bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved long‐term survival in all Sanz risk patients of newly diagnosed acute promyelocytic leukemia treated with a combination of retinoic acid and arsenic trioxide‐based front‐line therapy
Authors: Lou Yinjun , Lu Ying , Zhu Zhijuan , Ma Yafang , Suo Shanshan , Wang Yungui , Chen Dong , Tong Hongyan , Qian Wenbin , Meng Haitao , Mai Wenyuan , Yu Wenjun , Xu Weilai , Wang Lei , Mao Liping , Pei Renzhi , Jin Jie
Published: June 2018

Limited data was available for long‐term follow‐up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all‐trans‐retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)‐based front‐line therapy. The aim of this work was to retrospectively analyze the long‐term survival rate and frequency of therapy‐related myeloid neoplasia (t‐MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9.2% (70/760). Of the remaining 690 patients with complete remission, patients were grouped according to front‐line regimens: ATRA plus ATO with or without chemotherapy (ATO group) and ATRA with chemotherapy (non‐ATO group). The median duration of follow‐up was 7.5 years (1.0‐18.3 years). ATO group showed significant superior 10‐year estimated relapse‐free survival (RFS) up to 90.3% comparing with 65.5% in the non‐ATO group (P < 0.0001). In addition, the 10‐year estimated overall survival (OS) was 93.9% for patients in the ATO group and 89.1% for those in the non‐ATO group (P = 0.03). In the subgroup analysis, the RFS rate was also higher in ATO group comparing with non‐ATO group in both low‐to‐intermediate‐risk (94.2% vs 64.6%, P < 0.0001) and high‐risk subgroup (89.6% vs 74.7%, P = 0.04). Notably, the 3‐year RFS and OS rates in the chemotherapy‐free subgroup of the low‐to‐intermediate‐risk patients (n = 88) were 100% and 100%, respectively. In the entire cohort, a total of 10 patients developed secondary malignant neoplasms, including 7 patients with therapy‐related myeloid neoplasms (t‐MN). The estimated 5‐year cumulative incidence risk of t‐MN in the ATO and non‐ATO groups was 1.0% and 0.4%, respectively (P = 0.34). Thus, our data revealed that the long‐term outcome of patients treated with ATRA plus ATO‐based regimens was associated with continuing high efficacy in all Sanz risk patients with newly diagnosed APL.
Quality of life at diagnosis predicts overall survival in patients with aggressive lymphoma
Authors: Thompson Carrie A. , Yost Kathleen J. , Maurer Matthew J. , Allmer Cristine , Farooq Umar , Habermann Thomas M. , Inwards David J. , Macon William R. , Link Brian K. , Rosenthal Allison C. , Cerhan James R.
Published: June 2018

Our aim was to evaluate whether quality of life (QOL) scores at diagnosis predict survival among patients with aggressive lymphoma. Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE and systematically followed for event‐free and overall survival (OS). QOL was measured with the Functional Assessment of Cancer Treatment‐General (FACT‐G), which measures 4 domains: physical, social/family, emotional, and functional well‐being (WB); a single item Linear Analogue Self‐Assessment (LASA) measuring overall QOL; and a spiritual WB LASA. From 9/2002 to 12/2009, 701 patients with aggressive lymphoma who completed baseline QOL questionnaires were enrolled. At a median follow‐up of 71 months (range 6‐128), 316 patients (45%) had an event and 228 patients (33%) died. All baseline QOL measures but emotional WB were significantly associated with OS (all P < 0.04); of which all but LASA spiritual remained significant after adjusting for IPI and NHL subtype. The strongest associations were with total FACT‐G (adjusted HR = 0.86, 95% CI: 0.79‐0.94, P = 0.00062) and functional WB (adjusted HR = 0.88, 95% CI: 0.83‐0.93, P < .0001). QOL LASA was associated with OS (adjusted HR = 0.92, 95% CI: 0.87‐0.97, P = 0.0041). Patients with clinically deficient QOL (overall QOL ≤50) had a median OS of 92 months compared with 121 months for patients with QOL >50 (P = 0.0004). In this large sample of patients with aggressive lymphoma, we found that baseline QOL is independently predictive of OS. QOL should be assessed as a prognostic factor in patients with aggressive lymphoma.
Association of uterine leiomyoma and overactive bladder syndrome
Authors: Koch Marianne , Rauchenwald Tina , Kivaranovic Danijel , Schwab Stephanie , Umek Wolfgang , Koelbl Heinz , Rauchenwald Michael , Helmy Samir
Published: June 2018

Objective

To assess associations between anterior and/or fundal uterine leiomyoma and overactive bladder syndrome.

Methods

The present cohort study recruited women diagnosed with fundal/anterior uterine leiomyoma by standardized transvaginal ultrasonography at the Medical University of Vienna, Austria, between January 1, 2010, and December 31, 2013, in addition to an age‐matched control group of women without uterine leiomyoma. The International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ‐OAB) was mailed to all eligible participants. The main outcome was the ICIQ‐OAB sum score.

Results

Among 304 questionnaires sent out, 129 were returned. After the exclusion of incomplete datasets, 80 women were included in the analysis (uterine leiomyoma group, 43; control group, 37). The mean ± SD ICIQ‐OAB sum score was 9.7 ± 10.2 for women with uterine leiomyoma and 4.2 ± 5.3 for women in the control group; thus, the ICIQ‐OAB sum score was on average 5.5 points higher in the uterine leiomyoma group (P=0.003). The Spearman correlation coefficient between the total volume of leiomyoma per woman and the ICIQ‐OAB sum score was 0.072 (P=0.645).

Conclusion

The study found a significant association between anterior and/or fundal leiomyoma and overactive bladder syndrome. The presence of uterine leiomyoma should be ruled out during the evaluation of overactive bladder.
High mobility group box 1 as a biomarker in critically ill patients
Authors: Yagmur Eray , Buendgens Lukas , Herbers Ulf , Beeretz Anne , Weiskirchen Ralf , Koek Ger H. , Trautwein Christian , Tacke Frank , Koch Alexander
Published: June 2018

Background

Extracellular release of high mobility group box 1 (HMGB1) acts as a danger‐associated molecular pattern, thereby “alarming” the immune system and promoting systemic inflammation. We investigated plasma HMGB1 concentrations as a potential diagnostic and prognostic biomarker in critical illness.

Methods

Our study included 218 critically ill patients (145 with sepsis, 73 without sepsis), of whom blood samples were obtained at the time‐point of admission to the medical intensive care unit (ICU).

Results

High mobility group box 1 levels were significantly elevated in critically ill patients (n = 218) compared with healthy controls (n = 66). Elevated HMGB1 plasma levels were independent from the presence of sepsis. Moreover, HMGB1 was not associated with disease severity, organ failure, or mortality in the ICU. We observed a trend toward lower HMGB1 levels in ICU patients with pre‐existing obesity, type 2 diabetes and end‐stage renal disease patients on chronic hemodialysis.

Conclusion

In conclusion, our study did not reveal significant associations between HMGB1 levels at ICU admission and clinical outcomes in critically ill patients. Due to the pathogenic role of HMGB1 in the late phases of experimental sepsis, future studies might assess the potential value of HMGB1 by measuring its plasma concentrations at later time points during the course of critical illness.
A review of acid recovery from acidic mining waste solutions using solvent extraction
Authors: Kesieme Uchenna , Chrysanthou Andreas , Catulli Maurizio , Cheng Chu Yong
Published: June 2018

The minerals industry is increasingly being forced by regulatory and cost pressures to reduce the amount of liquid acidic waste they produce. This requires a strong focus on waste reduction by recycling, regeneration and reuse. Four mineral acids were examined for recovery from waste acidic solutions including H2SO4, HNO3, HCl, and H3PO4. The selection of the optimal extractant for acid recovery was based on extraction, stripping and scrubbing efficiencies. The extractants suitable for the recovery of H2SO4 and HCl are in the order of TEHA > Cyanex 923 > TBP > Alamine 336. TEHA has the highest degree of acid extraction and stripping compared with Cyanex 923 and almost 99% of the acid can be stripped. Alamine 336 can extract higher acid (for H2SO4 and HCl systems) than Cyanex 923 and TBP. However loaded acid for Alamine 336 system cannot be stripped using water at 60°C. For the recovery of nitric and phosphoric acids from acidic waste effluents, TBP was the best option. This work clearly demonstrates that extractant suitable for acid extraction may not be suitable for its recovery. However such extractant may be applied for the removal of acid from any waste acidic solution sacrificing the back extraction of the loaded acid. The effective implementation of options for acid recovery was examined to improve sustainability in the mineral industry. © 2018 Society of Chemical Industry
Static power characteristics of selective buried oxide CMOS devices
Authors: Younis Dana , Madathumpadical Narayanan , Al‐Nashash Hasan
Published: June 2018

Selective buried oxide (SELBOX) Metal‐Oxide‐Semiconductor Field‐Effect Transistor (MOSFET) structure can be used to reduce the kink effect and self‐heating problems associated with the silicon on insulator (SOI) MOSFET devices while maintaining the advantages of bulk MOSFET. In this paper, static power dissipation of SELBOX structure is investigated and compared with SOI and bulk structures. Various MOSFET structures are simulated and evaluated in terms of their static power dissipation. Only results from 90‐nm Complementary Metal Oxide Semiconductor (CMOS) technology devices are included in this paper. Simulation results using the Silvaco TCAD show that static power dissipation in SELBOX CMOS is similar to that of SOI devices but lower than that of bulk CMOS. Hence, SELBOX structure is found to produce relatively low‐static power dissipation while maintaining high operating speed and reducing self‐heating and kink effect. A mathematical model to describe the static power dissipation in the subthreshold region is also included. Statistical analysis show that the model and fabrication simulation results agree with P < .05 and correlation coefficient of 0.95.
Inflammation and atrial fibrillation: A comprehensive review
Authors: Korantzopoulos Panagiotis , Letsas Konstantinos P. , Tse Gary , Fragakis Nikolaos , Goudis Christos A. , Liu Tong
Published: June 2018

Atrial fibrillation (AF) has different underlying substrates. Atrial remodeling involves electrophysiological and structural abnormalities that promote the development and perpetuation of AF. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling. The mechanistic links between atrial remodeling and inflammation are complex while diverse underlying diseases and conditions may affect these pathways. Inflammatory markers have also been associated with AF development, recurrence, perpetuation, total AF burden as well as with thromboembolic complications. The development of specific anti‐inflammatory interventions in this setting seems to be challenging and complicated. Several agents with pleiotropic properties, including anti‐inflammatory, have been tested in experimental and clinical settings with variable results. This updated review provides a concise overview of all available data regarding the role of inflammation in AF including the predictive role of inflammatory markers. Also, current knowledge and future directions on anti‐inflammatory strategies are critically discussed.
Comparison of direct oral anticoagulants and warfarin regarding midterm adverse events in patients with atrial fibrillation undergoing catheter ablation
Authors: Sagawa Yuichiro , Nagata Yasutoshi , Yamaguchi Tetsuo , Iwai Takamasa , Yamaguchi Junji , Hijikata Sadahiro , Watanabe Keita , Masuda Ryo , Miyazaki Ryoichi , Miwa Naoyuki , Sekigawa Masahiro , Hara Nobuhiro , Nozato Toshihiro , Hirao Kenzo
Published: June 2018

Background

Oral anticoagulants, including direct oral anticoagulants (DOACs), are usually required in atrial fibrillation (AF) patients who are at a high risk of thromboembolism (TE), even if they had undergone catheter ablation (CA). Although several studies have reported the safety and efficacy of DOACs around CA in AF patients, there are only limited data regarding the midterm incidence of TE and bleeding complications post‐CA among AF patients treated with warfarin or DOACs.

Methods

We studied 629 AF patients (mean age: 65.3 ± 10.3 years; 442 men) undergoing CA, to calculate the midterm incidence of TE and bleeding complications associated with warfarin or DOACs.

Results

In total, 292 patients used warfarin and 337 used DOACs (dabigatran: 90 patients; rivaroxaban: 137; and apixaban: 110). At baseline, the CHA2DS2‐VASc and HAS‐BLED scores were similar between the 2 groups. During a median follow‐up period of 7 months, no TE complications occurred. The warfarin group had a significantly higher bleeding event rate than did the DOACs group (all bleeding complications: 32 [11.0%] vs 15 [4.5%], respectively, P = .002). The rate of all bleeding complications was significantly higher in the warfarin group than in the DOACs group (10.1% vs 3.7%, respectively, at 10 months; P = .024). In Cox proportional hazards modeling, DOAC use was significantly associated with a decreased risk of bleeding (adjusted hazard ratio: 0.497; 95% confidence interval: 0.261‐0.906, P = .022).

Conclusions

Direct oral anticoagulant use in AF patients undergoing CA may be associated with a similar risk of TE as warfarin but is associated with a lower risk of bleeding.
Academic leadership and commercial activities at research institutes: German evidence
Authors: Goel Rajeev K. , Göktepe‐Hultén Devrim
Published: June 2018

This paper focuses on entrepreneurship by academic leaders. With the use of patents, inventions, and spin‐offs to measure commercialization, and directors, research group leaders, and business owners as academic leaders, results, using a sample of more than 2,500 German researchers, show differences across academic leaders and commercialization. Findings for spin‐offs are different from those for patents and inventions. Academic leaders in sciences were more likely to commercialize. Doctoral degrees helped patents by business owners and spin‐offs by group leaders, whereas female business owners and female group leaders faced challenges patenting and inventing, respectively. For business owners, age increased the likelihood of patenting but lowered spin‐offs.
Business process optimization using the ant colony system
Authors: Ng C.Y.
Published: June 2018

Process optimization is a key consideration in workflow management. Implementing an efficient workflow may improve customer satisfaction and enhance productivity of an enterprise. Many optimization tools have been introduced to solve scheduling problems in the manufacturing environment, but most of them have not drawn much attention of decision makers for workflow analyses. This is mainly due to the difference between business operations and manufacturing processes that the process optimization tools cannot be directly applied for analyzing business workflows. Scholars have associated the attributes of workflow in the business environment with those of scheduling concepts to facilitate the use of job shop scheduling techniques for solving workflow problems. However, there is still not much discussion on the use of metaheuristic algorithms for workflow analyses. This paper proposes the use of a systematic approach that entails the ant colony optimization algorithm for identifying the best task sequence in support of processing time analyses. The applicability of the proposed approach is demonstrated with a case example. The result shows that a better operation sequence in terms of shorter processing duration can be obtained by the proposed approach.
Technical Note: Minimizing geometrical uncertainties of cylindrical well‐type ionization chamber measurements: There is an optimal chamber length
Authors: Keyvanloo Amir , Jans Hans‐S.
Published: June 2018

Purpose

The response of well‐type ionization chambers used, for example, in brachytherapy and nuclear medicine, depends on the location of the source. In cases where the source length is variable (typically in nuclear medicine), it is also dependent on length of the source. Here, the combined effect on chamber sensitivity of both source position and length is investigated in detail. This analysis is important if nominal values for source location and length are prescribed as (arbitrary but fixed) values in order to precisely define a chamber's sensitivity. During measurement, the actual values for source location and length can deviate from the nominal ones, altering sensitivity and thus giving rise to measurement uncertainties which, in turn, directly affect the doses administered to patients. Our aim is to investigate these uncertainties and minimize them with an optimized ion chamber design.

Methods

An analytical model for the chamber response is used to describe the variation of chamber sensitivity with respect to the two parameters, source position and length. The influence of the relative magnitude of uncertainty in both parameters is also accounted for. The effect of their combined variation on chamber sensitivity is required to be minimal and, employing differential geometry tools, a relationship is derived between them and the optimal height of the ionization chamber's sensitive volume.

Results

This relationship provides the chamber height h which minimizes its response variation for given nominal value of source location (quantified as insertion depth d) and prescribed source length l: , where ρ = δd/δl is defined as the quotient of uncertainty in insertion depth, δd, and uncertainty in source length, δl, and , so that the optimal ionization chamber length varies between and . Alternatively, if h is given, suitable combinations of d and l can be deduced.

Conclusions

The analysis presented here provides a tool for reducing the uncertainty budget of any cylindrically designed ionization chambers utilized for measuring extended on‐axis sources. In particular, these results can be applied to a calibration‐type ionization chamber design recently proposed for the cross‐calibration of unsealed radionuclides.
Feasibility of estimating volumetric breast density from mammographic x‐ray spectra using a cadmium telluride photon‐counting detector
Authors: Ghammraoui Bahaa , Badal Andreu , Glick Stephen J.
Published: June 2018

Purpose

Mammographic density of glandular breast tissue has a masking effect that can reduce lesion detection accuracy and is also a strong risk factor for breast cancer. Therefore, accurate quantitative estimation of breast density is clinically important. In this study, we investigate experimentally the feasibility of quantifying volumetric breast density with spectral mammography using a CdTe‐based photon‐counting detector.

Methods

To demonstrate proof‐of‐principle, this study was carried out using the single pixel Amptek XR‐100T‐CdTe detector. The total number of x rays recorded by the detector from a single pencil‐beam projection through 50%/50% of adipose/glandular mass fraction‐equivalent phantoms was measured. Material decomposition assuming two, four, and eight energy bins was then applied to characterize the inspected phantom into adipose and glandular using log‐likelihood estimation, taking into account the polychromatic source, the detector response function, and the energy‐dependent attenuation.

Results

Measurement tests were carried out for different doses, kVp settings, and different breast sizes. For dose of 1 mGy and above, the percent relative root mean square (RMS) errors of the estimated breast density was measured below 7% for all three phantom studies. It was also observed that some decrease in RMS errors was achieved using eight energy bins. For 3 and 4 cm thick phantoms, performance at 40 and 45 kVp showed similar performance. However, it was observed that 45 kVp showed better performance for a phantom thickness of 6 cm at low dose levels due to increased statistical variation at lower photon count levels with 40 kVp.

Conclusion

The results of the current study suggest that photon‐counting spectral mammography systems using CdTe detectors have the potential to be used for accurate quantification of volumetric breast density on a pixel‐to‐pixel basis, with an RMS error of less than 7%.
Characterizing the Preferences and Values of U.S. Recreational Atlantic Bluefin Tuna Anglers
Authors: Goldsmith William M. , Scheld Andrew M. , Graves John E.
Published: June 2018

The Atlantic Bluefin Tuna Thunnus thynnus is the target of a recreational fishery along the U.S. East Coast that is thought to be of considerable economic value. In some years, recreational landings have exceeded the sector's annual subquota due to changes in fish availability, limited predictability of angler effort, and difficulties in real-time monitoring of catch. Understanding the drivers of angler behavior is critical for predicting how effort and harvest may vary as a function of changing fish availability, regulations, or costs. To investigate angler decision making, preferences, and values, we surveyed private recreational anglers from Maine to North Carolina and employed discrete choice experiments to determine how regulatory and nonregulatory trip-specific variables influence trip-taking behavior. A latent class-ranked logit model identified two distinct classes of anglers who exhibited differing preferences in regard to the importance of nonconsumptive aspects of Bluefin Tuna fishing (e.g., catch and release). Income and recent Bluefin Tuna targeting were the primary determinants of class membership, and higher-income anglers who had targeted Bluefin Tuna in the past 5 years were significantly more likely to be in the class that derives substantive benefits from nonconsumptive angling activities. An annual consumer surplus exceeding US$14 million was estimated for the 2015 fishery. We considered potential angler welfare impacts of possible management changes (compensating surplus) and identified a large amount of latent effort currently present in the fishery in the form of consumptive-oriented anglers. As a result, liberalization of harvest regulations could potentially lead to a large influx of effort into the fishery, which could impede the ability of managers to maintain harvest levels within prescribed limits.
Ex vivo diffusion MRI of the human brain: Technical challenges and recent advances
Authors: Roebroeck Alard , Miller Karla L. , Aggarwal Manisha
Published: June 2018

This review discusses ex vivo diffusion magnetic resonance imaging (dMRI) as an important research tool for neuroanatomical investigations and the validation of in vivo dMRI techniques, with a focus on the human brain. We review the challenges posed by the properties of post‐mortem tissue, and discuss state‐of‐the‐art tissue preparation methods and recent advances in pulse sequences and acquisition techniques to tackle these. We then review recent ex vivo dMRI studies of the human brain, highlighting the validation of white matter orientation estimates and the atlasing and mapping of large subcortical structures. We also give particular emphasis to the delineation of layered gray matter structure with ex vivo dMRI, as this application illustrates the strength of its mesoscale resolution over large fields of view. We end with a discussion and outlook on future and potential directions of the field.
A narrative literature review of palliative care regarding patients with idiopathic pulmonary fibrosis
Authors: Igai Yasuko
Published: June 2018

Aim

The aim of this study was to examine the reported characteristics of extant studies on palliative care for patients with idiopathic pulmonary fibrosis.

Design

Narrative review.

Methods

A comprehensive search of the following electronic databases in English and Japanese commenced from 2002 ‐ December 2017. Eligibility criteria was determined by the inclusion and exclusion criteria.

Results

Nineteen articles were eligible. The characteristics of palliative care for patients with idiopathic pulmonary fibrosis were symptoms relief, start time of palliative care and palliative care needs of patients and care partners. Also, patients' education of disease management including advanced care planning and developing a palliative care system by the healthcare provider including multidisciplinary professional teams was identified. The care provided was a “care conference” and integrated palliative care was carried out in the patient's home. The majority of the studies were qualitative and retrospective in design. The palliative care system and the development of palliative care were limited.
Agreement between asthma questionnaire and health care register data
Authors: Hedman Anna M. , Gong Tong , Lundholm Cecilia , Dahlén Elin , Ullemar Vilhelmina , Brew Bronwyn K. , Almqvist Catarina
Published: June 2018

Purpose

Risk factors and consequences of asthma can be studied by using validated questionnaires. The overall objective of this study was to assess the agreement of parental‐reported asthma‐related questions regarding their children against Swedish health care registers.

Methods

We linked a population‐based twin cohort of 27 055 children aged 9 to 12 years to the Swedish Prescribed Drug Register, National Patient Register, and the primary care register. Parent‐reported asthma was obtained from questionnaires, and diagnoses and medication were retrieved from the registers. For the agreement between the questionnaire and the registers, Cohen's kappa was estimated.

Results

The kappa of the “reported ever asthma” against a “register‐based ever asthma” was 0.69 and 0.57 between the parental‐“reported doctor's diagnosis” and “register‐based doctor's diagnosis.” The highest agreement between “reported current asthma” and “register‐based current asthma” with at least 1 dispensed medication or a diagnosis applied to different time windows was seen for an 18‐month window (kappa = 0.70).

Conclusions

We found that parent‐reported asthma‐related questions showed on average good agreement with the Swedish health care registers. This implies that in‐depth questionnaires with rich information on phenotypes are suitable proxies for asthma in general and can be used for health care research purposes.
Management of Patients with Acute Methotrexate Nephrotoxicity with High‐Dose Leucovorin
Authors: Flombaum Carlos D. , Liu Dazhi , Yan Shirley Qiong , Chan Amelia , Mathew Sherry , Meyers Paul A. , Glezerman Ilya G. , Muthukumar Thangamani
Published: June 2018

Background

Acute kidney injury complicating high‐dose methotrexate (HDMTX) therapy increases the risk for severe mucositis, myelosuppression, and death. It is unclear whether high‐dose leucovorin and supportive therapy without the use of glucarpidase can reduce toxicity from HDMTX.

Study Design

The charts of all patients at Memorial Sloan Kettering Cancer Center whose methotrexate (MTX) drug levels at 48 or 72 hours after administration were 10 times or more the toxic level were reviewed between January 2000 and December 2011.

Results

Eighty‐eight patients (median age 51 years, range 9–90 years) who received 100 courses of HDMTX were identified. Serum creatinine increased by 2‐fold from baseline (median, range 1‐ to 10‐fold), but all patients recovered kidney function. Serum levels of MTX were 69 μmol/L (median, range 2.2–400), 6.9 μmol/L (1.3–64), and 2.0 μmol/L (0.05–26) at 24, 48, and 72 hours, respectively, after administration. A statistically significant correlation existed between MTX levels at 48, 72, 96, and 120 hours after administration but not between 24 and 72 hours or subsequent time points. High‐dose leucovorin was given in 81% of courses in accordance with institutional protocols in most cases. Myelosuppression was present in 42%; grade III or higher neutropenia in 29%, and thrombocytopenia in 25%. Infectious complications, oral mucositis, and diarrhea occurred in 21%, 17%, and 6% of patients, respectively. Five deaths occurred, none directly attributed to complications from MTX administration. Seven additional patients received glucarpidase at the discretion of a treating physician during the study period, and results are reported separately.

Conclusion

Patients who had 100 episodes of HDMTX‐associated acute kidney injury were treated with a strategy that only included usual supportive measures and high‐dose leucovorin. No deaths were directly attributed to complications related to HDMTX. Glucarpidase, an expensive drug, may not be necessary for a significant number of patients.
Subskill mastery among elementary and middle school students at risk in mathematics
Authors: Nelson Peter M. , Parker David C. , Van Norman Ethan R.
Published: June 2018

In the present study, we evaluated the number of attempts required to master specific subskills for working with whole and rational numbers among students at risk for math difficulties. Participants included a subset of students in grades four through eight receiving supplemental math support. Mastery—defined as 85% correct on short tests—was assessed following instruction for each subskill. Using survival analysis, we evaluated the number of attempts required to reach a .50 and a .90 probability of mastery on each subskill. The number of required attempts varied across subskills, with many subskills requiring more than one attempt to demonstrate mastery. Further, some of the most difficult content was aligned with curricular standards below students’ grade level. Thus, among students identified for supplemental support, it may be worthwhile to remediate select subskills that fall outside of the grade‐level curriculum before providing additional instruction on grade‐level content. Implications for math subskill assessment and remediation are discussed along with limitations and directions for future research.
A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis
Authors: Wołczański Grzegorz , Lisowski Marek
Published: June 2018

N‐(tert‐butyloxycarbonyl) or N‐(9‐fluorenylmethoxycarbonyl) dipeptides with C‐terminal (Z)‐α,β‐didehydrophenylalanine (∆ZPhe), (Z)‐α,β‐didehydrotyrosine (∆ZTyr), (Z)‐α,β‐didehydrotryptophan (∆ZTrp), (Z)‐α,β‐didehydromethionine (∆ZMet), (Z)‐α,β‐didehydroleucine (∆ZLeu), and (Z/E)‐α,β‐didehydroisoleucine (∆Z/EIle) were synthesised from their saturated analogues via oxidation of intermediate 2,5‐disubstituted‐oxazol‐5‐(4H)‐ones (also known as azlactones) with pyridinium tribromide followed by opening of the produced unsaturated oxazol‐5‐(4H)‐one derivatives in organic‐aqueous solution with a catalytic amount of trifluoroacetic acid or by a basic hydrolysis. In all cases, a very strong preference for Z isomers of α,β‐didehydro‐α‐amino acid residues was observed except of the ΔIle, which was obtained as the equimolar mixture of Z and E isomers. Reasons for the (Z)‐stereoselectivity and the increased stability of the aromatic α,β‐didehydro‐α‐amino acid residue oxazol‐5‐(4H)‐ones over the corresponding aliphatic ones are also discussed. It is the first use of such a procedure to synthesise peptides with the C‐terminal unsaturated residues and a peptide with 2 consecutive ΔPhe residues. This approach is very effective especially in the synthesis of peptides with aliphatic α,β‐didehydro‐α‐amino acid residues that are difficult to obtain by other methods. It allowed the first synthesis of the ∆Met residue. It is also more cost‐effective and less laborious than other synthesis protocols. The dipeptide building blocks obtained were used in the solid‐phase synthesis of model peptides on a polystyrene‐based solid support. Peptides containing aromatic α,β‐didehydro‐α‐amino acid residues were obtained with PyBOP or TBTU as a coupling agent with good yields and purities. In the case of aliphatic α,β‐didehydro‐α‐amino acid residues, a good efficiency was achieved only with DPPA as a coupling agent.
Comparing methods for estimation of heterogeneous treatment effects using observational data from health care databases
Authors: Wendling T. , Jung K. , Callahan A. , Schuler A. , Shah N. H. , Gallego B.
Published: June 2018

There is growing interest in using routinely collected data from health care databases to study the safety and effectiveness of therapies in “real‐world” conditions, as it can provide complementary evidence to that of randomized controlled trials. Causal inference from health care databases is challenging because the data are typically noisy, high dimensional, and most importantly, observational. It requires methods that can estimate heterogeneous treatment effects while controlling for confounding in high dimensions. Bayesian additive regression trees, causal forests, causal boosting, and causal multivariate adaptive regression splines are off‐the‐shelf methods that have shown good performance for estimation of heterogeneous treatment effects in observational studies of continuous outcomes. However, it is not clear how these methods would perform in health care database studies where outcomes are often binary and rare and data structures are complex. In this study, we evaluate these methods in simulation studies that recapitulate key characteristics of comparative effectiveness studies. We focus on the conditional average effect of a binary treatment on a binary outcome using the conditional risk difference as an estimand. To emulate health care database studies, we propose a simulation design where real covariate and treatment assignment data are used and only outcomes are simulated based on nonparametric models of the real outcomes. We apply this design to 4 published observational studies that used records from 2 major health care databases in the United States. Our results suggest that Bayesian additive regression trees and causal boosting consistently provide low bias in conditional risk difference estimates in the context of health care database studies.
UV‐Resistant and Thermally Stable Superhydrophobic CeO2 Nanotubes with High Water Adhesion
Authors: Li Xue‐Ping , Sun Ya‐Li , Xu Yao‐Yi , Chao Zi‐Sheng
Published: June 2018

A novel type of sticky superhydrophobic cerium dioxide (CeO2) nanotube material is prepared by hydrothermal treatment without any chemical modification. A water droplet on the material surface shows a static water contact angle of about 157° but the water droplet is pinned on the material surface even when the material surface is turned upside down. Interestingly, the as‐prepared CeO2 nanotube material displays durable superhydrophobicity and enhanced adhesion to water under ultraviolet (UV) light irradiation. Importantly, this change in water adhesion can be reversed by heat treatment to restore the original adhesive value of 20 µL. Further, the maximum volume of the water droplet adhered on the material surface of CeO2 nanotubes can be regulated without loss of superhydrophobicity during the heating treatment/UV‐irradiation cycling. Meanwhile, the superhydrophobic CeO2 nanotube material shows remarkable thermal stability even at temperatures as high as 450 °C, long‐term durability in chemical environment, and air‐storage and good resistance to oily contaminant. Finally, the potential application in no‐loss water transportation of this sticky superhydrophobic CeO2 material is demonstrated.
fib Model Code 2020: Towards a general code for both new and existing concrete structures
Authors: Matthews Stuart , Bigaj‐van Vliet Agnieszka , Walraven Joost , Mancini Giuseppe , Dieteren Gerrie
Published: June 2018

Discussions have been underway in fib (Fédération Internationale du Béton) about advancing the fib Model Code for concrete structures. These include the fib international workshop in The Hague (June 2015), the fib MC2020 Core Group meeting in Madrid (December 2015), and a series of follow‐up worldwide consultations on the fib ambition regarding the new developments in structural codes, including the special session on Model Code in the fib Symposium in Maastricht (June 2017). This paper discusses the main aspects of the development of fib MC2020, which is envisaged as a single‐merged general code fully integrating the provisions for the design of new concrete structures with matters relating to existing concrete structure. It needs to deal effectively with both the design of structures and all the activities associated with the through‐life management of existing concrete structures, including matters such as their in‐service assessment and interventions upon them. To that end, MC2020 will take sustainability as a fundamental requirement, based upon a holistic treatment of societal needs and impacts, life‐cycle cost and environmental impacts. This paper discusses the main aspects of the development of fib MC2020. As part of this, the envisaged contribution of fib T10.1: Model Code 2020 is reviewed. However, recognizing the overall ambition of the fib MC2020 project, it is clear that all fib commissions, along with other bodies able to make contributions on relevant topics, will need to work together to assemble the breadth of knowledge and expertise which will be required for the fib MC2020 project.
Computational anatomy and diffeomorphometry: A dynamical systems model of neuroanatomy in the soft condensed matter continuum
Authors: Miller Michael I. , Arguillère Sylvain , Tward Daniel J. , Younes Laurent
Published: June 2018

The nonlinear systems models of computational anatomy that have emerged over the past several decades are a synthesis of three significant areas of computational science and biological modeling. First is the algebraic model of biological shape as a Riemannian orbit, a set of objects under diffeomorphic action. Second is the embedding of anatomical shapes into the soft condensed matter physics continuum via the extension of the Euler equations to geodesic, smooth flows with inverses, encoding divergence for the compressibility of atrophy and expansion of growth. Third, is making human shape and form a metrizable space via geodesic connections of coordinate systems. These three themes place our formalism into the modern data science world of personalized medicine supporting inference of high‐dimensional anatomical phenotypes for studying neurodegeneration and neurodevelopment. The dynamical systems model of growth and atrophy that emerges is one which is organized in terms of forces, accelerations, velocities, and displacements, with the associated Hamiltonian momentum and the diffeomorphic flow acting as the state, and the smooth vector field the control. The forces that enter the model derive from external measurements through which the dynamical system must flow, and the internal potential energies of structures making up the soft condensed matter. We examine numerous examples on growth and atrophy.

This article is categorized under:

Analytical and Computational Methods > Computational Methods

Laboratory Methods and Technologies > Imaging

Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Spin State Variations and Spin‐Crossover in Diiron(II) Complexes of Bis(pentadentate) Pyrazolate‐Based Ligands
Authors: Schober Anne , Demeshko Serhiy , Meyer Franc
Published: June 2018

Compartmental pyrazolato‐bridged ligands [LPy]− and [LIm]−, each providing two {N5} binding sites but differing in the terminal N‐donors (pyridine vs. imidazole), were used to prepare a set of diferrous complexes; the ligand HLIm is new and its synthesis is reported. Complexes [LPyFe2(MeCN)2](OTf)3, (1OTf), [LPyFe2(MeCN)2](BF4)3 (1BF4), [LImFe{Fe(MeCN)}](OTf)3 (2OTf), and [LImFe{Fe(MeCN)}](BF4)3 (2BF4) were characterized by single‐crystal X‐ray diffraction, revealing a MeCN coligand at both (1OTf, 1BF4) or at only one (2OTf, 2BF4) of the two accessible Fe coordination sites that are directed into the bimetallic cleft. Magnetic measurements (SQUID) and 57Fe Mößbauer spectroscopy indicate low‐spin states for the six‐coordinate FeII ions in 1OTf and 1BF4 that are based on [LPy]−, but two high‐spin FeII ions in 2BF4 that is based on [LIm]−, in agreement with structural data. Complex 2OTf shows abrupt spin‐crossover (SCO) from a mixed high‐spin/low‐spin to an all high‐spin state at T½ = 264 K, which appears to be correlated with the Fe–N≡C(Me) bonding angle. SCO, though gradual, is observed for 2OTf also in solution (T½ = 273 K in MeCN, 248 K in EtCN), which was studied by Mössbauer spectroscopy of frozen solution samples, variable temperature UV/Vis spectroscopy and SQUID magnetometry; the latter methods consistently gave thermodynamic parameters ΔH = 24.2 kJ·mol–1, ΔS = 89 J·mol–1·K–1 for the SCO of 2OTf in MeCN, and ΔH = 19.1 kJ·mol–1, ΔS = 77 J·mol–1·K–1 in EtCN.
Metabolism of amino acid neurotransmitters: the synaptic disorder underlying inherited metabolic diseases
Authors: Kölker Stefan
Published: June 2018

Amino acids are involved in various metabolic pathways and some of them also act as neurotransmitters. Since biosynthesis of l‐glutamate and γ‐aminobutyric acid (GABA) requires 2‐oxoglutarate while 3‐phosphoglycerate is the precursor of l‐glycine and d‐serine, evolutionary selection of these amino acid neurotransmitters might have been driven by their capacity to provide important information about the glycolytic pathway and Krebs cycle. Synthesis and recycling of amino acid neurotransmitters as well as composition and function of their receptors are often compromised in inherited metabolic diseases. For instance, increased plasma l‐phenylalanine concentrations impair cerebral biosynthesis of protein and bioamines in phenylketonuria, while elevated cerebral l‐phenylalanine directly acts via ionotropic glutamate receptors. In succinic semialdehyde dehydrogenase deficiency, the neurotransmitter GABA and neuromodulatory γ‐hydroxybutyric acid are elevated. Chronic hyperGABAergic state results in progressive downregulation of GABAA and GABAB receptors and impaired mitophagy. In glycine encephalopathy, the neurological phenotype is precipitated by l‐glycine acting both via cortical NMDA receptors and glycine receptors in spinal cord and brain stem neurons. Serine deficiency syndromes are biochemically characterized by decreased biosynthesis of l‐serine, an important neurotrophic factor, and the neurotransmitters d‐serine and l‐glycine. Supplementation with l‐serine and l‐glycine has a positive effect on seizure frequency and spasticity, while neurocognitive development can only be improved if treatment starts in utero or immediately postnatally. With novel techniques, the study of synaptic dysfunction in inherited metabolic diseases has become an emerging research field. More and better therapies are needed for these difficult‐to‐treat diseases.
A Cause-of-Death Decomposition of Young Adult Excess Mortality
Authors: Remund Adrien , Camarda Carlo G. , Riffe Tim
Published: June 2018

We propose a method to decompose the young adult mortality hump by cause of death. This method is based on a flexible shape decomposition of mortality rates that separates cause-of-death contributions to the hump from senescent mortality. We apply the method to U.S. males and females from 1959 to 2015. Results show divergence between time trends of hump and observed deaths, both for all-cause and cause-specific mortality. The study of the hump shape reveals age, period, and cohort effects, suggesting that it is formed by a complex combination of different forces of biological and socioeconomic nature. Male and female humps share some traits in all-cause shape and trend, but they also differ by their overall magnitude and cause-specific contributions. Notably, among males, the contributions of traffic and other accidents were progressively replaced by those of suicides, homicides, and poisonings; among females, traffic accidents remained the major contributor to the hump.
Framing effects on bribery behaviour: experimental evidence from China and Uganda
Authors: Gaggero Alessio , Appleton Simon , Song Lina
Published: June 2018

In this study we investigate the effect of framing on bribery behaviour. To do this, we replicate Barr and Serra (Exp Econ, 12(4):488–503, (2009) and carry out a simple one-shot bribery game that mimics corruption. In one treatment, we presented the experiment in a framed version, in which wording was embedded with social context; in the other, we removed the social context and presented the game in a neutral manner. The contribution of this paper is that it offers a comparison of framing effects in two highly corrupt countries: China and Uganda. Our results provide evidence of strong and significant framing effects for Uganda, but not for China.
Utilizing a Sedation Decision Aid in Ambulatory Venous Access Device Placement: Effects on Patient Choice, Workup, and Recovery Time
Authors: Chittle Melissa D. , McIntyre Erin , Lotti Judy Borsody , Saltalamacchia Catherine , Sheridan Robert M. , Mueller Peter R. , Sepucha Karen
Published: June 2018

This study was undertaken to determine the influence of using a sedation decision aid when selecting a sedation option for totally implantable vascular access device placement on patient choice, workup, and recovery time. An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, retrospective study of 76 patients (aged 23–89 years, 58% female) presenting to a vascular interventional radiology department between January 2, 2017, and May 5, 2017. Patients were given a decision aid that inquired about personal values and goals, and provided information about expectations; benefits; and risks of the options, including undergoing the procedure with no sedation (local anesthetic), minimal sedation (anxiolysis with a benzodiazepine), or moderate sedation (benzodiazepine and opiate). No sedation was selected by 15 out of 76 patients (19.7%), minimal sedation was selected by 26 out of 76 patients (34.2%), and moderate sedation was selected by 34 out of 76 patients (44.7%). Postprocedure recovery time differences were significant (P < .001) with a mean of 17.4 minutes for no sedation, 49.3 minutes for minimal sedation, and 70.8 minutes for moderate sedation. The use of a decision aid did not slow down the process because workup times were not significantly different: 15.9 minutes for no sedation, 22.1 minutes for minimal sedation, and 18.4 minutes for moderate sedation. Patient sedation preference for totally implantable vascular access device is variable, signifying there is a role for utilizing a decision aid because it empowers a patient to select the option most aligned with his or her goals. Influence on departmental flow is notable because this does not slow down the workup and a majority of patients choose no or minimal sedation, resulting in a decreased postprocedure recovery time burden.