bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold nanoparticles for cleaning contaminated water
Authors: Qian Huifeng , Pretzer Lori A. , Velazquez Juan C. , Zhao Zhun , Wong Michael S.
Published: February 2013

Pollutants in the form of heavy metals, fertilizers, detergents, and pesticides have seriously reduced the supply of pure drinking water and usable water. Gold metal has intriguing potential to deal with the water pollution problem, as recent research on several fronts is advancing the concept of nanoscale gold as the basis for cost‐effective nanotechnology‐based water treatment. Nano‐gold has special properties, such as enhanced catalytic activity, visible surface plasmon resonance color changes, and chemical stability, that make it more useful than other materials. This Perspective article highlights the current use of gold nanoparticles for the efficient removal and the selective and sensitive detection of a variety of pollutants in water. The challenges in further developing nano‐gold to address water contamination are discussed, which should stimulate future research into improved removal and detection of undesirable chemical compounds. © 2013 Society of Chemical Industry
Ionic Liquid Promoted Multicomponent Reaction: A Good Strategy for the Eco‐Compatible Synthesis of Functionalized Pyrroles
Authors: Siddiqui I. R. , Kumar Devesh , Shamim Shayna
Published: February 2013

Task specific [bmim]BF4 was found to be reusable, alternative, and effective reaction media for multicomponent synthesis of highly functionalized pyrroles. Generality of the procedure was established by synthesizing various pyrroles from wide range of aromatic/aliphatic amine, phenacyl bromide, and electrophilic alkynes by utilizing this protocol without any acid or metal catalyst. Ecocompatibility, short reaction time, excellent yield, recyclability of [bmim]BF4, low cost, easy work‐up, and mild reaction conditions are additional advantages of the procedure in the context of sustainable and green chemistry.
Comparative Effectiveness of Noninvasive Ventilation vs Invasive Mechanical Ventilation in Chronic Obstructive Pulmonary Disease Patients With Acute Respiratory Failure
Authors: Tsai Chu‐Lin , Lee Wen‐Ya , Delclos George L. , Hanania Nicola A. , Camargo Carlos A.
Published: February 2013

BACKGROUND

Limited evidence exists on the comparative effectiveness of noninvasive ventilation (NIV) vs invasive mechanical ventilation (IMV) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with respiratory failure.

OBJECTIVES

To characterize the use of NIV and IMV, and to compare the effectiveness of NIV vs IMV in AECOPD.

DESIGN AND PATIENTS

Retrospective cohort study using data from the 2006–2008 Nationwide Emergency Department Sample. Emergency department visits for AECOPD with acute respiratory failure were identified with codes from the International Classification of Diseases, Ninth Revision, Clinical Modification.

MEASURES

The outcome measures were inpatient mortality, hospital length of stay, hospital charges, and complications.

RESULTS

There were an estimated 101,000 visits annually for AECOPD with acute respiratory failure; 96% were admitted to the hospital. Of these, NIV use increased from 14% in 2006 to 16% in 2008 (P=0.049). Use of NIV, however, varied widely between hospitals, ranging from 0% to 100% with a median of 11%. Noninvasive ventilation was more often used in higher–case volume, Northeastern hospitals. In a propensity score analysis, NIV use, compared with IMV, was associated with lower inpatient mortality (risk ratio: 0.54, 95% confidence interval [CI]: 0.50‐0.59), shortened hospital length of stay (−3.2 days; 95% CI: −3.4 to −2.9 days), lower hospital charges (−$35,012; 95% CI: −$36,848 to −$33,176), and lower risk of iatrogenic pneumothorax (0.05% vs 0.5%, P<0.001).

CONCLUSIONS

Although NIV use is increasing in US hospitals, its adoption remains low and varies widely between hospitals. Our observational study suggests NIV appears to be more effective and safer than IMV for AECOPD in the real‐world setting. Journal of Hospital Medicine 2013;8:165–172. © 2013 Society of Hospital Medicine
A particle model for fluid simulation on the multi‐graphics processing unit
Authors: Zhang Fengquan , Shen Xukun , Long Xiang , Hu Lei , Zhao Bin
Published: February 2013

Physics‐based fluid simulation has been widely used in manufacture and entertainment industry. However, numerically solving the three‐dimensional incompressible fluid equation is an expensive computation task. Recently, the general purpose graphics hardware allows to speed up the numerical computations. To this end, we explore a new unified particle model on a multi‐graphics processing unit (GPU) platform for interactive fluid simulation. In this paper, we present a parallel framework for fluid simulation with smoothed particle hydrodynamics. To begin with, we discuss the characteristics of storage dependence, data dependence, and decomposition method based on particles. And then, we design the computation model of simulation including kernel functions, adaptive time step, force, and pressure equations. The unified particle model not only ensures the mass and momentum conservation of simulation but also protects the volume of fluid and allows larger time steps, thus alleviating the calculation burden, contributing to the real‐time simulation. Moreover, an effective parallel architecture based on the multi‐GPU is implemented. For the fluid scene, the spatial domain is automatically partitioned into grid layers and assigned to multiple GPUs subsequently. A dynamic load balancing algorithm and an asynchronous data transferring strategy are proposed and implemented. Furthermore, we propose an adaptive density model for particle surface reconstruction. Finally, the quality and performance of the method are demonstrated using multiple scenes with different numbers of particle. Copyright © 2013 John Wiley & Sons, Ltd.
Sensors and the city: a review of urban meteorological networks
Authors: Muller Catherine L. , Chapman Lee , Grimmond C. S. B. , Young Duick T. , Cai Xiaoming
Published: February 2013

The heterogeneous nature of urban environments means that atmospheric research ideally requires a dense network of sensors to adequately resolve the local climate. With recent advances in sensor technology, a number of urban meteorological networks now exist with a range of research or operational objectives. This article reviews and assesses the current status of urban meteorological networks, by examining the fundamental scientific and logistical issues related to these networks. The article concludes by making recommendations for future deployments based on the challenges encountered by existing networks, including the need for better reporting and documentation of network characteristics, standardized approaches and guidelines, along with the need to overcome financial barriers via collaborative relationships in order to establish the long‐term urban networks essential for advancing urban climate research. Copyright © 2013 Royal Meteorological Society
Phase II study of preoperative chemotherapy with S‐1 and cisplatin followed by gastrectomy for clinically resectable type 4 and large type 3 gastric cancers (JCOG0210)
Authors: Iwasaki Yoshiaki , Sasako Mitsuru , Yamamoto Seiichiro , Nakamura Kenichi , Sano Takeshi , Katai Hitoshi , Tsujinaka Toshimasa , Nashimoto Atsushi , Fukushima Norimasa , Tsuburaya Akira ,   on behalf of the Gastric Cancer Surgical Study Group of the Japan Clinical Oncology Group
Published: February 2013

Background and Objectives

We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S‐1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero‐invasive‐type (type 3) gastric cancer.

Methods

Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28‐day courses of preoperative chemotherapy of S‐1 (80–120 mg/body, p.o., days 1–21) and cisplatin (CDDP; 60 mg/m2, i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment‐related death (TRD).

Results

Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7–81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3‐year overall survival were 17.3 months and 24.5%, respectively.

Conclusions

Preoperative chemotherapy with S‐1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment. J. Surg. Oncol. 2013;107:741–745. © 2013 Wiley Periodicals, Inc.
Tumor size increase following preoperative radiation of soft tissue sarcomas does not affect prognosis
Authors: Delisca Gadini O. , Alamanda Vignesh K. , Archer Kristin R. , Song Yanna , Schwartz Herbert S. , Holt Ginger E.
Published: February 2013

Background and Objectives

Administration of preoperative radiotherapy for extremity soft tissue sarcoma improves local control, while allowing for a more conservative surgical resection. During radiation treatment tumor size typically decreases or remains constant. In a subset of patients, however, a size increase in the tumor occurs. Our goal was to investigate the prognosis of patients who had a size increase of at least 20% over the course of preoperative radiotherapy versus those who did not.

Methods

This retrospective study evaluated 70 patients treated for localized primary STS of the extremities between January 2000 and December 2008. Kaplan–Meier curves for disease‐specific and metastasis‐free survival were calculated for both groups.

Results

Sixty‐one patients had stable or decrease local tumor size following preoperative radiotherapy and nine patients had an increase of at least 20% in tumor size. There were no statistically significant differences found in disease‐specific survival and metastasis‐free survival (Gray's test, P = 0.93 and P = 0.68, respectively) among the two groups.

Conclusion

Our results indicate that a 20% increase in tumor size following preoperative radiotherapy did not result in a worse outcome for patients when compared to those who had stable or decrease local tumor size following preoperative radiotherapy. J. Surg. Oncol. 2013;107:723–727. © 2013 Wiley Periodicals, Inc.
Anatomical analysis of nasal obstruction
Authors: Lee Dong Chang , Shin Ji‐Hyeon , Kim Sung Won , Kim Soo Whan , Kim Byung Guk , Kang Jun Myung , Cho Jin Hee , Park Yong Jin
Published: February 2013

Objectives/Hypothesis

To evaluate the relationship between subjective symptoms of nasal obstruction and the corresponding nasal anatomical parameters using paranasal computed tomography (PNS CT).

Study Design

Retrospective chart review at a tertiary referral center.

Methods

We studied 277 patients who underwent evaluation by the Nasal Obstruction Symptom Evaluation scale and a visual analogue scale of nasal obstruction for preoperative evaluation; 197 patients with nasal obstruction who underwent septoplasty were enrolled in the study group, and 80 patients without nasal septal deviation and without nasal obstruction who underwent a trans‐sphenoidal pituitary tumor operation were enrolled in the control group. A preoperative coronal CT image was used to calculate both nasal cavity cross‐sectional areas and the septal deviation angle at the three levels (internal nasal valve, ostiomeatal unit [OMU], and choana).

Results

Differences between the study group and the control group were found in all nasal anatomical parameters at the internal nasal valve, OMU, and choana. In the study group, subjective nasal obstruction symptoms were correlated with the septal deviation angle and the nasal cavity cross‐sectional area at the OMU and the choana levels. However, there was no correlation between subjective symptoms of nasal obstruction and anatomical factors at the nasal valve level (P < .05).

Conclusions

Coronal PNS CT revealed a relationship between subjective nasal obstructive symptoms and anatomical factors at the middle and posterior nasal levels, especially in patients complaining of stuffy nose. When septoplasty is performed, we must pay attention to correction of middle and posterior nasal septal deviation.

Level of Evidence

3.
Molecular Dynamics Study of Interface Structure in Composites Comprising Surface‐Modified SiO2 Nanoparticles and a Polyimide Matrix
Authors: Komarov P. V. , Mikhailov I. V. , Chiu Y.‐T. , Chen S.‐M. , Khalatur P. G.
Published: February 2013

The method of atomistic molecular dynamics simulations is used to investigate the static properties of the organic–inorganic interface in a polymer nanocomposite consisting of polyimide and silica nanoparticles with modified surface. Alkylsilane chains are used as the surface modifiers. The surface density and chains length of the modifier are the main parameters of the simulations. For simplicity, the model of the composite has been constructed as a polymer layer sandwiched between two solid surfaces. Our results show that one can change the properties of the interface between the polymer matrix and the inorganic filler by choosing the molecular weight and surface density of the modifier.

magnified image
Primary progressive aphasia with parkinsonism
Authors: Doherty Karen M. , Rohrer Jonathan D. , Lees Andrew J. , Holton Janice L. , Warren Jason
Published: February 2013

A 65‐year‐old man presented with word‐finding difficulty and gait disturbance. His speech was nonfluent with word retrieval impairment and difficulties with sentence repetition. Other cognitive domains were intact initially. He developed asymmetrical bradykinesia, rigidity and a rest tremor. Over the following 8 years, his speech production impairment slowly deteriorated with the development of a motor speech disorder, anomia, impaired repetition of single words as well as sentences, and impaired comprehension of initially sentences then single words. His parkinsonian syndrome also deteriorated with limited response to levodopa. Serial brain MRI revealed progressive asymmetric perisylvian atrophy. He died after a disease duration of 12 years. The clinical syndrome is discussed by an expert, the pathology is described, and important clinical points from the case are highlighted. © 2013 Movement Disorder Society
Lewy body pathology in a patient with a homozygous Parkin deletion
Authors: Miyakawa Saori , Ogino Mieko , Funabe Sayaka , Uchino Akiko , Shimo Yasushi , Hattori Nobutaka , Ichinoe Masaaki , Mikami Tetuo , Saegusa Makoto , Nishiyama Kazutoshi , Mori Hideo , Mizuno Yoshikuni , Murayama Shigeo , Mochizuki Hideki
Published: February 2013

Background

We report neuropathologic findings in a patient with homozygous deletions of exons 2 to 4 of parkin.

Results

Although the absence of Lewy bodies has been considered a neuropathologic characteristic of parkin mutation, here we report a pathologic finding with the presence of Lewy bodies.

Methods

The patient was a 72‐year‐old woman with onset of the disease at age 61. Her autopsy revealed marked decrease in melanized neurons in the substantia nigra and the locus coeruleus. Lewy bodies were found in the substantia nigra, the locus coeruleus, the dorsal motor nucleus of the vagus, the basal nucleus of Meynert, the amygdaloid nucleus, and the sympathetic nerve bundles in the myocardium.

Conclusions

Only 3 previous case reports described Lewy body formation in patients carrying parkin mutations. The distribution of Lewy bodies in our patient appeared to be reminiscent of sporadic Parkinson's disease. © 2013 Movement Disorder Society
Sustained relief of generalized dystonia despite prolonged interruption of deep brain stimulation
Authors: Cheung Tyler , Zhang Cen , Rudolph Joseph , Alterman Ron L. , Tagliati Michele
Published: February 2013

Background

Pallidal deep brain stimulation (DBS) is an established treatment for disabling, medication‐refractory generalized dystonia. Patients typically regress to their preoperative baseline when stimulation is discontinued.

Methods

Presented are case reports of 2 dystonia patients.

Results

Two patients with primary generalized dystonia (1 with the DYT1 mutation) who were treated successfully with bilateral pallidal DBS for periods of 18 months and 5 years retained motor benefit for several months after inadvertent interruption of stimulation. Stimulation was interrupted unilaterally for 3 and 7 months and bilaterally for 2 days and 2 months, respectively. Symptoms of dystonia returned only partially during the period of therapy interruption and rapidly and completely resolved after resuming stimulation.

Conclusions

We report unexpected and prolonged retention of motor benefits despite transient cessation of pallidal DBS in 2 dystonia patients. Factors that appear to differentiate these individuals are young age, short duration of disease, and chronic DBS therapy with relatively low energy of stimulation. © 2013 International Parkinson and Movement Disorder Society
Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein
Authors: Cernaro Valeria , Lacquaniti Antonio , Lupica Rosaria , Buemi Antoine , Trimboli Domenico , Giorgianni Grazia , Bolignano Davide , Buemi Michele
Published: February 2013

Human relaxin‐2 (hereafter simply defined as “relaxin”) is a 6‐kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in‐depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.
Accelerated fractional ventilation imaging with hyperpolarized Gas MRI
Authors: Emami Kiarash , Xu Yinan , Hamedani Hooman , Profka Harrilla , Kadlecek Stephen , Xin Yi , Ishii Masaru , Rizi Rahim R.
Published: February 2013

Purpose

To investigate the utility of accelerated imaging to enhance multibreath fractional ventilation (r) measurement accuracy using hyperpolarized gas MRI. Undersampling shortens the breath‐hold time, thereby reducing the O2‐induced signal decay and allows subjects to maintain a more physiologically relevant breathing pattern. Additionally, it may improve r estimation accuracy by reducing radiofrequency destruction of hyperpolarized gas.

Methods

Image acceleration was achieved using an eight‐channel phased array coil. Undersampled image acquisition was simulated in a series of ventilation images and data was reconstructed for various matrix sizes (48–128) using generalized auto‐calibrating partially parallel acquisition. Parallel accelerated r imaging was also performed on five mechanically ventilated pigs.

Results

Optimal acceleration factor was fairly invariable (2.0–2.2×) over the range of simulated resolutions. Estimation accuracy progressively improved with higher resolutions (39–51% error reduction). In vivo r values were not significantly different between the two methods: 0.27 ± 0.09, 0.35 ± 0.06, 0.40 ± 0.04 (standard) versus 0.23 ± 0.05, 0.34 ± 0.03, 0.37 ± 0.02 (accelerated); for anterior, medial, and posterior slices, respectively, whereas the corresponding vertical r gradients were significant (P < 0.001): 0.021 ± 0.007 (standard) versus 0.019 ± 0.005 (accelerated) (cm−1).

Conclusion

Quadruple phased array coil simulations resulted in an optimal acceleration factor of ∼2× independent of imaging resolution. Results advocate undersampled image acceleration to improve accuracy of fractional ventilation measurement with hyperpolarized gas MRI. Magn Reson Med 70:1353–1359, 2013. © 2013 Wiley Periodicals, Inc.
Improved slice‐selective adiabatic excitation
Authors: Balchandani Priti , Glover Gary , Pauly John , Spielman Daniel
Published: February 2013

Purpose

The purpose of this work is to design an improved Slice‐selective Tunable‐flip AdiaBatic Low peak‐power Excitation (STABLE) pulse with shorter duration and increased off‐resonance immunity to make it suitable for use in a greater range of applications and at higher field strengths. An additional aim is to design a variant of this pulse to achieve B1‐insensitive, fat‐suppressed excitation.

Methods

The adiabatic SLR algorithm was used to generate a more uniform spectral pulse envelope for this improved radiofrequency pulse for adiabatic slice‐selective excitation, called STABLE‐2. Pulse parameters were adjusted to design a version of STABLE‐2 with a spectral null centered on lipids.

Results

In vivo images obtained of the human brain at 3 and 7 T demonstrate that STABLE‐2 provides robust, uniform, slice‐selective excitation over a range of B1 values. Phantom and in vivo knee images obtained at 3 T demonstrate the effectiveness of STABLE‐2 for fat suppression.

Conclusions

STABLE‐2 achieves B1‐insensitive slice‐selective excitation while providing greater off‐resonance immunity and a shorter pulse duration, when compared to the original STABLE pulse. In particular, the 9.8‐ms STABLE‐2 pulse provides slice selectivity over 120 Hz whereas the 21‐ms STABLE pulse is limited to 80 Hz off‐resonance. B1‐Insensitive fat‐suppressed excitation may also be achieved by using a variant of this pulse. Magn Reson Med 71:75–82, 2014. © 2013 Wiley Periodicals, Inc.
High‐resolution, large dynamic range field map estimation
Authors: Dagher Joseph , Reese Timothy , Bilgin Ali
Published: February 2013

Purpose

We present a theory and a corresponding method to compute high‐resolution field maps over a large dynamic range.

Theory and Methods

We derive a closed‐form expression for the error in the field map value when computed from two echoes. We formulate an optimization problem to choose three echo times which result in a pair of maximally distinct error distributions. We use standard field mapping sequences at the prescribed echo times. We then design a corresponding estimation algorithm which takes advantage of the optimized echo times to disambiguate the field offset value.

Results

We validate our method using high‐resolution images of a phantom at 7T. The resulting field maps demonstrate robust mapping over both a large dynamic range, and in low SNR regions. We also present high‐resolution offset maps in vivo using both, GRE and multiecho gradient echo sequences. Even though the proposed echo time spacings are larger than the well known phase aliasing cutoff, the resulting field maps exhibit a large dynamic range without the use of phase unwrapping or spatial regularization techniques.

Conclusion

We demonstrate a novel three‐echo field map estimation method which overcomes the traditional noise‐dynamic range trade‐off. Magn Reson Med 71:105–117, 2014. © 2013 Wiley Periodicals, Inc.
Sensitivity and Source of Amine‐Proton Exchange and Amide‐Proton Transfer Magnetic Resonance Imaging in Cerebral Ischemia
Authors: Zong Xiaopeng , Wang Ping , Kim Seong‐Gi , Jin Tao
Published: February 2013

Purpose

Amide‐proton transfer (APT) and amine–water proton exchange (APEX) MRI can be viable to map pH‐decreasing ischemic regions. However, their exact contributions are unclear.

Methods

We measured APEX‐ and APT‐weighted magnetization transfer ratio asymmetry (denoted as APEXw and APTw), apparent diffusion coefficient, T2, and T1 images and localized proton spectra in rats with permanent middle cerebral artery occlusion at 9.4 T. Phantoms and theoretical studies were also performed.

Results

Within 1‐h postocclusion, APEXw and APTw maps showed hyperintensity (3.1% of M0) and hypointensity (−1.8%), respectively, in regions with decreased apparent diffusion coefficient. Ischemia increased lactate and gamma aminobutyric acid concentrations, but decreased glutamate and taurine concentrations. Over time, the APEXw contrast decreased with glutamate, taurine, and creatine, whereas the APTw contrast and lactate level were similar. Phantom and theoretical studies suggest that the source of APEXw signal is mainly from proteins at normal pH, whereas at decreased pH, gamma aminobutyric acid and glutamate contributions increase, inducing the positive APEXw contrast in ischemic regions. The APTw contrast is sensitive to lactate concentration and pH, but contaminated from contributions of the faster APEX processes.

Conclusion

Positive APEXw contrast is more sensitive to ischemia than negative APTw contrast. They may provide complementary tissue metabolic information. Magn Reson Med 71:118–132, 2014. © 2013 Wiley Periodicals, Inc.
Imaging of Endogenous Exchangeable Proton Signals in the Human Brain Using Frequency Labeled Exchange Transfer Imaging
Authors: Yadav Nirbhay N. , Jones Craig K. , Hua Jun , Xu Jiadi , van Zijl Peter C. M.
Published: February 2013

Purpose

To image endogenous exchangeable proton signals in the human brain using a recently reported method called frequency labeled exchange transfer (FLEX) MRI.

Methods

As opposed to labeling exchangeable protons using saturation (i.e., chemical exchange saturation transfer, or CEST), FLEX labels exchangeable protons with their chemical shift evolution. The use of short high‐power frequency pulses allows more efficient labeling of rapidly exchanging protons, while time domain acquisition allows removal of contamination from semi‐solid magnetization transfer effects.

Results

FLEX‐based exchangeable proton signals were detected in human brain over the 1–5 ppm frequency range from water. Conventional magnetization transfer contrast and the bulk water signal did not interfere in the FLEX spectrum. The information content of these signals differed from in vivo CEST data in that the average exchange rate of these signals was 350–400 s−1, much faster than the amide signal usually detected using direct saturation (∼30 s−1). Similarly, fast exchanging protons could be detected in egg white in the same frequency range where amide and amine protons of mobile proteins and peptides are known to resonate.

Conclusions

FLEX MRI in the human brain preferentially detects more rapidly exchanging amide/amine protons compared to traditional CEST experiments, thereby changing the information content of the exchangeable proton spectrum. This has the potential to open up different types of endogenous applications as well as more easy detection of rapidly exchanging protons in diaCEST agents or fast exchanging units such as water molecules in paracest agents without interference of conventional magnetization transfer contrast. Magn Reson Med 69:966–973, 2013. © 2013 Wiley Periodicals, Inc.
Post‐mortem apparent resolution of fetal ventriculomegaly: evidence from magnetic resonance imaging
Authors: Sebire Neil J. , Miller Sarah , Jacques Thomas S. , Taylor Andrew M. , Rennie Janet M. , Kendall Giles , Chitty Lyn S.
Published: February 2013

Objective

This study aims to determine the accuracy of post‐mortem magnetic resonance imaging (MRI) and autopsy for confirmation of sonographically detected fetal ventriculomegaly.

Methods

This study uses retrospective review of fetuses with sonographically diagnosed ventriculomegaly, where the pregnancy was terminated and post‐mortem examination was performed during a period in which post‐mortem MRI was being offered.

Results

Sixteen cases were identified. In nine (56%), autopsy and/or post‐mortem MRI confirmed the prenatal findings. In the other seven, both autopsy and post‐mortem MRI demonstrated no ventriculomegaly, but antenatal MRI confirmed the ultrasound findings in 6/7 cases where it had been performed. Post‐mortem investigations confirmed antenatal findings in 8/9 cases with severe ventriculomegaly (posterior horn measurement >15 mm), whereas only 2/7 in which ventriculomegaly was not confirmed had severe ventriculomegaly.

Conclusions

Post‐mortem examination, both by traditional neuropathological examination, and post‐mortem MRI may fail to confirm prenatal ventriculomegaly in around half of cases. The post‐mortem MRI findings indicate that this is due to resolution of ventriculomegaly rather than autopsy artefact, and is presumably a consequence of post‐mortem fluid redistribution. Parents should be advised before termination of pregnancy that post‐mortem confirmation of ventriculomegaly, especially in mild cases, may not be possible. Antenatal MRI may be a better approach for confirming prenatal ultrasound findings. © 2013 John Wiley & Sons, Ltd.
Pharmacokinetics of Intravenous Voriconazole in Obese Patients: Implications of CYP2C19 Homozygous Poor Metabolizer Genotype
Authors: Moriyama Brad , Jarosinski Paul F. , Figg William D. , Henning Stacey A. , Danner Robert L. , Penzak Scott R. , Wayne Alan S. , Walsh Thomas J.
Published: February 2013

There is a paucity of pharmacokinetic studies describing weight‐based dosing of intravenous voriconazole in obese patients. In this case report, we describe the pharmacokinetics of intravenous voriconazole in an obese CYP2C19 homozygous poor metabolizer and review previously reported data regarding the use of intravenous voriconazole in obese patients. A 17‐year‐old obese Hispanic male patient (body mass index 35 kg/m2) received intravenous voriconazole for the treatment of suspected aspergillosis. After 2.5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight, the voriconazole area under the serum concentration–time curve over the course of a single (12‐hr) dosing interval and trough concentration were 86,100 ng · hr/ml and 6.2 µg/ml, respectively. Six days later, the voriconazole dosage was decreased. A trough concentration measured just before the dosage reduction (after 8.5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight) remained elevated at 5.8 µg/ml. Genotyping revealed a CYP2C19 homozygous poor metabolizer (CYP2C19*2/*2). Voriconazole was subsequently discontinued due to QTc prolongation. These data and those from two recent publications suggest that voriconazole does not distribute extensively into human adipose tissue and that obese patients should be dosed on an adjusted body weight basis. If an obese patient dosed on total body weight is also a CYP2C19 poor metabolizer, serum voriconazole concentrations will be further elevated, potentially leading to drug‐induced toxicity.
Rash Associated with Dabigatran Etexilate
Authors: To Kim , Reynolds Carl , Spinler Sarah A.
Published: February 2013

Patients experiencing atrial fibrillation are at an increased risk for thromboembolic events. Therefore, anticoagulation therapy is imperative to prevent thrombus formation and stroke. Dabigatran etexilate was approved by the Food and Drug Administration in 2010 as anticoagulant prophylaxis for patients with nonvalvular atrial fibrillation. The frequency of dermatologic reactions to dabigatran etexilate is estimated in the product labeling to be less than 0.1%. To date, five cases of dabigatran etexilate–associated rash have reported, including three published cases. We describe the sixth reported case of dabigatran etexilate–associated rash, in a 59‐year‐old man with a history of atrial fibrillation who received dabigatran etexilate 150 mg twice/day for atrial flutter before cardioversion. The patient had taken dabigatran etexilate for 5 days before the rash was noted on hospital admission. He had no known previous drug allergies, and his platelet count, serum creatinine concentration, and hepatic function were normal. The rash resolved 7 days after the discontinuation of dabigatran etexilate, and the patient was stabilized on warfarin therapy. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient's development of the rash and dabigatran etexilate therapy. Clinicians should be aware of this adverse effect of dabigatran etexilate and monitor for dermatologic reactions during follow‐up visits.
Desired Professional Development Pathways for Clinical Pharmacists
Authors:   American College of Clinical Pharmacy, Shord Stacy S. , Schwinghammer Terry L. , Badowski Melissa , Banderas Julie , Burton Michael E. , Chapleau Christopher A. , Gallagher Jason C. , Matsuura Gregory , Parli Sara E. , Yunker Nancy
Published: February 2013

The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists. This document summarizes recommendations for postgraduate education and training for graduates of U.S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists. After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes. An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists. Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education. Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting. Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification. Traineeships, practice‐based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth. Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies.
Key Articles and Guidelines in the Acute Management and Secondary Prevention of Ischemic Stroke
Authors: Baker William L. , Marrs Joel C. , Davis Lindsay E. , Nutescu Edith A. , Rowe A. Shaun , Ryan Melody , Splinter Michele Y. , Vardeny Orly , Fagan Susan C.
Published: February 2013

Ischemic stroke is a prevalent disease with a large burden on the health system. It is essential for practitioners caring for patients who have experienced an ischemic stroke to be familiar with the literature supporting both acute management as well as secondary preventive strategies. Due to the large amount of literature available on this topic, this bibliography (the second of a two‐part series) aims to provide a comprehensive resource for medical practitioners charged with caring for this population. Acute management strategies involve controlling patients' blood pressure and administering thrombolysis (either pharmacologic or mechanical) to improve blood flow and preserve neurologic function. Various neuroprevention strategies have also been investigated. Secondary prevention strategies, similar to primary prevention, focus on modulation of various risk factors including antiplatelet treatments and control of blood pressure, and lipid levels, amongst others.
Proteomics, transcriptomics and lipidomics of exosomes and ectosomes
Authors: Choi Dong‐Sic , Kim Dae‐Kyum , Kim Yoon‐Keun , Gho Yong Song
Published: February 2013

Mammalian cells secrete two types of extracellular vesicles either constitutively or in a regulated manner: exosomes (50–100 nm in diameter) released from the intracellular compartment and ectosomes (also called microvesicles, 100–1000 nm in diameter) shed directly from the plasma membrane. Extracellular vesicles are bilayered proteolipids enriched with proteins, mRNAs, microRNAs, and lipids. In recent years, much data have been collected regarding the specific components of extracellular vesicles from various cell types and body fluids using proteomic, transcriptomic, and lipidomic methods. These studies have revealed that extracellular vesicles harbor specific types of proteins, mRNAs, miRNAs, and lipids rather than random cellular components. These results provide valuable information on the molecular mechanisms involved in vesicular cargo‐sorting and biogenesis. Furthermore, studies of these complex extracellular organelles have facilitated conceptual advancements in the field of intercellular communication under physiological and pathological conditions as well as for disease‐specific biomarker discovery. This review focuses on the proteomic, transcriptomic, and lipidomic profiles of extracellular vesicles, and will briefly summarize recent advances in the biology, function, and diagnostic potential of vesicle‐specific components.
Integrative network analysis of signaling in human CD34+ hematopoietic progenitor cells by global phosphoproteomic profiling using TiO2 enrichment combined with 2D LC‐MS/MS and pathway mapping
Authors: Guo Hongbo , Isserlin Ruth , Chen Xiaoji , Wang Weijia , Phanse Sadhna , Zandstra Peter W. , Paddison Patrick J. , Emili Andrew
Published: February 2013

Protein kinase signaling regulates human hematopoietic stem/progenitor cell (HSPC) fate, yet little is known about critical pathway substrates. To address this, we have developed and applied a large‐scale, empirically optimized phosphopeptide affinity enrichment strategy with high‐throughput 2D LC‐MS/MS screening to evaluate the phosphoproteome of an isolated human CD34+ HSPC population. We first used hydrophilic interaction chromatography as a first dimension separation to separate and simplify protein digest mixtures into discrete fractions. Phosphopeptides were then enriched off‐line using TiO2‐coated magnetic beads and subsequently detected online by C18 RP nanoflow HPLC using data‐dependent MS/MS high‐energy collision‐activated dissociation fragmentation on a high‐performance Orbitrap hybrid tandem mass spectrometer. We identified 15 533 unique phosphopeptides in 3574 putative phosphoproteins. Systematic computational analysis revealed biological pathways and phosphopeptide motifs enriched in CD34+ HSPC that are markedly different from those observed in an analogous parallel analysis of isolated human T cells, pointing to the possible involvement of specific kinase‐substrate relationships within activated cascades driving hematopoietic renewal, commitment, and differentiation.
Rapid and sensitive MRM‐based mass spectrometry approach for systematically exploring ganglioside‐protein interactions
Authors: Tian Ruijun , Jin Jing , Taylor Lorne , Larsen Brett , Quaggin Susan E. , Pawson Tony
Published: February 2013

Gangliosides are ubiquitous components of cell membranes. Their interactions with bacterial toxins and membrane‐associated proteins (e.g. receptor tyrosine kinases) have important roles in the regulation of multiple cellular functions. Currently, an effective approach for measuring ganglioside‐protein interactions especially in a large‐scale fashion is largely missing. To this end, we report a facile MS‐based approach to explore gangliosides extracted from cells and measure their interactions with protein of interest globally. We optimized a two‐step protocol for extracting total gangliosides from cells within 2 h. Easy‐to‐use magnetic beads conjugated with a protein of interest were used to capture interacting gangliosides. To measure ganglioside‐protein interaction on a global scale, we applied a high‐sensitive LC‐MS system, containing hydrophilic interaction LC separation and multiple reaction monitoring‐based MS for ganglioside detection. Sensitivity for ganglioside GM1 is below 100 pg, and the whole analysis can be done in 20 min with isocratic elution. To measure ganglioside interactions with soluble vascular endothelial growth factor receptor 1 (sFlt1), we extracted and readily detected 36 species of gangliosides from perivascular retinal pigment epithelium cells across eight different classes. Twenty‐three ganglioside species have significant interactions with sFlt1 as compared with IgG control based on p value cutoff <0.05. These results show that the described method provides a rapid and high‐sensitive approach for systematically measuring ganglioside‐protein interactions.
Plasma glucose monitoring in psychiatric inpatients with primary affective disorder
Authors: Kelbrick Marlene , Picchioni Marco
Published: February 2013

People with affective disorders are at increased risk of diabetes mellitus; however, glucose monitoring practices vary widely in mental health settings across the UK. Here, Drs Kelbrick and Picchioni describe their audit to identify patients with a primary affective disorder and co‐morbid diabetes admitted to a Northamptonshire acute inpatient unit and to establish the level of compliance with local and national guidelines regarding plasma glucose and diabetes monitoring.
Pesticides and Parkinson's disease pathogenesis: the controversy continues
Authors: Greener Mark
Published: February 2013

A possible link between pesticide exposure and Parkinson's disease has been postulated for many years and recent studies help clarify this association. Mark Greener reports.
Mind: advocating support and respect for everyone with mental health problems
Authors: Farmer Paul
Published: February 2013

Mind is the leading mental health charity in England and Wales. Here, Mind's Chief Executive, Paul Farmer, explains how Mind is working hard to improve things for people with mental health problems in challenging times.
Is autoimmunity involved in the aetiology of schizophrenia?
Authors: Pandarakalam James Paul
Published: February 2013

A century of research into the aetiology of schizophrenia has not been substantially productive. However, in recent years, there has been a resurgence of interest in a possible autoimmune involvement in a subset of patients with schizophrenia. Here, Dr Pandarakalam discusses the evidence.
Molecular Self‐Assembly of Multifunctional Nanoparticle Composites with Arbitrary Shapes and Functions: Challenges and Strategies
Authors: Kim Jin‐Woo , Deaton Russell
Published: February 2013

The assembly of nanoparticles into complicated, anisotropic shapes has much promise for advanced materials and devices. Developing effective and efficient anisotropic mono‐functionalization strategies is an imperative step in realizing this potential. By functionalizing DNA one at a time to the nanoparticle, a DNA‐nanoparticle building block could have distinct DNA sequences at different locations on the surface of the particle. Since this technology could incorporate nanoparticles of different composition, generating toolboxes of various nanoparticle building blocks (“nano‐toolboxes”) with DNA at defined locations and in defined 3D orientations on a nanoparticle, it promises not only complicated shapes, but also the ability to tune the function of the assembly. The challenges of programmable and scalable multifunctional nanostructure self‐assembly with DNA conjugated to nanoparticles are reviewed. The first difficulty is to control the assembly process so that designed products are formed, and unwanted products are minimized. The design problem for nanostructure construction is both physically and computationally complex. Thus, the other major challenge is to devise design methodologies that move nanostructure construction from trial and error to principled approaches. Strategies to overcome these challenges are also presented by realizing greater control over the final shapes and functions of the self‐assembled nanostructures. Finally, the future perspectives of nano‐toolboxes and their promise in applications such as multifunctional, multicolor, and multimodal contrast nanoagents for medical therapy and diagnostics (theranostics) are described.
Investigation on Ultraviolet Absorption Properties, Migration, and Catalytic Performances of Ferrocene‐Modified Hyper‐Branched Polyesters
Authors: Xiao Fengjuan , Feng Feifei , Li Lanlan , Zhang Dan
Published: February 2013

The ultraviolet absorption properties of a series of ferrocene‐modified hyper‐branched polyesters (HBPE‐Fcs) were analyzed by Ultraviolet/visible spectrometry. HBPE‐Fcs were used as burning rate catalyst components added into hydroxyl‐terminated polybutadiene (HTPB) based elastomers to investigate their migration behavior. Migration inhibition effects of HBPE‐Fcs in different aging conditions were analyzed. The diffusion coefficients (D) of the migration components were calculated according to Fick’s law of diffusion. The catalytic performances of HBPE‐Fcs for the thermal decomposition of cyclotrimethylenetrinitramine (RDX) were also investigated by non isothermal measurements using Kissinger method. The incorporation of ferrocenes into hyper‐branched polyesters (HBPEs) endows HBPEs with new ultraviolet absorption properties. The migration of HBPE‐Fc was minimized by grafting ferrocene on the hyper‐branched structures compared to that of simple ferrocene derivatives. HBPE‐Fcs present efficient catalytic effects on the thermal degradation of RDX; and, the catalytic reactions were characterized by decreased activation energies and increased rate constants.
Energetically unfavorable amide conformations for N6‐acetyllysine side chains in refined protein structures
Authors: Genshaft Alexander , Moser Joe‐Ann S. , D'Antonio Edward L. , Bowman Christine M. , Christianson David W.
Published: February 2013

The reversible acetylation of lysine to form N6‐acetyllysine in the regulation of protein function is a hallmark of epigenetics. Acetylation of the positively charged amino group of the lysine side chain generates a neutral N‐alkylacetamide moiety that serves as a molecular “switch” for the modulation of protein function and protein–protein interactions. We now report the analysis of 381 N6‐acetyllysine side chain amide conformations as found in 79 protein crystal structures and 11 protein NMR structures deposited in the Protein Data Bank (PDB) of the Research Collaboratory for Structural Bioinformatics. We find that only 74.3% of N6‐acetyllysine residues in protein crystal structures and 46.5% in protein NMR structures contain amide groups with energetically preferred trans or generously trans conformations. Surprisingly, 17.6% of N6‐acetyllysine residues in protein crystal structures and 5.3% in protein NMR structures contain amide groups with energetically unfavorable cis or generously cis conformations. Even more surprisingly, 8.1% of N6‐acetyllysine residues in protein crystal structures and 48.2% in NMR structures contain amide groups with energetically prohibitive twisted conformations that approach the transition state structure for cis‐trans isomerization. In contrast, 109 unique N‐alkylacetamide groups contained in 84 highly accurate small molecule crystal structures retrieved from the Cambridge Structural Database exclusively adopt energetically preferred trans conformations. Therefore, we conclude that cis and twisted N6‐acetyllysine amides in protein structures deposited in the PDB are erroneously modeled due to their energetically unfavorable or prohibitive conformations. Proteins 2013; © 2012 Wiley Periodicals, Inc.