bluuebunny/crossref_metadata_2025 huggingface dataset:
Nickel‐Catalyzed Cross‐Coupling of Organolithium Reagents with (Hetero)Aryl Electrophiles
Authors: Heijnen Dorus , Gualtierotti Jean‐Baptiste , Hornillos Valentín , Feringa Ben L.
Published: December 2015

Nickel‐catalyzed selective cross‐coupling of aromatic electrophiles (bromides, chlorides, fluorides and methyl ethers) with organolithium reagents is presented. The use of a commercially available nickel N‐heterocyclic carbene (NHC) complex allows the reaction with a variety of (hetero)aryllithium compounds, including those prepared via metal‐halogen exchange or direct metallation, whereas a commercially available electron‐rich nickel‐bisphosphine complex smoothly converts alkyllithium species into the corresponding coupled product. These reactions proceed rapidly (1 h) under mild conditions (room temperature) while avoiding the undesired formation of reduced or homocoupled products.
Water‐Stable Homochiral Cluster Organic Frameworks Built by Two Kinds of Large Tetrahedral Cluster Units
Authors: Fang Wei‐Hui , Zhang Lei , Zhang Jian , Yang Guo‐Yu
Published: December 2015

Compared with metal organic frameworks (MOFs), the proton conductivity of cluster organic frameworks has been less studied. Herein, two supertetrahedral cluster organic frameworks (SCOFs) have been made that show two‐fold interpenetrated networks built by trivalent lanthanide tetrahedral clusters and monovalent cuprous T3‐supertetrahedral clusters. The structure analysis, second harmonic generation signals, and solid‐state circular dichroism spectroscopy consistently reveal the chirality of these SCOFs. Remarkably, the water‐stable SCOFs show a high proton conductivity value of 1.4×10−3 S cm−1 at 80 °C and 95 % RH (relative humidity).
Environmental Fluctuations and Stochastic Resonance in Protein Folding
Authors: Dave Kapil , Davtyan Aram , Papoian Garegin A. , Gruebele Martin , Platkov Max
Published: December 2015

Stochastic resonance is a mechanism whereby a weak signal becomes detectable through the addition of noise. It is common in many macroscopic biological phenomena, but here we ask whether it can be observed in a microscopic biological phenomenon, protein folding. We investigate the folding kinetics of the protein VlsE, with a folding relaxation time of about 0.7 seconds at 38 °C in vitro. First we show that the VlsE unfolding/refolding reaction can be driven by a periodic thermal excitation above the reaction threshold. We detect the reaction by fluorescence from FRET labels on VlSE and show that accurate rate coefficients and activation barriers can be obtained from modulated kinetics. Then we weaken the periodic temperature modulation below the reaction threshold, and show that addition of artificial thermal noise speeds up the reaction from an undetectable to a detectable rate. We observe a maximum in the recovered signal as a function of thermal noise, a stochastic resonance. Simulation of a small model‐protein, analysis in an accompanying theory paper, and our experimental result here all show that correlated noise is a physically and chemically plausible mechanism by which cells could modulate biomolecular dynamics during threshold processes such as signaling.
A possible aid in targeted insertion of large DNA elements by CRISPR/Cas in mouse zygotes
Authors: Nakao Harumi , Harada Takeshi , Nakao Kazuki , Kiyonari Hiroshi , Inoue Kenichi , Furuta Yasuhide , Aiba Atsu
Published: December 2015

The CRISPR/Cas system has rapidly emerged recently as a new tool for genome engineering, and is expected to allow for controlled manipulation of specific genomic elements in a variety of species. A number of recent studies have reported the use of CRISPR/Cas for gene disruption (knockout) or targeted insertion of foreign DNA elements (knock‐in). Despite the ease of simple gene knockout and small insertions or nucleotide substitutions in mouse zygotes by the CRISPR/Cas system, targeted insertion of large DNA elements remains an apparent challenge. Here the generation of knock‐in mice with successful targeted insertion of large donor DNA elements ranged from 3.0 to 7.1 kb at the ROSA26 locus using the CRISPR/Cas system was achieved. Multiple independent knock‐in founder mice were obtained by injection of hCas9 mRNA/sgRNA/donor vector mixtures into the cytoplasm of C57BL/6N zygotes when the injected zygotes were treated with an inhibitor of actin polymerization, cytochalasin. Successful germ line transmission of three of these knock‐in alleles was also confirmed. The results suggested that treatment of zygotes with actin polymerization inhibitors following microinjection could be a viable method to facilitate targeted insertion of large DNA elements by the CRISPR/Cas system, enabling targeted knock‐in readily attainable in zygotes. genesis 54:65–77, 2016. © 2016 Wiley Periodicals, Inc.
Obstetric and gynecologic problems associated with eating disorders
Authors: Kimmel M.C. , Ferguson E.H. , Zerwas S. , Bulik C.M. , Meltzer‐Brody S.
Published: December 2015

Objective

This article summarizes the literature on obstetric and gynecologic complications associated with eating disorders.

Method

We performed a comprehensive search of the current literature on obstetric and gynecologic complications associated with eating disorders using PubMed. More recent randomized‐controlled trials and larger data sets received priority. We also chose those that we felt would be the most relevant to providers.

Results

Common obstetric and gynecologic complications for women with eating disorders include infertility, unplanned pregnancy, miscarriage, poor nutrition during pregnancy, having a baby with small head circumference, postpartum depression and anxiety, sexual dysfunction and complications in the treatment for gynecologic cancers. There are also unique associations by eating disorder diagnosis, such as earlier cessation of breastfeeding in anorexia nervosa; increased polycystic ovarian syndrome in bulimia nervosa; and complications of obesity as a result of binge eating disorder.

Discussion

We focus on possible biological and psychosocial factors underpinning risk for poor obstetric and gynecological outcomes in eating disorders. Understanding these factors may improve both our understanding of the reproductive needs of women with eating disorders and their medical outcomes. We also highlight the importance of building multidisciplinary teams to provide comprehensive care to women with eating disorders during the reproductive years.
Physical activity and post‐treatment weight trajectory in anorexia nervosa
Authors: Gianini Loren M. , Klein Diane A. , Call Christine , Walsh B. Timothy , Wang Yuanjia , Wu Peng , Attia Evelyn
Published: December 2015

Objective

This study compared an objective measurement of physical activity (PA) in individuals with anorexia nervosa (AN) at low‐weight, weight‐restored, and post‐treatment time points, and also compared PA in AN with that of healthy controls (HC).

Method

Sixty‐one female inpatients with AN wore a novel accelerometer (the IDEEA) which measured PA at three time points: a) low‐weight, b) weight‐restored, and c) one month post‐hospital discharge. Twenty‐four HCs wore the IDEEA at one time point.

Results

Inpatients with AN became more physically active than they were at low‐weight at weight restoration and following treatment discharge. Post‐treatment patients with AN were more physically active than HCs during the day and less active at night, which was primarily accounted for by amount of time spent on feet, including standing and walking. Greater time spent on feet during the weight‐restoration time point of inpatient treatment was associated with more rapid decrease in BMI over the 12 months following treatment discharge. Fidgeting did not differ between patients and controls, did not change with weight restoration, and did not predict post‐treatment weight change.

Discussion

Use of a novel accelerometer demonstrated greater PA in AN than in HC. PA following weight restoration in AN, particularly time spent in standing postures, may contribute to weight loss in the year following hospitalization. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:482–489).
Dynamic changes in host–virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta)
Authors: Manfredini Fabio , Shoemaker DeWayne , Grozinger Christina M.
Published: December 2015

The dynamics of host–parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host–viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host–parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV‐1 and SINV‐2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV‐2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations.
Community dynamics of nematodes after Larsen ice‐shelf collapse in the eastern Antarctic Peninsula
Authors: Hauquier Freija , Ballesteros‐Redondo Laura , Gutt Julian , Vanreusel Ann
Published: December 2015

Free‐living marine nematode communities of the Larsen B embayment at the eastern Antarctic Peninsula were investigated to provide insights on their response and colonization rate after large‐scale ice‐shelf collapse. This study compares published data on the post‐collapse situation from 2007 with new material from 2011, focusing on two locations in the embayment that showed highly divergent communities in 2007 and that are characterized by a difference in timing of ice‐shelf breakup. Data from 2007 exposed a more diverse community at outer station B.South, dominated by the genus Microlaimus. On the contrary, station B.West in the inner part of Larsen B was poor in both numbers of individuals and genera, with dominance of a single Halomonhystera species. Re‐assessment of the situation in 2011 showed that communities at both stations diverged even more, due to a drastic increase in Halomonhystera at B.West compared to relatively little change at B.South. On a broader geographical scale, it seems that B.South gradually starts resembling other Antarctic shelf communities, although the absence of the genus Sabatieria and the high abundance of Microlaimus still set it apart nine years after the main Larsen B collapse. In contrast, thriving of Halomonhystera at B.West further separates its community from other Antarctic shelf areas.
A limit on the extent to which increased egg size can compensate for a poor postnatal environment revealed experimentally in the burying beetle, Nicrophorus vespilloides
Authors: Schrader Matthew , Crosby Rachel M. , Hesketh Aimee R. , Jarrett Benjamin J. M. , Kilner Rebecca M.
Published: December 2015

It is often assumed that there is a positive relationship between egg size and offspring fitness. However, recent studies have suggested that egg size has a greater effect on offspring fitness in low‐quality environments than in high‐quality environments. Such observations suggest that mothers may compensate for poor posthatching environments by increasing egg size. In this paper we test whether there is a limit on the extent to which increased egg size can compensate for the removal of posthatching parental care in the burying beetle, Nicrophorus vespilloides. Previous experiments with N. vespilloides suggest that an increased egg size can compensate for a relatively poor environment after hatching. Here, we phenotypically engineered female N. vespilloides to produce large or small eggs by varying the amount of time they were allowed to feed on the carcass as larvae. We then tested whether differences between these groups in egg size translated into differences in larval performance in a harsh postnatal environment that excluded parental care. We found that females engineered to produce large eggs did not have higher breeding success, and nor did they produce larger larvae than females engineered to produce small eggs. These results suggest that there is a limit on the extent to which increased maternal investment in egg size can compensate for a poor posthatching environment. We discuss the implication of our results for a recent study showing that experimental N. vespilloides populations can adapt rapidly to the absence of posthatching parental care.
Microenvironmental stresses induce HLA‐E/Qa‐1 surface expression and thereby reduce CD8+ T‐cell recognition of stressed cells
Authors: Sasaki Takanori , Kanaseki Takayuki , Shionoya Yosuke , Tokita Serina , Miyamoto Sho , Saka Eri , Kochin Vitaly , Takasawa Akira , Hirohashi Yoshihiko , Tamura Yasuaki , Miyazaki Akihiro , Torigoe Toshihiko , Hiratsuka Hiroyoshi , Sato Noriyuki
Published: December 2015

Hypoxia and glucose deprivation are often observed in the microenvironment surrounding solid tumors in vivo. However, how they interfere with MHC class I antigen processing and CD8+ T‐cell responses remains unclear. In this study, we analyzed the production of antigenic peptides presented by classical MHC class I in mice, and showed that it is quantitatively decreased in the cells exposed to either hypoxia or glucose deprivation. In addition, we unexpectedly found increased surface expression of HLA‐E in human and Qa‐1 in mouse tumor cells exposed to combined oxygen and glucose deprivation. The induced Qa‐1 on the stressed tumor model interacted with an inhibitory NKG2/CD94 receptor on activated CD8+ T cells and attenuated their specific response to the antigen. Our results thus suggest that microenvironmental stresses modulate not only classical but also nonclassical MHC class I presentation, and confer the stressed cells the capability to escape from the CD8+ T‐cell recognition.
NK cells lacking FcεRIγ are associated with reduced liver damage in chronic hepatitis C virus infection
Authors: Oh Jun S. , Ali Alaa K. , Kim Sungjin , Corsi Daniel J. , Cooper Curtis L. , Lee Seung‐Hwan
Published: December 2015

A novel subset of human natural killer (NK) cells, which displays potent and broad antiviral responsiveness in concert with virus‐specific antibodies, was recently uncovered in cytomegalovirus (CMV)+ individuals. This NK‐cell subset (g‐NK) was characterized by a deficiency in the expression of FcεRIγ adaptor protein and the long‐lasting memory‐like NK‐cell phenotype, suggesting a role in chronic infections. This study investigates whether the g‐NK‐cell subset is associated with the magnitude of liver disease during chronic hepatitis C virus (HCV) infection. Analysis of g‐NK‐cell proportions and function in the PBMCs of healthy controls and chronic HCV subjects showed that chronic HCV subjects had slightly lower proportions of the g‐NK‐cell subset having similarly enhanced antibody‐dependent cellular cytotoxicity responses compared to conventional NK cells. Notably, among CMV+ chronic HCV patients, lower levels of liver enzymes and fibrosis were found in those possessing g‐NK cells. g‐NK cells were predominant among the CD56neg NK cell population often found in chronic HCV patients, suggesting their involvement in immune response during HCV infection. For the first time, our findings indicate that the presence of the g‐NK cells in CMV+ individuals is associated with amelioration of liver disease in chronic HCV infection, suggesting the beneficial roles of g‐NK cells during a chronic infection.
Tuning of stochastic ground motion models for compatibility with ground motion prediction equations
Authors: Vetter Christopher R. , Taflanidis Alexandros A. , Mavroeidis George P.
Published: December 2015

Stochastic ground motion models can facilitate a versatile description of earthquake acceleration time‐histories by modulating a white‐noise sequence through functions that address spectral and temporal properties of the excitation. This is established by relating the parameters of these functions to earthquake and site characteristics through appropriate predictive relationships. This study focuses on the selection of these predictive relationships to establish direct compatibility to the mean predictions of ground motion prediction equations (GMPEs). A record‐based ground motion model is selected as a stochastic ground motion model, and its match to both elastic and inelastic GMPEs is examined. The novel contribution of the present work is that it develops a computationally efficient approach for providing ground motions that can match any chosen GMPE for any desired set of seismicity characteristics or structural periods. Foundation of the methodology is the development of a metamodel to approximate the median predictions of the ground motion model. This is established by selecting a wide range for the parameters of the model, generating ground motions for each of them, and then calculating the median (over different white‐noise sequences) spectral acceleration for different structural periods. Based on this database, a Kriging metamodel is developed to provide an efficient approximation of the predictions of the ground motion model. This metamodel is subsequently used to efficiently select the predictive relationships that optimize the match to the chosen GMPE. The numerical accuracy of the metamodel predictions is also explicitly incorporated in this optimization. Copyright © 2015 John Wiley & Sons, Ltd.
Historically unprecedented erosion from Tropical Storm Irene due to high antecedent precipitation
Authors: Yellen Brian , Woodruff Jonathan D. , Cook Timothy L. , Newton Robert M.
Published: December 2015

Lacustrine sediment archives indicate that flooding during Tropical Storm Irene (2011) in the north‐eastern United States caused the most severe erosion of any flood in the historic record, surpassing that of events with greater precipitation and peak discharges. Compared to deposition from historic floods, Irene's event layer was more massive and more enriched in unweathered upland sediments, indicating an anomalously high incidence of mass wasting and sediment entrainment. Precipitation records indicate that neither precipitation intensity nor total accumulation distinguished Irene from less erosive historic floods. However, cumulative precipitation prior to Irene exceeded the 95th percentile of all days in the record. When allowing for non‐stationarity in the twentieth century background precipitation, we find a four‐fold increase in the probability of Irene‐like conditions, where impacts of extreme rainfall are enhanced by high antecedent precipitation. We conclude that irrespective of increases in extreme precipitation, the risk of highly erosive flooding in the region is increasing due to the influence of wetter baseline conditions associated with a changing climate. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation of erosion and surface roughness in peatland forest ditches using pin meter measurements and terrestrial laser scanning
Authors: Stenberg Leena , Tuukkanen Tapio , Finér Leena , Marttila Hannu , Piirainen Sirpa , Kløve Bjørn , Koivusalo Harri
Published: December 2015

Anthropogenic activities on peatlands, such as drainage, can increase sediment transport and deposition downstream resulting in harmful ecological impacts. The objective of this study was to quantify changes in erosion/deposition quantities and surface roughness in peatland forest ditches by measuring changes in ditch cross‐sections and surface microtopography with two alternative methods: manual pin meter and terrestrial laser scanning (TSL). The methods were applied to a peat ditch and a ditch with a thin peat layer overlaying erosion sensitive mineral soil within a period of two years following ditch cleaning. The results showed that erosion was greater in the ditch with exposed mineral soil than in the peat ditch. The two methods revealed rather similar estimates of erosion and deposition for the ditch with the thin peat layer where cross‐sectional changes were large, whereas the results for smaller scale erosion and deposition at the peat ditch differed. The TLS‐based erosion and deposition quantities depended on the size of the sampling window used in the estimations. Surface roughness was smaller when calculated from the pin meter data than from the TLS data. Both methods indicated that roughness increased in the banks of the ditch with a thin peat layer. TLS data showed increased roughness also in the peat ditch. The increase in surface roughness was attributed to erosion and growth of vegetation. Both methods were suitable for the measurements of surface roughness and microtopography at the ditch cross‐section scale, but the applicability, rigour, and ease of acquisition of TLS data were more evident. The main disadvantage of the TLS instrument (Leica ScanStation 2) compared with pin meter was that even a shallow layer of humic (dark brown) water prevented detection of the ditch bed. The geomorphological potential of the methods was shown to be limited to detection of surface elevation changes >~0.1 m. Copyright © 2016 John Wiley & Sons, Ltd.
Autophagic myelin destruction by schwann cells during wallerian degeneration and segmental demyelination
Authors: Jang So Young , Shin Yoon Kyung , Park So Young , Park Joo Youn , Lee Hye Jeong , Yoo Young Hyun , Kim Jong Kuk , Park Hwan Tae
Published: December 2015

As lysosomal hydrolysis has long been suggested to be responsible for myelin clearance after peripheral nerve injury, in this study, we investigated the possible role of autophagolysosome formation in myelin phagocytosis by Schwann cells and its final contribution to nerve regeneration. We found that the canonical formation of autophagolysosomes was induced in demyelinating Schwann cells after injury, and the inhibition of autophagy via Schwann cell‐specific knockout of the atg7 gene or pharmacological intervention of lysosomal function caused a significant delay in myelin clearance. However, Schwann cell dedifferentiation, as demonstrated by extracellular signal‐regulated kinase activation and c‐Jun induction, and redifferentiation were not significantly affected, and thus the entire repair program progressed normally in atg7 knockout mice. Finally, autophagic Schwann cells were also found during segmental demyelination in a mouse model of inflammatory peripheral neuropathy. Together, our findings suggest that autophagy is the self‐myelin destruction mechanism of Schwann cells, but mechanistically, it is a process distinct from Schwann cell plasticity for nerve repair. GLIA 2016;64:730–742
Regional variation in head and neck cancer mortality: Role of patient and hospital characteristics
Authors: Divi Vasu , Ma Yifei , Rhoads Kim F.
Published: December 2015

Background

The purpose of this study was to determine whether outcomes in head and neck cancer would vary based on geographic location of patients.

Methods

A dataset from the California Cancer Registry was linked to publicly available discharge abstracts. Patients were separated into geographic areas based on health service areas (HSAs). Multilevel logistic regression models were constructed to include geographic, patient, and hospital‐level characteristics.

Results

There was significant variation in 5‐year survival hazard ratios (HRs) among the majority of the 14 HSAs in the unadjusted model. After adjusting for patient and hospital characteristics, the differences between regions were not significant except for Orange County (HR = 0.75). Commission on Cancer certification (HR = 0.82; p < .01) and hospital volume (HR = 0.975; p < .01) were each independently associated with differences in survival.

Conclusion

Geographic variation in 5‐year survival outcomes is seen in head and neck cancer. Patient characteristics and treating hospitals explain much of this variation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1896–E1902, 2016
Transformation of 1,2,3‐Thiadiazolyl Hydrazones as Method for Preparation of 1,2,3‐Triazolo[5,1‐b][1,3,4]thiadiazines
Authors: Kalinina Tatiana A. , Bystrykh Olga A. , Glukhareva Tatiana V. , Morzherin Yuri Yu.
Published: December 2015

The transformation of 1,2,3‐thiadiazolyl hydrazones of aldehydes and ketones including Dimroth rearrangement giving 1‐alkylidenamino‐5‐mercapto‐1,2,3‐triazoles, alkylation of mercapto group of these heterocyclic compounds by α‐bromoacetophenones and cyclization giving 6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadizines have been investigated. It was shown that the reaction for hydrazones of acetophenones and benzoaldehydes is diastereoselective. Triazolothiadiazine spiro derivatives were prepared with transformation of hydrazones of cyclic ketones.
Synthesis and Anticancer Activity of Novel N‐trisazole/isoxazole Alkyl Functionalized Quinolin‐2(1H)‐one Derivatives
Authors: Gaddameedi Jitender Dev , Yedla Poornachandra , Kuchukulla Ratnakar Reddy , Chavva Kurumurthy , Pillalamarri Sambasiva Rao , Gautham Santhosh Kumar , Chityal Ganesh Kumar , Banda Narsaiah
Published: December 2015

A series of novel N‐triazole/isoxazole alkyl quinolin‐2(1H)‐one derivatives 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 9a, 9b, 9c, 9d, and 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h, 7i, 7j, 7k, 7l, 7m, 7n, 7o, 7p, 7q, 7r were prepared. Compounds 6d and 6k, which showed promising anticancer activity at micromolar concentration, have been identified.
Synthesis and Antimicrobial Evaluations of New 5‐aryl Linked Bispyrazolines
Authors: Yusuf Mohamad , Kaur Manvinder
Published: December 2015

Syntheses of new bispyrazolines 4a, 4b, 4c, 4d, 4e, 4f, 4g built around the aliphatic linkers of varying lengths have been described. The intermediate bischalcones and final bishetrocyclics were also evaluated for their antimicrobial activities.
Temporal resolution improvement of calibration‐free dynamic contrast‐enhanced MRI with compressed sensing optimized turbo spin echo: The effects of replacing turbo factor with compressed sensing accelerations
Authors: Han SoHyun , Cho HyungJoon
Published: December 2015

Purpose

To enhance the temporal resolution of calibration‐free dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) by implementing compressed sensing assisted turbo spin echo (CS‐TSE) acquisition.

Materials and Methods

The dynamic sparse sampling variables including acceleration factor, randomized phase encoding distributions, and reconstruction constraints were retrospectively optimized by minimizing the difference from fully sampled dynamic TSE at 7T. The degree of contrast enhancement and the calibration‐free quantification of gadolinium (Gd) concentration were evaluated among fast low‐angle shot (FLASH), TSE, and CS‐TSE acquisitions with multiple phantoms (0.1–6 mM). The kidney‐feeding in vivo arterial input function (AIF) was measured at multiple administration doses (0.1–0.3 mmol/kg) to evaluate the benefit of CS‐TSE for quantifying rapidly changing high Gd concentrations in C57BL/6 mice (n = 22).

Results

In phantom studies, both calibration‐free and calibrated conversions estimated equivalent Gd concentrations for CS‐TSE (scatterplot slope = 0.9801, r2 = 0.9998, P < 0.001). In in vivo studies, 4‐fold higher temporal resolution (0.96 sec) of CS‐TSE over the corresponding TSE enabled robust measurement of AIF first‐pass peak and resulting peak enhancement with CS‐TSE were observed, with 1.1439‐ and 2.1258‐fold times higher than those with TSE and FLASH acquisitions, respectively, at the 0.1 mmol/kg dose. Calibration‐free estimates of AIF peak concentration with CS‐TSE were in good agreement with the calibrated approach at multiple administration doses (scatterplot slope = 0.7800, r2 = 0.8014, P < 0.001).

Conclusion

Temporal resolution‐improved CS‐TSE provides practical subsecond (0.96s) calibration‐free dynamic MR quantification of high Gd concentration. J. Magn. Reson. Imaging 2016;44:138–147.
Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double‐blind, randomized, active‐ and placebo‐controlled SONIC urodynamic study
Authors: Amarenco G. , Sutory M. , Zachoval R. , Agarwal M. , Del Popolo G. , Tretter R. , Compion G. , De Ridder D.
Published: December 2015

Aims

To investigate the effect on urodynamics of 4 weeks treatment with solifenacin succinate in patients with neurogenic detrusor overactivity (NDO) due to multiple sclerosis (MS) or spinal cord injury (SCI).

Methods

SONIC was a prospective, multicenter, double‐blind, phase 3b/4 study investigating the efficacy and safety of solifenacin 10 mg in patients with NDO due to MS or SCI. Patients (n = 189) were randomized to placebo or active treatment (solifenacin 5 mg, 10 mg or oxybutynin hydrochloride 15 mg) for 4 weeks, after a 2‐week, single‐blind, placebo run‐in period. The primary endpoint was change in maximum cystometric capacity (MCC) from baseline to end of treatment. The primary analysis compared solifenacin 10 mg versus placebo; all other comparisons were considered secondary. Secondary endpoints included changes in urodynamic parameters, patient‐reported outcomes, and safety assessments.

Results

In the primary analysis, solifenacin 10 mg significantly improved mean change from baseline MCC versus placebo (P < 0.001) and was associated with improvements in bladder volume at first contraction and at first leak as well as detrusor pressure at first leak. Similar results were obtained for oxybutynin versus placebo. Patient perception of bladder condition significantly improved with solifenacin 10 mg versus placebo (P = 0.041). There was a clear improvement in quality of life (QoL) in the solifenacin arms versus placebo. The overall incidence of adverse events was low.

Conclusions

In patients with NDO due to MS and SCI, 4 weeks of treatment with solifenacin 10 mg improved urodynamic variables and QoL versus placebo and was well tolerated. Neurourol. Urodynam. 36:414–421, 2017. © 2015 Wiley Periodicals, Inc.
Increasing use of prescription drugs in the United Kingdom
Authors: Zhang Frank , Mamtani Ronac , Scott Frank I. , Goldberg David S. , Haynes Kevin , Lewis James D.
Published: December 2015

Background

Prescription drugs are a central component of healthcare worldwide. We investigated changes in drug‐prescribing patterns over time in the general population.

Methods

Secular trends were analyzed using 1999–2012 prescription data from The Health Improvement Network. Prevalence of receipt of medication prescriptions was computed by age, sex, and therapeutic category for each calendar year. Spearman correlations were computed to assess change over time.

Results

Between 1999 and 2012, the percentage of the population that received at least one medication prescription increased from 64.5% to 69.2% (rho = 0.96, p < 0.001). The percentage of patients receiving prescriptions for one to four unique agents declined from 45.6% to 42.1% (Spearman's rho = −0.98, p < 0.001). Meanwhile, the percentage receiving five to nine and 10 or more unique agents increased from 14.1% to 17.5% (rho = 0.996, p < 0.001) and 4.7% to 9.6% (rho = 1.000, p < 0.001) respectively. Largest increases were seen in use of drugs for gastrointestinal disease among women and cardiovascular disease among men. In 2012, the most commonly used agents were for infection or nervous system drugs, with 32.0% and 28.9% of patients receiving at least one prescription, respectively.

Conclusions

Nearly 70% of the United Kingdom population has received prescriptions for one or more medication with increasing proportions receiving prescriptions for five or more. The high rates of medication use increase the complexity and cost of healthcare. These data can be used for public health planning and to design pharmacoepidemiology and comparative effectiveness studies. Copyright © 2015 John Wiley & Sons, Ltd.
Trends in prescribing of sedative‐hypnotic medications in the USA: 1993–2010
Authors: Kaufmann Christopher N. , Spira Adam P. , Alexander G. Caleb , Rutkow Lainie , Mojtabai Ramin
Published: December 2015

Purpose

Non‐benzodiazepine receptor agonists (nBZRAs) were developed as an alternative to benzodiazepines (BZDs) to treat insomnia. Little is known about how the introduction of nBZRAs influenced trends in BZD prescribing. We examined BZD and nBZRA prescribing trends from 1993 to 2010.

Methods

We used the National Ambulatory Medical Care Survey to examine 516,118 patient visits between 1993 and 2010. We categorized visits as BZD, nBZRA, or BZD + nBZRA visits based on medications prescribed in each visit and applied linear probability regression models to assess trends in visits.

Results

Increases were observed in proportions of visits that were BZD (2.6% in 1993 to 4.4% in 2010, p < 0.001) and nBZRA (0% to 1.4%, p < 0.001). Increases in BZD visits were primarily after 2002, with prescribing in the preceding years remaining relatively stable. We also found increases in BZD + nBZRA visits (0% to 0.4%, p < 0.001). Among patients with sleep disorders, there was an increase in nBZRA visits (2.3% to 13.7%, p < 0.001), and decline in BZD visits (23.5% to 10.8%, p = 0.015). Just under a third (30.8%) of any sedative‐hypnotic visits were for adults aged 65+ years, among whom increases in BZD, nBZRA, and BZD + nBZRA visits were observed across the study period.

Conclusions

There were increases in prescribing of nBZRAs between 1993 and 2010. Increases in prescribing of BZDs were also observed, especially after 2002. The introduction of nBZRAs likely resulted in declines in BZD prescribing among those with a sleep disorder, but not other groups. Delivery of behavioral treatments should be encouraged to avert adverse outcomes associated with sedative‐hypnotic use. Copyright © 2015 John Wiley & Sons, Ltd.
Transient spectroscopic characterization of the ring‐opening reaction of tetrahydrochromeno[2,3‐dimethyl]indole
Authors: Marshall Ariel S. , Rogers Robert A. , Perry Joseph W. , Brittain W. J.
Published: December 2015

Tetrahydrochromeno is a structural variant of spiropyran that undergoes a reversible ring‐opening to generate a colored nitrophenolate intermediate. Earlier work confirmed this intermediate through trimethylsilyl cyanide trapping under continuous irradiation. We have performed transient absorption spectroscopy to further characterize the mechanism of the ring‐opening reaction. Excitation at 355 nm produced a transient species with an absorption maximum at 445 nm, which we assign to the nitrophenolate unit of the ring‐opened product. The transient absorption decays after ~970 ns with small optical density changes corresponding to a 0.15 quantum yield. Exposure to oxygen did not exhibit a significant deleterious effect on the photoisomerization of the chromeno dye. Time‐dependent density functional theory corroborated spectroscopic assignments of the starting chromeno and the putative ring‐opened intermediate. The excited state behavior of this system parallels the structurally similar oxazine system reported by Raymo and coworkers. The one significant difference is the longer lifetime of the photochemically generated intermediate from chromeno. Copyright © 2015 John Wiley & Sons, Ltd.
From Autocatalysis to Market Relations: A Systems Approach to the Material Flows Needed by Living Systems
Authors: Nechansky Helmut
Published: December 2015

The paper analyses how the control of material flows needed by living systems determines evolutionary patterns. A simplification of Miller's living systems theory, distinguishing only three functional units, (i) production systems, (ii) storage, and (iii) controller structures, is used to investigate the importance of these units on various evolutionary stages. In the internal evolution of biological systems, storage is crucial to control the availability of intermediate products of autocatalytic cycles. This is the base for continuous production and maintenance of controller structures (brains). In the external, technical evolution storage enables building external production systems and controller structures (like computers). In the dyadic coevolution of living systems, control of material flows and/or storage enable power positions in interaction patterns ranging from competition for scarce resources, via market relations, to egalitarian cooperation. Such power positions open access to different markets and exclusive evolutionary options. Economic theory widely ignores that. Copyright © 2015 John Wiley & Sons, Ltd.
From pluripotency to myogenesis: a multistep process in the dish
Authors: Świerczek Barbara , Ciemerych Maria A. , Archacka Karolina
Published: December 2015

Pluripotent stem cells (PSCs), such as embryonic stem cells or induced pluripotent stem cells are a promising source of cells for regenerative medicine as they can differentiate into all cell types building a mammalian body. However, protocols leading to efficient and safe in vitro generation of desired cell types must be perfected before PSCs can be used in cell therapies or tissue engineering. In vivo, i.e. in developing mouse embryo or teratoma, PSCs can differentiate into skeletal muscle, but in vitro their spontaneous differentiation into myogenic cells is inefficient. Numerous attempts have been undertaken to enhance this process. Many of them involved mimicking the interactions occurring during embryonic myogenesis. The key regulators of embryonic myogenesis, such as Wnts proteins, fibroblast growth factor 2, and retinoic acid, have been tested to improve the frequency of in vitro myogenic differentiation of PSCs. This review summarizes the current state of the art, comparing spontaneous and directed myogenic differentiation of PSCs as well as the protocols developed this far to facilitate this process.
Longitudinal outcome and recovery of social problems after pediatric traumatic brain injury (TBI): Contribution of brain insult and family environment
Authors: Ryan Nicholas P. , van Bijnen Loeka , Catroppa Cathy , Beauchamp Miriam H. , Crossley Louise , Hearps Stephen , Anderson Vicki
Published: December 2015

Pediatric traumatic brain injury (TBI) can result in a range of social impairments, however longitudinal recovery is not well characterized, and clinicians are poorly equipped to identify children at risk for persisting difficulties. Using a longitudinal prospective design, this study aimed to evaluate the contribution of injury and non‐injury related risk and resilience factors to longitudinal outcome and recovery of social problems from 12‐ to 24‐months post‐TBI. 78 children with TBI (injury age: 5.0–15.0 years) and 40 age and gender‐matched typically developing (TD) children underwent magnetic resonance imaging including a susceptibility‐weighted imaging (SWI) sequence 2–8 weeks post‐injury (M= 39.25, SD = 27.64 days). At 12 and 24‐months post‐ injury, parents completed questionnaires rating their child's social functioning, and environmental factors including socioeconomic status, caregiver mental health and family functioning. Results revealed that longitudinal recovery profiles differed as a function of injury severity, such that among children with severe TBI, social problems significantly increased from 12‐ to 24‐months post‐injury, and were found to be significantly worse than TD controls and children with mild and moderate TBI. In contrast, children with mild and moderate injuries showed few problems at 12‐months post‐injury and little change over time. Pre‐injury environment and SWI did not significantly contribute to outcome at 24‐months, however concurrent caregiver mental health and family functioning explained a large and significant proportion of variance in these outcomes. Overall, this study shows that longitudinal recovery profiles differ as a function of injury severity, with evidence for late‐emerging social problems among children with severe TBI. Poorer long‐term social outcomes were associated with family dysfunction and poorer caregiver mental health at 24‐months post injury, suggesting that efforts to optimize the child's environment and bolster family coping resources may enhance recovery of social problems following pediatric TBI.
Facilitation of accurate and effective radiation therapy using fentanyl pectin nasal spray (FPNS) to reduce incidental breakthrough pain due to procedure positioning
Authors: Prieto Isabel , Pardo José , Luna Javier , Marin Juan P. , Olivera Jesús , Garcia Antonio J. , Perez Ana M.
Published: December 2015

Graphical Abstract
Keeping It Implicit: A Defense of Foucault's Archaeology of Knowledge
Authors: TIISALA TUOMO
Published: December 2015

This paper defends Michel Foucault's notion of archaeology of knowledge against the influential and putatively devastating criticism by Dreyfus and Rabinow that Foucault's archaeological project is based on an incoherent conception of the rules of the discursive practices it purports to study. I argue first that Foucault's considered view of these rules as simultaneously implicit and historically efficacious corresponds to a general requirement for the normative structure of a discursive practice. Then I argue that Foucault is entitled to that view despite the charges to the contrary by Dreyfus and Rabinow. I also explain in detail how the argument by Dreyfus and Rabinow arises from a misunderstanding of Foucault's archaeological project as transcendental inquiry, while archaeology of knowledge is, in fact, a diagnostic project. The result is a novel understanding of the notion of archaeology of knowledge that enables a reassessment of Foucault's philosophical work in connection with current debates regarding the relationship between reflection and practice in the structure of thought.
Anti-Meaning and Why It Matters
Authors: CAMPBELL STEPHEN M. , NYHOLM SVEN
Published: December 2015

It is widely recognized that lives and activities can be meaningful or meaningless, but few have appreciated that they can also beanti-meaningful. Anti-meaning is the polar opposite of meaning. Our purpose in this essay is to examine the nature and importance of this new and unfamiliar topic. In the first part, we sketch four theories of anti-meaning that correspond to four leading theories of meaning. In the second part, we argue that anti-meaning has significance not only for our attempts to theorize about meaning in life but also for our ability to lead meaningful lives in the modern world.
Withdrawal from Employment Gained Post-SCI: Precipitating Factors
Authors: O'Hare Mary Alice , Murphy Gregory
Published: December 2015

Despite the high prevalence of withdrawal from employment gained post-traumatic spinal cord injury (tSCI), relatively few studies have examined the factors that precipitate job withdrawal. Within the context of general systems theory, the aim of the present study was to identify and classify the factors that led to job withdrawal post-tSCI. Using purposive sampling and a structured proforma, 30 participants completed an in-depth telephone interview. Job withdrawal was precipitated more frequently by micro-system (person-centred) factors or meso-system (job-related) factors than macro-system (socio-economic) factors. Micro-system factors fell into five groups (SCI-related, psychological/psychosocial, mobility, general health and knowledge/skills/abilities) as did meso-system factors (job design, psychosocial climate, ergonomics, human resources and work cycles). Two groups of macro-system factors were identified (proximal and distal). Classifying job withdrawal factors within the context of general systems theory provides an integrated framework for intervention development and furnishes decision-makers with guidance as to whether a top-down or bottom-up approach would be more feasible/beneficial to address preventable job withdrawal post-tSCI.
V. Observations upon Shrines; by John Loveday, of Caversham, Esquire
Authors: Loveday John
Published: December 2015

Dr. Stukeley has accurately distinguished two kinds of shrines, both equally made for receiving the reliques of saints: but with this difference, that one sort was portable, and used in processions; and the other fixed, as being built of stone, marble, and other heavy materials. The former of these were called Feretra, under which word Du Fresne says: “Feretra reliquias sanctorum continentia cum processionibus circumlata non semel legere “est.” And although this sort could only with propriety bear that name, yet was it also given to the immoveable fixed shrines; as to our protomartyr's at St. Alban's, Thomas Becket's at Canterbury, Birinus's at Dorchester, Cuthbert's at Durham, and Edward the Confessor's at Westminster.
VII. A Letter from Maurice Johnson, Esq; to Mr. New, relating to the Registers of the Bishops of Lincoln
Authors: Johnson Maurice
Published: December 2015

The registers of the bishops of Lincoln, in the bishop's office at Lincoln, begin earlier than those which are remaining either at Canterbury or York, or perhaps any other in England, viz. from bishop Wells, who was consecrated anno 1209, to bishop William Barlow anno 1608. The series is in good preservation. The institutions of Wells, Greethead, Lexington, and Sutton, are wrote on long narrow rolls; the Mss. of appropriations, confirmation of abbots, priors, &c. being endorsed on the same, excepting Sutton's, which are wrote in a vellum book; as all the succeeding bishops institutions and Mss. are down to the Reformation; after which period they are most carelessly written on paper. One of the most curious and useful records in that repository is a thin quarto, which contains all the endowments of all the vicarages in the diocese, written about 1210.
XI. Account of Lesnes Abby; by Dr. Stukeley, in a Letter to the Right Honourable the Lord Chancellor Hardwicke
Authors: Stukeley Wm.
Published: December 2015

Yesterday, I made a most agreeable journey, though it may be called a pilgrimage, to visit the venerable remains of Lesnes Abby, at Earith in Kent, founded by Richard de Lucie, lord chancellor, and chief justice to Henry II. He was a near relation to your Lordship's neighbour, Lady Roisia of Roiston. It was impossible that I should not think of giving your Lordship the subsequent account of my observations there, for an amusement during your retirement from business and cares of state.
XIX. A Letter from Smart Lethieullier, Esq; to Mr. G. Vertue, relating to some Antiquities at Bourdeaux, in France
Authors: Lethieullier Smart
Published: December 2015

I promised to send you some account of what remains of our English princes I was able to observe during my stay at Bourdeaux, in France, once the capital of the large dominions they possessed in that country; but you will soon perceive, how trifling and insignificant they are; pride and revenge having exercised all their fury against them. However, as I know the pleasure you take, and the indefatigable pains you have bestowed, in collecting and preserving whatever relates to any part of our English history, or antiquities, I shall make the less scruple of sending you them just as I found them.