bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of CYP3A‐mediated drug–drug interactions with romidepsin in patients with advanced cancer
Authors: Laille Eric , Patel Manish , Jones Suzanne F. , Burris Howard A. , Infante Jeffrey , Lemech Charlotte , Liu Liangang , Arkenau Hendrik‐Tobias
Published: June 2015

Two multicenter, single‐arm, single‐infusion, open‐label studies were conducted to evaluate the effect of ketoconazole (a strong CYP3A inhibitor) or rifampin (a strong CYP3A inducer) daily for 5 days on the pharmacokinetics (PK) and safety of romidepsin (8 mg/m2 intravenous 4‐hour infusion for the ketoconazole study or a 14 mg/m2 intravenous 4‐hour infusion for the rifampin study) in patients with advanced cancer. Romidepsin coadministered with ketoconazole (400 mg) or rifampin (600 mg) was not bioequivalent to romidepsin alone. With ketoconazole, the mean romidepsin AUC and Cmax were increased by approximately 25% and 10%, respectively. With rifampin, the mean romidepsin AUC and Cmax were unexpectedly increased by approximately 80% and 60%, respectively; this is likely because of inhibition of active liver uptake. For both studies, romidepsin clearance and volume of distribution were decreased, terminal half‐life was comparable, and median Tmax was similar. Overall, the safety profile of romidepsin was not altered by coadministration with ketoconazole or rifampin, except that a higher incidence and greater severity of thrombocytopenia was observed when romidepsin was given with rifampin. The use of romidepsin with rifampin and strong CYP3A inducers should be avoided. Toxicity related to romidepsin exposure should be monitored when romidepsin is given with strong CYP3A inhibitors.
Interaction of 3‐(2‐Aminophenyl)‐6‐R1‐1,2,4‐triazin‐5‐ones with Acylating Reagents: An Efficient Method for Preparation of 6‐Substituted 3‐R1‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐ones
Authors: Voskoboynik Alexey Yu. , Scorina Dmitriy Yu. , Sergeieva Tetiana Yu. , Kovalenko Sergiy I. , Okovytyy Sergiy I. , Omelchenko Irina V. , Shishkin Oleg V.
Published: June 2015

The series of 6‐substituted 3‐R1‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐one was prepared via condensation of 3‐(2‐aminophenyl)‐6‐R1‐1,2,4‐triazin‐5‐ones with acylating reagents. Particularities of 1H NMR spectra have been also discussed based on the comparison of experimental and theoretical results for 3‐methyl‐6‐phenyl‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐one and its 4,3‐isomer.
Convenient Synthesis of Functionalized 3,4,10,11‐tetrahydroindolo[1,2‐a]Quinoxalines Via Three‐component Reaction of Dimedone, 3‐nitrochromenes and Ammonium Acetate
Authors: Fang Jun , Yan Chao‐Guo
Published: June 2015

An efficient synthetic procedure for the functionalized 3,4,10,11‐tetrahydroindolo[1,2‐a]quinoxalines was successfully developed by the three‐component reaction of dimedone, 3‐nitrochromenes, and ammonium acetate in ethanol. This reaction has the advantages of using common starting material, short reaction process, and good yields high‐atom efficiency.
Stereoselective Synthesis, Structural and Spectroscopic Study of 4,5,11‐Triazatricyclo[6.2.1.0*2,6*]Undec‐5‐ene
Authors: Mabied Ahmed F. , Girgis Adel S. , Shalaby El‐Sayed M. , George Riham F. , El‐Gendy Bahaa El‐Dien M. , Baselious Fady N.
Published: June 2015

3‐(2,4‐Dichlorophenyl)‐7‐[(2,4‐dichlorophenyl)methylidene]‐11‐methyl‐4‐phenyl‐4,5,11‐triazatricyclo[6.2.1.0*2,6*]undec‐5‐ene (3) was synthesized in a stereoselective manner. Single crystal X‐ray study of 3 revealed that the structure belongs to the triclinic system with space group
. The structure is further stabilized by an intermolecular CH…π interaction. Molecular mechanics force field (MM+), followed by either semi‐empirical AM1 or PM3, was used to calculate the optimized geometrical parameters of 3. The determined theoretical geometry parameters were found to be in good agreement with the parameters obtained by a single‐crystal study. Vibrational frequencies and gauge‐independent atomic orbital, 1H‐NMR and 13C‐NMR chemical shifts were computed at B3LYP/6‐31G(d) level of theory. Moreover, the molecular electrostatic potential of 3 has been calculated exhibiting that the most electrophilic site of 3 is the N‐3 atom; however, the nucleophilic site is distributed on the H atoms of dichlorophenyl groups. The frontier molecular orbitals of 3 have been determined by the same technique.
Observation of the multiple halogenation of peptides in the electrospray ionization source
Authors: Kostyukevich Yury , Zhdanova Ekaterina , Kononikhin Alexey , Popov Igor , Kukaev Eugene , Nikolaev Eugene
Published: June 2015

The chlorination of peptides and proteins is an important posttranslational modification, which is a physiological signature of an enzyme myeloperoxidase and can serve as a potential biomarker of some diseases (Parkinson's disease, Alzheimer's disease, etc.). The quantification of the chlorinated peptides has been very challenging in part due to their low levels and artifacts associated with sample preparation. One of the most convenient and promising methods to detect and investigate the chlorinated peptides in the biological samples is the electrospray ionization (ESI) mass spectrometry coupled to the fragmentation techniques (collision‐induced dissociation and electron capture dissociation/electron transfer dissociation). We have shown that if the chlorine anions are present in the solution, then the peptide can undergo the chlorination during the ESI ionization. The effect was found to depend on the values of electric potentials of metal parts of the ESI interface. It was found that the grounding of ESI syringe results in the formation of an additional electric loop leading to the electrolytic production of Cl2 and as a consequence the hypochlorous acid inside the ESI needle. Hypochlorous acid reacts with amino groups of peptides and proteins producing chloramine or causing the protein cleavage. In the paper, it is shown on the example of the solution of the several peptides in the presence of HCl that by manipulating the ESI syringe potential, it is possible to create complexes with up to five Cl atoms for sample peptides when the ESI is operated in the positive mode. Copyright © 2015 John Wiley & Sons, Ltd.
110 years of temperature observations at Orcadas Antarctic Station: multidecadal variability
Authors: Zitto Miguel E. , Barrucand Mariana G. , Piotrkowski Rosa , Canziani Pablo O.
Published: June 2015

There is growing evidence of significant changes in components of the Antarctic climate system, an important issue given the influence Antarctica has on global climate. It is important to infer to what extent these regional changes could be attributed to human‐induced processes and to what extent to natural variability. Standard methods such as linear trend estimates or piecewise linear trends can be inadequate because they may result in erratic, non‐systematic results, particularly if different scales of variability are present in each record and various records are to be compared. The Orcadas Antarctic Station (Argentina), with daily surface meteorological observations since April 1903, provides Antarctica's longest observational record. This study analyses the Orcadas seasonal surface temperature variability. Multidecadal variability and short‐term trends are studied to provide an improved assessment of climate evolution and necessary information for the determination of mechanisms driving regional/local change. A combined method using wavelet transform (WT), non‐linear statistical model approaches and derivative of fits is developed. This methodology is also applied for validation and comparison to the Gomez ice core oxygen isotope record for the 1857–2006 and 1903–2006 time intervals. Significant quasi 50‐year and quasi 20‐year variability bands were obtained, both for the quarterly and seasonal Orcadas temperature records, with warming (cooling) periods detected between 1903–1912, 1927–1961 and 1972–2004 (1912–1927 and 1962–1972). If seasons are considered, the only one with a fairly sustained warming is summer, where actual cooling is observed only at the beginning, prior to the early 1930s. Quasi 50‐year variability was also detected in the Gomez record. Long periods are obtained in the model fits, longer than the time series, which varied with window length. Although not representing variability cycles, they could represent the best fit of the non‐linear, non oscillating asymptotic stationary component of the series, i.e. a non‐linear trend.
A Model of Creativity in Organizations: John Holland's Theory of Vocational Choice (1973) at Multiple Levels of Analysis
Authors: Sharif Rukhsar
Published: June 2015

This conceptual paper serves to create a model of creativity and innovation at different organizational levels. It draws on John Holland's Theory of Vocational Choice (1973) as the basis for its structure by incorporating the six different personality types from his theory: conventional, enterprising, realistic, social, investigative, and artistic, as working together with each other within and between teams in organizations. The model begins with opposite personalities working together in two‐person groups to generate creative ideas and then expands to all six personalities working together as one team to implement innovative products and services. It is the underlying contrast of personalities in Holland's (1973) theory, where each personality contributes diverse ideas and skills, that when combined, produce new products and services that are financially beneficial, useful, and enhancing of well‐being for organizations and society.
Rapid and non‐destructive determination of rancidity levels in butter cookies by multi‐spectral imaging
Authors: Xia Qing , Liu Changhong , Liu Jinxia , Pan Wenjuan , Lu Xuzhong , Yang Jianbo , Chen Wei , Zheng Lei
Published: June 2015

BACKGROUND

Rancidity is an important attribute for quality assessment of butter cookies, while traditional methods for rancidity measurement are usually laborious, destructive and prone to operational error. In the present paper, the potential of applying multi‐spectral imaging (MSI) technology with 19 wavelengths in the range of 405–970 nm to evaluate the rancidity in butter cookies was investigated.

RESULTS

Moisture content, acid value and peroxide value were determined by traditional methods and then related with the spectral information by partial least squares regression (PLSR) and back‐propagation artificial neural network (BP‐ANN). The optimal models for predicting moisture content, acid value and peroxide value were obtained by PLSR. The correlation coefficient (r) obtained by PLSR models revealed that MSI had a perfect ability to predict moisture content (r = 0.909), acid value (r = 0.944) and peroxide value (r = 0.971).

CONCLUSION

The study demonstrated that the rancidity level of butter cookies can be continuously monitored and evaluated in real‐time by the multi‐spectral imaging, which is of great significance for developing online food safety monitoring solutions. © 2015 Society of Chemical Industry
Land Use and Precipitation Affect Organic and Microbial Carbon Stocks and the Specific Metabolic Quotient in Soils of Eleven Ecosystems of Mt. Kilimanjaro, Tanzania
Authors: Pabst Holger , Gerschlauer Friederike , Kiese Ralf , Kuzyakov Yakov
Published: June 2015

Tropical ecosystems are under increasing pressure of land‐use changes, strongly affecting the carbon cycle. Conversion from natural to agri‐cultural ecosystems is often accompanied by a decrease in the stocks of organic and microbial carbon (Corg, Cmic) as well as changes in microbial activity and litter decomposition. Eleven ecosystems along an elevation gradient on the slopes of Mt. Kilimanjaro were used to investigate impacts of land‐use changes on Corg and Cmic stocks as well as the specific metabolic respiration quotient (qsCO2) in surface soils. Six natural, two semi‐natural and three intensively used agricultural ecosystems were investigated on an elevation gradient from 950 to 3,880 m asl. To estimate the effects of precipitation, rainfall regimes of 3·6 and 20·0 mm were simulated. Corg stocks were controlled by water availability, temperature and net primary production. Agricultural management resulted in decreases of Corg and Cmic stocks by 38% and 76%, respectively. In addition, agricultural systems were characterized by low Cmic:Corg ratios, indicating a decline in available substrate. Enhanced land‐use intensity leads to increased qsCO2 (agricultural > semi‐natural > natural). The traditional homegardens stood out as a sustainable land‐use form with high substrate availability and microbial efficiency. Soil CO2 efflux and qsCO2 generally increased with precipitation level. We conclude that soils of Mt. Kilimanjaro's ecosystems are highly sensitive to land‐use changes and are vulnerable to changes in precipitation, especially at low elevations. Even though qsCO2 was measured under different water contents, it can be used as an indicator of ecosystem disturbances caused by land‐use and management practices. Copyright © 2015 John Wiley & Sons, Ltd.
Intraoperative, real‐time monitoring of blood flow dynamics associated with laser surgery of port wine stain birthmarks
Authors: Yang Bruce , Yang Owen , Guzman John , Nguyen Paul , Crouzet Christian , Osann Kathryn E. , Kelly Kristen M. , Nelson J. Stuart , Choi Bernard
Published: June 2015

Background and Objective

Port‐wine stain (PWS) birthmarks affect ∼22 million people worldwide. After several treatment sessions, complete disappearance of the PWS occurs in only ∼10% of treated patients. There is a need to develop a new strategy to improve the efficacy of each treatment session and the overall treatment outcome. The study objective was to determine how intraoperative measurements of blood flow correlate with treatment response assessed several weeks post treatment.

Study Design/Materials and Methods

We employed Laser Speckle Imaging (LSI) to measure intraoperative blood‐flow dynamics. We collected data from 24 subjects undergoing laser therapy for facial PWS birthmarks. Photographs were taken before treatment and at a follow‐up visit, and analyzed by two expert observers.

Results

Intraoperative LSI enables real‐time monitoring of blood‐flow dynamics in response to laser treatment and can inform clinicians on the need for focused re‐treatment. The degree of PWS blanching achieved is positively correlated with the log‐transformed acute blood‐flow reduction (P = 0.022).

Conclusion

LSI is a simple, intraoperative monitoring tool during laser therapy of PWS birthmarks. LSI provides a single value for blood flow that correlates well with the degree of blanching achieved with laser therapy. Lasers Surg. Med. 47:469–475, 2015. © 2015 Wiley Periodicals, Inc.
Effect of mechanical optical clearing on near‐infrared spectroscopy
Authors: Idelson Christopher R. , Vogt William C. , King‐Casas Brooks , LaConte Stephen M. , Rylander Christopher G.
Published: June 2015

Near‐infrared Spectroscopy (NIRS) is a broadly utilized technology with many emerging applications including clinical diagnostics, sports medicine, and functional neuroimaging, to name a few. For functional brain imaging NIR light is delivered at multiple wavelengths through the scalp and skull to the brain to enable spatial oximetry measurements. Dynamic changes in brain oxygenation are highly correlated with neural stimulation, activation, and function. Unfortunately, NIRS is currently limited by its low spatial resolution, shallow penetration depth, and, perhaps most importantly, signal corruption due to light interactions with superficial non‐target tissues such as scalp and skull. In response to these issues, we have combined the non‐invasive and rapidly reversible method of mechanical tissue optical clearing (MOC) with a commercially available NIRS system. MOC utilizes a compressive loading force on tissue, causing the lateral displacement of blood and water, while simultaneously thinning the tissue. A MOC‐NIRS Breath Hold Test displayed a ∼3.5‐fold decrease in the time‐averaged standard deviation between channels, consequentially promoting greater channel agreement. A Skin Pinch Test was implemented to negate brain and muscle activity from affecting the recorded signal. These results displayed a 2.5–3.0 fold increase in raw signal amplitude. Existing NIRS instrumentation has been further integrated within a custom helmet device to provide a uniform force distribution across the NIRS sensor array. These results showed a gradual decrease in time‐averaged standard deviation among channels with an increase in applied pressure. Through these experiments, and the development of the MOC‐NIRS helmet device, MOC appears to provide enhancement of NIRS technology beyond its current limitations. Lasers Surg. Med. 47:495–502, 2015. © 2015 Wiley Periodicals, Inc.
A Study of HCl Gas Adsorption/Desorption Properties of PNIPAM Brushes
Authors: Zhao Xin Jun , Gao Zhi Fu , Jiang Zhong Ying
Published: June 2015

In this paper, we employ a molecular theory to study HCl gas‐adsorption/desorption properties of PNIPAM brushes. Here, PNIPAM–HCl hydrogen bonds and theirs explicit coupling to the PNIPAM conformations are considered. We find that hydrogen bonding becomes a key element in determining HCl gas‐adsorption/desorption behaviors of PNIPAM brushes. Our results indicate that, when at moderate grafting densities, the association of PNIPAM–HCl hydrogen bonds can result in a dependence of PNIPAM brush‐height on HCl concentration, and the morphology of PNIPAM brushes may have a significant effect on the HCl gas‐adsorption/desorption properties.
Complex abdominal wall defect reconstruction using a latissimus dorsi free flap with mesh after malignant tumor resection
Authors: Bodin Frédéric , Dissaux Caroline , Romain Benoît , Rohr Serge , Brigand Cécile , Bruant‐Rodier Catherine
Published: June 2015

Purpose

Extended and full‐thickness abdominal wall defects are commonly reconstructed using free flaps. Published surgical outcomes involving the latissimus dorsi (LD) free flap procedure are limited and are less numerous than those with free flaps involving the thigh. The aim of this report was to describe the immediate and long‐term evaluation of complex abdominal wall reconstruction using a LD free flap with mesh.

Patients and Methods

Between 2005 and 2013, nine patients with extended malignant tumors of the abdominal wall underwent surgeries. After the surgical resection, the mean defect size was 385 cm2 (range: 190–650 cm2). Full‐thickness abdominal wall reconstruction was performed with a combination of LD free flaps and meshes. The immediate and long‐term outcomes were assessed regarding the complications, sustainable strength of the abdominal wall and cancer recurrence.

Results

The meshes measured 927 cm2 in average (range: 500–1036 cm2). Eight Parietex Composite® and 1 Bard Collamend Implant® were used. No donor site complications occurred, and complete LD flap survival was achieved without partial necrosis or thrombosis. One obese patient who received a porcine dermis mesh developed an eventration four days postoperatively and exhibited a limited amount of abdominal skin necrosis around the flap. Two patients died from cancer evolution. After a mean follow‐up of 60.4 months (range: 29–94 months), clinical evaluation of the abdomen revealed 2 patients without anomalies, 4 cases of abdominal bulging without functional discomfort and 1 case of major abdominal distension.

Conclusions

Complex abdominal reconstruction with LD free flap and mesh allows extended satisfactory coverage with a low incidence of flap and donor site complications. However, patients should be advised of the significant risk of abdominal bulging. © 2014 Wiley Periodicals, Inc. Microsurgery 37:38–43, 2017.
An implicit pseudospectral scheme to solve propagating fronts in reaction‐diffusion equations
Authors: Olmos‐Liceaga Daniel , Segundo‐Caballero Israel
Published: June 2015

Some Reaction‐Diffusion equations present solutions of the traveling wave form. In this work, we present an implicit numerical scheme based on finite difference originally proposed to solve hyperbolic equations. Then, this method is improved using a pseudospectral approach to discretize the spatial variable. The results prove that this new scheme is useful to solve equations of the parabolic type which presents traveling wave solutions. In particular, problems where a reduction in the number of discretization points and an increase of the size of the time step play an important role in their solution are considered. The implicit scheme presented involves the solution of linear systems only. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 86–105, 2016
Numerical analysis and iteration acceleration of a fully implicit scheme for nonlinear diffusion problem with second‐order time evolution
Authors: Cui Xia , Yuan Guang‐wei , Yue Jing‐yan
Published: June 2015

Fully implicit schemes with second‐order time evolutions have been applied to simulate nonlinear diffusion problems precisely for a long time, but there is seldom theoretical study for either their convergence properties or efficient iterations. Here, a second‐order time evolution fully implicit scheme for two‐dimensional nonlinear divergence diffusion problem is analyzed. The unique existence of its solution is given. Two new methods are provided to prove its convergence, including entire inductive hypothesis reasoning and a two‐step reasoning process. Rigorous analysis shows the scheme is stable; its solution has second‐order convergence in both space and time to the exact solution of the problem. The convergence is applied to analyze a Newton iteration accelerating the computation and show its quadratic convergent speed and second‐order accuracy. The reasoning techniques also adapt to first‐order time accuracy schemes, and can be extended to analyze a wide class of nonlinear schemes for nonlinear problems. Numerical tests highlight the theoretical results and demonstrate the high performance of the algorithms. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 121–140, 2016
Numerical analysis of the Crank–Nicolson extrapolation time discrete scheme for magnetohydrodynamics flows
Authors: Zhang Yuhong , Hou Yanren , Shan Li
Published: June 2015

In this article, we consider the time‐discrete method for three‐dimensional incompressible magnetohydrodynamics (MHD) equations. The Crank–Nicolson extrapolation scheme is used for time discretization. From the previous articles, under the assumption that the solution has high regularity which cannot be realistically assumed, the convergence of this scheme is optimal two‐order. In this article, under modest assumptions of initial values and the body force, we prove some new regularity results of the MHD equations. In addition, we derive the unconditional convergence of our scheme, but the convergent order is not optimal. Furthermore, we provide another conditional convergence estimation to increase the order. It is shown that the convergent rate increase half order in ‐norm, and at least a quarter order increased in ‐norm than the uncondtional results. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 2169–2208, 2015
Necessary and sufficient optimality conditions for fractional nonhomogeneous Roesser model
Authors: Kamocki Rafał
Published: June 2015

In the paper, we study an optimal control problem connected with a fractional Roesser model described by partial Riemann–Liouville derivatives. A theorem on the existence optimal solutions and the maximum principle for such problem with nonhomogeneous boundary conditions are proved. Copyright © 2015 John Wiley & Sons, Ltd.
Methodological considerations in assessing the effectiveness of antidepressant medication continuation during pregnancy using administrative data
Authors: Swanson Sonja A. , Hernandez‐Diaz Sonia , Palmsten Kristin , Mogun Helen , Olfson Mark , Huybrechts Krista F.
Published: June 2015

Purpose

The decision whether to continue antidepressant use for depression during pregnancy requires weighing maternal and child risks and benefits. Little is known about the effectiveness of antidepressant therapy during pregnancy. The goal of this study is to evaluate whether standard administrative claims data can be used to evaluate the effectiveness of antidepressants.

Methods

Using prescription and healthcare visit Medicaid claims (2000–2007), we identified 28 493 women with a depression diagnosis and antidepressant fill in the 90 days before their last menstrual period. Antidepressant continuation was defined based on prescription fills during the first trimester. Depression hospitalizations and deliberate self‐harm served as measures of the effectiveness of treatment continuation during pregnancy. Propensity score and instrumental variable analyses were used to attempt to account for confounding.

Results

Relative to women who discontinued antidepressant therapy, women who continued were more likely to have a depression inpatient stay (odds ratio [OR] = 2.2, 95% confidence interval [95%CI]: 2.0–2.4) and deliberate self‐harm code (OR = 1.4, 95%CI: 0.7–2.7). Accounting for measured covariates in the propensity score analysis, including age, race, comorbidities, comedications, features of the depression diagnosis, and antidepressant class, led to slightly attenuated estimates (OR = 2.0, 95%CI: 1.8–2.2; OR = 1.1, 95%CI: 0.5–2.4). Similar associations were estimated in subgroups with different levels of baseline depression severity. Proposed preference‐time, calendar‐time‐based, and geography‐based instruments were unlikely to meet the required conditions for a valid analysis.

Conclusions

Our findings suggest that either antidepressant medications do not reduce the risk of depression relapse in pregnant women, or that administrative data alone could not be used to validly estimate the effectiveness of psychotropic medications during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.
Management of Drug Interaction between Posaconazole and Sirolimus in Patients Who Undergo Hematopoietic Stem Cell Transplant
Authors: Cho Eunah , Chan Holly , Nguyen Huan (Mark) , Shayani Sepideh , Nakamura Ryotaro , Pon Doreen
Published: June 2015

Study Objective

To determine an appropriate empiric oral sirolimus dose adjustment when given concurrently with posaconazole oral suspension in patients who undergo hematopoietic stem cell transplant (HSCT).

Design

Retrospective cohort study.

Setting

Comprehensive cancer center in the United States.

Subjects

Seventy five allogeneic HSCT patients who received posaconazole oral suspension and oral sirolimus concurrently between 2009 and 2011.

Measurements and Main Results

Sirolimus concentrations were recorded at baseline and for up to 28 days after posaconazole initiation. The sirolimus concentration/dose (C/D) ratio was determined for each sirolimus concentration obtained. Following analysis of patient data and based on the initial empiric sirolimus dose reduction, patients were stratified into two groups: ≥50% sirolimus dose reduction (Group 1) and <50% sirolimus dose reduction (Group 2). The mean sirolimus C/D ratio was 2.29 ng/mL/mg prior to posaconzole initiation. Coadministration of posaconazole and sirolimus resulted in an increase in the steady state sirolimus C/D ratio to 6.24 ng/mL/mg, which occurred approximately 17–20 days after initiation of posaconazole. The mean maximum sirolimus concentration was significantly higher in Group 2 compared to Group 1 (12.64 ng/mL vs. 9.24 ng/mL, p=0.001). Significantly more patients in Group 2 than Group 1 experienced at least one sirolimus concentration >15 ng/mL (27% vs. 2.6%, p=0.003).

Conclusion

Coadministration of posaconazole oral suspension with oral sirolimus increases the sirolimus C/D ratio by approximately 2.7‐fold in HSCT patients. An initial empiric oral sirolimus dose reduction between 50% and 65% may be recommended for most clinically stable patients with close sirolimus concentration monitoring for at least 3 weeks following posaconazole initiation.
The balance of clinician and patient input into treatment decision‐making in older women with operable breast cancer
Authors: Morgan Jenna L. , Burton Maria , Collins Karen , Lifford Kate J. , Robinson Thompson G. , Cheung Kwok‐Leung , Audisio Riccardo , Reed Malcolm W. , Wyld Lynda ,   on behalf of the Bridging the Age Gap Trial Management Team
Published: June 2015

Objective

Primary endocrine therapy (PET) is an alternative to surgery for oestrogen receptor positive operable breast cancer in some older women. However the decision to offer PET involves complex trade‐offs and is influenced by both patient choice and healthcare professional (HCP) preference. This study aimed to compare the views of patients and HCPs about this decision and explore decision‐making (DM) preferences and whether these are taken into account during consultations.

Methods

This multicentre, UK, mixed methods study had three components: (a) questionnaires to older women undergoing counseling about breast cancer treatment options which assessed their DM preferences and realities; (b) qualitative interviews with older women with operable breast cancer offered a choice of either surgery or PET and (c) qualitative interviews with HCPs (both of which focused on DM preferences in this setting).

Results

Thirty‐three patients and 34 HCPs were interviewed. A range of opinions about patient involvement in DM were identified. Patients indicated varying preferences for DM involvement which were variably taken into account by HCPs. These qualitative findings were broadly supported by the questionnaire results. Most patients (536/729; 73.5%) achieved their preferred DM style; however, the remainder felt that their DM preferences had not been taken into consideration.

Conclusions

These results suggest that whilst many older women achieve their desired level of DM engagement, some do not, raising the possibility that they may be making choices which are not concordant with their treatment preferences. Copyright © 2015 John Wiley & Sons, Ltd.
Does time heal all wounds? A longitudinal study of the development of posttraumatic stress symptoms in parents of survivors of childhood cancer and bereaved parents
Authors: Ljungman Lisa , Hovén Emma , Ljungman Gustaf , Cernvall Martin , von Essen Louise
Published: June 2015

Background

A lack of longitudinal studies has hampered the understanding of the development of posttraumatic stress symptoms (PTSS) in parents of children diagnosed with cancer. This study examines level of PTSS and prevalence of posttraumatic stress disorder (PTSD) from shortly after diagnosis up to 5 years after end of treatment or child's death, in mothers and fathers.

Methods

A design with seven assessments (T1–T7) was used. T1–T3 were administered during treatment and T4–T7 after end of treatment or child's death. Parents (N = 259 at T1; n = 169 at T7) completed the PTSD Checklist Civilian Version. Latent growth curve modeling was used to analyze the development of PTSS.

Results

A consistent decline in PTSS occurred during the first months after diagnosis; thereafter the decline abated, and from 3 months after end of treatment only minimal decline occurred. Five years after end of treatment, 19% of mothers and 8% of fathers of survivors reported partial PTSD. Among bereaved parents, corresponding figures were 20% for mothers and 35% for fathers, 5 years after the child's death.

Conclusions

From 3 months after end of treatment the level of PTSS is stable. Mothers and bereaved parents are at particular risk for PTSD. The results are the first to describe the development of PTSS in parents of children diagnosed with cancer, illustrate that end of treatment is a period of vulnerability, and that a subgroup reports PTSD 5 years after end of treatment or child's death. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.
Family caregiver communication in oncology: advancing a typology
Authors: Goldsmith Joy , Wittenberg Elaine , Platt Christine Small , Iannarino Nicholas T. , Reno Jenna
Published: June 2015

Objectives

The quality of communication between the patient and family caregiver impacts quality of life and well‐being for the two; however, providers have few tools to understand communication patterns and assess the communication needs and preferences of caregivers. The aims of this study were to examine family communication patterns among oncology patients and their caregivers and to identify common characteristics among four different types of family caregivers.

Methods

Nurses recruited oncology patient–caregiver dyads through a large cancer treatment center in the Southeast. Patients and caregivers were separated from one another and interviewed during chemotherapeutic infusions. Interviews were recorded, transcribed, coded, and thematized.

Results

A sample of 24 patients and their caregivers (n = 48) were interviewed. The majority of dyads (21, 88%) shared the same family communication pattern. Common caregiver communication features support previous work identifying four caregiver communication types: Manager, Carrier, Partner, and Lone caregivers. Manager caregivers lead patients by utilizing extensive medical knowledge, whereas Carrier caregivers were led by patients and described tireless acts to maintain the family and avoid difficult conversations. Partner caregivers facilitated family involvement and open communication on a variety of topics, while Lone caregivers focused solely on biomedical matters and a hope for cure.

Conclusions

Caregiver communication types were corroborated by patient–caregiver descriptions of caregiving. However, more information is needed to ascertain the variables associated with each caregiver type. Future work to improve identification of caregiver types and create targeted caregiver care plans will require further study of health literacy levels and tested communication interventions per type. Copyright © 2015 John Wiley & Sons, Ltd.
Incidence and risk factors for psychiatric comorbidity among people newly diagnosed with cancer based on Korean national registry data
Authors: Lee Byung Ook , Choi Won‐Jung , Sung Na Young , Lee Seon‐Koo , Lee Chong Gul , Kang Jee In
Published: June 2015

Objective

The present study investigates the incidence of psychiatric disorders, related risk factors, and the use of mental health services among people newly diagnosed with one of five major cancers (stomach, liver, colorectal, lung, and breast cancer) based on national registry data from the National Health Insurance Service (NHIS) in the Korean population.

Methods

We collected data on people newly diagnosed with one of the five major cancers between 2005 and 2008 using the nationwide claims data and cancer registration files of the NHIS. We analyzed the data of those diagnosed with psychiatric disorders over a 5‐year period, from 2004 to 2009.

Results

Among 302 844 people with newly diagnosed cancer, we identified 31 579 patients (10.43%) who were also newly diagnosed with psychiatric disorders after their cancer diagnosis. Among psychiatric diagnoses, anxiety disorders and depression showed the highest incidences of 18.13 and 13.16 per 1000 person‐years, respectively. Among major cancers, patients with lung cancer showed the highest incidence of psychiatric disorders. Older age and female gender were shown to be risk factors associated with psychiatric comorbidity, and no significant differences were found for region of residence.

Conclusion

The present study showed a low incidence of psychiatric comorbidity and suggests that psychiatric disorders in cancer patients tend to be underrecognized in actual clinical practice. Greater risk for psychiatric comorbidity was associated with lung cancer, older age, and female gender. The present findings provide important information for establishing national policies to detect and manage mental health problems during cancer care.Copyright © 2015 John Wiley & Sons, Ltd.
He2@C60: Thoughts of the concept of a molecule and of the concept of a bond in quantum chemistry
Authors: Kryachko Eugene S. , Nikolaienko Tymofii Yu.
Published: June 2015

We present a broad palette of discussions of the concepts of a molecule and a chemical bond that always lay down behind all computational modeling in quantum chemistry and of the endohedral fullerene He2@C60 in particular. For this purpose, we offer the definition of quantum chemistry as composed of three ingredients. Each of them is illustrated by its particular concept, either that of a molecule or a bond. The third, computational ingredient is tackled to resolve the bonding manifold of He2@C60 and to demonstrate that van‐der‐Waals binding of HeHe is converted within He2@C60 into a stronger bond due to that C60 acts as an electronic buffer and [He2] moiety mimics a fractionally charged
. Experimental fingerprints of He2@C60 are computed. © 2015 Wiley Periodicals, Inc.
Political ecology of water conflicts
Authors: Rodríguez‐Labajos Beatriz , Martínez‐Alier Joan
Published: June 2015

This article reviews methodologies, types, and political implications of water conflicts from a political ecology perspective. The political ecology of water studies the conflicts on water use, whether as an input or as a vehicle for waste disposal. Both the quantity and the quality of water are relevant for conflicts on water as a commodity and also indirectly in conflicts on water from oil and gas extraction, mining, or biomass production. This study provides an overview and classification of water conflicts, showing how social movements born from such conflicts are creatively generating new modalities of water management and governance in the process. To this end, this article first examines methodological approaches for the analysis of water conflicts and water justice. Then, a taxonomy of water conflicts based on the stages of the commodity chain is presented and discussed. Afterward, empirical evidence is collected showing how social mobilizations in water conflicts become effective providers of management alternatives and governance modalities. Water justice movements and organizations have formed networks, have proposed new principles of water management, and have not only been active in the promotion of the human right to water but also in the recognition of water, along with other elements of nature, as a subject of rights. WIREs Water 2015, 2:537–558. doi: 10.1002/wat2.1092

This article is categorized under:

Engineering Water > Planning Water

Human Water > Rights to Water

Human Water > Water Governance
Climate change and the ethics of discounting
Authors: Davidson Marc D.
Published: June 2015

Climate policy‐making requires a balancing, however rudimentary, of the costs of reducing greenhouse gas emissions against the benefits of reduced risks of climate change. Since those creating and those facing the risks of climate change belong to different generations, striking the balance is preeminently a matter of ethics. In climate policy‐making, this issue of intergenerational ethics is hidden behind the choice of thediscount rate, a parameter used in economic analysis to compare changes in consumption occurring in different years. There is a long‐standing debate in ethics and economics as to whether discounting the future is morally justifiable. Some economists have argued that the future should always be discounted against the marginal rate of return on alternative investments, whether for reasons of efficiency, or for reasons of consumer sovereignty and democracy. Other authors, however, have argued against this position, instead proposing discount rates based on a variety of moral principles. Although these counterarguments may be convincing, the debate between the two positions is far from settled. Neither has the debate been settled as to which moral theory the discount rate should be based on. This is hardly surprising, though, given the fact that within ethics itself, the debate over the various moral principles is still ongoing.WIREs Clim Change2015, 6:401–412. doi: 10.1002/wcc.347

This article is categorized under:

Climate, Nature, and Ethics > Ethics and Climate Change
YNL134C from Saccharomyces cerevisiae encodes a novel protein with aldehyde reductase activity for detoxification of furfural derived from lignocellulosic biomass
Authors: Zhao Xianxian , Tang Juan , Wang Xu , Yang Ruoheng , Zhang Xiaoping , Gu Yunfu , Li Xi , Ma Menggen
Published: June 2015

Furfural and 5‐hydroxymethylfurfural (HMF) are the two main aldehyde compounds derived from pentoses and hexoses, respectively, during lignocellulosic biomass pretreatment. These two compounds inhibit microbial growth and interfere with subsequent alcohol fermentation. Saccharomyces cerevisiae has the in situ ability to detoxify furfural and HMF to the less toxic 2‐furanmethanol (FM) and furan‐2,5‐dimethanol (FDM), respectively. Herein, we report that an uncharacterized gene, YNL134C, was highly up‐regulated under furfural or HMF stress and Yap1p and Msn2/4p transcription factors likely controlled its up‐regulated expression. Enzyme activity assays showed that YNL134C is an NADH‐dependent aldehyde reductase, which plays a role in detoxification of furfural to FM. However, no NADH‐ or NADPH‐dependent enzyme activity was observed for detoxification of HMF to FDM. This enzyme did not catalyse the reverse reaction of FM to furfural or FDM to HMF. Further studies showed that YNL134C is a broad‐substrate aldehyde reductase, which can reduce multiple aldehydes to their corresponding alcohols. Although YNL134C is grouped into the quinone oxidoreductase family, no quinone reductase activity was observed using 1,2‐naphthoquinone or 9,10‐phenanthrenequinone as a substrate, and phylogenetic analysis indicates that it is genetically distant to quinone reductases. Proteins similar to YNL134C in sequence from S. cerevisiae and other microorganisms were phylogenetically analysed. Copyright © 2015 John Wiley & Sons, Ltd.
Puromycin‐ and methotrexate‐resistance cassettes and optimized Cre‐recombinase expression plasmids for use in yeast
Authors: MacDonald Chris , Piper Robert C.
Published: June 2015

Here we expand the set of tools for genetically manipulating Saccharomyces cerevisiae. We show that puromycin‐resistance can be achieved in yeast through expression of a bacterial puromycin‐resistance gene optimized to the yeast codon bias, which in turn serves as an easy‐to‐use dominant genetic marker suitable for gene disruption. We have constructed a similar DNA cassette expressing yeast codon‐optimized mutant human dihydrofolate reductase (DHFR), which confers resistance to methotrexate and can also be used as a dominant selectable marker. Both of these drug‐resistant marker cassettes are flanked by loxP sites, allowing for their excision from the genome following expression of Cre‐recombinase. Finally, we have created a series of plasmids for low‐level constitutive expression of Cre‐recombinase in yeast that allows for efficient excision of loxP‐flanked markers. Copyright © 2015 John Wiley & Sons, Ltd.
Conflicting intersexual mate choices maintain interspecific sexual interactions
Authors: Takakura Koh‐Ichi , Nishida Takayoshi , Iwao Keisuke
Published: June 2015

Reproductive interference, interspecific sexual interactions that affect reproductive success, is found in various taxa and has been considered as a fundamental source of reproductive character displacement (RCD). Once RCD has occurred, persistent interspecific sexual interactions between species pairs are expected to diminish. However, reproductive interference has been reported from some species pairs that sympatrically coexist. Thus, the question arises, can reproductive interference persist even after RCD? We modeled the evolutionary dynamics of signal traits and mate recognition that determine whether interspecific sexual interactions occur. Our models incorporate male decision making based on the recognition of signal traits, whereas most previous models incorporate only female decision making in mate selection. Our models predict the following: (1) even when male decision making is incorporated, males remain promiscuous; (2) nevertheless, the frequency of interspecific mating is maintained at a low level after trait divergence; (3) the rarity of interspecific mating is due to strict female mate recognition and the consequent refusal of interspecific courtship by females; and (4) the frequency of interspecific mating becomes higher as the cost to females of refusing interspecific courtship increases. These predictions are consistent with empirical observations that males of some species engage in infrequent heterospecific mating. Thus, our models predict that reproductive interference can persist even after RCD occurred.
Trophic level, food chain length and omnivory in the Paraná River: a food web model approach in a floodplain river system
Authors: Saigo M. , Zilli F. L. , Marchese M. R. , Demonte D.
Published: June 2015

To determine the mean trophic level and food chain length and to quantify omnivory in a floodplain lake of the Middle Paraná River, we constructed a food web model based on available data. Because proper selection of basal resources is essential, we performed stepwise model selection to decide which sources to include in the model. We estimated mean trophic level, food chain length and omnivory using a binary web (non‐weighted trophic links) and a weighted web (trophic links weighted using stable isotopes). Model selection excluded macrophytes as relevant resources for the food web of this floodplain lake. In general, trophic links were relatively even, leading to similar estimations of mean trophic level and omnivory in both binary and weighted webs. Food chain length, however, was higher for the binary web, which was caused by the strong link of top predators with lower‐trophic level prey in this ecosystem. Overall, the estimate of food chain length in the Paraná River was not particularly high, despite the high productivity and size of this ecosystem. We suggest that the periodical hydrological fluctuations of large rivers could be a major factor precluding the occurrence of long food chains.
Synthesis, Structure Characterization and Biological Activity of Co (II), Cu (II), and Zn (II) Complexes with (Z)‐3‐((3‐hydroxybenzylidene)amino)pyridin‐1‐ium 4‐(dodecan‐4‐yl)benzenesulfonate Surfactant
Authors: Tawfik Salah M. , Zaky Mohamad F.
Published: June 2015

(Z)‐3‐((3‐hydroxybenzylidene)amino)pyridin‐1‐ium4‐dodecylbenzenesulfonate anionic surfactant and its cobalt, copper and zinc complexes were synthesized (I, I‐Co, I‐Cu and I‐Zn). The chemical structures of it were characterized by elemental analysis, FTIR, 1H‐NMR, UV–Vis spectroscopy and atomic adsorption. The effects of the chemical structures of the synthesized anionic surfactant and the type of transition metals on the surface activity are presented in this paper. The thermodynamic parameters show that adsorption and micellization processes are spontaneous. The results of biological activity measurements showed that the synthesized compounds have a great efficiency against gram positive (Bacillus subtilis and Staphylococcus aureus), gram‐ negative bacteria (Pseudomonas aeruginosa and Escherichia coli) and fungi (Candida albicans and Aspergillus niger) as well as the sulfate reducing bacteria (Desulfomonas pigra). The complexation of the anionic surfactant with Co2+, Cu2+ and Zn2+ increase the antimicrobial activity values.
Shape of Long Chain Alkyl Sulfonate Micelle upon Salt Addition: a Molecular Dynamics Study
Authors: Poghosyan Armen H. , Arsenyan Levon H. , Shahinyan Aram A.
Published: June 2015

Here we report a molecular dynamics simulation on the state of long chain alkyl sulfonate micelle which occurs in the presence of salt. We tracked the formation of a large micelle with a dumbbell‐like shape, which has hemispherical end caps with a large radius rather than the middle cylindrical body, where the shape bending angle was around 160o. The data from chain analysis indicate that the micelle hydrocarbon layer is covered with disordered tails. We also report micelle fission controlled by changes in salt concentration. Overall, the parameters obtained are compared with existing experimental findings.