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At Earth’s bow shock, the supersonic solar wind is slowed down and deflected around the magnetosphere. To many this is "just a bow shock", a simple and quite passive element of solar-terrestrial physics. However, it has recently been realized that the bow shock plays a significantly more important role with currents on the bow shock connecting through the magnetosheath to the magnetospheric current systems. The bow shock current cannot close locally, since the magnetic field compression in the magnetosheath cannot be maintained globally. The bow shock current is inevitably a generator current extracting mechanical energy from the supersonic solar wind, and feeding it to other processes such as acceleration of the magnetosheath flow, local particle acceleration at the bow shock and dissipation in the distant ionosphere. Here we use data from the first dayside season of the Magnetospheric Multiscale (MMS) mission to investigate the generator properties of the terrestrial bow shock. Typically, the main shock ramp shows clear generator properties, but for some of the more turbulent bow shocks, generator properties may also be observed slightly downstream the ramp. This may be due to effects from shock motions and shock nonstationaity and reformation. Moreover, sometimes a weaker load can be seen in the upstream foot region due to local particle acceleration. We also find that the generator capacity of the bow shock decreases with decreasing bow shock angle as well as with increasing upstream plasma beta and solar Mach number. A better understanding of the energy conversion properties of the terrestrial bow shock will be useful also for the understanding of other astrophysical shock currents. The currents must close somewhere and deposit energy somewhere.

Background and importance Adalimumab is an anti-TNFα monoclonal antibody used in inflammatory bowel disease (IBD). Its efficacy can benefit from therapeutic drug monitoring (TDM). However, because there are several population pharmacokinetic models (PopPK) published, it is necessary to perform an evaluation of these models in the target population before being used in clinical practice. Aim and objectives To evaluate the predictive performance and adequacy of four PopPK of adalimumab in adult patients diagnosed with IBD, using TDM in a clinical setting. Material and methods A retrospective observational study (2014–2018) was conducted. Inclusion criteria were adult patients with IBD treated with adalimumab, with at least one trough concentration (TC). Four different PopPK were evaluated: Mod-A (FDA-2007), Mod-B Ternant-2015, Mod-C Sharma-2015 and Mod-D Berends-2018. The models were implemented in NONMEM V.7.3. The individual and population predictions of TCs were estimated from the four PopPK models. Two datasets were created; DATASET-1 was used to evaluate the model adequacy, all patients and TCs were included, and their population predictions were compared with the observed TCs; DATASET-2 was used to assess the predictive performance and only patients with two or more TCs were included. Only the first TC of these patients was used to estimate the Bayesian estimates, and the individual predictions were compared with observed TCs. To validate these models, bias and precision of estimated concentrations were calculated as the mean predictive error and the mean square predictive error in the population, respectively. Results A total of 171 patients with 245 TCs in DATASET-1 and 55 patients with 74 TCs in DATASET-2 were included; 5.85% of patients in DATASET-1 and 3.64% in DATASET-2 developed anti-adalimumab antibodies. Conclusion and relevance Mod-B performed better both in the evaluation of adequacy (DATASET-1) and for predictive performance (DATASET-2). All four models overestimated TC although Mod-B had better bias and precision (ie, closer to zero). Implementation of this PopPK in clinical practice should be done with caution. References and/or acknowledgements No conflict of interest.

This article estimates the economic rents received by the 10 mines that comprise Chile’s large-scale private-sector copper-mining industry. The methodology used produces a conservative calculation and includes two corrections that have hitherto been ignored in the literature: the reimbursement of exploration expenses and the compensation needed for volatility in the copper price. Estimates show that the wealth transferred to these firms between 2005 and 2014 was at least US$ 114 billion. These rents are neutral in terms of investment and production decisions; in other words, if the private mining companies had paid the Chilean Treasury the calculated amount, their total investment and output would have been unchanged, but the country at large could have benefited from the huge voluminous resources in question. Moreover, in the absence of any other distortion, the firms would still have earned returns equivalent to what they would have obtained under perfect competition.

En este trabajo se estiman las rentas economicas de los diez yacimientos que constituyen la gran mineria privada del cobre en Chile. La metodologia utilizada asegura un calculo conservador e incluye dos correcciones ignoradas en la literatura: el resarcimiento de los gastos en exploracion y la indispensable compensacion por la volatilidad del precio del cobre. Las estimaciones muestran que la riqueza regalada a estas empresas alcanza un valor piso de 114.000 millones de dolares entre 2005 y 2014. Estas rentas son neutras en relacion con las decisiones de inversion y produccion, es decir, si estas empresas privadas hubiesen pagado al fisco chileno el monto calculado, su inversion y produccion totales no habrian cambiado, pero el pais habria podido disponer de esos cuantiosos recursos. Ademas, en ausencia de cualquier otra distorsion, estas empresas igualmente habrian tenido rentabilidades equivalentes a las que hubiesen logrado en una economia de competencia perfecta.

Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.

Purpose Human mesenchymal stromal cells (MSCs) may aid the regeneration of ionizing radiation (IR)–induced tissue damage. They can be harvested from different tissues for clinical purposes; however, the role of the tissue source on the radiation response of human MSCs remains unknown. Methods and Materials Human MSCs were isolated from adipose tissue, bone marrow, and umbilical cord, and cellular survival, proliferation, and apoptosis were measured after irradiation. The influence of IR on the defining functions of MSCs was assessed, and cell morphology, surface marker expression, and the differentiation potential were examined. Western blot analyses were performed to assess the activation of DNA damage signaling and repair pathways. Results MSCs from adipose tissue, bone marrow, and umbilical cord exhibited a relative radioresistance independent of their tissue of origin. Defining properties including cellular adhesion and surface marker expression were preserved, and irradiated MSCs maintained their potential for multilineage differentiation irrespective of their tissue source. Analysis of activated DNA damage recognition and repair pathways demonstrated an efficient repair of IR-induced DNA double-strand breaks in MSCs from different tissues, thereby influencing the induction of apoptosis. Conclusions These data show for the first time that MSCs are resistant to IR and largely preserve their defining functions after irradiation irrespective of their tissue of origin. Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction of apoptosis induction may contribute to the tissue-independent radiation resistance of MSCs.

Background: Increased number of tumor-infiltrating lymphocytes (TILs) at baseline is associated with pathological complete response (pCR) and improved outcomes in HER2-positive early breast cancer treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is currently unknown. Methods: The PAMELA (NCT01973660)neoadjuvant trial treated 151 women with HER2-positive breast cancer with lapatinib and trastuzumab (and hormonal therapy if hormone receptor-positive) for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (n=148) and after 2 weeks of treatment (n=134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated using univariate and multivariable logistic regression models. The regression coefficients were used to derive a score based on TILs and tumor cellularity measured at week 2 (CelTIL) was derived in PAMELA,and tested in week 2 samples from 65 patients with HER2+ disease recruited in the LPT109096 (NCT00524303) phase 2 neoadjuvant trial, where anti-HER2 therapy-only (trastuzumab, lapatinib or the combination) was administered for 2 weeks, followed by the addition of standard multi-agent chemotherapy for 24 weeks. Results: In PAMELA, at baseline, TILs were significantly associated with pCR in univariate analysis but not in multivariable analysis (adjusted odds ratio [OR]=1.01, 0.98-1.03; p-value=0.620). A statistically significant increase in TILs was observed at week 2 compared to baseline (mean difference +6.9%; p-value Conclusions: A combined score of TILs and tumor cellularity at week 2 following anti-HER2 therapy-only is associated with pCR upon completion of neoadjuvant anti-HER2-based therapy. Citation Format: Nuciforo P, Holgado E, Llombart A, Fasani R, Paré L, Pascual T, Oliveira M, Martínez N, Bermejo B, Vidal M, Pernas S, López R, Muñoz M, Garau I, Manso L, Alarcón J, Martínez E, Villagrasa P, Cortés J, Prat A. A predictive model of pathological response following dual HER2 blockade-only based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-14.

This paper explores the role of tax policy in shaping incentives for executive effort (labor supply) and rent seeking within the firm. We develop a theoretical model that distinguishes between effort and rent‐seeking responses to income taxes, and provides a framework to estimate a lower bound for the rent‐seeking response. Using executive compensation and governance data, we find that rent seeking represents an important component of the response to changes in tax rates, especially among executives in firms with the worst corporate governance. (JEL D31, G30, H21)

// Alexander Ruhle 1, 2 , Ramon Lopez Perez 1, 2 , Christin Glowa 1, 2 , Klaus-Josef Weber 2, 3 , Anthony D. Ho 4 , Jurgen Debus 2, 3 , Rainer Saffrich 4 , Peter E. Huber 1, 2, 3 and Nils H. Nicolay 1, 2, 3 1 Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany 2 Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Research in Oncology, 69120 Heidelberg, Germany 3 Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany 4 Department of Hematology and Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany Correspondence to: Nils H. Nicolay, email: n.nicolay@dkfz.de Keywords: mesenchymal stem cells, cisplatin, radiotherapy, DNA double-strand breaks, radiosensitization Received: July 19, 2017 Accepted: August 17, 2017 Published: September 23, 2017 ABSTRACT Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated radiosensitivity was associated with a cell cycle shift of MSCs towards the radiosensitive G2/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent radiosensitization effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients.

The magnetopause is the boundary established by pressure balance between the solar wind flow in the magnetosheath and the magnetosphere. Generally this pressure balance is represented to be between the solar wind the dynamic pressure and the magnetic pressure of Earth's dipole field. The plasma actually in contact with the magnetosphere is the slowed, compressed, and heated solar wind downstream of the shock. The force exerted on the magnetosheath plasma is the JxB force produced by the Chapman-Ferraro current that flows on the magnetopause. Under typical solar wind conditions of relatively high magnetosonic Mach number flow (>6), this simple picture is a reasonable description of the situation. However, under conditions of low solar wind magnetosonic Mach number flow (~2) the force on the solar wind plasma is not exerted at the magnetopause and must be exerted at the bow shock by currents that connect to the Region 1 currents. In this paper we present observations from two magnetopause crossings observed by the THEMIS spacecraft to compare and contrast the force balance with the solar wind for two situations with two very different solar wind magnetosonic Mach numbers.

This paper presents the design and implementation of a versatile high speed data acquisition system for GNSS signals capable of transferring large amounts of data to a PC. Results obtained of partial validation tests are also shown. The proposed acquisition board is intended as a laboratory instrument that allows simultaneous reception and sampling of GNSS signals in the L1 and L5 bands and their transmission to a PC via a USB 3.0 protocol for subsequent processing. This device is suitable for development and testing of new GNSS signal processing algorithms for which real signal samples are required. The correct functioning of the device was verified for GPS L1, Galileo E1b and GLONASS L1 signals by performing a satellite acquisition analysis on a PC. In addition the satellite tracking performance was validated for a satellite of Galileo using the recorded data.

Photovoltaic energy harvest in distributed maximum power point tracking systems has demonstrated to be superior to the traditional photovoltaic systems under mismatch conditions. The distributed architecture usually consists of series-connected DC/DC converters forming a string, dedicated to process the power of individual photovoltaic panels. However, the classical approach assumes an independent control of the DC/DC converters preventing them from knowing the operating condition of the other converters in the string. The adoption of centralized algorithms allows full control of the variables in distributed maximum power point tracking systems and hence further increases the energy harvest. This paper proposes a novel centralized control that matches distributed and central maximum power point tracking functions, as well as an innovative functionality that improves the dynamic performance in photovoltaic applications.

This article proposes a new control algorithm that improves the dynamic performance in distributed maximum power point tracking systems. Systems with these architectures allow to increase the photovoltaic power harvested in case of partial shading and irradiance mismatch. The classical approach adopts distributed DC/DC power electronics and control without any centralized action, which makes difficult to know whether the system is working on its optimal operating point or not. The new control algorithm presented in this paper exploits the benefits of the vectorial multi-variable perturb & observe logic and acts on the control sequence under varying irradiance conditions, reducing voltage stresses at the DC/DC converters output terminals. In addition, the matching with the DC-bus voltage control is discussed, providing a centralized control to the overall system, a fact barely addressed in literature. Simulation results and experimental measurements validate the proposed approach showing improved dynamic performance and system stability.

Physics education research has focused much more on lower-level, introductory courses as compared to upper division and graduate physics education. However, there are general principles and findings that extend across all areas of learning, such as the strong evidence in favor of active learning environments. But taking the theoretical basis and pedagogical strategies generated by research at one level of education and applying it to create a learning environment appropriate to upper division and graduate physics courses requires careful consideration of the issues facing students, and the instructor, in such courses. For example, the motivations of students in an introductory course are very different from the motivations of students in a graduate course. The number of students in a classroom is often quite different. The size of the research base on student difficulties and the amount of research-based instructional resources available to an instructor will be different. In this paper, we discuss several examples of the application of research-based techniques to classroom instruction in upper division and graduate physics courses, how the specifics of the student audience have resulted in modifications of the pedagogical approach, and the student response to these instructional strategies.

Degloving injuries of the foot involve the management of extensive soft tissue and osseous damage secondary to significant forced avulsion of soft tissue, which can present a major challenge for the surgeon. Surgical procedures on pediatric foot degloving involving split-thickness and/or full-thickness skin grafts and rotational flaps can result in negative consequences, such as donor site comorbidities and psychosocial implications when the pediatric patient returns to daily life.The authors report the case of a 16-year-old girl with no past medical history who sustained an extensive degloving injury to her right foot involving severe subcutaneous and muscular soft tissue disruption and contamination. The initial treatment consisted of debridement, copious irrigation, primary wound closure at several sites, and application of an extracellular matrix (ECM) substitute graft. Shortly thereafter, secondary treatment consisted of application of primary musculoskeletal repair, negative pressure wound therapy (NPWT), and application of a dermal regeneration template. Over the 5-month course of treatment, an additional 3 trips to the operating room occurred, involving serial irrigation and debridement, NPWT application, and dermal/ECM substitute graft applications, leading to full epithelialization.To the best of the authors' knowledge, this is the first reported case in which an instance of pediatric foot degloving is presented with serial debridement, NPWT, and biological dressings, resulting in no additional plastic surgical techniques needed to provide return to functional outcome.

The presented method or slightly modified versions have been devised to study specific treatment responses and side effects of various anti-cancer treatments as used in clinical oncology. It enables a quantitative and longitudinal analysis of the DNA damage response after genotoxic stress, as induced by radiotherapy and a multitude of anti-cancer drugs. The method covers all stages of the DNA damage response, providing endpoints for induction and repair of DNA double-strand breaks (DSBs), cell cycle arrest and cell death by apoptosis in case of repair failure. Combining these measurements provides information about cell cycle-dependent treatment effects and thus allows an in-depth study of the interplay between cellular proliferation and coping mechanisms against DNA damage. As the effect of many cancer therapeutics including chemotherapeutic agents and ionizing radiation is limited to or strongly varies according to specific cell cycle phases, correlative analyses rely on a robust and feasible method to assess the treatment effects on the DNA in a cell cycle-specific manner. This is not possible with single-endpoint assays and an important advantage of the presented method. The method is not restricted to any particular cell line and has been thoroughly tested in a multitude of tumor and normal tissue cell lines. It can be widely applied as a comprehensive genotoxicity assay in many fields of oncology besides radio-oncology, including environmental risk factor assessment, drug screening and evaluation of genetic instability in tumor cells.

The presented method or slightly modified versions have been devised to study specific treatment responses and side effects of various anti-cancer treatments as used in clinical oncology. It enables a quantitative and longitudinal analysis of the DNA damage response after genotoxic stress, as induced by radiotherapy and a multitude of anti-cancer drugs. The method covers all stages of the DNA damage response, providing endpoints for induction and repair of DNA double-strand breaks (DSBs), cell cycle arrest and cell death by apoptosis in case of repair failure. Combining these measurements provides information about cell cycle-dependent treatment effects and thus allows an in-depth study of the interplay between cellular proliferation and coping mechanisms against DNA damage. As the effect of many cancer therapeutics including chemotherapeutic agents and ionizing radiation is limited to or strongly varies according to specific cell cycle phases, correlative analyses rely on a robust and feasible method to assess the treatment effects on the DNA in a cell cycle-specific manner. This is not possible with single-endpoint assays and an important advantage of the presented method. The method is not restricted to any particular cell line and has been thoroughly tested in a multitude of tumor and normal tissue cell lines. It can be widely applied as a comprehensive genotoxicity assay in many fields of oncology besides radio-oncology, including environmental risk factor assessment, drug screening and evaluation of genetic instability in tumor cells.

Chemotherapy constitutes one of the key treatment modalities for solid and hematological malignancies. Albeit being an effective treatment, chemotherapy application is often limited by its damage to healthy tissues, and curative treatment options for chemotherapy-related side effects are largely missing. As mesenchymal stromal cells (MSCs) are known to exhibit regenerative capacity mainly by supporting a beneficial microenvironment for tissue repair, MSC-based therapies may attenuate chemotherapy-induced tissue injuries. An increasing number of animal studies shows favorable effects of MSC-based treatments; however, clinical trials for MSC therapies in the context of chemotherapy-related side effects are rare. In this concise review, we summarize the current knowledge of the effects of MSCs on chemotherapy-induced tissue toxicities. Both preclinical and early clinical trials investigating MSC-based treatments for chemotherapy-related side reactions are presented, and mechanistic explanations about the regenerative effects of MSCs in the context of chemotherapy-induced tissue damage are discussed. Furthermore, challenges of MSC-based treatments are outlined that need closer investigations before these multipotent cells can be safely applied to cancer patients. As any pro-tumorigenicity of MSCs needs to be ruled out prior to clinical utilization of these cells for cancer patients, the pro- and anti-tumorigenic activities of MSCs are discussed in detail.

The data for X‐ray images studied in this paper can be downloaded from Zenodo (https://doi.org/10.5281/zenodo.1415285).

Background Voriconazole is an antifungal drug used for invasive fungal infection with high pharmacokinetic variability and narrow therapeutic range and, therefore, therapeutic drug monitoring (TDM) is recommended. Purpose The objective was to evaluate the standard dosage regimen of voriconazole in a paediatric and adult population through TDM. Material and methods Retrospective observational study (January 2015 and October 2017). Inclusion criteria: adult and paediatric patients treated with voriconazole (oral/intravenous) with at least one trough plasma concentrations (C_trough) of voriconazole at steady state (>5 days) with the standard dosage and without concomitant use of potent inducers or inhibitors. Standard dose was: paediatric 8 mg/kg IV BID or 9 mg/kg PO BID, and adult 4 mg/kg IV BID or 200 mg PO BID. Variables: age, weight, indication (treatment or prophylaxis) and C_trough at steady state. Data was stratified by paediatric and adult patients. Primary outcome was: percentage of patients with C_trough at steady state of voriconazol within the therapeutic range at the standard dose (therapeutic window by indication: treatment: 1–5 mg/L; prophylaxis: 0.5–5 mg). Results A total of 56 patients were included (26.7% children and 73.2% adults). In the paediatric group, the mean age and weight was 6.4 years (95% CI: 3.9 to 9.0) and 25.5 kg (95% CI: 16.4 to 34.5). The mean age and weight for the adult patients were 61.0 years (95% CI: 56.4 to 65.6) and 69.9 kg (95% CI: 65.3 to 74.5). 17.7% of the patients were treated with voriconazole for prophylaxis and 82.2% for treatment. The median C_trough in paediatrics was lower than in adults: 0.7 mg/L (p25–75: 0–5.5) vs 2.5 mg/L (p25–75: 0.1–8.0), respectively (p 66.7% and 22% of patients had infra-therapeutic C_trough in paediatrics and adults (p Conclusion The C_trough with the standard maintenance dose of voriconazol were within the therapeutic range in only 26.7% in paediatrics, while in the adult group it was 70.7%. Given the high variability observed in the C_trough, it was necessary to perform TDM at the beginning of the treatment to make an individualised dosage adjustment in both paediatric and adult patients. References and/or acknowledgements https://www.ema.europa.eu/documents/product-information/vfend-epar-product-information_es.pdf No conflict of interest.

In this work we analyze the coupling between two patch antennas designed to be placed on a vehicle. One antenna transmits high power signals, while the other antenna is intended for receiving signals of global satellite navigation systems (GNSS). Although both antennas operate in different frequency bands, the out of band interference generated by the transmitting antenna can affect the performance of the GNSS receiver because of its high sensitivity. In addition, other intentional or unintentional out of band interferences coming from different sources represent a risk for the receiver. Simulation and measurement results show that due to the coupling between the antennas, the interference produced by the transmitter has a detrimental effect on the GNSS receiver. Several solutions to overcome this problem are presented and evaluated according to the requirements of the current application.

Adalimumab is a monoclonal antibody used for inflammatory bowel disease. Due to its considerably variable pharmacokinetics, the loss of response and the development of anti-antibodies, it is highly recommended to use a model-informed precision dosing approach. The aim of this study is to evaluate the predictive performance of different population-pharmacokinetic models of adalimumab for inflammatory bowel disease to determine the pharmacokinetic model(s) that best suit our population to use in the clinical routine. A retrospective observational study with 134 patients was conducted at the General University Hospital of Alicante between 2014 and 2019. Model adequacy of each model was evaluated by the distribution of the individual pharmacokinetic parameters and the NPDE plots whereas predictive performance was assessed by calculating bias and precision. Moreover, stochastic simulations were performed to optimize the maintenance doses in the clinical protocols, to reach the target of 8 mg/L in at least 75% of the population. Two population-pharmacokinetic models were selected out of the six found in the literature which performed better in terms of adequacy and predictive performance. The stochastic simulations suggested the benefits of increasing the maintenance dose in protocol to reach the 8 mg/L target.

Background: Eribulin is the only cancer agent that has demonstrated a significant prolongation in overall survival on previously treated breast cancer patients. To date, no biomarker exists to prospectively select patients who will derive the maximum benefit from this chemotherapeutic. In the SOLTI1007-NeoEribulin study, we explored, in a prospective clinical trial, the efficacy and the association of pre-treatment expression of RNA in patients with HER2-negative breast cancer treated with neoadjuvant eribulin. Methods: SOLTI1007 is a phase II, open-label, single-arm, exploratory pharmacogenomic study of single agent eribulin as neoadjuvant treatment for stage I-II HER2-negative breast cancer (planned n=100 hormonal receptor-positive [HR+] and n=100 HR-negative). Patients received 1.4 mg/m2 of eribulin intravenously on Days 1 and 8 every 21-day cycle, for 4 cycles. Baseline and post-treatment (surgical) formalin-fixed, paraffin-embedded tissue samples were collected and gene expression profiled. PAM50 intrinsic subtype and the Risk of Relapse based on subtype and proliferation (ROR-P) were evaluated in each time-point. The association of each PAM50 signature and pathological complete response in the breast (pCRB) was evaluated using univariate logistic regression models. Results: Between September 2012 and October 2015, one hundred and seventy-four patients (TNBC n=73 and HR+ n=101) were recruited. Mean age (55.5), stage II (90%), negative axilla (78% and 67%), grade 3 (62% and 26%), mean tumor size (3 cm and 3.6 cm) and mean Ki-67 (61% and 31%). Completion of 4 cycles of eribulin was achieved by 85% of the patients. Grade 3-4 toxicities were observed in 19.54%, mostly due to neutropenia (5.1%) and alopecia (4.02%). The overall pCRB was 5.4%. No significant differences were observed between HR+ and TNBC disease. Distribution of the PAM50 intrinsic subtypes was as follows: Luminal A (n=43, 27.7%), Luminal B (n=42, 27.1%), Basal-like (n=63, 40.6%) and HER2-enriched (n=7, 4.5%). pCRB rates by subtype were the following: HER2-enriched (28.6%, 2/7), Luminal B (7.1%, 3/42), Basal-like (4.8%, 3/63), Luminal A (2.3%, 1/43). pCRB rates significantly (p=0.047) differed when HER2-enriched was compared to the other subtypes (odds ratio = 8.06, 95% CI 1.32-49.1). pCRB rate differed significantly by ROR-P (p=0.006): ROR-P high (17.1%, 6/35), ROR-P med (2.7%, 2/75), ROR-P low (2.2%, 1/45). Ki67 % by IHC did not predict pCRB (p=0.918). Subtype change at surgery occurred in 60% (3/5) HER2-enriched, 44.1% (15/34) of Luminal Bs, 10.3% (4/39) of Luminal A and 5.4% (2/37) of Basal-like tumors. 100% of subtype changes in Luminal B disease were to Luminal A. Conclusions: From a response and biological perspective, patients with HER2-enriched and Luminal B disease may benefit the most from eribulin therapy. Mechanistically, our gene expression data further supports previous preclinical evidence suggesting that eribulin triggers a phenotypic conversion. Citation Format: Prat A, Ortega V, Villagrasa P, Paré L, Galván P, Oliveira M, Nucíforo P, Lluch A, Morales S, Amillano K, Lopez R, Gonzalez R, Manso L, Martinez J, Llombart A, De la Peña L, Di Cosimo S, Rubio IT, Harbeck N, Baselga J, Cortés J. Efficacy and gene expression results from SOLTI1007 NEOERIBULIN phase II clinical trial in HER2-negative early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-09.