bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on influencing factors and survival analysis of patients with malignant tumors treated by music therapy.
Authors: Hong Lei , Wang Junyan , Zhang Fan , Ma Minting , Jiang Da , Wei Suju
Published: May 2019

e23144

Background: Music therapy is not easy to carry out. After carrying out music therapy propaganda, many patients still question the efficacy of it, and won’t be included in music therapy group. This study retrospectively analyzed the related factors and survival analysis of patients enrolled in music therapy, and provided reference for appropriate music therapy propaganda methods. Methods: From March 2014 to January 2016, 258 patients with malignant tumors diagnosed in Fourth Hospital of Hebei Medical University were collected. Music therapy was divided into control group and intervention group according to whether they were willing to be included in the group or not. Questionnaire survey was used to investigate the effect of factors on music therapy in the two groups. Follow-up was conducted by telephone to analyze the effect of music therapy on PFS. Single factor analysis was used to analyze the relationship between factors and music therapy. The differences of PFS between control group and intervention group was analyzed by Log-Rank test (P < 0.05). Results: A total of 258 patients were enrolled in the questionnaire survey, and 240 patients completed the questionnaire effectively. Age, education level, music hobby, and knowledge of illness had significant influence on whether the patients were enrolled in music therapy group (P < 0.05). Gender, occupation, type of disease, stage of disease and DT score had no significant effect on whether patients were enrolled in music therapy group (P > 0.05). Age and music preference were independent influencing factors of music therapy (P = 0.025, P = 0.000). The median PFS of lung cancer patients was 8 months and 8 months, respectively (P = 0.760). The median PFS of breast cancer patients was 9 months and 8 months, respectively (P = 0.726). The median PFS of digestive tract cancer patients was 8 months and 10 months, respectively (P = 0.684). The median PFS of gynecologic tumor patients was 8 months and 8 months, respectively (P = 0.310). Conclusions: Age, education level, music hobby and condition information have significant influence on whether patients are included in music therapy group or not. Age and music hobby are independent influencing factors of music therapy. PFS of patients with malignant tumors who are willing to be included in music therapy group tends to prolong, but there is no statistical significance.
How often do metastatic brain disease patients prescribed ten fractions of whole brain radiation therapy die without completing treatment?
Authors: McClelland Shearwood , Agrawal Namita , Shiue Kevin , Bartlett Gregory , Zellars Richard C. , Watson Gordon A , Ellsworth Susannah G.
Published: May 2019

e23146

Background: Palliative whole brain radiation therapy (WBRT) is an established treatment modality for optimizing intracranial disease control in patients with metastatic brain disease, most commonly prescribed to a dose of 30 Gy in 10 fractions. The fidelity of WBRT course completion has not been rigorously evaluated. Methods: Two prospective institutional databases evaluating patients treated from April 2015 through December 2018 identified patients who received WBRT. Information analyzed included prescribed and delivered dose/fractionation, Karnofsky Performance Status (KPS), admission status, treatment duration, and time between WBRT completion and patient hospice referral/death. Results: 52 consecutive patients prescribed WBRT to 30 Gy in 10 fractions were evaluated. Twenty-six (50%) were inpatients, and only 17 (33%) had a KPS of 70 or greater (able to care for self). More than 30% failed to finish more than 5 of their 10 scheduled fractions before either death or hospice referral; only 29 of 52 patients (56%) finished WBRT as prescribed. Twenty-five patients (48%) died within 30 days of WBRT. Of the 29 patients who finished WBRT as prescribed, 9 (31%) died within 30 days of completing treatment. Of the 23 patients who failed to complete standard fractionation WBRT, nearly 70% died within 30 days of receiving their final radiation therapy fraction. Conclusions: These findings indicate that greater than 40% of patients prescribed the standard 10 fraction regimen of WBRT do not remain well enough to tolerate the full duration of treatment. With nearly half of patients dying within 30 days of standard fraction WBRT, there should be strong incentive to reduce the physical and financial burden on this patient population by prescribing WBRT with significantly shorter (i.e. single-fraction or 20 Gy in 5 fractions) fractionation schemes.
Oncology Associated Symptoms and Individualized strategies (OASIS): Precision symptoms management for rural patients with advanced cancer.
Authors: Vikas Praveen , Gilbertson-White Stephanie , Saeidzadeh Tannaz , Perkhounkova Yelena
Published: May 2019

e23155

Background: Rural cancer patients have limited access to symptom management specialists. OASIS is an 8-week, web-based intervention addressing this access gap by providing the right symptom management to the right patients at the right time. This feasibility study seeks to describe recruitment and retention patterns and evaluate symptom severity, distress, and interference at 4, 8, and 12 weeks. Methods: Eligibility included: advanced cancer diagnosis, > 18 years old, and living in small town or rural area. Reasons for non-enrollment and dropout were collected. Descriptive statistics were calculated to evaluate recruitment and retention rates along with symptom severity and interference at each time point. The mean severity and distress scores using the 0-10 NRS of the five symptoms with the highest rating was computed for each time point (i.e., baseline, week 4, and week 8). By averaging the five highest rated symptoms, we evaluated the worst symptoms the individual is experiencing at each data point. Results: Fifty-nine people were approached about the study over 18 months, 38 people signed consents, 12 dropped before completing baseline questionnaires, and 9 completed baseline questionnaires but did not start the intervention. Seventeen people completed baseline questionnaires and started the intervention. The recruitment rate was 66%, the retention rates were 50% and 33% at 4 and 12 weeks.Reasons for drop out included lack of bothersome symptoms, too busy, and generally overwhelmed. Mean age of sample was 62 years and majority men (62.5%). Fatigue (M = 6.4), drowsiness (M = 5.4), numbness/tingling (M = 4.4), and sleep disturbance (M = 4.4) were the most severe symptoms at baseline. Mean symptom severity was M = 3.03 and mean interference was M = 2.53 at baseline. For participants who received the full OASIS-WN intervention, between baseline and week 8, the mean interference rating decreased by 1.6±2.1 points (p = .019), mean severity and distress ratings for the five worst symptoms decreased by 1.72±1.72 (p = .004) and 2.2±2.4 (p = .006), respectively. Conclusions: Symptom severity, distress, and interference improved for participants who received the full intervention. Reasons for early drop out suggest symptom management ought to be provided when the situation is optimal for learning. Future research will evaluate the efficacy of OASIS.
The efficacy of placebo for the treatment of cancer-related fatigue: A systematic review and meta-analysis.
Authors: Barreto Carmelia Maria Noia , Aguiar Pedro Nazareth , Cubero Daniel de Iracema Gomes , Del Giglio Auro
Published: May 2019

e23157

Background: Cancer-related fatigue (CRF) is a common symptom among patients with cancer. The efficacy of placebo, however, was never the main objective of any meta-analysis. Predicting the efficacy of placebo may facilitate researchers in designing future clinical trials for the treatment of CRF. Methods: We performed a systematic review searching for prospective clinical trials comparing any treatment versus placebo for the treatment of CRF. We included studies that enrolled patients with any primary site of neoplasia and any stage of cancer. We excluded all studies that assessed fatigue related to any treatment. The primary endpoint of this study is the mean effect of placebo on fatigue according to the Functional Assessment of Chronic Illness (FACIT-F) and Brief Fatigue Inventory (BFI) scales. The secondary endpoint was the proportion of patients who reported improvement in fatigue (response rate). Results: We found 520 studies, and 29 studies with 3,758 participants were included in the meta-analysis. Placebo had a mean effect of +4.88 (95%CI +2.45 to +7.29) using the FACIT-F scale, although it was statistically worse than the interventions studied (p = 0.005). Using the BFI scale, placebo had an average effect of +0.64 (95%CI +0.02 to +1.30), although it was also worse than the other interventions studied (p = 0.002). In terms of the response rate, 29% (95%CI 25%–32%) of patients taking a placebo reported a significant improvement in CRF compared to 36% of patients treated with other interventions (p = 0.030). Conclusions: Placebo treatments had a significant effect on CRF, and predicting these effects may help design future studies for CRF.
eMouvoir: Randomized study estimating the impact of a personalized and remote support centered on physical activity (PA) for patients (pts) after breast cancer (BC).
Authors: Vanlemmens Laurence , Anota Amelie , Bogart Emilie , Nerich Virginie , Cauchois Didier , Dewitte Alain , Dormeuil Etienne , Lartigau Eric , Le Gall Flora , Mocaer Hervé , Thenot Aurelie , Brochard Marc-Antoine , Le Deley Marie-Cecile
Published: May 2019

TPS11631

Background: BC pts can reduce their health-related quality of life (HRQoL) encompassing physical, psychological and social components due to cancer and treatments (trts). Despite the strong evidence of the beneficial effects of EPA for BC pts on HRQoL, the cancer pts’ EPA levels most often decline after diagnosis and trts due to physical and psychological components, accessibility to exercise programs, time constraints. Connected watches can now contribute to pts’ deeper commitment to their program by providing reliable trends of their EPA metrics. Notwithstanding this recent progress, cancer pts keep facing challenges to maintain a regular EPA. We aim at evaluating a holistic intervention including a physical activity educator, coaching pts remotely for 4 months (mo), to improve HRQoL after BC. Methods: eMouvoir is a multicenter randomized, controlled phase 3 trial started 4-6 mo after the end of trt among non-metastatic BC pts. It assesses the benefit of a personalized remote EPA coaching, including a connected watch, access to a digital platform, personalized objectives, ≥2 messages per week, weekly lessons, for a 4-mo duration, compared to the standard supportive approach (recommendations for EPA made during visits with the oncologist) in terms of HRQoL. The randomization is balanced 1:1 and controlled for HRQoL at inclusion, trts, exercise practice, age, access to the Internet and center. Main eligibility criteria are: age ≥18; adjuvant or neoadjuvant trt for non-metastatic BC; medical certificate for sports practice. Patients without a connected device are eligible. HRQoL is evaluated using the SF-36 questionnaire, at 4, 8 and 12 mo. Both components (physical and mental summary) at 12 mo are used as co-primary endpoints. The study includes a health-economics evaluation, using EQ-5D and EQ VAS, to estimate the incremental cost-utility ratio. Based on the following assumptions: expected mean difference for each SF-36 component at 12 mo =3 points, standard deviation=15, power=90%, 2-sided alpha=2.5%, 10% drop-outs, 1242 evaluable pts are required, leading to 1380 pts. The trial is funded by the French ministry of health and should open enrollment soon.
Understanding and predicting fatigue, cardiovascular (CV) decline, and events after breast cancer treatment (UPBEAT): A prospective cardio-oncology study.
Authors: Reding Kerryn , D'Agostino Ralph , Lesser Glenn Jay , Klepin Heidi D. , Wagner Lynne I. , Kitzman Dalane , Brubaker Peter H. , Mihalko Shannon , Jordan Jennifer , Avis Nancy E. , Winkfield Karen Marie , Ky Bonnie , Dent Susan Faye , Crotts Teresa , Calhoun Tonya , Lane Kimberly , Hundley W. Gregory
Published: May 2019

TPS11634

Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients,treated with modern cancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and future development of CV events. The comprehensive assessment of factors includes ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, Expanded SPPB), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points, include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2peak via cardiopulmonary exercise test), fatigue (via FACT-F). Eligibility criteria are: age >18 years; ECOG 0-2, able to walk without symptoms; and for BC patients, treatment with chemotherapy. 143 participants are accrued and currently enrolling through ECOG and NCORP sites. Participants will be followed for 9 years with active surveillance of CV events, i.e., heart failure, myocardial infarction, stroke, all-cause and CV death. Clinical trial information: NCT02791581.
Biomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study.
Authors: Gutierrez Martin , Hellmann Matthew David , Gubens Matthew A. , Aggarwal Charu , Tan Daniel Shao Weng , Felip Enriqueta , Chiu Joanne Wing Yan , Lee Jong Seok , Yang James Chih-Hsin , Garon Edward B. , Basso Andrea , Ma Hua , Fong Lawrence , Snyder Alex , Yuan Jianda , Herbst Roy S.
Published: May 2019

TPS9117

Background: Pembrolizumab-based combination immunotherapy aims to improve clinical outcomes over pembrolizumab monotherapy. A biomarker-based therapeutic approach may be associated with improved response to different combination therapies of immune checkpoint inhibitors and may improve overall outcomes in NSCLC. The randomized, multicenter, open-label, phase 2 KEYNOTE-495 trial ( NCT03516981 ) will evaluate the clinical usefulness of biomarker-informed, pembrolizumab-based combination therapy in patients with treatment-naive, advanced NSCLC. Methods: This is a group-sequential, adaptive randomization trial. Patients will have histologically or cytologically confirmed treatment-naive, advanced NSCLC, documented absence of EGFR and B-Raf mutations and ALK and ROS1 gene rearrangements, measurable disease per RECIST v1.1, and ECOG PS 0-1. Tumor tissue from patients will be initially screened for 2 validated, independent, next-generation biomarkers: T cellinflamed gene expression profile (GEP) and tumor mutational burden (TMB). Based on results of biomarker screening, patients will be assigned to 1 of 4 groups: TMBlowGEPlow, TMBhighGEPlow, TMBlowGEPhigh, and TMBhighGEPhigh. Within each group, patients will be randomly assigned to receive pembrolizumab 200 mg Q3W intravenously (IV) combined with either MK-4280 200 mg Q3W (antiLAG-3) IV or lenvatinib 20 mg orally once daily, with the randomization assignment adaptively modified based on interim efficacy analyses. Response will be assessed by imaging every 9 weeks for the first year and every 12 weeks thereafter using RECIST v1.1. Treatment will continue for 35 cycles (~2 years). Patients in the pembrolizumab + lenvatinib arm who complete 35 treatments may continue with lenvatinib monotherapy until disease progression or toxicity. Treatment arms may be terminated during the interim analysis due to safety, prespecified futility criteria, or both. Primary end point is investigator-assessed objective response rate (RECIST v1.1). Secondary end points are progression-free survival, overall survival, and safety. Recruitment and screening are ongoing in more than 8 countries. Clinical trial information: NCT03516981.
Randomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non–small-cell lung cancer (NSCLC): LEAP-006.
Authors: Hui Rina , Nishio Makoto , Reck Martin , Rodriguez-Abreu Delvys , Fouad Tamer M. , Flaim Doreen , Yin Lina , Dang Thao , Herbst Roy S.
Published: May 2019

TPS9118

Background: Lenvatinib (multiple-receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1–3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptors α, c-kit, and RET) has antitumor activity in combination with pembrolizumab (anti–PD-1 inhibitor) or with chemo in advanced NSCLC. LEAP-006 (NCT03829319) evaluates first-line lenvatinib with pembrolizumab + chemo for metastatic nonsquamous NSCLC. Methods: This randomized, double-blind, 2-part, phase 3 study enrolls pts ≥18 years with histologically/cytologically confirmed metastatic, nonsquamous, treatment-naive NSCLC without sensitizing genetic aberrations. Pts receive lenvatinib 8 mg daily or matching placebo + pembrolizumab 200 mg + pemetrexed 500 mg/m2 + carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 Q3W (4 cycles) followed by maintenance pembrolizumab (35 cycles) + lenvatinib/placebo + pemetrexed (no limit). In part 1 (open-label safety run-in), ~12 pts receive lenvatinib + pembrolizumab + chemo (n ≥6 in each chemo arm). If < 3 dose-limiting toxicities (DLTs; select prespecified AEs) occur in 6 pts in each arm in cycle 1, part 2 will begin enrolling. If ≥3 DLTs occur in 6 pts in each arm, enrollment in part 1 may continue with advisement by the study oversight committee. In part 2, pts are randomized 1:1 to lenvatinib or placebo + pembrolizumab + chemo, stratified by PD-L1 tumor proportion score ( < 50%/≥50%), geographic site (East Asian/other), and ECOG PS (0/1). Tumor imaging occurs at baseline and Q6W until wk 18; then Q9W until wk 54; then Q12W until verified PD, initiation of new cancer therapy, study withdrawal, or death. AEs are graded by NCI CTCAE v4.0. The primary endpoint in part 1 is safety. The primary endpoints in part 2 are PFS (RECIST v1.1 by BICR) and OS, analyzed by Kaplan-Meier method and stratified log-rank test. Secondary endpoints in part 2 are ORR and DOR (RECIST v1.1 by BICR), safety, and quality of life. Enrollment into part 1 will begin in March 2019. For part 2, approximately 714 pts will enroll in 160 sites in 17 countries. Clinical trial information: NCT03829319.
SAVANNAH: A Phase II trial of osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-driven (MET+), locally advanced or metastatic non-small cell lung cancer (NSCLC), following disease progression on osimertinib.
Authors: Oxnard Geoffrey R. , Cantarini Mireille , Frewer Paul , Hawkins George , Peters Jane , Howarth Paul , Ahmed Ghada F. , Sahota Tarjinder , Hartmaier Ryan , Li-Sucholeiki Xiaocheng , Ahn Myung-Ju
Published: May 2019

TPS9119

Background: The toxicity profile of the third-generation EGFR-tyrosine kinase inhibitor (TKI) osimertinib makes it an attractive backbone for combination with other targeted agents, possibly overcoming acquired resistance mechanisms. Combination with a MET-inhibitor is an intuitive approach as MET-amplification was identified as the most common mechanism of resistance to osimertinib in preliminary ctDNA data from the Phase III FLAURA (15% of pts) and AURA3 (19% of pts) studies. Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, potent and highly selective MET-TKI that had an acceptable safety profile when combined with osimertinib in the Phase Ib TATTON study, providing the basis for this Phase II SAVANNAH study (NCT03778229). Other mechanisms of acquired resistance to osimertinib, including secondary EGFR mutations (e.g. C797S), RAS/RAF activation, and oncogenic gene fusions, provide additional opportunities for developing osimertinib-based combinations. Methods: Eligible pts will have histologically/cytologically confirmed EGFR-mutant NSCLC, and MET+ disease by central FISH, central IHC, or local NGS (retrospectively confirmed by central FISH/IHC). Pts must have documented radiological progression following 1–3 lines of prior therapy (must include osimertinib). Pts will receive osimertinib 80 mg plus weight-based dosing with savolitinib 300 or 600 mg PO QD, in 28-day cycles. The primary objective is efficacy (RECIST 1.1) by overall response rate (ORR) in pts who are MET+ by central FISH. Secondary endpoints include: ORR ( MET+ by central IHC and all pts); progression-free survival, overall survival, duration of response, percent change in tumor size, HRQoL, and EGFR mutation ctDNA clearance ( MET+ by central FISH, central IHC, and all pts); safety, and pharmacokinetics (all pts). Based on the TATTON study, we anticipate enrolling ~172 MET+ pts to include ≥117 pts with MET+ disease by central FISH. Enrolment began in Q1 2019. Ongoing development of complementary trials targeting other osimertinib resistance mechanisms will also be discussed. Clinical trial information: NCT03778229.
ORION: A Phase 2, randomized, multicenter, double-blind study to assess efficacy and safety of durvalumab+olaparib vs durvalumab alone as maintenance therapy in Stage IV non-small cell lung cancer (NSCLC).
Authors: Ahn Myung-Ju , Liu Yufan , Improta Teresa , Marcovitz Michelle , DiPiazza Kate , Lanasa Mark C.
Published: May 2019

TPS9126

Background: Systemic chemotherapy for first-line (1L) metastatic NSCLC shows mixed outcomes. Results from studies using immunotherapy alone or combined with chemotherapy as 1L treatment in patients (pts) with metastatic NSCLC represent a substantial advance, but further improvement is needed. Increased DNA damage triggered by polyadenosine 5’diphosphoribose polymerase inhibition may confer antitumor activity, modify tumor immunogenicity, and further sensitize tumors to immune checkpoint inhibition, thus promoting a more durable antitumor response. This Phase 2, randomized, multicenter, double-blind study (NCT03775486) is designed to assess the efficacy and safety of durvalumab + olaparib vs durvalumab alone as maintenance therapy in pts whose Stage IV NSCLC has not progressed following 1L platinum-based chemotherapy + durvalumab. Methods: Adult pts with Stage IV NSCLC with tumors lacking activating EGFR mutations and ALK fusions are eligible. In the initial therapy phase, all pts will receive durvalumab (1500 mg IV) concurrent with platinum-based doublet therapy. Durvalumab + chemotherapy will be administered for 4 cycles for both squamous NSCLC (nanoparticle albumin-bound [nab]-paclitaxel + carboplatin or gemcitabine + carboplatin/cisplatin) and nonsquamous NSCLC (nab-paclitaxel + carboplatin or pemetrexed + carboplatin/cisplatin). Pts whose disease does not progress (complete or partial response [CR/PR] or stable disease [SD]; investigator-assessed RECIST 1.1) will be randomized (1:1) to durvalumab (1500 mg IV, every 4 weeks) + either olaparib (300 mg, oral, BID) or its matching placebo until disease progression. Randomization will be stratified based on objective response to durvalumab + chemotherapy (CR/PR or SD) during the initial therapy phase and histology (squamous or nonsquamous). The primary endpoint is PFS (investigator-assessed, RECIST 1.1). Secondary endpoints are OS, PFS in pts with homologous recombination repair related gene mutation, ORR, duration of response, HRQoL, pharmacokinetics and immunogenicity of durvalumab, and safety. Pt enrollment is ongoing. Clinical trial information: NCT03775486.
Spindle checkpoint silencing at kinetochores with submaximal microtubule occupancy
Authors: Etemad Banafsheh , Vertesy Abel , Kuijt Timo E. F. , Sacristan Carlos , van Oudenaarden Alexander , Kops Geert J. P. L.
Published: May 2019

The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by monitoring kinetochore–microtubule interactions. SAC proteins are shed from kinetochores once stable attachments are achieved. Human kinetochores consist of hundreds of SAC protein recruitment modules and bind up to 20 microtubules, raising the question of how the SAC responds to intermediate attachment states. We show that one protein module (‘RZZS-MAD1-MAD2’) of the SAC is removed from kinetochores at low microtubule occupancy and remains absent at higher occupancies, while another module (‘BUB1-BUBR1’) is retained at substantial levels irrespective of attachment states. These behaviours reflect different silencing mechanisms: while BUB1 displacement is almost fully dependent on MPS1 inactivation, MAD1 (also known as MAD1L1) displacement is not. Artificially tuning the affinity of kinetochores for microtubules further shows that ∼50% occupancy is sufficient to shed MAD2 and silence the SAC. Kinetochores thus respond as a single unit to shut down SAC signalling at submaximal occupancy states, but retain one SAC module. This may ensure continued SAC silencing on kinetochores with fluctuating occupancy states while maintaining the ability for fast SAC re-activation.
Internally coupled middle ears enhance the range of interaural time differences heard by the chicken
Authors: Köppl Christine
Published: May 2019

Interaural time differences (ITD) are one of several principle cues for localizing sounds. However, ITD are in the sub-millisecond range for most animals. Because the neural processing of such small ITDs pushes the limit of temporal resolution, the precise ITD-range for a given species and its usefulness - relative to other localization cues - was a powerful selective force in the evolution of the neural circuits involved. Birds and other non-mammals have internally coupled middle ears working as pressure-difference receivers that may significantly enhance ITD, depending on the precise properties of the interaural connection. Here, the extent of this internal coupling was investigated in chickens, specifically under the same experimental conditions as typically used in neurophysiology of ITD-coding circuits, i.e. with headphone stimulation and skull openings. Cochlear microphonics (CM) were recorded simultaneously from both ears of anesthetized chickens under monaural and binaural stimulation, using pure tones from 0.1 to 3 kHz. Interaural transmission peaked at 1.5 kHz at a loss of only −5.5 dB; the mean interaural delay was 264 µs. CM amplitude strongly modulated as a function of ITD, confirming significant interaural coupling. The “ITD heard” derived from the CM phases in both ears showed enhancement, compared to the acoustic stimuli, by a factor of up to 1.8. However, the experimental conditions impaired interaural transmission at low frequencies (< 1 kHz). We identify factors that need to be considered when interpreting neurophysiological data obtained under these conditions, and relating them to the natural free-field condition.
Hornets possess long-lasting olfactory memories
Authors: Gong Zhiwen , Tan Ken , Nieh James C.
Published: May 2019

The ability of animals to learn and remember is an important adaptation for coping with environmental changes. The fitness benefits provided by these cognitive skills, in conjunction with social behaviours, contributes to the success of social insects. How these abilities are shared among the different castes and the long-term persistence of memory are now being elucidated in diverse systems, work that should shed light on general principles underlying cognitive evolution. Here we provide the first evidence of olfactory learning and long-term olfactory memory in all three castes of an Asian hornet, Vespa velutina. Using the first proboscis extension reflex assay developed for hornets or wasps, we found that all hornet castes could learn and remember odours associated with a food reward. Moreover, long-lasting memory was retained without significant decay in gynes (virgin queens) and drones even up to 30 d. Workers did not survive for 30 d. Drones learned and remembered simple odorant molecules and gyne sex pheromone with equal facility. These results increase our understanding of the outstanding cognitive abilities of social insects and suggest the likely importance of long-lasting memory in different castes of the same species.
Section-specific H+ fluxes in renal tubules of fasted and fed goldfish
Authors: Fehsenfeld Sandra , Kolosov Dennis , Wood Chris M. , O'Donnell Michael J.
Published: May 2019

A recent study demonstrated that in response to a feeding-induced metabolic acidosis, goldfish Carassius auratus adjust epithelial protein and/or mRNA expression in their kidney tubules for multiple transporters known to be relevant for acid-base regulation. These include Na+/H+-exchanger, V-H+-ATPase, cytoplasmic carbonic anhydrase, HCO3−-transporters, and Rhesus proteins. Consequently, renal acid output in the form of protons and NH4+ increases. Little, however, is known about mechanistic details of renal acid-base regulation in C. auratus and teleost fishes in general. The present study applied the Scanning Ion-selective Electrode Technique (SIET) to measure proton flux in proximal, distal and connecting tubules of goldfish. We detected increased H+ efflux into the extracellular fluid from the tubule in fed animals, resulting from paracellular back-flux of H+ through the tight junction. By applying inhibitors for selected acid-base regulatory epithelial transporters, we found that cytosolic carbonic anhydrase and HCO3− transporters were important in mediating H+ flux in all three tubule segments of fed goldfish. Contrastingly, V-H+-ATPase seemed to play a role for H+ flux only in proximal and distal tubule, and Na+/H+-exchanger in proximal and connecting tubule. We develop working models for transport of acid-base relevant equivalents (H+, HCO3−, NH3/NH4+) for each tubule segment in C. auratus kidney. While the proximal tubule appears to play a major role in both H+ secretion and HCO3− reabsorption, the distal and connecting tubules seem to mainly serve for HCO3− reabsorption and NH3/NH4+ secretion.
Molecular physiology of chemical defenses in a poison frog
Authors: Caty Stephanie N. , Alvarez-Buylla Aurora , Byrd Gary D. , Vidoudez Charles , Roland Alexandre B. , Tapia Elicio E. , Budnik Bogdan , Trauger Sunia A. , Coloma Luis A. , O'Connell Lauren A.
Published: May 2019

Poison frogs sequester small molecule lipophilic alkaloids from their diet of leaf litter arthropods for use as chemical defenses against predation. Although the dietary acquisition of chemical defenses in poison frogs is well-documented, the physiological mechanisms of alkaloid sequestration has not been investigated. Here, we used RNA sequencing and proteomics to determine how alkaloids impact mRNA or protein abundance in the Little Devil Frog (Oophaga sylvatica) and compared wild caught chemically defended frogs to laboratory frogs raised on an alkaloid-free diet. To understand how poison frogs move alkaloids from their diet to their skin granular glands, we focused on measuring gene expression in the intestines, skin, and liver. Across these tissues, we found many differentially expressed transcripts involved in small molecule transport and metabolism, as well as sodium channels and other ion pumps. We then used proteomic approaches to quantify plasma proteins, where we found several protein abundance differences between wild and laboratory frogs, including the amphibian neurotoxin binding protein saxiphilin. Finally, because many blood proteins are synthesized in the liver, we used thermal proteome profiling as an untargeted screen for soluble proteins that bind the alkaloid decahydroquinoline. Using this approach, we identified several candidate proteins that interact with this alkaloid, including saxiphilin. These transcript and protein abundance patterns suggest the presence of alkaloids influences frog physiology and that small molecule transport proteins may be involved in toxin bioaccumulation in dendrobatid poison frogs.
Robot Arithmetic: New Technology and Wages
Authors: Caselli Francesco , Manning Alan
Published: May 2019

Existing economic models show how new technology can cause large changes in relative wages and inequality. But there are also claims, based largely on verbal expositions, that new technology can harm workers on average or even all workers. This paper shows— under plausible assumptions—that new technology is unlikely to cause wages for all workers to fall and will cause average wages to rise if the prices of investment goods fall relative to consumer goods (a condition supported by the data). We outline how results may change with different assumptions. (JEL D31, G31, J22, J24, J31, O31, O33)
Labor Supply and the Value of Non-Work Time: Experimental Estimates from the Field
Authors: Mas Alexandre , Pallais Amanda
Published: May 2019

We estimate the marginal value of non-work time (MVT) using a field experiment. We offered job applicants randomized wage-hour bundles. Choices over these bundles yield estimates of the MVT as a function of hours, tracing out a labor supply relationship. The substitution effect is positive. Individual labor supply is highly elastic at low hours and more inelastic at higher hours. For unemployed applicants, our preferred estimate of the average opportunity cost of a full-time job due to lost leisure and household production is 60 percent of after-tax marginal product, and 72 percent when including fixed costs of employment and child-care costs. (JEL C93, J22, J24, J31, J64, J65)
Stealth Consolidation: Evidence from an Amendment to the Hart-Scott-Rodino Act
Authors: Wollmann Thomas G.
Published: May 2019

Prospective merger review is the most frequent application of antitrust law. It exempts transactions on the basis of size, though small deals can have large anticompetitive effects in segmented industries. I examine its impact on antitrust enforcement and merger activity in the context of an abrupt increase in the US exemption threshold. I find that among newly-exempt deals, antitrust investigations fall to almost zero while mergers between competitors rise sharply. Effectively all of the rise reflects an endogenous response of firms to reduced premerger scrutiny, consistent with large deterrent effects of antitrust enforcement. (JEL G34, G38, K21, L41)
The Culture of Overconfidence
Authors: Bhaskar V. , Thomas Caroline
Published: May 2019

Perceptions of overconfidence can exacerbate the tendency of reputationally concerned leaders to continue bad projects. Reputation concerns alone induce a bias toward inefficient continuation in a leader receiving information privately. When she is overconfident— or holds a more favorable prior than observers—this tendency is aggravated. This remains true even when she is not really overconfident, but merely perceived to be so. Higher-order beliefs regarding overconfidence induce inefficient equilibrium selection even when there is “almost common knowledge” that the leader is not over-confident. This provides a novel perspective on how culture selects among equilibria: via higher-order beliefs. (JEL D82, D83, Z13)
Democratic Values and Institutions
Authors: Besley Timothy , Persson Torsten
Published: May 2019

This paper builds a model of the two-way interaction between democratic values and institutions to bridge sociological research, focusing on values, with economics research, which studies strategic decisions. Some citizens hold values that make them protest to preserve democracy with the share of such citizens evolving endogenously over time. There is then a natural complementarity between values and institutions creating persistence without assuming any form of commitment. The approach unifies ideas in the literature, explains observed patterns in the data on democratic values and political institutions, and suggests new insights into sources of heterogeneity in values. (JEL D02, D72)
Assessing drug target suitability using TargetMine
Authors: Chen Yi-An , Yogo Erika , Kurihara Naoko , Ohno Tomoshige , Higuchi Chihiro , Rokushima Masatomo , Mizuguchi Kenji
Published: May 2019

In selecting drug target candidates for pharmaceutical research, the linkage to disease and the tractability of the target are two important factors that can ultimately determine the drug efficacy. Several existing resources can provide gene-disease associations, but determining whether such a list of genes are attractive drug targets often requires further information gathering and analysis. In addition, few resources provide the information required to evaluate the tractability of a target. To address these issues, we have updated TargetMine, a data warehouse for assisting target prioritization, by integrating new data sources for gene-disease associations and enhancing functionalities for target assessment. As a data mining platform that integrates a variety of data sources, including protein structures and chemical compounds, TargetMine now offers a powerful and flexible interface for constructing queries to check genetic evidence, tractability and other relevant features for the candidate genes. We demonstrate these features by using several specific examples.
A new method for detecting abrupt shifts in time series
Authors: Boulton Chris A. , Lenton Timothy M.
Published: May 2019

Abrupt shifts in time series are a topic of growing interest in a number of research areas. They can be caused by a range of different underlying dynamics, for example, via a mathematical bifurcation, or potentially as the result of an auto-correlated stochastic process (i.e. ‘red’ noise). Here we present a method that detects abrupt shifts by searching for gradient changes that occur over a short space of time. It can be automated, allowing many time series to be analysed by the user at once, such as from high spatial resolution data. Our method detects abrupt shifts regardless of their origin (which it cannot deduce). We present a comparison with the method of abrupt shift detection from the changepoint R package, which is based on changes in mean over the time series. Our method performs better on data with an underlying trend where comparisons of means may fail.
Teaching Followership in Leadership Education
Authors: Raffo Deana M.
Published: May 2019

This paper provides leadership educators with a resource for teaching followership. It presents a lesson for teaching students about followership in contemporary society by including key concepts and follower characteristics followed by class activities and assignments designed to engage students in active learning and self-reflective processes. A dose of whimsy enhances this lesson with the use of a YouTube video that eloquently and humorously illustrates the crucial role followers play in organizational life.
Why Does Leadership Exist?
Authors: Caulfield Jay
Published: May 2019

What style of leadership is most effective in a particular situation with a specific group of followers? How do leaders best motivate followers in achieving goals? Although important questions, before we may come to fully understand the how and what of leadership, in this brief I suggest that we reflect upon a more basic leadership question. In the context of a paradigm from the work of the late educator and social critic, Neil Postman (1931-2003), I explore the question, “Why does leadership exist?” For when we reflect upon the answer to that question, we may gain further insight into ourselves as leaders, which may enhance our understanding of what good leadership looks like and how we might best achieve it.
The Inaugural National Leadership Education Research Agenda: A New Direction for the Field
Authors: Andenoro Anthony C.
Published: May 2019

This commentary details the process aimed at developing the Inaugural National Leadership Education Research Agenda. The goal of the project is to create a guiding document to assist in further defining Leadership Education as a discipline and provide directional research priorities for that discipline. The commentary provides a foundational understanding and creates transparency for the process in an effort to solicit collaborative partnerships and dialogue that will ultimately provide more holistic research priorities and enhanced opportunities for scholarship within Leadership Education.
Appreciative Inquiry: A Tool for Organizational, Programmatic, and Project-Focused Change
Authors: Priest Kerry L. , Kaufman Eric K. , Brunton Kelsey , Seibel Megan
Published: May 2019

This practice paper describes how leadership education faculty and students at Virginia Tech have facilitated change through the use of appreciative inquiry (Ai) at the departmental level, program level, and project level. Appreciative inquiry has been found to be a useful tool for leadership educators, as its foundation in social constructionist philosophy aligns with contemporary leadership and learning theories. This paper outlines (a) the philosophy of Ai as it applies to organizational development (b) illustrates Ai practices associated with a five-stage model, and (c) highlights three examples that can be used as models for leading change in a variety of organizational situations. The authors suggest that leadership educators are uniquely positioned to serve academic communities as facilitators of change by bridging theory and practice in pursuit of new ways of knowing and working together.
Examining the Intersections between Undergraduates’ Engagement in Community Service and Development of Socially Responsible Leadership
Authors: Soria Krista , Nobbe June , Fink Alex
Published: May 2019

This paper examined relationships between students’ engagement in community service in different contexts through classes, student organizations, work study, and on their own as well as their development of socially responsible leadership at a large, public, research university in the Upper Midwest. Results from the Multi-Institutional Study of Leadership survey distributed at a single institution (n = 1,282) suggest, among other things, that students who participated in community service on their own consistently reported higher socially responsible leadership while students who participated in service both on their own and in a student organization reported higher socially responsible leadership in all areas save for consciousness of self.
Contributing to the Development of Student Leadership through Academic Advising
Authors: McClellan Jeffrey L.
Published: May 2019

One of the major foci of universities in relation to the educational missions is to promote the growth and development of students as leaders. This article discusses the role of academic advising as a strategic partner with classroom and extracurricular leadership development programs. To that end, this article reviews the roles of academic advising in higher education and discusses the viability of expanding these roles to include the role of advisor as leadership educator. In so doing, I provide a review of the literature related to student leadership development, discuss the similarity in advising outcomes and leadership development outcomes, and examine how the roles of academic advisors in higher education relate to leadership development as well as how advisors can become intentional leadership educators.
Learning Leadership Abroad: An Overview of a Short-Term Leadership-Focused Study Abroad Program in Italy
Authors: Rosch David M. , Haber-Curran Paige
Published: May 2019

We provide a brief description of a leadership-oriented short-term (nine days) study abroad program offered in May 2012. The program centered in Rome, Italy, combined classroom curricula with field experiences in the city as well as in Bologna and Florence. Initial quantitative and qualitative assessment suggested the program helped student development both in their leadership practices as well as their personal development.
Business without the Math: Competing Discourses and the Struggle to Develop an Undergraduate Leadership Program
Authors: McLaren Patricia Genoe , McGowan Rosemary A. , Gerhardt Kris , Diallo Lamine , Saeed Akbar
Published: May 2019

Despite widespread acknowledgement of the importance of leadership education, undergraduate leadership degree programs in Canada are limited and, in some cases, struggling for survival. This case study examines the ways in which competing discourses of careerism, postsecondary corporatization, liberal arts education, and business education impact an undergraduate leadership program’s sustainability.
Exploring the Multicultural Competence of Leadership Educators
Authors: Wilson Amy B.
Published: May 2019

Research examining multicultural competence among higher education professionals responsible for leadership education demonstrated significant correlations with racial identity and multicultural education and experiences. The Multicultural Competence in Student Affairs-Preliminary 2 (MCSA-P2) scale was used to measure multicultural competence. Variances in multicultural competence scores were significant in relation to racial identity and select multicultural education and experience measures, above and beyond controlled for demographic variables.
VIEWS AND PRACTICES OF HIGH SCHOOL COACHES ON THE EDUCATION AND TRAINING OF TEAM CAPTAINS IN LEADERSHIP
Authors: Voelker Dana K. , Martin Eric M. , Blanton Jedediah E. , Gould Daniel
Published: May 2019

This cross-sectional study (1) described the views and practices of a national U.S. sample of high school coaches on the education and training of team captains in leadership; and (2) examined if their views and practices differed as a function of leadership behavior and coaching efficacy. Results of 255 online surveys showed nearly 90% of coaches thought formal captain leadership development programs were beneficial; only 12% used such a program. Coaches with higher character-building and motivation efficacy more strongly endorsed the intentional education and training of their captains and perceived fewer barriers to this process. These findings encourage coaches, others working directly with scholastic athletes, and leadership educators more broadly to leverage and examine sport, including captaincy, as a valuable leadership development opportunity for youth.
LEARNINGTOLEAD:LISTENINGTOTHEVOICEOFST.LUCIAN YOUTH
Authors: Landwehr Erik B. , Lloyd Carrie A.
Published: May 2019

An exploratory, qualitative multiple case study approach was used to investigate perceptions of leadership through the voice of young (ages 18-24) citizens of St. Lucia, West Indies.Specifically, investigators were interested in better understanding the young peoples’ leadership beliefs, experiences, and people of influence. Participants perceived leadership to be about helping other people, communication, teamwork, and morality.The most valuable leader development experiences were experiences that the young people perceived were connected to leadership.Participants viewed familiar adults, rather than famous foreigners or youth peers asthemostimportantpeopletoaidinyouthleaderdevelopment.