 1.3.5. The 3,158,922 bp genome was assembled into 41 contigs with a mean GC content of 63.5 % and 2823 coding sequences. Strain CT6T was found to harbour genes involved in both the Entner-Duodoroff pathway and non-phosphorylated ED pathway. Strain CT6T also contained genes responsible for imparting resistance to arsenic, copper, cobalt, zinc, cadmium and magnesium, providing survival advantages at a thermal location. Additionally, the presence of genes associated with biofilm formation, pyrroloquinoline-quinone production, isoquinoline degradation and mineral phosphate solubilisation in the genome demonstrate the diverse genetic potential for survival at stressed niches.
Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations
Authors: Albiges Laurence , Hakimi A. Ari , Xie Wanling , McKay Rana R. , Simantov Ronit , Lin Xun , Lee Jae-Lyun , Rini Brian I. , Srinivas Sandy , Bjarnason Georg A. , Ernst Scott , Wood Lori A. , Vaishamayan Ulka N. , Rha Sun-Young , Agarwal Neeraj , Yuasa Takeshi , Pal Sumanta K. , Bamias Aristotelis , Zabor Emily C. , Skanderup Anders J. , Furberg Helena , Fay Andre P. , de Velasco Guillermo , Preston Mark A. , Wilson Kathryn M. , Cho Eunyoung , McDermott David F. , Signoretti Sabina , Heng Daniel Y.C. , Choueiri Toni K.
Published: September 2016

Purpose

Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC.

Methods

The impact of BMI (high BMI: ≥ 25 kg/m2 v low BMI: < 25 kg/m2) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors.

Results

In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P = .034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend = .015).

Conclusion

High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway.
Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors
Authors: Leijen Suzanne , van Geel Robin M.J.M. , Pavlick Anna C. , Tibes Raoul , Rosen Lee , Razak Albiruni R. Abdul , Lam Raymond , Demuth Tim , Rose Shelonitda , Lee Mark A. , Freshwater Tomoko , Shumway Stuart , Liang Li Wen , Oza Amit M. , Schellens Jan H.M. , Shapiro Geoffrey I.
Published: September 2016

Purpose

AZD1775 is a WEE1 kinase inhibitor targeting G2 checkpoint control, preferentially sensitizing TP53-deficient tumor cells to DNA damage. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of oral AZD1775 as monotherapy or in combination with chemotherapy in patients with refractory solid tumors.

Patients and Methods

In part 1, patients received a single dose of AZD1775 followed by 14 days of observation. In part 2, patients received AZD1775 as a single dose (part 2A) or as five twice per day doses or two once per day doses (part 2B) in combination with one of the following chemotherapy agents: gemcitabine (1,000 mg/m2), cisplatin (75 mg/m2), or carboplatin (area under the curve, 5 mg/mL⋅min). Skin biopsies were collected for pharmacodynamic assessments. TP53 status was determined retrospectively in archival tumor tissue.

Results

Two hundred two patients were enrolled onto the study, including nine patients in part 1, 43 in part 2A (including eight rollover patients from part 1), and 158 in part 2B. AZD1775 monotherapy given as single dose was well tolerated, and the maximum-tolerated dose was not reached. In the combination regimens, the most common adverse events consisted of fatigue, nausea and vomiting, diarrhea, and hematologic toxicity. The maximum-tolerated doses and biologically effective doses were established for each combination. Target engagement, as a predefined 50% pCDK1 reduction in surrogate tissue, was observed in combination with cisplatin and carboplatin. Of 176 patients evaluable for efficacy, 94 (53%) had stable disease as best response, and 17 (10%) achieved a partial response. The response rate in TP53-mutated patients (n = 19) was 21% compared with 12% in TP53 wild-type patients (n = 33).

Conclusion

AZD1775 was safe and tolerable as a single agent and in combination with chemotherapy at doses associated with target engagement.
Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non–Clear Cell Renal Cell Carcinoma
Authors: Voss Martin H. , Molina Ana M. , Chen Ying-Bei , Woo Kaitlin M. , Chaim Joshua L. , Coskey Devyn T. , Redzematovic Almedina , Wang Patricia , Lee William , Selcuklu S. Duygu , Lee Chung-Han , Berger Michael F. , Tickoo Satish K. , Reuter Victor E. , Patil Sujata , Hsieh James J. , Motzer Robert J. , Feldman Darren R.
Published: September 2016

Purpose

The decreased effectiveness of single-agent targeted therapies in advanced non–clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC.

Patients and Methods

In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing.

Results

Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit.

Conclusion

The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.
“Little Big Things”: A Qualitative Study of Ovarian Cancer Survivors and Their Experiences With the Health Care System
Authors: Long Roche Kara , Angarita Ana M. , Cristello Angelica , Lippitt Melissa , Haider Adil H. , Bowie Janice V. , Fader Amanda N. , Tergas Ana I.
Published: September 2016

Purpose:

Navigation of a complex and ever-changing health care system can be stressful and detrimental to psychosocial well-being for patients with serious illness. This study explored women’s experiences with navigating the health care system during treatment for ovarian cancer.

Methods:

Focus groups moderated by trained investigators were conducted with ovarian cancer survivors at an academic cancer center. Personal experiences with cancer treatment, provider relationships, barriers to care, and the health care system were explored. Sessions were audiotaped, transcribed, and coded by using grounded theory. Subsequently, one-on-one interviews were conducted to further evaluate common themes.

Results:

Sixteen ovarian cancer survivors with a median age of 59 years participated in the focus group study. Provider consistency, personal touch, and patient advocacy positively affected the care experience. Treatment with a known provider who was well acquainted with the individual’s medical history was deemed an invaluable aspect of care. Negative experiences that burdened patients, referred to as the “little big things,” included systems-based challenges, which were scheduling, wait times, pharmacy, transportation, parking, financial, insurance, and discharge. Consistency, a care team approach, effective communication, and efficient connection to resources were suggested as ways to improve patients’ experiences.

Conclusion:

Systems-based challenges were perceived as burdens to ovarian cancer survivors at our institution. The role of a consistent, accessible care team and efficient delivery of resources in the care of women with ovarian cancer should be explored further.
A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs
Authors: Haslem Derrick S. , Van Norman S. Burke , Fulde Gail , Knighton Andrew J. , Belnap Tom , Butler Allison M. , Rhagunath Sharanya , Newman David , Gilbert Heather , Tudor Brian P. , Lin Karen , Stone Gary R. , Loughmiller David L. , Mishra Pravin J. , Srivastava Rajendu , Ford James M. , Nadauld Lincoln D.
Published: September 2016

Purpose:

The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported.

Patients and Methods:

We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7).

Results:

The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126).

Conclusion:

These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.
Understanding Teamwork in the Provision of Cancer Care: Highlighting the Role of Trust
Authors: Lazzara Elizabeth H. , Keebler Joseph R. , Day Soosi , DiazGranados Deborah , Pan Minggui , King Michael A. , Tu Shin-Ping
Published: September 2016

Team science research has indicated that trust is a critical variable of teamwork, contributing greatly to a team’s performance. Trust has long been examined in health care with research focusing on the development of trust by patients with their health care practitioners. Studies have indicated that trust is linked to patient satisfaction, adherence to treatment, continuity of care, and improved outcomes. We explore the construct of trust using a case example of a patient who received a surgical procedure for a precancerous polyp. We apply the principle of trust to the case as well as present the literature on trust and key definitions for understanding trust. Additionally, we apply the definitions presented to the specific case example by highlighting moments where trust is developed or violated. Lastly, we offer insights to health care practitioners on the development of trust in their own patient interactions to improve care.
Social Learning with Costly Search
Authors: Mueller-Frank Manuel , Pai Mallesh M.
Published: September 2016

We study a sequential social learning model where agents privately acquire information by costly search. Search costs of agents are private, and are independently and identically distributed. We show that asymptotic learning occurs if and only if search costs are not bounded away from zero. We explicitly characterize equilibria for the case of two actions, and show that the probability of late moving agents taking the suboptimal action vanishes at a linear rate. Social welfare converges to the social optimum as the discount rate converges to one if and only if search costs are not bounded away from zero. (JEL D81, D83)
Falling Dominoes: A Theory of Rare Events and Crisis Contagion
Authors: Chen Heng , Suen Wing
Published: September 2016

Crises, such as revolutions and currency attacks, rarely occur; but when they do they typically arrive in waves. The rarity of crises is an important contagion mechanism in a multiple-country dynamic global game model. When players are uncertain about the true model of the world, observing a rare success elsewhere can substantially change their expectations concerning the payoffs from attacking or defending the regime. Such dramatic revisions in beliefs, amplified by strategic complementarity in actions, may lead to a series of attacks in other countries. The crisis period can be long-lasting, but will eventually come to an end. (JEL D74, D83, F33, G01)
Intermediaries in Two-Sided Markets: An Empirical Analysis of the US Cable Television Industry
Authors: Boik Andre
Published: September 2016

Local television stations are platforms in a two-sided market connecting advertisers and viewers. This paper explicitly examines the effect that important intermediaries (such as cable, telephone, and satellite distributors) may have on a platform's pricing behavior in a two-sided market. I find that stations raise their fees to cable distributors because stations prefer that viewers access their content through satellite distributors with whom they do not compete in the local advertising market, and that station mergers lower stations' fees to distributors by partially internalizing a pricing externality that results from the mandatory bundling of local content. (JEL C78, D12, G34, L11, L82, M37)
Reallocation Costs and Efficiency
Authors: Salant Yuval , Siegel Ron
Published: September 2016

We study the efficient allocation of a divisible asset when reallocation is costly. Two players initially divide an asset between them. At the time of this initial division the players' valuations for the asset are uncertain. After the uncertainty resolves, costly reallocation may take place. We first establish that the surplus associated with efficient reallocation monotonically increases or decreases in the concentration of the initial division for a wide range of cost specifications. We then characterize how the budget necessary to implement the efficient reallocation changes with the initial division. (JEL D11, D63, D81)
Up in Smoke: The Influence of Household Behavior on the Long-Run Impact of Improved Cooking Stoves
Authors: Hanna Rema , Duflo Esther , Greenstone Michael
Published: September 2016

Laboratory studies suggest that improved cooking stoves can reduce indoor air pollution, improve health, and decrease greenhouse gas emissions in developing countries. We provide evidence, from a large-scale randomized trial in India, on the benefits of a common, laboratory-validated stove with a four-year follow-up. While smoke inhalation initially falls, this effect disappears by year two. We find no changes across health outcomes or greenhouse gas emissions. Households used the stoves irregularly and inappropriately, failed to maintain them, and usage declined over time. This study underscores the need to test environmental technologies in real-world settings where behavior may undermine potential impacts. (JEL D12, O12, O13, Q53, Q54, Q55)
Physicians Treating Physicians: Information and Incentives in Childbirth
Authors: Johnson Erin M. , Rehavi M. Marit
Published: September 2016

This paper provides new evidence on the interaction between patient information and physician financial incentives. Using rich microdata on childbirth, we compare the treatment of physicians when they are patients with that of comparable nonphysicians. We also exploit the presence of HMO-owned hospitals to determine how the treatment gap varies with providers’ financial incentives. Consistent with induced demand, physicians are approximately 10 percent less likely to receive a C-section, with only a quarter of this effect attributable to differential sorting. While financial incentives affect the treatment of nonphysicians, physician-patients are largely unaffected. Physicians also have better health outcomes. (JEL D83, I11, J16, J44)
Paying on the Margin for Medical Care: Evidence from Breast Cancer Treatments
Authors: Einav Liran , Finkelstein Amy , Williams Heidi
Published: September 2016

We present a simple graphical framework to illustrate the potential welfare gains from a “top-up” health insurance policy requiring patients to pay the incremental price for more expensive treatment options. We apply this framework to breast cancer treatments, where lumpectomy with radiation therapy is more expensive than mastectomy but generates similar average health benefits. We estimate the relative demand for lumpectomy using variation in distance to the nearest radiation facility, and estimate that the “top-up” policy increases social welfare by $700–2,500 per patient relative to two common alternatives. We briefly discuss additional tradeoffs that arise from an ex ante perspective. (JEL G22, I11, I13, I18)
Cardiothoracic manifestations of primary histiocytoses
Authors: Vargas Daniel , Richards J Caleb , Ocazionez Daniel , Sirajuddin Arlene , Browne Lorna , Restrepo Carlos S
Published: September 2016

The objectives of this article were: (1) to review common and rare manifestations of systemic and pulmonary Langerhans cell histiocytosis, Rosai–Dorfman disease, Erdheim–Chester disease and juvenile xanthogranuloma; (2) to provide the reader with important pathologic, epidemiologic and clinical features of these diseases. The histiocytoses are a diverse group of diseases which typically manifest with multiorgan involvement. Understanding the pathologic, epidemiologic and clinical features of these entities can help the radiologist suggest an accurate diagnosis of histiocytosis when typical imaging features are encountered.
Salutary effects of high-intensity interval training in persons with elevated cardiovascular risk
Authors: Fleg Jerome L.
Published: September 2016

Although moderate-intensity continuous training (MICT) has been the traditional model for aerobic exercise training for over four decades, a growing body of literature has demonstrated equal if not greater improvement in aerobic capacity and similar beneficial effects on body composition, glucose metabolism, blood pressure, and quality of life from high-intensity interval training (HIIT). An advantage of HIIT over MICT is the shorter time required to perform the same amount of energy expenditure. The current brief review summarizes the effects of HIIT on peak aerobic capacity and cardiovascular risk factors in healthy adults and those with various cardiovascular diseases, including coronary artery disease, chronic heart failure, and post heart transplantation.
Multiple statistical tests: Lessons from a d20
Authors: Madan Christopher R.
Published: September 2016

Statistical analyses are often conducted with α= .05. When multiple statistical tests are conducted, this procedure needs to be adjusted to compensate for the otherwise inflated Type I error. In some instances in tabletop gaming, sometimes it is desired to roll a 20-sided die (or 'd20') twice and take the greater outcome. Here I draw from probability theory and the case of a d20, where the probability of obtaining any specific outcome is 1/20, to determine the probability of obtaining a specific outcome (Type-I error) at least once across repeated, independent statistical tests.
Deep brain stimulation in Gilles de la Tourette syndrome: killing several birds with one stone?
Authors: Hartmann Andreas
Published: September 2016

In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation. Moreover, I question whether DBS should really be expected to alleviate multiple symptoms at a time. Rather, I argue that tic reduction should remain our primary objective in severe GTS patients and that this intervention may subsequently allow an improved psychotherapeutic and/or pharmacological treatment of comorbidities. Thus, I consider DBS in GTS not as a single solution for all our patients’ ailments but as a stepping stone to improved holistic care made possible by tic reduction.
Video Tutorials Within an Undergraduate Operations Research Course: Student Perception on Their Integration and Creating A Blended Learning Environment
Authors: Sharkey Thomas C. , Nurre Sarah G.
Published: September 2016

In this paper, we discuss the impact of video tutorials on an undergraduate operations research (OR) course and analyze important aspects of student perception of their impact on the learning experience. Supplementary video tutorials offer additional examples of OR concepts; thus, class time can be more focused on letting students gain intuition about these concepts. We analyze students’ survey responses to help determine the perceived impact of the video tutorials on office hours and whether students’ familiarity with the creator of the tutorials impacted the tutorials’ effectiveness. Our results demonstrate that students saw significant advantages in using these supplementary video tutorials and that the creator of the tutorials did not impact the tutorials’ effectiveness as long as they were properly integrated into the course. Therefore, our results show that the overhead required to offer online video tutorials may be low (i.e., similar to selecting a course textbook) since their success relies more on proper integration into the course than having the professor of the course produce them. In addition, a preliminary assessment demonstrates that our blended learning environment has a positive impact on the learning experience.
Case Article—ABCtronics: Manufacturing, Quality Control, and Client Interfaces
Authors: Adhikari Arnab , Biswas Indranil , Bisi Arnab
Published: September 2016

Teaching statistics in an undergraduate or a graduate business administration course, business analytics course, or engineering program remains a challenging task for the instructors. Often students fail to comprehend the real-life application of statistical concepts with the help of disconnected textbook examples. This failure inspires scholars to develop case studies on statistical theories in real-life industry backgrounds or realistic industrial settings. Recognizing the students’ difficulty to understand the diverse statistical concepts in a realistic setting, we design a case study in an industrial background to facilitate students’ learning. It is constructed by drawing inspiration from real-life business scenarios in the context of the integrated chip manufacturing industry. It helps to bridge the gap between theoretical understanding and practical application. The case starts with introducing various probability distributions and gradually incorporates intricate concepts of statistics like sampling distribution, hypothesis testing, and regression models in realistic scenarios. Each assignment question enables the teacher to engage in the in-depth discussion regarding the applications of different statistical concepts about business problems of integrated chip manufacturing. Also, it involves the application of the software tools for solving statistical problems. This case article demonstrates different usages of the case, ranging from a common thread for classroom discussion throughout the course to a class reading for providing a holistic approach to understanding and applying different statistical concepts in real-life scenarios by the end of the course.

Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Beyond Model Formulation: Assessment of Novices Graphing, Interpreting, and Writing About Their Model and Solution
Authors: Williams Julie Ann Stuart , Rankin Maxwell , Gallamore Kristine , Reid Randall
Published: September 2016

Operations Research/Management Science educators need to promote learning outcomes related to building, solving, and interpreting a model, and producing associated business communications. In this paper, we present a test instrument that requires an evaluation of a two-decision business scenario in three domains. The first domain is formulating a linear programming model. The second is a graphical solution analysis. The third is describing the problem and interpreting the recommendation in a professional memo. Using this three-domain format in a quiz, we assess the quality of student performance across three domains, i.e., model formulation, graphical analysis, and management interpretation, for multiple problem components. Statistical results of the current study indicate that students struggle more with graphically solving and interpreting the model and its solution than with formulating the model. In the current study, students are least successful in graphing the isoprofit line, graphing the constraints, and describing those constraints in the management interpretation. To our knowledge, these domains have not been previously reported for objective functions or constraints. Our study also shows that many students exhibit deficiencies in the mechanics of writing.
Case Article—U.S. Army Deployment to the Middle East
Authors: Dillenburger Steven P.
Published: September 2016

This paper describes a modeling and simulation case study relating to Army platoons deploying to the Middle East. The study tasks students with analyzing routes for deploying troops travel through in an effort to decrease the average time a soldier spends in transit. Students with little simulation experience are able to become familiar with modeling software. Student groups are instructed to identify where bottlenecks occur in the queuing system and to find creative solutions to alleviate those bottlenecks. Additionally, the case study illustrates the concepts of input and output analysis, random numbers, random variate generation, and probability distributions.

Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Exploring the synergistic relationship between research and teaching
Authors: Fredericks Suzanne
Published: September 2016

Despite ongoing discussion of the relationship between research and teaching, these are often considered separately in academic practice. In this comment, Suzanne Fredericks discusses the importance of recognising and applying this synergistic relationship
Analisis kesesuaian dan daya dukung ekowisata bahari Pulau Sebesi, Provinsi Lampung
Authors: Johan Yar
Published: September 2016

Abstract. The Sebesi Island has coral reefs, mangrove and seagrass ecosystems, and therefore this island has the potenticy to be developed as a tourism destination object. The objectives of the present study were to analysis the suitability and carrying of Sebesi Island for for marine ecotourism activities of diving and snorkeling. The primary data were collected through field sampling, direct observation of field conditions, questionnaires and interviews. The secondary data were collected from previous studies, journals, technical reports and related agencies. The results showed that the Sebesi Island was suitable for diving and snorkeling activities  (S2 category) with the carrying capacity for diving and snorkeling activities were 2,394 person/day and 2,489 person/day, respectively.Keywords: coral reef, marine ecotourism, suitability, carrying capacity, Sebesi Island Abstrak. Pulau Sebesi berpotensi untuk dikembangkan menjadi salah satu Objek Daerah Tujuan Wisata (ODTW). Ekosistem Pulau Sebesi sebagian besar merupakan ekosistem terumbu karang, mangrove dan lamun. Penelitian tentang analisis kesesuaian dan daya dukung ekowisata bahari Pulau Sebesi Provinsi Lampung bertujuan mengkaji kesesuaian kawasan Pulau Sebesi untuk kegiatan ekowisata bahari yaitu diving dan snorkeling dan menganalisis daya dukung (carryng capacity) kawasan Pulau Sebesi. Pengumpulan data primer dilakukan melalui sampling, observasi langsung di lapangan, kuisioner, wawancara terbuka/langsung dan wawancara mendalam  di lokasi penelitian. Data sekunder dikumpulkan dengan penelusuran berbagai pustaka, dan instansi terkait. Hasil penelitian menunjukkan bahwa jenis kegiatan ekowisata bahari diving dan snorkling termasuk dalam kategori sesuai (S2), dengan daya dukung kawasan 2.394/hari orang untuk diving dan 2.489 orang/hari untuk snorkling.Kata kunci: terumbu karang, ekowisata bahari, kesesuaian, daya dukung, Pulau Sebesi