bluuebunny/crossref_metadata_2025 huggingface dataset:
Applicability of randomized trials in radiation oncology to standard clinical practice
Authors: Apisarnthanarax Smith , Swisher‐McClure Samuel , Chiu Wing K. , Kimple Randall J. , Harris Stephen L. , Morris David E. , Tepper Joel E.
Published: May 2013

BACKGROUND

Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic.

METHODS

The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence.

RESULTS

Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty‐seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001).

CONCLUSIONS

A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence‐based health care. Cancer 2013;119:3092—3099. © 2013 American Cancer Society.
Safety, Pharmacokinetics, and Pharmacodynamic Effects of a Selective TGR5 Agonist, SB‐756050, in Type 2 Diabetes
Authors: Hodge Rebecca J. , Lin Jiang , Vasist Johnson Lakshmi S. , Gould Elizabeth P. , Bowers Gary D. , Nunez Derek J. ,   on behalf of the SB‐756050 Project Team
Published: May 2013

TGR5 is a bile acid receptor and a potential target for the treatment of type 2 diabetes (T2D). We report here the safety, pharmacokinetics, and pharmacodynamic effects of a selective TGR5 agonist, SB‐756050, in patients with T2D. Fifty‐one subjects were randomized to receive either placebo or one of four doses of SB‐756050 for 6 days. A single 100 mg dose of sitagliptin was co‐administered on Day 6 to all subjects. SB‐756050 was well‐tolerated; it was readily absorbed, exhibited nonlinear pharmacokinetics with a less than dose‐proportional increase in plasma exposure above 100 mg, and demonstrated no significant changes in exposure when co‐administered with sitagliptin. SB‐756050 demonstrated highly variable pharmacodynamic effects both within dose groups and between doses, with increases in glucose seen at the two lowest doses and no reduction in glucose seen at the two highest doses. The glucose effects of SB‐756050 + sitagliptin were comparable to those of sitagliptin alone, even though gut hormone plasma profiles were different. This study was registered at ClinicalTrials.gov (NCT00733577).
Performance evaluation of Amazon Elastic Compute Cloud for NASA high‐performance computing applications
Authors: Mehrotra Piyush , Djomehri Jahed , Heistand Steve , Hood Robert , Jin Haoqiang , Lazanoff Arthur , Saini Subhash , Biswas Rupak
Published: May 2013

Cloud computing environments are now widely available and are being increasingly utilized for technical computing. They are also being touted for high‐performance computing (HPC) applications in science and engineering. For example, Amazon Elastic Compute Cloud (EC2) Services offers specialized Cluster Compute instance types to run HPC applications. In this paper, we compare the performance characteristics of two Amazon EC2 HPC instance types with that of National Aeronautics and Space Administration's (NASA) Pleiades supercomputer, an SGI® ICE™ cluster. For this study, we utilized the HPC Challenge kernels and the NAS Parallel Benchmarks along with four full‐scale applications from the repertoire of codes that are being used by NASA scientists and engineers. We compare the total runtime of these codes for varying number of cores. We also break out the computation and communication times for a subset of these applications to explore the effect of interconnect differences on the two systems. In general, the single node performance of the two platforms is equivalent. However, for most of the codes when scaling to larger core counts, the performance of the EC2 HPC instances generally lags that of Pleiades because of worse network performance of the former. In addition to analyzing application performance, we also briefly touch upon the overhead due to virtualization and the usability of cloud environments such as Amazon EC2. Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.
Glow Discharge Positive Column with Dust Particles in Neon
Authors: Vasilyak L. M. , Polyakov D. N. , Shumova V. V.
Published: May 2013

Experimental and numerical study of positive column of glow discharge in neon with dust particles is presented. The influence of dust structures on integral parameters was measured and simulated. Spatial distributions of electrons and electric field configuration in presence of dust cloud are represented. The reverse radial electric field direction is shown to appear within the dust cloud at high dust particle concentration. The current‐voltage characteristics of discharge in neon with and without dust particles are represented. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Electron Transport Coefficients of Boron and Silicon Plasma
Authors: Apfelbaum E. M.
Published: May 2013

The conductivity, thermal conductivity and thermal power of Silicon and Boron plasma have been calculated within the relaxation time approximation. The plasma composition has been obtained by means of correspond‐ing system of coupled mass action laws. We have considered the atom ionization up to +4. The results of our simulations are in good agreement with recent measurement data at T ≥ 10 kK. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dielectric Model for Electromagnetic Waves Generated in the E‐Layer of the Earth's Ionosphere by Infrasound
Authors: Meister C.‐V. , Erhard H. , Hoffmann D.H.H.
Published: May 2013

A dielectric model for waves of the Earth's ionosphere is developed. In doing so, in comparison to the wellknown dielectric wave model by R.O. Dendy [1] for homogeneous systems, the stratification of the atmosphere is taken into account. Moreover, within the frame of many‐fluid magnetohydrodynamics also the momentum transfer between the charged and neutral particles is considered. Acoustic‐type waves causing the excitation of electromagnetic waves in the warm, weakly‐collisional E‐layer are introduced in the magnetohydrodynamic system by a fluctuating neutral‐particle component. Models of the altitudinal scales of the plasma parameters and the electromagnetic wave field are derived. In case of the electric wave field, a method is given to calculate the altitudinal scale based on the Poisson equation for the electric field and the magnetohydrodynamic description of the particles. Further, an expression is derived to estimate the temperatur changes in the E‐layer because of the propagation of acoustic‐type wave modes and the generation of the electromagnetic waves. And last not least, a formula is derived to determine the dispersion and polarisation of the excited electromagnetic waves, which is necessary to find quantitative results for the turbulent heating of the ionospheric E‐layer. The electromagnetic waves which may be obtained in the E‐layer by the newly developed dielectric model are, amongst others, Alfvén and magnetoacoustic modes, but also waves of the Farley‐Buneman type. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Static and Collective Properties of Dusty Non‐Equilibrium Plasmas
Authors: Filippov A. V. , Starostin A. N. , Tkachenko I. M. , Fortov V. E.
Published: May 2013

The static dielectric function and dust acoustic waves are considered of non‐equilibrium dusty plasmas. The dynamic characteristics are considered using an effective potential applicable at elevated pressure, but this is not a limitation. A three‐species model capable of describing the collective processes is suggested, and a first order phase transition in such systems is previewed. The OCP static characteristics are calculated within the HNC approach. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Synthesis, X‐ray Crystal Structures, and Spectroscopic, Electrochemical, and Theoretical Studies of MnIII Complexes of Pyridoxal Schiff Bases with Two Diamines
Authors: Naskar Sumita , Naskar Subhendu , Butcher Ray J. , Corbella Montserrat , Espinosa Ferao Arturo , Chattopadhyay Shyamal Kumar
Published: May 2013

Six MnIII complexes of general formula [Mn(L)XY], in which L is a dideprotonated Schiff base ligand N,N′‐bis(pyridoxylidene)ethylenediamine (L1H2 or pydxen) or N,N′‐bis(pyridoxylidene)‐1,3‐propanediamine (L2H2 or pydxpn), X = Cl, N3, NCS, and Y = H2O, MeOH, EtOH, and another MnIII compound [Mn(L1)(H2O)2]Cl have been synthesized. The structures of five of the complexes were determined by single‐crystal X‐ray diffraction studies. The compounds show a quasireversible MnIII/MnII couple at ca. 0 V (vs. Ag/AgCl) and two to three overlapping oxidations at 1.0–1.3 V, which are assigned to MnIII/MnIV oxidation and ligand (phenolate) oxidation. The redox potential of the phenolate moiety reported here is very similar to the Yz/Yz·+ potential of photosystem II (PS II, Yz = tyrosine). Spectrochemical studies and DFT calculations support this assignment. The DFT calculations also show that there is considerable covalence in the metal–ligand bonds and the covalence increases with the oxidation state of the central metal ion. The geometry of the metal ion is found to be dependent on the oxidation state as well as spin state of the metal ion, the nature of the N,O‐donor ligand used as model, and solvation effects. In silico stepwise one and two electron oxidation of a model pydxen‐type complex shows strengthening of the metal–ligands interactions, but three‐electron oxidation could significantly weaken one of the Mn–O bonds, which might trigger splitting into a diphenoxyl diradical species and a transient MnIV complex, in agreement with the experimental results.
An Updated View of Cisplatin Transport
Authors: Arnesano Fabio , Losacco Maurizio , Natile Giovanni
Published: May 2013

Invited for the cover of this issue is the group of Giovanni Natile at the University of Bari. The cover image poses the question whether platinum exchange occurs between transporters as it happens for copper – a major question still lacking an answer. In the background is “the near‐touching hands”, a detail of the Creation of Adam by Michelangelo.
Synthesis of 3‐Azabicyclo[3.2.0]heptane Derivatives as γ‐Aminobutyric Acid Analogues through Intermolecular [2+2] Photo­cycloaddition
Authors: Petz Susanne , Wanner Klaus T.
Published: May 2013

The synthesis of 3‐azabicyclo[3.2.0]heptane‐6‐carboxylic acid and 7‐substituted derivatives was developed as bicyclic analogues of γ‐aminobutyric acid. A sensitized, intermolecular [2+2] photocycloaddition of maleic anhydride with N‐protected 3‐pyrroline served as the key step in these syntheses. Upon transformation of the anhydride function of the primary cycloaddition product, 6‐monosubstituted and 6,7‐disubstituted 3‐azabicyclo[3.2.0]heptane derivatives were obtained.
C12‐Helix Development in (αγ)n Sequences – Spectroscopic Characterization of Boc–[Aib–γ4(R)Val]–OMe Oligomers
Authors: Dinesh Bhimareddy , Vinaya Vishwanathan , Raghothama Srinivasarao , Balaram Padmanabhan
Published: May 2013

The solution conformations of the αγ‐hybrid oligopeptides Boc–[Aib–γ4(R)Val]n–OMe (n = 1–8) in organic solvents have been probed by NMR, IR, and CD spectroscopic methods. In the solid state, this peptide series favors C12‐helical conformations, which are backbone‐expanded analogues of 310 helices in α‐peptide sequences. NMR studies of the six‐ (n = 3) and 16‐residue (n = 8) peptides reveal that only two NH protons attached the N‐terminus residues Aib(1) and γ4(R)Val(2) are solvent‐exposed. Sequential NiH–Ni+1H NOEs characteristic of local helical conformations are also observed at the α residues. IR studies establish that chain extension leads to a large enhancement in the intensities of the hydrogen‐bonded NH stretching bands (3343–3280 cm–1), which suggest elongation of intramolecularly hydrogen‐bonded structures. The development of C12‐helical structures upon lengthening of the αγ sequence is supported by the NMR and IR observations. The CD spectra of the (αγ)n peptides reveal a negative maximum at ca. 206 nm and a positive maximum at ca. 192 nm, spectral feature that are distinct from those of 310 helices in α‐peptides.
BRCA1 Polymorphisms and Breast Cancer Epidemiology in the Western New York Exposures and Breast Cancer (WEB) Study
Authors: Ricks‐Santi Luisel J. , Nie Jing , Marian Catalin , Ochs‐Balcom Heather M. , Trevisan Maurizio , Edge Stephen B. , Freudenheim Jo L. , Shields Peter G.
Published: May 2013

Results of studies for the association of BRCA1 genotypes and haplotypes with sporadic breast cancer have been inconsistent. Therefore, a candidate single nucleotide polymorphism (SNP) approach was used in a breast cancer case‐control study to explore genotypes and haplotypes that have the potential to affect protein functions or levels. In a breast cancer case‐control study, genotyping of BRCA1 polymorphisms Q356R, D693N, and E1038G was performed on 1,005 cases and 1,765 controls. Unconditional, polytomous logistic regression and χ2‐tests were used to examine the associations of breast cancer with genotypes and haplotypes. In addition, interactions between genotype and smoking, benign breast disease, family history of breast cancer, body mass index (BMI), alcohol consumption, and hormonal risk factors, hormone receptor status, and breast cancer pathology were calculated also using logistic regression and χ2. Although sporadic breast cancer was not associated with BRCA1 genotypes or haplotypes overall or by menopausal status, there was evidence of an interaction between the E1038G BRCA1 genotype, smoking, and BMI among premenopausal women (P for interaction = 0.01 and 0.045, respectively) and between E1038G and D693N BRCA1 genotypes and hormone therapy use among postmenopausal women (P for interaction = 0.01 and 0.02, respectively). There were no other associations found between BRCA1 genotypes and stage, histological grade, or nuclear grade. However, the D693N SNP was associated with the risk of triple negative breast cancer (odds ratio = 2.31 95% confidence interval 1.08–4.93). The BRCA1 variants studied may play a role in the etiology of triple negative breast cancer and may interact with environmental factors such as hormone therapy or smoking and increase sporadic breast cancer risk.
On Association Analysis of Rare Variants Under Population Substructure: An Approach for the Detection of Subjects That Can Cause Bias in the Analysis—Topt: An Outlier Detection Method
Authors: Qiao Dandi , Mattheisen Manuel , Lange Christoph
Published: May 2013

For the analysis of rare‐variant data in population‐based designs, we propose a method to detect study subjects that may create population substructure in the study sample. Our approach is computationally fast and simple, permitting applications to whole‐genome sequencing studies. The method does not require the variants to be in linkage equilibrium and can be applied to all the genetic loci that are available in the study. For both rare and common variants, we assess the performance of our approach by its application to the 1000 Genome Project data, and in simulation studies. The results are compared to the commonly used outlier detection algorithm based on principal component analysis (PCA). The statistical power of both approaches to detect outliers are comparable in most of the scenarios, but the power of PCA to detect outliers is lower than the novel approach in the presence of linkage disequilibrium and for subpopulations that are genetically similar. The data analysis and the simulation studies suggest that the number of false‐positive results appears to be different for the two approaches. Our approach maintains the type I error rate while the outlier detection approach based on PCA does not. Taking additionally into account the minimal computational requirements of our approach and the ability to incorporate all the marker information, the proposed method will have important application in sequencing studies and genome‐wide association studies.
The spatial and temporal evolution of strain during the separation of Australia and Antarctica
Authors: Ball Philip , Eagles Graeme , Ebinger Cynthia , McClay Ken , Totterdell Jennifer
Published: May 2013

A re‐evaluation of existing onshore and offshore gravity, magnetic, seismic reflection, and well data from the Australo‐Antarctic margins suggests that magmatism and along‐strike lithospheric heterogeneities have influenced the localization of initial rifting. The 3‐D crustal architecture of the Australian and Antarctic margins, which formed during multiple rifting episodes spanning ∼80 Myr, reveal local asymmetries along strike. Rift structures from the broad, late Jurassic (165–145 Ma) rift zone are partially overprinted by a narrower, mid‐to‐late Cretaceous rift zone (∼100 Ma), which evolved in highly extended crust. This late‐stage rift zone is located within a region of heterogeneous crust with faults that cut late syn‐rift strata, interpreted as a continent ocean transition zone. This late stage transitional rift is populated by seismically identified rift‐parallel basement highs and intracrustal bodies with corresponding positive Bouguer gravity and magnetic anomalies. These undrilled features can be interpreted as exposures of exhumed mantle rocks, lower crustal rocks and/or as discrete magmatic bodies. Our results suggest that strain across an initially broad Australo‐Antarctic rift system (165–145 Ma) migrated to a narrow rift zone with some magmatism at 100–83 Ma. Breakup did not occur until ∼53 Ma within the eastern Bight‐Wilkes and Otway‐Adélie margin sectors, suggesting a west to east propagation of seafloor spreading. The prolonged eastward propagation of seafloor spreading processes and the increased asymmetry of the Australian‐Antarctic margins coincides with a change from rift‐perpendicular to oblique rifting processes, which in turn coincide with along‐strike variations in cratonic to Palaeozoic lithosphere.
Insight in Alzheimer's disease and its relation to psychiatric and behavioral disturbances
Authors: Horning Sheena M. , Melrose Rebecca , Sultzer David
Published: May 2013

Objective

Individuals suffering from Alzheimer's disease (AD) often have impaired awareness or a lack of insight into their cognitive deficits and functional abilities, especially in the later stages of the disease. Previous research has documented a relationship between depression and insight in AD, such that greater awareness of one's disease has been associated with a higher degree of depression. However, little is known about the relationship between insight, cognitive decline, and other psychiatric or behavioral problems associated with AD.

Methods

This study included 107 outpatients who met criteria for probable AD. Instruments included the Neurobehavioral Rating Scale, the Apathy Evaluation Scale, and the mini mental state exam. A series of hierarchical regression analyses were conducted to determine the relationship between insight and depressed mood, anxiety, psychosis, apathy, agitation, and behavioral retardation in AD patients after controlling for cognitive skills.

Results

Insight was found to significantly predict depressed mood, anxiety, and apathy even after controlling for global cognition. Greater insight was found to be associated with depressed mood and anxiety. However, impaired insight was associated with higher levels of apathy.

Conclusion

Insight may be differentially related to mood symptoms and apathy within AD, such that patients with intact insight are more depressed, whereas patients with impaired insight are more apathetic. This suggests that assessment of insight in AD may complement the clinical evaluation of depression and apathy in AD and help guide the most appropriate interventions. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
A new way to detect volcanic plumes
Authors: Larson Kristine M.
Published: May 2013

Detection of volcanic plumes, especially ash‐laden ones, is important both for public health and aircraft safety. A variety of geophysical tools and satellite data are used to monitor volcanic eruptions and to predict the movement of ash. However, satellite‐based methods are restricted by time of day and weather, while radars are often unavailable because of cost/portability. Here a method is proposed to detect volcanic plumes using GPS signal strength data. The strengths and limitations of the method are assessed using GPS data collected during the 2008 and 2009 eruptions of the Okmok and Mt. Redoubt volcanoes. Plume detections using this GPS technique are consistent with independently collected seismic and radar data.
Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults
Authors: Cheng Dominic T. , Meintjes Ernesta M. , Stanton Mark E. , Desmond John E. , Pienaar Mariska , Dodge Neil C. , Power John M. , Molteno Christopher D. , Disterhoft John F. , Jacobson Joseph L. , Jacobson Sandra W.
Published: May 2013

This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I‐II, lateral lobules IV‐IX, and vermis IV–VI) in all participants, suggesting multiple sites of associative learning‐related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC. Hum Brain Mapp 35:1390–1403, 2014. © 2013 Wiley Periodicals, Inc.
Surprisingly correct: Unexpectedness of observed actions activates the medial prefrontal cortex
Authors: Schiffer Anne‐Marike , Krause Kim H. , Schubotz Ricarda I.
Published: May 2013

Not only committing errors, but also observing errors has been shown to activate the dorsal medial prefrontal cortex, particularly BA 8 and adjacent rostral cingulate zone (RCZ). Currently, there is a debate on whether this activity reflects a response to the incorrectness of the committed action or to its unexpectedness. This article reports two studies investigating whether activity in BA 8/RCZ is due to the unexpectedness of observed errors or the incorrectness of the specific observed action. Both studies employed an action observation paradigm reliant on the observation of an actor tying sailing knots. The reported behavioral experiment delivered evidence that the paradigm successfully induced the expectation of incorrect actions as well as the expectation of correct actions. The functional magnetic resonance imaging study revealed that unexpectedly correct as well as unexpectedly incorrect actions activate the BA 8/RCZ. The same result was confirmed for a coordinate in the vicinity that has been previously reported to be activated in separate studies either by the error observation or by the unexpectedness of committed errors, and has been associated with the error‐related negativity. The present results suggest that unexpectedness has an impact on the medial prefrontal correlate of observed errors. Hum Brain Mapp 35:1615–1629, 2014. © 2013 Wiley Periodicals, Inc.
Top‐down and bottom‐up influences on the left ventral occipito‐temporal cortex during visual word recognition: An analysis of effective connectivity
Authors: Schurz Matthias , Kronbichler Martin , Crone Julia , Richlan Fabio , Klackl Johannes , Wimmer Heinz
Published: May 2013

The functional role of the left ventral occipito‐temporal cortex (vOT) in visual word processing has been studied extensively. A prominent observation is higher activation for unfamiliar but pronounceable letter strings compared to regular words in this region. Some functional accounts have interpreted this finding as driven by top‐down influences (e.g., Dehaene and Cohen []: Trends Cogn Sci 15:254–262; Price and Devlin []: Trends Cogn Sci 15:246–253), while others have suggested a difference in bottom‐up processing (e.g., Glezer et al. []: Neuron 62:199–204; Kronbichler et al. []: J Cogn Neurosci 19:1584–1594). We used dynamic causal modeling for fMRI data to test bottom‐up and top‐down influences on the left vOT during visual processing of regular words and unfamiliar letter strings. Regular words (e.g., taxi) and unfamiliar letter strings of pseudohomophones (e.g., taksi) were presented in the context of a phonological lexical decision task (i.e., “Does the item sound like a word?”). We found no differences in top‐down signaling, but a strong increase in bottom‐up signaling from the occipital cortex to the left vOT for pseudohomophones compared to words. This finding can be linked to functional accounts which assume that the left vOT contains neurons tuned to complex orthographic features such as morphemes or words [e.g., Dehaene and Cohen []: Trends Cogn Sci 15:254‐262; Kronbichler et al. []: J Cogn Neurosci 19:1584–1594]: For words, bottom‐up signals converge onto a matching orthographic representation in the left vOT. For pseudohomophones, the propagated signals do not converge, but (partially) activate multiple orthographic word representations, reflected in increased effective connectivity. Hum Brain Mapp 35:1668–1680, 2014. © 2013 Wiley Periodicals, Inc.
Dynamic functional connectomics signatures for characterization and differentiation of PTSD patients
Authors: Li Xiang , Zhu Dajiang , Jiang Xi , Jin Changfeng , Zhang Xin , Guo Lei , Zhang Jing , Hu Xiaoping , Li Lingjiang , Liu Tianming
Published: May 2013

Functional connectomes (FCs) have been recently shown to be powerful in characterizing brain conditions. However, many previous studies assumed temporal stationarity of FCs, while their temporal dynamics are rarely explored. Here, based on the structural connectomes constructed from diffusion tensor imaging data, FCs are derived from resting‐state fMRI (R‐fMRI) data and are then temporally divided into quasi‐stable segments via a sliding time window approach. After integrating and pooling over a large number of those temporally quasi‐stable FC segments from 44 post‐traumatic stress disorder (PTSD) patients and 51 healthy controls, common FC (CFC) patterns are derived via effective dictionary learning and sparse coding algorithms. It is found that there are 16 CFC patterns that are reproducible across healthy controls, and interestingly, two additional CFC patterns with altered connectivity patterns [termed signature FC (SFC) here] exist dominantly in PTSD subjects. These two SFC patterns alone can successfully differentiate 80% of PTSD subjects from healthy controls with only 2% false positive. Furthermore, the temporal transition dynamics of CFC patterns in PTSD subjects are substantially different from those in healthy controls. These results have been replicated in separate testing datasets, suggesting that dynamic functional connectomics signatures can effectively characterize and differentiate PTSD patients. Hum Brain Mapp 35:1761–1778, 2014. © 2013 Wiley Periodicals, Inc.
Anatomical correlates of quality of life: Evidence from voxel‐based morphometry
Authors: Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Hashizume Hiroshi , Sassa Yuko , Sekiguchi Atsushi , Kotozaki Yuka , Nakagawa Seishu , Nagase Tomomi , Miyauchi Carlos Makoto , Kawashima Ryuta
Published: May 2013

Quality of life (QOL) has been defined in many ways, and these definitions usually emphasize happiness and satisfaction with life. Health‐related problems are known to cause lower QOL. However, the neural mechanisms underlying individual differences in QOL measured by questionnaire (QOLMQ) in young healthy subjects are unknown. QOL is essential to our well‐being, and investigation of the neural mechanisms underlying QOL in uncompromised subjects is obviously of great scientific and social interest. We used voxel‐based morphometry to investigate the association between regional gray matter volume (rGMV) and QOLMQ across the brain in healthy young adults (age, 21.4 ± 1.8 years) men (n = 88) and women (n = 68) in humans. We found significant negative relationships between QOLMQ and rGMV in a region in the left rostrolateral prefrontal cortex and regions in the dorsal part of the anterior cingulate gyrus and contingent cingulate regions. These findings show that structural variations in regions associated with processing of negative emotions such as fear and anger as well as those associated with evaluation of internally generated information are associated with QOLMQ. These findings suggest that these processes might be related to QOLMQ in healthy young adults. Hum Brain Mapp 35:1834–1846, 2014. © 2013 Wiley Periodicals, Inc.
COMPETITION AND QUALITY IN HOME HEALTH CARE MARKETS
Authors: Jung Kyoungrae , Polsky Daniel
Published: May 2013

Market‐based solutions are often proposed to improve health care quality; yet evidence on the role of competition in quality in non‐hospital settings is sparse. We examine the relationship between competition and quality in home health care. This market is different from other markets in that service delivery takes place in patients' homes, which implies low costs of market entry and exit for agencies. We use 6 years of panel data for Medicare beneficiaries during the early 2000s. We identify the competition effect from within‐market variation in competition over time. We analyze three quality measures: functional improvements, the number of home health visits, and discharges without hospitalization. We find that the relationship between competition and home health quality is nonlinear and its pattern differs by quality measure. Competition has positive effects on functional improvements and the number of visits in most ranges, but in the most competitive markets, functional outcomes and the number of visits slightly drop. Competition has a negative effect on discharges without hospitalization that is strongest in the most competitive markets. This finding is different from prior research on hospital markets and suggests that market‐specific environments should be considered in developing polices to promote competition. Copyright © 2013 John Wiley & Sons, Ltd.
The long and bumpy road to outcome‐oriented management of long‐term care in Germany: implementation of the Resident Assessment Instrument in home‐care services
Authors: Roth Günter , Wolter Annika , Stolle Claudia , Rothgang Heinz
Published: May 2013

Objective

Although the quality of long‐term care has improved, many problems still remain, and better processes seem to be necessary. Hence, outcome‐oriented management is of particular importance. The Resident Assessment Instrument (RAI) is a tool that has been used successfully in many countries to improve quality of care. However, there are problems of implementation and it lacks information on the conditions of successful or failing information of the RAI. The aim of this article is to find out to what extent technical/qualification requirements help to introduce or lead to failure of the implementation of an assessment instrument like RAI.

Methods

Therefore, a cluster randomized controlled trial showed services using RAI intensively tend to have better outcomes after 12 months. But the effects depend on the success of the implementation. Using a factor analysis, an index was built to divide the care providers into “optimal” and “suboptimal” RAI users.

Results

Some factors that seem to lead to a rather successful implementation could be detected: A higher proportion of qualified staff, a lower perceived quantitative workload, a small size of care providers, the type of ownership (for‐profit) and a late entry in study [Correction made here after initial online publication.].

Conclusion

The success or failure of the implementation of an outcome‐oriented control instrument is determined by professional, organizational restrictions. The results show that a better implementation leads to better outcomes for clients. Copyright © 2013 John Wiley & Sons, Ltd.
Towards quantifying the negative feedback regulation of peatland evaporation to drought
Authors: Kettridge Nicholas , Waddington J. M.
Published: May 2013

The frequency and intensity of drought is projected to increase within the boreal region under future climatic conditions. Peatlands are widely considered to regulate water loss under drought conditions, increasing surface resistance (rs) and reducing evaporative losses. This maintains peat moisture content, increasing the resilience of these globally important carbon stores. However, the magnitude and form of this important negative feedback response remains uncertain. To address this, we monitored the response of rs to drought within four peat cores under controlled meteorological conditions. When the water‐table was dropped to a depth of 0.30 m and the humidity reduced to ≤40%, a step shift in rs from ~50 s m‐1 up to 1000 s m‐1 was observed within burned and unburned peat, which virtually shuts down evaporation, limiting water loss. We show that measured near‐surface tension cannot be used to directly calculate this transition in peat surface resistance. However, empirical relationships that account for strong vertical variations in tension through the near‐surface and/or disequilibrium between pore air and near‐surface pore water pressure provide the potential to incorporate this negative feedback response into peatland ecohydrological models. Further observations are necessary to examine this response under dynamic atmospheric conditions. We suggest that the link between surface temperature and evaporation provides potential to further examine this feedback in either burned peatlands or peatlands with a low vascular vegetation cover. Copyright © 2013 John Wiley & Sons, Ltd.
Role of energy‐ and nutrient‐sensing kinases AMP‐activated Protein Kinase (AMPK) and Mammalian Target of Rapamycin (mTOR) in Adipocyte Differentiation
Authors: Fernández‐Veledo Sonia , Vázquez‐Carballo Ana , Vila‐Bedmar Rocio , Ceperuelo‐Mallafré Victòria , Vendrell Joan
Published: May 2013

Recent advances have demonstrated that the adipose tissue plays a central role in regulating overall energy balance. Obesity results from a chronic deregulation of energy balance, with energy intake exceeding energy expenditure. Recently, new mechanisms that control the obesity phenotype such as the equilibrium between white and brown adipose tissue function has been identified. In this context, it is becoming increasingly clear that in addition to cellular growth, AMP‐activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) also regulate lipid metabolism and adipogenesis. Here, we review recent advances in the understanding of the molecular mechanisms involved in white and brown differentiation programs focusing on AMPK and mTOR signaling pathways, which may play differential roles in white adipose tissue and brown adipose tissue development. In view of the worldwide epidemic of obesity and its associated metabolic disorders such as insulin resistance and type 2 diabetes, targeting these kinases may represent a potential approach for reducing adiposity and improving obesity‐related diseases. © 2013 IUBMB Life, 65(7):572–583, 2013.
The influence of dead time related distortions on live cell fluorescence lifetime imaging (FLIM) experiments
Authors: Turgeman Lior , Fixler Dror
Published: May 2013

Recent developments in the field of fluorescence lifetime imaging microscopy (FLIM) techniques allow the use of high repetition rate light sources in live cell experiments. For light sources with a repetition rate of 20–100 MHz, the time‐correlated single photon counting (TCSPC) FLIM systems suffer serious dead time related distortions, known as “inter‐pulse pile‐up”. The objective of this paper is to present a new method to quantify the level of signal distortion in TCSPC FLIM experiments, in order to determine the most efficient laser repetition rate for different FLT ranges. Optimization of the F ‐value, which is the relation between the relative standard deviation (RSD) in the measured FLT to the RSD in the measured fluorescence intensity (FI), allows quantification of the level of FI signal distortion, as well as determination of the correct FLT of the measurement. It is shown that by using a very high repetition rate (80 MHz) for samples characterized by high real FLT's (4–5 ns), virtual short FLT components are added to the FLT histogram while a F ‐value that is higher than 1 is obtained. For samples characterized with short real FLT's, virtual long FLT components are added to the FLT histogram with the lower repetition rate (20–50 MHz), while by using a higher repetition rate (80 MHz) the “inter‐pulse pile‐up” is eliminated as the F ‐value is close to 1. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Coherent anti‐Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation
Authors: Tu Haohua , Boppart Stephen A.
Published: May 2013

Clinical translation of coherent anti‐Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label‐free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro‐spectroscopy for identifying vibrational biomolecular markers of disease and single‐frequency (or hyperspectral) Raman imaging of these specific biomarkers for real‐time in vivo diagnostics and monitoring. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Forum on bone and skeletal muscle interactions: Summary of the proceedings of an ASBMR workshop
Authors: Bonewald Lynda F , Kiel Douglas P , Clemens Thomas L , Esser Karyn , Orwoll Eric S , O'Keefe Regis J , Fielding Roger A
Published: May 2013

Annual costs are enormous for musculoskeletal diseases such as osteoporosis and sarcopenia and for bone and muscle injuries, costing billions annually in health care. Although it is clear that muscle and bone development, growth, and function are connected, and that muscle loads bone, little is known regarding cellular and molecular interactions between these two tissues. A conference supported by the National Institutes of Health (NIH) and the American Society for Bone and Mineral Research (ASBMR) was held in July 2012 to address the enormous burden of musculoskeletal disease. National and international experts in either bone or muscle presented their findings and their novel hypotheses regarding muscle-bone interactions to stimulate the exchange of ideas between these two fields. The immediate goal of the conference was to identify critical research themes that would lead to collaborative research interactions and grant applications focusing on interactions between muscle and bone. The ultimate goal of the meeting was to generate a better understanding of how these two tissues integrate and crosstalk in both health and disease to stimulate new therapeutic strategies to enhance and maintain musculoskeletal health.
Quantum wave packet and quasiclassical trajectory studies of the reaction H(2S) + CH(X2Π; v = 0, j = 1) → C(1D) + H2(X1): Coriolis coupling effects and stereodynamics
Authors: Lu Ruifeng , Wang Yunhui , Deng Kaiming
Published: May 2013

The quantum mechanics (QM) and quasiclassical trajectory (QCT) calculations have been carried out for the title reaction with the ground minimal allowed rotational state of CH (j = 1) on the 1 1A′ potential energy surface. For the reaction probability at total angular momentum J = 0, a similar trend of the QM and QCT calculations is observed, and the QM results are larger than the latter almost in the whole considered energy range (0.1–1.5 eV). The QCT integral cross sections are larger than the QM results with centrifugal sudden approximation, while smaller than those from QM method including Coriolis coupling for collision energies bigger than 0.25 eV. The quantum wave‐packet computations show that the Coriolis coupling effects get more and more pronounced with increasing of J. In addition to the scalar properties, the stereodynamical properties, such as the average rotational alignment factor , the angular distributions P(θr), P(ϕr), P(θr,ϕr), and the polarization‐dependent generalized differential cross sections have been explored in detail by QCT approach. © 2013 Wiley Periodicals, Inc.
Corrected small basis set Hartree‐Fock method for large systems
Authors: Sure Rebecca , Grimme Stefan
Published: May 2013

A quantum chemical method based on a Hartree‐Fock calculation with a small Gaussian AO basis set is presented. Its main area of application is the computation of structures, vibrational frequencies, and noncovalent interaction energies in huge molecular systems. The method is suggested as a partial replacement of semiempirical approaches or density functional theory (DFT) in particular when self‐interaction errors are acute. In order to get accurate results three physically plausible atom pair‐wise correction terms are applied for London dispersion interactions (D3 scheme), basis set superposition error (gCP scheme), and short‐ranged basis set incompleteness effects. In total nine global empirical parameters are used. This so‐called Hartee‐Fock‐3c (HF‐3c) method is tested for geometries of small organic molecules, interaction energies and geometries of noncovalently bound complexes, for supramolecular systems, and protein structures. In the majority of realistic test cases good results approaching large basis set DFT quality are obtained at a tiny fraction of computational cost. © 2013 Wiley Periodicals, Inc.
Sorafenib and HDAC inhibitors synergize with TRAIL to kill tumor cells
Authors: Hamed Hossein A. , Yamaguchi Yukihiro , Fisher Paul B. , Grant Steven , Dent Paul
Published: May 2013

The present studies were designed to compare and contrast the abilities of TRAIL (death receptor agonist) and obatoclax (BCL‐2 family inhibitor) to enhance sorafenib + HDAC inhibitor toxicity in GI tumor cells. Sorafenib and HDAC inhibitor treatment required expression of CD95 to kill GI tumor cells in vitro and in vivo. In cells lacking CD95 expression, TRAIL treatment, and to a lesser extent obatoclax, enhanced the lethal effects of sorafenib + HDAC inhibitor exposure. In hepatoma cells expressing CD95 a similar data pattern emerged with respect to the actions of TRAIL. Downstream of the death receptor the ability of TRAIL to enhance cell killing correlated with reduced AKT, ERK1/2, p70 S6K, and mTOR activity and enhanced cleavage of pro‐caspase 3 and reduced expression of MCL‐1 and BCL‐XL. Over‐expression of BCL‐XL or MCL‐1 or expression of dominant negative pro‐caspase 9 protected cells from drug toxicity. Expression of activated AKT, p70 S6K, mTOR, and to a lesser extent MEK1EE also protected cells that correlated with maintained c‐FLIP‐s expression, reduced BIM expression, and increased BAD phosphorylation. In vivo sorafenib + HDAC inhibitor toxicity against tumors was increased in a greater than additive fashion by TRAIL. Collectively, our data argue that TRAIL, rather than obatoclax, is the most efficacious agent at promoting sorafenib + HDAC inhibitor lethality. J. Cell. Physiol. 228: 1996–2005, 2013. © 2013 Wiley Periodicals, Inc.
Geostationary infrared methods for detecting lightning‐producing cumulonimbus clouds
Authors: Matthee Retha , Mecikalski John R.
Published: May 2013

This study documents the behavior of cloud top infrared (IR) fields known to describe physical processes associated with growing convective clouds, for 30 nonlightning and 33 cloud‐to‐ground (CG) lightning‐producing convective storms. The goal is to define “critical” threshold values for up to 10 IR fields that delineate lightning from nonlightning convective storms. Meteosat Second Generation and United Kingdom Meteorological Office very low frequency arrival time difference satellite and lightning data, respectively, were used in this study. These were collected during the National Aeronautics and Space Administration (NASA) African Monsoon Multidisciplinary Analyses (NAMMA) field campaign in August–September 2006 in Equatorial Africa. The main conclusions show that eight of 10 IR fields that describe updraft strength, cloud depth, and glaciation (or ice at cloud top) are significantly different between the nonlightning and lightning‐producing convective clouds. The lack of notch overlap in “box and whiskers” plots confirms a 95% confidence that the two data sets are different. Nonlightning‐producing clouds are far less vertically developed and possess >50% weaker updrafts (as estimated from satellite trends), as well as little to no evidence of ice or glaciation at cloud top. Results from this study therefore can be used to nowcast and identify with high confidence convective clouds that are producing or are going to produce CG lightning using Meteosat data, assuming appropriate tracking of growing cumulus clouds is performed.