bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer
Authors: Ingold Heppner Barbara , Untch Michael , Denkert Carsten , Pfitzner Berit M. , Lederer Bianca , Schmitt Wolfgang , Eidtmann Holger , Fasching Peter A. , Tesch Hans , Solbach Christine , Rezai Mahdi , Zahm Dirk M. , Holms Frank , Glados Manfred , Krabisch Petra , Heck Esther , Ober Angelika , Lorenz Petra , Diebold Kurt , Habeck Jörg-Olaf , Loibl Sibylle 
Published: May 2016

Abstract
Purpose: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting.
Experimental Design: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; ≥ 60% TILs), and correlated with pCR rate and DFS.
Results: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR.
Conclusions: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747–54. ©2016 AACR.
A new species of Trachytherus (Notoungulata: Mesotheriidae) from the late Oligocene (Deseadan) of Southern Peru and the middle latitude diversification of early diverging mesotheriids
Authors: SHOCKEY BRUCE J. , BILLET GUILLAUME , SALAS-GISMONDI RODOLFO 
Published: May 2016

Herein we describe a new species of early diverging mesotheriid notoungulate from the late Oligocene of Moquegua, Peru. This taxon, Trachytherus ramirezi sp. nov., is distinctive in terms of a few characteristics that appear plesiomorphic as compared to those of other described mesotheriids, even other species referred to Trachytherus. Such plesiomorphic traits include the absence of an upper diastema and a lack of heart-shaped incisive foramina, traits that are generally present in other mesotheriids. Our phylogenetic analysis of described early divergent mesotheriids indicates that T. ramirezi was the earliest to diverge. This analysis also confirms the paraphyletic nature of the “genus” Trachytherus. Geographically, T. ramirezi clusters among T. alloxus, T. subandinus, and T. spegazzinianus, all of which are known from a discrete region in the middle latitudes of western South America that we refer to as the Bolivian Orocline Region (BOR). Our palaeobiogeographic reconstruction using maximum parsimony identifies the BOR as a possible ancestral area for the Mesotheriidae and as an important region for their diversification. For the more exclusive Mesotheriinae, the BOR was reconstructed as the ancestral area, an area from which some mesotheriines would have later dispersed to southern South America. Uncertainty concerning the ancestral area, for the Mesotheriidae—which could be BOR or southern South America area (or both)—is possibly due to the ignorance of the phylogenetic affinities for the undescribed mesotheriid remains reported from Tinguirirican localities. The present description of T. ramirezi therefore adds to the high taxonomic diversity of early mesotheriid species in the relatively small area of the BOR and emphasizes the likely role played by this topographically dynamic area on mesotheriid evolution during a significant time in the history of the clade.
Evolution of a Long-Track Violent Tornado within a Simulated Supercell
Authors: Orf Leigh , Wilhelmson Robert , Lee Bruce , Finley Catherine , Houston Adam 
Published: May 2016

Abstract
Tornadoes are among nature’s most destructive forces. The most violent, long-lived tornadoes form within supercell thunderstorms. Tornadoes ranked EF4 and EF5 on the Enhanced Fujita scale that exhibit long paths are the least common but most damaging and deadly type of tornado. In this article we describe an ultra-high-resolution (30-m gridpoint spacing) simulation of a supercell that produces a long-track tornado that exhibits instantaneous near-surface storm-relative winds reaching as high as 143 m s−1. The computational framework that enables this work is described, including the Blue Waters supercomputer, the CM1 cloud model, a data management framework built around the HDF5 scientific data format, and the VisIt and Vapor visualization tools. We find that tornadogenesis occurs in concert with processes not clearly seen in previous supercell simulations, including the consolidation of numerous vortices and vorticity patches along the storm’s forward-flank downdraft boundary and the intensification of a feature we call a streamwise vorticity current (SVC), a current of horizontal vorticity that is tilted upward into the storm’s low-level mesocyclone. The SVC is found throughout the genesis and much of the maintenance phase of the tornado, where it appears to help drive the storm’s vigorous low-level updraft. We compare stages of the storm’s maintenance phase to observations. We find that tornado decay occurs rapidly throughout the depth of the tornado and is associated with a weakening of the SVC and the development of a strong rainy downdraft that encircles the tornado, which has moved rearward into the storm’s cold pool.
Untangling Microphysical Impacts on Deep Convection Applying a Novel Modeling Methodology. Part II: Double-Moment Microphysics
Authors: Grabowski Wojciech W. , Morrison Hugh 
Published: May 2016

Abstract
The suggested impact of pollution on deep convection dynamics, referred to as the convective invigoration, is investigated in simulations applying microphysical piggybacking and a comprehensive double-moment bulk microphysics scheme. The setup follows the case of daytime convective development over land based on observations during the Large-Scale Biosphere–Atmosphere (LBA) experiment in Amazonia. In contrast to previous simulations with single-moment microphysics schemes and in agreement with results from bin microphysics simulations by others, the impact of pollution simulated by the double-moment scheme is large for the upper-tropospheric convective anvils that feature higher cloud fractions in polluted conditions. The increase comes from purely microphysical considerations: namely, the increased cloud droplet concentrations in polluted conditions leading to the increased ice crystal concentrations and, consequently, smaller fall velocities and longer residence times. There is no impact on convective dynamics above the freezing level and thus no convective invigoration. Polluted deep convective clouds precipitate about 10% more than their pristine counterparts. The small enhancement comes from smaller supersaturations below the freezing level and higher buoyancies inside polluted convective updrafts with velocities between 5 and 10 m s−1. The simulated supersaturations are large, up to several percent in both pristine and polluted conditions, and they call into question results from deep convection simulations applying microphysical schemes with saturation adjustment. Sensitivity simulations show that the maximum supersaturations and the upper-tropospheric anvil cloud fractions strongly depend on the details of small cloud condensation nuclei (CCN) that can be activated in strong updrafts above the cloud base.
Tobramycin Elimination Rate Change from First to Later Doses in Older Cystic Fibrosis Patients
Authors: Horner Gary W. , Stempel David A. 
Published: May 2016

Adults with cystic fibrosis frequently require larger than usual tobramycin dosages in order to achieve desired serum concentrations. The application of dosing methods utilizing first-dose pharmacokinetics has been advocated as a means for rapidly attaining therapeutic serum concentrations. Review of ten cystic fibrosis patients between ages 13 and 33 years admitted for exacerbation of pulmonary disease caused primarily by Pseudomonas aeruginosa ( Staphylococcus aureus in two patients) was conducted. Elimination rate constant (ke, h−1) was calculated from two concentration-time pairs obtained following the first dose. Two concentration-time pairs were again measured between cumulative doses (n) 7 to 19, and ke was calculated. First dose ke varied significantly from nth dose ke (p = 0.018). First-dose pharmacokinetic analysis may not be a reliable predictor of maintenance tobramycin dosage requirements due to apparent changes in ke over time.
Factors Influencing the Transit of a Gelatin Capsule in the Esophagus
Authors: Bailey Robert T. , Bonavina Luigi , McChesney Lawrence , Spires Kelly J. , Muilenburg Mark I. , McGill James E. , DeMeester Tom R. 
Published: May 2016

The tendency of a gelatin capsule to lodge in the esophagus, dissolve, and release its contents, as a potential etiology of drug-induced esophageal injury, was studied in 18 asymptomatic volunteers. Their ages ranged from 21 to 81 years, with nine subjects over 70 years old. Esophageal transit time of liquids was measured in all subjects after which the esophageal transit time of a #00 gelatin capsule containing technetium (99mTc) sulfur colloid was measured with a 120 ml and a 15 ml water bolus. The capsule lodged in three subjects (17 percent) with the 120 ml bolus and in 11 subjects (61 percent) with the 15 ml bolus. Esophageal manometry demonstrated a lower mean amplitude of esophageal contractions in subjects in whom the capsule lodged with the 120 ml bolus and in the elderly subjects. We conclude that the esophageal transit time of a gelatin capsule is related to the volume of fluid chaser. Our findings that a lower amplitude of esophageal contractions was associated with elderly patients and those in whom the capsule lodged with the large fluid bolus are worthy of further investigation.
Plasma Amino Acids in Patients with Acute Nonlymphocytic Leukemia Receiving Parenteral Nutrition
Authors: Christensen Michael L. , Burgess Julienne , Helms Richard A. , Mirro Joseph , Kalwinsky David K. , Storm Michael C. 
Published: May 2016

Objective To assess the effect of parenteral amino acid solutions on plasma amino acid concentrations in patients with acute nonlymphocytic leukemia (ANLL) receiving parenteral nutrition (PN). Design Ten patients were studied at diagnosis, on the morning PN was started, and three times during PN therapy coinciding with the sequential administration of three different amino acid solutions (Aminosyn, FreAmine HBC, and TrophAmine). The order of amino acid solution administration in each patient was by a randomized, block design. Results The patients were undergoing identical intensive induction therapy. There was no significant difference in the number of days they received PN or the amount of protein or calories received during the three PN study periods. At diagnosis, phenylalanine and glutamic acid concentrations were elevated compared with previously published normal values and remained elevated at all observation times. During PN, asparagine, aspartic acid, and tyrosine concentrations were significantly lower with all three amino acid solutions compared with their concentrations at diagnosis. Glycine and threonine concentrations were also significantly lower with FreAmine HBC and TrophAmine administration and cysteine concentrations were significantly lower with FreAmine HBC administration than at the time of diagnosis. Aminosyn was associated with plasma amino acid concentrations most similar to those measured at diagnosis. Conclusions These results indicate that most amino acid concentrations fall within the normal range at diagnosis in the ANLL patients studied. Plasma concentrations for certain amino acids can be influenced by the amino acid solution used in PN. Further understanding of the derangements in amino acid metabolism and the influence of parenterally administered amino acid solutions on plasma amino acid concentrations may lead to improvements in the nutritional support of cancer patients.
Isoniazid-Associated Psychosis: Case Report and Review of the Literature
Authors: Pallone Karen A. , Goldman Morton P. , Fuller Matthew A. 
Published: May 2016

Objective To describe a case of isoniazid-associated psychosis and review the incidence of this adverse effect. Data Sources Information about the patient was obtained from the medical chart. A MEDLINE search of the English-language literature published from 1950 to 1992 was conducted and Index Medicus was manually searched for current information. Study Selection All case reports describing isoniazid-associated psychosis were reviewed. Data Extraction Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid. Data Synthesis The case report is compared with others reported in the literature. The incidence of isoniazid-associated psychosis is rare. Conclusions The mechanism of isoniazid-associated psychosis is uncertain. It appears that isoniazid was associated with the psychosis evident in our patient and in the cases reviewed.
Hypersensitivity Reactions Associated with Parenteral Nutrition: Case Report and Review of the Literature
Authors: Nagata Marianne J. 
Published: May 2016

Objective To report a case of a hypersensitivity reaction to total parenteral nutrition (TPN) and to review the available literature on this rare adverse effect. Case Summary The reaction occurred in a 52-year-old woman with pancreatic carcinoma who received intravenous metronidazole, tobramycin, vancomycin, ranitidine, morphine, TPN, and lipid emulsion postoperatively. Within 30 minutes of starting the TPN and lipid emulsion, the patient complained of dyspnea and pruritus. She began hyperventilating and was hypoxic. The reaction resolved after discontinuation of the TPN and lipid emulsion. The reaction recurred when lipid-free TPN was initiated on two subsequent occasions, and resolved spontaneously following the discontinuation of the lipid-free TPN. The antibiotics, ranitidine, and morphine therapy were continued with no further adverse effects and the patient was discharged on postoperative day 17. Discussion Case reports in the literature on TPN-related hypersensitivity reactions were reviewed. It was speculated that the multivitamin preparation (MVI) may have been the causative agent in our patient; however, this was not confirmed by MVI-free TPN administration or by epicutaneous allergy testing. Conclusions Hypersensitivity reactions to TPN can be managed by withholding the TPN and treating with antihistamines if needed until the reaction resolves. Identification, possibly by epicutaneous allergy testing, and removal of the offending agent(s) from the TPN is necessary if TPN therapy must be restarted.
Nurses’ Performance of Inhalation Technique with Metered-Dose Inhaler plus Spacer Device
Authors: Self Timothy H. , Kelso Tiffany M. , Arheart Kristopher L. , Morgan Joyce H. , Meduri G. Umberto 
Published: May 2016

Objective To determine if nurses could correctly use a metered-dose inhaler plus spacer (MDI–spacer) device after a brief description and demonstration of proper use by a clinical pharmacist. Design Pretest, educational intervention, posttest. Setting University hospital. Participants Twenty-three nurses. Interventions Nurses were asked to use the MDI-spacer (Aerochamber) and were scored using a nine-point checklist (pretest). Educational intervention by the clinical pharmacist consisted of a five-minute discussion and correct demonstration of the device. Nurses were then asked to use the device again (posttest). Main Outcome Measures Pre- and posttest scores. Results Total scores were improved after the educational intervention (66 percent pretest vs. 88 percent posttest, p=0.0001). In an item analysis, four of the nine steps had improved significantly. Conclusions A brief discussion and demonstration of correct use of MDI–spacers is effective in improving nurses’ skill in using the device.
Vancomycin and Tobramycin Clearance in an Infant during Continuous Hemofiltration
Authors: Armstrong Deborah K. , Hidalgo Hanneli A. , Eldadah Maher , Reed MICHAEL D. 
Published: May 2016

Objective To report a case of vancomycin and tobramycin clearance by continuous veno-venous hemofiltration in an infant. Hemofiltration clearance (ClHF) was calculated by two methods and compared for ease and reliability. Methodology Case report of a hospitalized four-month-old infant With method A, ClHF calculation for vancomycin and tobramycin was determined by accurate collection of ultrafiltrate in five 24-hour periods and a midpoint serum sample. With method B, C1HF calculation was determined by obtaining prefilter sample, postfilter sample, and blood flow through filter (Fick principle) over three study periods, correlating to three of five study periods in method A. Results The infant received continuous veno-venous hemofiltration. With method A, vancomycin C1HF ranged from 0.27 to 0.80 mL/min; tobramycin C1HF ranged from 0.32 to 0.91 mL/min. With method B, ClHF for vancomycin ranged from 0 to 2.08 mL/min. Tobramycin ClHF ranged from 0 to 1.6 mL/min when calculated with method B. Conclusions Continuous veno-venous hemofiltration increased the clearance of vancomycin and tobramycin requiring dosage modifications. It appears that method A, which uses the ultrafiltration concentration compared with the serum concentration is more accurate than method B, as it averages fluctuations in ultrafiltrate flow rates. Method B compares a single pre- to postfilter drug concentration and relies on an accurate measurement of ultrafiltration flow rate. Determining ClHF based upon one point in time may overestimate ClHF when the ultrafiltration flow rate varies, as it does in the critically ill. Daily serum concentrations for vancomycin and tobramycin are recommended during continuous veno-venous hemofiltration.
RNA motif search with data-driven element ordering
Authors: Rampášek Ladislav , Jimenez Randi M. , Lupták Andrej , Vinař Tomáš , Brejová Broňa 
Published: May 2016

Abstract
Background
In this paper, we study the problem of RNA motif search in long genomic sequences. This approach uses a combination of sequence and structure constraints to uncover new distant homologs of known functional RNAs. The problem is NP-hard and is traditionally solved by backtracking algorithms.

Results
We have designed a new algorithm for RNA motif search and implemented a new motif search tool RNArobo. The tool enhances the RNAbob descriptor language, allowing insertions in helices, which enables better characterization of ribozymes and aptamers. A typical RNA motif consists of multiple elements and the running time of the algorithm is highly dependent on their ordering. By approaching the element ordering problem in a principled way, we demonstrate more than 100-fold speedup of the search for complex motifs compared to previously published tools.

Conclusions
We have developed a new method for RNA motif search that allows for a significant speedup of the search of complex motifs that include pseudoknots. Such speed improvements are crucial at a time when the rate of DNA sequencing outpaces growth in computing. RNArobo is available at http://compbio.fmph.uniba.sk/rnarobo.
Synchronous activity lowers the energetic cost of nest escape for sea turtle hatchlings
Authors: Rusli Mohd Uzair , Booth David T. , Joseph Juanita 
Published: May 2016

ABSTRACTA potential advantage of group movement in animals is increased locomotion efficiency. This implies a reduced energetic cost for individuals that occur in larger groups such as herds, flocks and schools. When chelonian hatchlings hatch in the underground nest with finite energy for their post-hatching dispersal phase, they face the challenge of minimizing energetic expenditure while escaping the nest. The term ‘social facilitation’ has been used to describe the combined digging effort of sea turtle hatchlings during nest escape. Given that in a normal clutch, a substantial part of the energy reserve within the residual yolk is used by hatchlings in the digging out process, a decreased cohort size may reduce the energy reserve available to cross the beach and sustain the initial swimming frenzy. This hypothesis was experimentally tested by varying cohort size in hatchling green turtles (Chelonia mydas) and measuring energy expenditure during the nest escape process using open-flow respirometry. The energetic cost of escaping through 40 cm of sand was calculated to vary between 4.4 and 28.3 kJ per individual, the cost decreasing as the number of individuals in the cohort increased. This represents 11–68% of the energy contained in a hatchling's residual yolk at hatching. The reduced energetic cost associated with large cohorts resulted from both a lower metabolic rate per individual and a shortened nest escape time. We conclude that synchronous digging activity of many hatchlings during nest escape evolved not only to facilitate rapid nest emergence but also to reduce the energetic cost to individuals.
When Friends Become Competitors: The Design of Resource Exchange Alliances
Authors: Chun So Yeon , Kleywegt Anton J. , Shapiro Alexander 
Published: May 2016

Many carriers, such as airlines and ocean carriers, collaborate through the formation of alliances. The rules of alliances are important for both the stability of the alliance and the profitability of the alliance members. In this paper, we address the design of resource exchange alliances, a type of alliance agreement widely used in practice, especially in the ocean cargo industry. Resource exchange alliances often increase competition among alliance members since the members can sell substitutable products after the exchange. We propose a resource exchange model that takes into account the resulting competition and alliance profit allocation among alliance members. The problem of determining the optimal amounts of resources to exchange is formulated as a stochastic mathematical program with equilibrium constraints (MPECs). Although MPEC problems are, in general, very difficult to solve, we successfully demonstrate an efficient solution approach and provide valuable insights for the resource exchange design problem. In particular, we show that the resource exchange alliance we propose can induce greater profit for the alliance members (both total and individual profits) even though it leads to greater competition. This paper was accepted by Yinyu Ye, optimization.
Bare below the elbows — is there any evidence?
Authors: Mann Alison 
Published: May 2016

A new policy was placed on healthcare workers in 2008 that they should all be ‘bare below the elbows’ when dealing with patients. This rule was introduced to try and tackle the problem of hospital acquired infections despite concerns from leaders in the field that it was made hastily as a response to all the media surrounding hospital infections at the time. This rule is now becoming commonplace in veterinary hospitals and practices despite there still being a lack of evidence. This article looks at whether there is any evidence supporting the ‘bare below the elbows’ policy and whether it is a good idea for veterinary establishments to once again follow on from human counterparts.