bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging tumour distribution of a polymeric drug delivery platform in vivo by PET‐MRI
Authors: Puttick Simon , Boase Nathan R.B. , Blakey Idriss , Thurecht Kristofer J.
Published: July 2014

BACKGROUND

Over the past decade, molecular imaging has played a key role in the progression of drug delivery platforms from concept to commercialization. Of the molecular imaging techniques commonly utilized, positron emission tomography (PET) can yield a breadth of information not easily accessible by other methodologies and when combined with other complementary imaging modalities, is a powerful tool for pre‐ and clinical development of therapeutics. However, very little research has focused on the information available from complimentary imaging modalities. This paper reports on the data‐rich methodologies of contrast enhanced PET/CT and PET/MRI for probing efficacy of polymer drug delivery platforms.

RESULTS

The information available from an ExiTron nano 6000 contrast enhanced PET/CT and a gadolinium (Gd) enhanced PET/MRI image of a 64Cu labeled HBP in the same mouse was compared qualitatively.

CONCLUSIONS

Gd contrast enhanced PET/MRI offers a powerful methodology for investigating the distribution of polymer drug delivery platforms in vivo and throughout a tumour volume. Furthermore, information about depth of penetration away from primary blood vessels can be gleaned, potentially leading to development of more efficacious delivery vehicles for clinical use. © 2014 Society of Chemical Industry
A review on fermentative hydrogen production from dairy industry wastewater
Authors: Karadag Dogan , Köroğlu Oguz Emre , Ozkaya Bestami , Cakmakci Mehmet , Heaven Sonia , Banks Charles
Published: July 2014

Hydrogen (H2) is one of the most promising alternative fuel sources for satisfying future energy demand, and fermentative hydrogen production is advantageous over other processes. In recent decades, considerable research has been conducted on H2 production from carbohydrate‐rich materials since it is a cost‐effective approach and has the ability to generate intensive renewable energy from organic wastes. Dairy wastewater is a high volume industrial wastewater and with its immense carbohydrate content is an attractive candidate for sustainable fermentative H2 production. The present paper provides comprehensive evaluation of recent reports on fermentative H2 production from dairy wastewater. Important effective parameters and current bioreactor technologies for H2 production from dairy wastewater are discussed. © 2014 Society of Chemical Industry
Bioconversion of cholesterol to 4‐cholesten‐3‐one by recombinant Bacillus subtilis expressing choM gene encoding cholesterol oxidase from Mycobacterium neoaurumJC‐12
Authors: Shao Minglong , Rao Zhiming , Zhang Xian , Xu Meijuan , Yang Taowei , Li Hui , Xu Zhenghong , Yang Shangtian
Published: July 2014

BACKGROUND

Bacillus subtilis 168 was used to express the cholesterol oxidase (EC 1.1.3.6) genes cloned from Mycobacterium neoaurum JC‐12 and the bioconversion of cholesterol to 4‐cholesten‐3‐one was realized.

RESULTS

Expression of cholesterol oxidase ChoM1 and ChoM2 from M. neoaurum in B. subtilis was confirmed by SDS‐PAGE and enzyme activity analysis. The activities of the recombinant ChoM1 and ChoM2 were 5.27 and 7.44 U mg−1, which were 5.2‐fold and 7.3‐fold, respectively, of the cholesterol oxidases activities in M. neoaurum JC‐12. Enzyme properties showed that the optimum pH and temperature for both ChoM1 and ChoM2 was 7.5 and 40 °C. Both enzymes were stimulated by Mg2+ and Mn2+ and showed higher activity towards the 3β‐hydroxy steroids with long alkyl chains at C17. Whole‐cells of the recombinant strains were used as catalysts, the recombinant strains B. subtilis 168/pMA5‐choM1 and B. subtilis 168/pMA5‐choM2 catalyzed the bioconversion of cholesterol to 4‐cholesten‐3‐one with a percentage conversion of 67% and 83% at 21 h.

CONCLUSION

The recombinant strains demonstrated efficient and stable enzyme activities and showed obvious pre‐eminence on the bioconversion of cholesterol into 4‐cholesten‐3‐one. As a safe microorganism, B. subtilis 168 would be a promising cell factory to produce 4‐cholesten‐3‐one in the pharmaceutical industry. © 2014 Society of Chemical Industry
18‐Crown‐6 Catalyzed Microwave‐mediated Synthesis of Symmetric Bis‐Heterocyclic Compounds under Solvent‐free Condition
Authors: Rishikesan Rathnasamy , Prabakaran Kamalakannan , Murugesan Rajamani , Venkataraman Ramaswamy , Ranjith Pakkath Karuvalam , Arvind Sivasubramanian , Thennarasu Sathiah
Published: July 2014

An efficient, solvent‐free and 18‐crown‐6 catalyzed method for the synthesis of N‐alkyl‐4‐(4‐(5‐(2‐(alkyl‐amino)thiazol‐4‐yl)pyridin‐3‐yl)phenyl)thiazol‐2‐amine, N‐alkyl‐4‐(5‐(2‐alkyamino)thiazol‐4‐yl)pyridine‐3‐yl)thiazol‐2‐amine, and 4,4′‐bis‐{2‐[amino]‐4‐thiazolyl}biphenyl bis‐heterocyclic derivatives via microwave accelerated cyclization is presented.
Action of Hydrazines on 2‐(2‐Oxindolin‐3‐ylidene)malononitrile, (E,Z)‐Ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate and Isatin‐β‐thiosemicarbazone as a Source of Spiro Indoline‐pyrazole Systems
Authors: Youssef Ahmed S. A. , Hemdan Magdy M. , Emara Samir A. , Kamel Rabaa M.
Published: July 2014

2‐(2‐Oxindolin‐3‐ylidene)malononitrile (1a) or (E,Z)‐ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate (1b) or isatin‐β‐thiosemicarbazone (1c) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline‐2‐one moiety (2). The hydrazone derivatives (2) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives (3a,3b). Also, cinnoline derivative (9) is obtained by action of hydrazine hydrate on theN‐acetyl derivative of (6a). The structures of the newly synthesized compounds were evaluated by IR,1H‐NMR spectroscopy, mass spectra and elemental analyses.
An Efficient Synthesis of Pemetrexed Disodium
Authors: Qi H. , Wen J. , Li L. , Bai R. , Chen L. , Wang D.
Published: July 2014

An efficient synthetic method for the pemetrexed disodium has been developed using methyl 4‐iodobenzoate and 3‐buten‐1‐ol as starting materials via six steps. The developed process avoided some tedious workup procedures and unfriendly reagents compared with the reported synthetic routes. In addition, two impurities generated in the process were isolated and characterized by 1H NMR, 13C NMR, and HRMS. The mechanisms of the two impurities were also discussed, and the impurities could be easily removed by suitable workup procedures. The overall yield of pemetrexed disodium was increased from 12.8% (literature) to 34.9%. Therefore, this cost‐effective, environmental friendly, and high‐yielding process is more suitable for scale‐up production of pemetrexed disodium.
Applications of Azoalkenes in the Synthesis of Fused Ring Pyridazine Derivatives
Authors: Gaonkar Santosh L. , Lokanatha Rai K. M.
Published: July 2014

Cyclic ketohydrazones containing α‐methylene group are oxidized by chloramine‐T followed by treatment with triethylamine leads to the formation of azoalkenes via azochloride, which are trapped by olefinic compounds to produce fused ring pyridazine derivatives in good yield.
Electroacupuncture and A‐317491 depress the transmission of pain on primary afferent mediated by the P2X3 receptor in rats with chronic neuropathic pain states
Authors: Wang Wan‐Sheng , Tu Wen‐Zhan , Cheng Rui‐Dong , He Rong , Ruan Li‐Hua , Zhang Li , Gong Yong‐Sheng , Fan Xiao‐Fang , Hu Jie , Cheng Bo , Lai Yin‐Ping , Zou En‐Miao , Jiang Song‐He
Published: July 2014

P2X is a family of ligand‐gated ion channels that act through adenosine ATP. The P2X3 receptor plays a key role in the transmission of neuropathic pain at peripheral and spinal sites. Electroacupuncture (EA) has been used to treat neuropathic pain effectively. To determine the role of EA in neuropathic pain mediated through the P2X3 receptor in dorsal root ganglion neurons and the spinal cord, a chronic constriction injury (CCI) model was used. Sprague‐Dawley rats were divided into four groups: sham CCI, CCI, CCI plus contralateral EA, and CCI plus ipsilateral EA. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded. Furthermore, the expression of the P2X3 receptor was evaluated through Western blotting and immunofluorescence. The effects of EA and A‐317491 were investigated through the whole‐cell patch‐clamp method and intrathecal administration. Our results show that the MWT and TWL of EA groups were higher than those in the CCI group, whereas the expression of the P2X3 receptor was lower than that in the CCI group. However, no significant difference was detected between the two EA groups. EA depressed the currents created by ATP and the upregulation of the P2X3 receptor in CCI rats. Additionally, EA was more potent in reducing mechanical allodynia and thermal hyperalgesia when combined with A‐317491 through intrathecal administration. These results show that both contralateral and ipsilateral EA might inhibit the primary afferent transmission of neuropathic pain induced through the P2X3 receptor. In addition, EA and A‐317491 might have an additive effect in inhibiting the transmission of pain mediated by the P2X3 receptor. © 2014 Wiley Periodicals, Inc.
Observed changes in southwest monsoon rainfall over India during 1901–2011
Authors: Guhathakurta P. , Rajeevan M. , Sikka D. R. , Tyagi Ajit
Published: July 2014

The trends and epochal variability of southwest monsoon over the country as a whole and four homogeneous regions are examined using monthly rainfall data (1901–2011) of 640 political districts of India. The district rainfall data is computed from station rainfall data. The same station data is used to analyse the trends in the frequency of rainfall events of different intensities for examining extreme rainfall events. The existence of the multidecadal epochal variability of rainfall is clearly established in the all‐India monsoon rainfall as well as monsoon rainfall over the four homogenous regions. However, over different homogenous regions, the phases of multidecadal variability are found to be different. Principal component analysis brings out Northeast India (NEI) rainfall as more dominant mode for all‐India rainfall. Significant decrease in southwest monsoon rainfall over NEI is observed during the post 1950 period. Decreasing trends are also observed over the monsoon core region during the post‐1950 period. Over these regions, monsoon rainfall has increased significantly during the pre‐1950 period. It has been shown that the decreasing trend in monsoon rainfall during the post 1950 period is the result of multidecadal epochal variability. Geographical regions that experienced significant changes in the frequency of days of rainfall with different intensities are also identified. Significant change/turning points are also detected in the southwest monsoon rainfall. Frequency of moderate rainfall events (5 mm ≤ daily rainfall < 100 mm) decreased significantly during the period 1951–2010 over the monsoon core region of India whereas no significant changes are observed in the frequencies of heavy (daily rainfall >100 mm) or very heavy rain (daily rainfall >150 mm) during the southwest monsoon season. Climatic shift or change point in monsoon rainfall in India is also detected by an established statistical test.
Properties of Carboxylated Nitrile Rubber/Hydrotalcite Composites Containing Imidazolium Ionic Liquids
Authors: Marzec Anna , Laskowska Anna , Boiteux Gisele , Zaborski Marian , Gain Olivier , Serghei Anatoli
Published: July 2014

In the present study, two types imidazolium salts containing the common cation 1‐butyl‐3‐methylimidazolium‐hydrophilic tetrachloroaluminate (BMIM AlCl4) and hydrophobic bis(trifluoromethylsulfonyl)imide (BMIM TFSI) are analyzed for effects on the ionic conductivity and the state of cure of carboxylated nitrile rubber/hydrotalcite composites (XNBR/HT). Imidazolium salt containing tetrachloroaluminate ions effectively participates in the crosslinking process of carboxylated nitrile rubber and contributes to an increase in the crosslink density of the composites. Hydrophobic 1‐butyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide was found to be compatible with carboxylated nitrile rubber. In the presence of 15 parts per hundred rubber (phr) of BMIM TFSI, the ionic conductivity of the composites increases from 10−10 to 10−7 S·cm−1, and the glass transition temperature (Tg) of the XNBR shifts towards lower temperatures from ‐23 °C to ‐33 °C.
Effect of Mechanical Compression and Hydrostatic Pressure on the Molecular Mobility of Poly(lactic acid)
Authors: Bouthegourd Emilie , Esposito Antonella , Saiter Allisson
Published: July 2014

The molecular mobility of an organic glass (PLA with 4.3% of D‐lactic acid content) was investigated by calculating the size of the Cooperative Rearranging Regions (CRR) at its glass transition. The samples were exposed to different external constraints – namely a large deformation by mechanical compression at T < Tg (prior to measurement) or different hydrostatic pressures (during the measurement). The measurements were performed by Differential Scanning Calorimetry (DSC) techniques: standard, temperature modulated (TM‐DSC) and high pressure (HP‐DSC). It was shown that mechanical deformations above the elastic limit increase the CRR size and shift the Tg value to higher temperatures, but have no effect on the value of ΔCp(Tg). On the other hand, increasing the hydrostatic pressure during the measurement (1 to 100 bar) decreases the CRR size, slightly influences Tg and does not change the value of ΔCp(Tg).
Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment
Authors: Orruño Maite , Garaizabal Idoia , Bravo Zaloa , Parada Claudia , Barcina Isabel , Arana Inés
Published: July 2014

Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free‐living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling.
Population pharmacokinetics of maslinic acid, a triterpene from olives, after intravenous and oral administration in rats
Authors: Sánchez‐González Marta , Colom Helena , Lozano‐Mena Glòria , Juan M. Emília , Planas Joana M.
Published: July 2014

Scope

Maslinic acid is a bioactive minor component of Olea europaea L. with health‐enhancing activities and no harmful effects. A pharmacokinetic (PK) study was conducted to determine its bioavailability for future studies of maslinic acid in humans.

Methods and results

Intravenous (1 mg/kg) and oral (50 mg/kg) administrations to Sprague‐Dawley rats were performed. Blood was obtained several times over 24 h and PKs were analyzed with NONMEM 7.2, applying a population approach. Body weight was included a priori in the model with fixed allometric exponents, based on allometric principles. Plasma concentrations versus time were best characterized by a two‐open compartment model with first‐order absorption and linear elimination. Maslinic acid had a relative rapid oral absorption with a peak concentration after administration at 0.51 h and a bioavailability of 5.13%. Once in bloodstream, it distributed extensively into tissues, since the central and peripheral distribution volumes were 8.41 L/70 kg and 63.6 L/70 kg, respectively. The clearance (8 L/h/70 kg) was related to unaltered renal excretion. The prediction‐corrected visual predictive check confirmed its stability and predictive ability.

Conclusion

An allometric population PK model was performed for maslinic acid, which adequately described and predicted plasma concentrations.
Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops
Authors: van Breemen Richard B. , Yuan Yang , Banuvar Suzanne , Shulman Lee P. , Qiu Xi , Alvarenga René F. Ramos , Chen Shao‐Nong , Dietz Birgit M. , Bolton Judy L. , Pauli Guido F. , Krause Elizabeth , Viana Marlos , Nikolic Dejan
Published: July 2014

Scope

Women seeking alternatives to hormone‐replacement therapy for menopausal symptoms often try botanical dietary supplements containing extracts of hops (Humulus lupulus L.). Hops contain 8‐prenylnaringenin (8‐PN), a potent phytoestrogen, the related flavanones 6‐prenylnaringenin and isoxanthohumol (IX), and the prenylated chalcone xanthohumol (XN).

Methods and results

After chemically and biologically standardizing an extract of spent hops to these marker compounds, an escalating dose study was carried out in menopausal women to evaluate safety and pharmacokinetics. 8‐PN, 6‐prenylnaringenin, IX, and XN, sex hormones, and prothrombin time were determined in blood samples and/or 24 h urine samples. There was no effect on sex hormones or blood clotting. The maximum serum concentrations of the prenylated phenols were dose‐dependent and were reached from 2 to 7 h, indicating slow absorption. The marker compounds formed glucuronides that were found in serum and urine. Secondary peaks at 5 h in the serum concentration‐time curves indicated enterohepatic recirculation. The serum concentration‐time curves indicated demethylation of IX to form 8‐PN and cyclization of XN to IX. Slow absorption and enterohepatic recirculation contributed to half‐lives exceeding 20 h.

Conclusion

This human study indicated long half‐lives of the estrogenic and proestrogenic prenylated phenols in hops but no acute toxicity.
Dixon‐type and subtraction‐type contrast‐enhanced magnetic resonance angiography: A theoretical and experimental comparison of SNR and CNR
Authors: Stinson Eric G. , Trzasko Joshua D. , Weavers Paul T. , Riederer Stephen J.
Published: July 2014

Purpose

The purpose of this work is to compare the behavior of the signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) in contrast‐enhanced MR angiography with background suppression performed by either a Dixon‐type or subtraction‐type method.

Theory and Methods

Theoretical expressions for the SNR and CNR for both background suppression techniques were derived. The theoretical Dixon:subtraction SNR and CNR ratios were compared to empirical ratios measured from phantom and in vivo studies for Dixon techniques utilizing one, two, and three echoes. Specifically, the SNR and CNR ratios were compared as the concentration of contrast material in the blood changed.

Results

Empirical measurements of the SNR and CNR ratios compared favorably with the ratios predicted by theory. As the contrast concentration was reduced, the SNR advantage of the Dixon techniques increased asymptotically. In the ideal case, the SNR improvement over subtraction contrast‐enhanced MR angiography was at least twofold for one‐ and two‐echo Dixon techniques and at least a factor of
for the three‐echo Dixon technique.

Conclusion

Expressions showing a contrast concentration‐dependent SNR and CNR improvement of at least a factor of two when Dixon‐type contrast‐enhanced MR angiography is used in place of subtraction‐type contrast‐enhanced MR angiography were derived and validated with phantom and in vivo experiments. Magn Reson Med 74:81–92, 2015. © 2014 Wiley Periodicals, Inc.
Temperature‐induced evolution of micro‐morphology of polyaniline prepared by gradually adding oxidants: Experiments and mechanism
Authors: Li Benxiang , Liu Dengyou
Published: July 2014

This research aims to investigate the morphology evolution of polyaniline prepared by gradually adding oxidants at different temperatures. Results showed that the polyaniline nanofibers can readily be acquired when increasing the temperature from 25 to 75°C by gradual oxidants addition, even using 5 M LiCl solution as a solvent. The further study revealed that the morphology evolution of polyaniline at temperature 75°C follows the mechanism of continuously preferential homogeneous oxidation nucleation, which remarkably differs from the well‐known secondary growth mechanism. Moreover, this morphology evolution mechanism led by temperature effect may be applied for the general synthesis of the nanostructures of other conjugated conducting polymers. POLYM. COMPOS., 28–36, 2016. © 2014 Society of Plastics Engineers
Styrene/isoprene/butadiene integrated rubber prepared by anionic bulk polymerization in a twin‐screw extruder
Authors: Yuan Xieyao , Wang Jiming , Shan Dong , Zheng Anna
Published: July 2014

Styrene/isoprene/butadiene integrated rubber (SIBR) was synthesized using anionic bulk polymerization in a corotating intermeshing twin‐screw extruder. In order to study the relationship between microstructure and physical properties, three SIBRs were synthesized using different initiator complexes: n‐BuLi (N‐butyl lithium), n‐BuLi/THF (tetrahydrofuran), and n‐BuLi/TMEDA (tetramethylethylenediamine). The microstructure of the rubber products was analyzed by gel permeation chromatography and H nuclear magnetic resonance. SIBR prepared with pure n‐BuLi exhibited a multiblock microstructure. With the addition of THF or TMEDA, the vinyl content of the alkadiene increased; and the microstructure of SIBRs was randomized, indicated by the presence of a high weight content of styrene microblocks. Transmission electron microscopy demonstrated similar morphology in both the SIBRs and SSBR2003 (an industrial product). Dynamic mechanical analysis of the vulcanized SIBRs showed that the randomized SIBRs were quite suitable for the preparation of high‐performance tires. Tensile and tear test results of SIBRs were equivalent to those of SSBR2003. The low manufacturing cost of reactive extrusion technology will allow the large‐scale industrialization of SIBRs. POLYM. ENG. SCI., 55:1163–1169, 2015. © 2014 Society of Plastics Engineers
Representation of transport and scavenging of trace particlesin the Emanuel moist convection scheme
Authors: Pilon Romain , Grandpeix Jean‐Yves , Heinrich Philippe
Published: July 2014

In the Tropics, cumulus convection has a major influence on precipitation and vertical transport of atmospheric particles, which are subject to scavenging by precipitation. A new parametrization of transport and scavenging of trace particles by convective clouds and precipitation has been developed and introduced in the Laboratoire de Météorologie Dynamique general circulation model (LMDz). This model uses the deep convection scheme of Emanuel, which is particularly suited for the Tropics. Our parametrization of transport and scavenging is closely linked to this scheme and our developments follow step‐by‐step the building of this convection representation. The purpose of this study is to understand better the influence of convection on the tracer vertical distribution and to assess the role of the convection parametrization.

Short‐term and long‐term simulations have been performed focusing on the concentrations of the natural radionuclide 7Be, which is produced mainly in the stratosphere and upper troposphere and attaches to available aerosols. Single‐column simulations forced by data from the Tropical Ocean–Global Atmosphere–Coupled Ocean–Atmosphere Response Experiment (TOGA–COARE) show the high efficiency of in‐cloud scavenging by convective and large‐scale processes in the removal of the tracer. These simulations show that, in the LMDz model, convection does not affect radionuclide concentrations as much as stratiform clouds and associated precipitation. In the free troposphere and in the boundary layer, below‐cloud evaporation of rain has a major effect on tracer distribution, unlike impaction, which has a negligible effect. Three‐dimensional model simulation results are compared with surface data of a station belonging to the worldwide network of the Comprehensive Nuclear Test Ban Treaty Organization (CTBTO). We show that this new parametrization is able to reproduce the observed yearly averaged concentrations of 7Be at the surface and decrease by a third the overestimation of radionuclides formerly simulated without convective scavenging. LMDz simulations have been also performed over the year 2007 on a global scale using the terragenic 210Pb and cosmogenic 7Be radionuclides.
Context and Implications Document for: Teaching English language arts methods in the United States: a review of the research
Authors: Pasternak Donna L. , Caughlan Samantha , Hallman Heidi , Renzi Laura , Rush Leslie
Published: July 2014

This guide accompanies the following article: Donna L. Pasternak, Samantha Caughlan, Heidi Hallman, Laura Renzi and Leslie Rush. Teaching English language arts methods in the United States: a review of the research, Review of Education, DOI:10.1002/rev3.3031
Voluntary Genital Ablations: Contrasting the Cutters and Their Clients
Authors: Jackowich R. A. , Vale R. , Vale K. , Wassersug R. J. , Johnson T. W.
Published: July 2014

Introduction

Some healthy males voluntarily seek castration without a recognized medical need. There are currently no standards of care for these individuals, which cause many of them to obtain surgery outside of a licensed medical setting. We seek to understand who performs these surgeries.

Aim

This study aims to characterize individuals who perform or assist in genital ablations outside of the healthcare system.

Methods

A cross-sectional Internet survey posted on eunuch.org received 2,871 responses. We identified individuals who had performed or assisted in human castrations (“cutters”; n = 98) and compared this group with all other survey respondents (n = 2,773), who had not assisted in castrations. Next we compared the cutters with the voluntary eunuchs. Lastly, because many of the cutters have themselves been castrated, we also divided the physically castrated population (n = 278) into cutters (n = 44) and noncutters (n = 234) and compared them.

Main Outcome Measures

Self-reported questionnaires were used to collect demographic information, gender identity and presentation, selected childhood experiences, and history of aggressive behaviors, self-harming behaviors, and hospitalization.

Results

Distinguishing characteristics of cutters included: (i) presenting themselves as very masculine, (ii) having had their longest sexual relationship with a man, (iii) growing up on a farm, (iv) witnessing animal castrations, (v) having a history of sexually inappropriate behavior, (vi) having been threatened with genital mutilation as a child, (vii) having a history of self-harm, (viii) being raised in a devoutly Christian household, (ix) having had an underground castration themselves, and (x) having body piercings and/or tattoos.

Conclusions

This study may help identify individuals who are at risk of performing illegal castrations. That information may help healthcare providers protect individuals with extreme castration ideations from injuring themselves or others.
DOCK2 Is Critical for CD8+TCR− Graft Facilitating Cells to Enhance Engraftment of Hematopoietic Stem and Progenitor Cells
Authors: Wen Yujie , Elliott Mary J. , Huang Yiming , Miller Thomas O. , Corbin Deborah R. , Hussain Lala-Rukh , Ratajczak Mariusz Z. , Fukui Yoshinori , Ildstad Suzanne T.
Published: July 2014

CD8+TCR− graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic and syngeneic recipients. The mechanisms by which FCs promote HSC engraftment and tolerance induction have not been fully elucidated. Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of FCs function. DOCK2−/− FCs exhibit compromised facilitative function in vivo as evidenced by the loss of engraftment-enhancing capability for c-Kit+Sca-1+lineage− (KSL) cells, and compromised ability to promote KSL cell homing and lodgment in hematopoietic niche. Deletion of DOCK2 abrogates the ability of FCs to induce differentiation of naïve CD4+CD25− T cells into FoxP3+ regulatory T cells and interleukin-10-producing type 1 regulatory T cells in vitro. Moreover, DOCK2−/− FCs are unable to promote survival of KSL cells when cocultured with KSL cells. DOCK2−/− FCs also exhibit compromised migration to stroma-derived factor-1 in vitro and impaired homing to the bone marrow in vivo. In conclusion, our results demonstrate that DOCK2 is critical for FCs to maintain its immunomodulatory function and exert its trophic effects on KSL cells. These findings may have direct clinical relevance to promote HSC engraftment for treatment of autoimmunity, hemoglobinopathies, and to induce transplantation tolerance. Stem Cells  2014;32:2732–2743
Developmental exposure to the organochlorine insecticide endosulfan alters expression of proteins associated with neurotransmission in the frontal cortex
Authors: Wilson W. Wyatt , Onyenwe Wellington , Bradner Joshua M. , Nennig Sadie E. , Caudle W. Michael
Published: July 2014

Exposure to environmental contaminants, such as organochlorine insecticides during critical periods of neurodevelopment has been shown to be a major contributor to several neuropsychological deficits seen in children, adolescence, and adults. Although the neurobehavioral outcomes resulting from exposure to these compounds are known the neurotransmitter circuitry and molecular targets that mediate these endpoints have not been identified. Given the importance of the frontal cortex in facilitating numerous neuropsychological processes, our current study sought to investigate the effects of developmental exposure to the organochlorine insecticide, endosulfan, on the expression of specific proteins associated with neurotransmission in the frontal cortex. Utilizing in vitro models we were able to show endosulfan reduces cell viability in IMR‐32 neuroblastoma cells in addition to reducing synaptic puncta and neurite outgrowth in primary cultured neurons isolated from the frontal cortex of mice. Elaborating these findings to an in vivo model we found that developmental exposure of female mice to endosulfan during gestation and lactation elicited significant alterations to the GABAergic (GAT1, vGAT, GABAA receptor), glutamatergic (vGlut and GluN2B receptor), and dopaminergic (DAT, TH, VMAT2, and D2 receptor) neurotransmitter systems in the frontal cortex of male offspring. These findings identify damage to critical neurotransmitter circuits and proteins in the frontal cortex, which may underlie the neurobehavioral deficits observed following developmental exposure to endosulfan and other organochlorine insecticides. Synapse 68:485–497, 2014. © 2014 Wiley Periodicals, Inc.
Procedure‐related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta‐analysis
Authors: Akolekar R. , Beta J. , Picciarelli G. , Ogilvie C. , D'Antonio F.
Published: July 2014

Objectives

To estimate procedure‐related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta‐analysis.

Methods

A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000–2014) was performed to review relevant citations reporting procedure‐related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I2 statistic and Egger bias. Meta‐analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence–rate difference meta‐analysis was used to estimate pooled procedure‐related risks.

Results

The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58–1.08%) and 2.18% (95% CI, 1.61–2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46–0.91%) for amniocentesis and 1.79% (95% CI, 0.61–3.58%) for CVS. The weighted pooled procedure‐related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, –0.04 to 0.26%) and 0.22% (95% CI, –0.71 to 1.16%), respectively.

Conclusion

The procedure‐related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Lesser Tuberosity Avulsions in Adolescents
Authors: Nardo Lorenzo , Ma Benjamin C. , Steinbach Lynne S.
Published: July 2014

Background

Subscapularis tendon avulsions of the lesser tuberosity are relatively rare and often missed acutely and their characteristic appearance is frequently not recognized or is misinterpreted for an osteochondroma or a neoplastic process.

Questions/Purposes

This report reviews our experience with six adolescents who had subscapularis tendon avulsions of the lesser tuberosity.

Methods

Six male adolescents (12–15 years) presented with shoulder pain following history of trauma during amateur sport. Clinical notes including range of motion, strength tests, and pain assessment were reviewed along with imaging studies pre- and post treatment. Treatment consisted of either surgical or conservative measures.

Results

Two of the six patients had a large avulsion that simulated an exostosis of the proximal humerus that was misdiagnosed as an osteochondroma at two different outside institutions. All six cases were diagnosed with subscapularis tendon avulsion of the lesser tuberosity following clinical and imaging evaluation at our institution. Five of the patients underwent surgical repair and fixation of the tendon and the lesser tuberosity with suture anchors. One patient was treated conservatively. All patients had a good outcome with recovery of full shoulder strength and motion upon follow-up.

Conclusion

Clinicians should have a high index of suspicion of lesser tuberosity avulsions in adolescents who present with loss of internal rotation and anterior shoulder pain following traumatic injuries. In addition, an osseous fragment or exostosis along the inferomedial humeral head should suggest a subscapularis tendon avulsion and also should not be confused with an osteochondroma or a neoplastic process.
Massive parallele Sequenzierung in der Diagnostik hereditärer BRCA1-/-2-Mutationen
Authors: Auber B. , Heinecke K. , Morlot S. , Schlegelberger B. , Steinemann D.
Published: July 2014

Die massive parallele Sequenzierung (MPS) findet in der molekulargenetischen Diagnostik erblicher Krebserkrankungen zunehmend Einsatz, hier insbesondere bei Verdacht auf erblichen Brust- und Eierstockkrebs. Die potenziellen Vorteile von MPS im Vergleich zu bisher verwendeten (z. B. Sanger-sequenzbasierten) Methoden sind ein höherer Probendurchsatz, kürzere Bearbeitungszeiten und verminderte Kosten. Der Einsatz in der Routinediagnostik wird durch die Verfügbarkeit von zertifizierten Kits für die Probenvorbereitung vereinfacht. Hier wird die Validierung von 2 verschiedenen MPS-Geräten für die BRCA1-/-2-Diagnostik beschrieben. Bei Verwendung der Technik müssen die jeweiligen Vor- und Nachteile der einzelnen Geräte bedacht werden. Die Ergebnisse der MPS-Sequenzierung entsprechen denen, die mit Sanger-Sequenzierung ermittelt wurden.
Society of Fetal Medicine Practice Guidelines for the Second Trimester Anomalies Scan
Authors: Khurana Ashok , Makhija Bela , Deka Dipika , Rama Murthy B. S. , Sachdev Rahul , Chawla Deepak , Lulla Chander P. , Chaubal Nitin , Acharya Prashant , Shah Mohit V. , Malhotra Narendra , Praveen T. L. N. , Radhakrishnan Prathima , Gokhale Sudheer , Sahani Bimal J. , Pai Muralidhar V. ,   (Committee for the Guidelines)
Published: July 2014

Ultrasound is now an established tool in the clinical management of pregnancy. Consequent to its major role in clinical decision-making and its remarkable operator dependence, it is necessary to have guidelines for minimum standards of performance of this modality in each area of obstetric ultrasound. The Society of Fetal Medicine guidelines have been developed for use by all the practitioners performing antenatal ultrasound scans. They are intended to provide the entire medical community with standards for the performance of quality ultrasound examinations. Practitioners are encouraged to go beyond these standards in relevant clinical situations. Each guideline in this document has undergone extensive discussion followed by a consensus. In a rapidly evolving technological and research environment, it is imperative to constantly re-evaluate and update these guidelines. Practitioners are advised to be aware of these updates and incorporate these into their daily practice.
Link between hippocampus' raised local and eased global intrinsic connectivity in AD
Authors: Pasquini Lorenzo , Scherr Martin , Tahmasian Masoud , Meng Chun , Myers Nicholas E. , Ortner Marion , Mühlau Mark , Kurz Alexander , Förstl Hans , Zimmer Claus , Grimmer Timo , Wohlschläger Afra M. , Riedl Valentin , Sorg Christian
Published: July 2014

Background

The hippocampus (HP) is part of the default mode network (DMN), and both are key targets of Alzheimer's disease (AD). Because of widespread network degeneration, it has been suggested that increasing HP disconnection from the DMN may lead to progressive disinhibition of intra‐HP synchronized activity.

Methods

To analyze HP local (i.e., within HP) and global (i.e., within DMN) intrinsic functional connectivity (local/global intrinsic functional connectivity [iFC]), healthy controls and patients with mild cognitive impairment and AD dementia were assessed by spatial high and normal resolution resting‐state functional magnetic resonance imaging.

Results

Although patients' parietal local‐iFC was reduced and positively correlated with reduced global‐iFC within the DMN, HP local connectivity was progressively increased and negatively correlated with HP decreased global connectivity. Increased intra‐HP connectivity was associated with impaired memory.

Conclusion

Our result demonstrates a link between increased local and reduced global hippocampal connectivity in AD. Increased intra‐HP synchrony may contribute to distinct symptoms such as memory impairment or more speculatively epileptic seizure.
Selective activity over a constitutively active RET‐variant of the oral multikinase inhibitor dovitinib: Results of the CNIO‐BR002 phase I‐trial
Authors: Quintela-Fandino Miguel , Bueno Maria J. , Lombardia Luis , Gil Marta , Gonzalez-Martin Antonio , Marquez Raul , Bratos Raquel , Guerra Juan , Tan Eugene , Lopez Antonio , Colomer Ramon , Salazar Ramon
Published: July 2014

Background

Given our preclinical data showing synergy between dovitinib and paclitaxel in preclinical models we conducted this phase I trial aiming to define the recommended phase II‐dose (RP2D) on the basis of toxicity and pharmacodynamic criteria while searching for genetic variants that could sensitize patients to the regimen under study.

Patients and methods

A 3+3 escalation schedule was adopted. Seriated FGF23 and dovitinib and paclitaxel pharmacokinetic profiles were determined along a single‐agent dovitinib “priming‐phase” followed by a dovitinib + paclitaxel combination phase. RECIST 1.1 criteria and NCI CTCAE V.4.0 were used. In fresh pre‐treatment tumor biopsy samples, FGFR1, 2 and 3 amplifications were revealed by FISH probes; 32 missense variants were genotyped in tumors and peripheral blood mononuclear cells with Taqman genotyping assays (FGFR1‐3 and RET). Constructs encoding for wild‐type and variant genes associated with clinical benefit were transfected into HEK‐293 cells for preclinical experiments checking constitutive activation and dovitinib sensitivity of the variants.

Results

twelve patients were recruited in three dose‐levels. At level 1B (200 mg dovitinib 5‐days‐on/2‐days‐off plus 60 mg/m 2‐week of paclitaxel) more than 50% FGF23 upregulation was observed and no dose‐limiting‐toxicities (DLTs) occurred. The most frequent toxicities were asthenia, neutropenia, nausea/vomiting and transaminitis. Two patients with progressive disease prior to trial inclusion achieved prolonged disease stabilization. Both had the germline variant G2071A in the RET gene, which led to constitutive activation of the protein product and Y‐905 phosphorylation, both in transfectants and in patients with the alteration. This variant was sensitive to dovitinib; in addition both patients experienced progression upon medication withdrawal.

Conclusions

Level 1B was the RP2D as it provided adequate pharmacodynamic exposure to dovitinib. The G2071A germline variant act as a genetic modifier that renders different tumors sensitive to dovitinib.
Biomechanical Deficiencies in Women with Semitendinosus‐Gracilis Anterior Cruciate Ligament Reconstruction During Drop Jumps
Authors: Ortiz Alexis , Capo‐Lugo Carmen E. , Venegas‐Rios Heidi L.
Published: July 2014

Objective

To compare landing mechanics and neuromuscular recruitment strategies between women with semitendinosus‐gracilis anterior cruciate ligament reconstruction (SG‐ACLr) and noninjured women during double‐ and single‐legged drop jumps.

Design

Cross‐sectional biomechanical study.

Setting

Single university‐based biomechanics laboratory.

Participants

Fourteen women 1‐5 years post–SG‐ACLr and 16 noninjured women participated in this study.

Methods

After anthropometric measurements, warm‐up, and familiarization procedures, participants performed 5 trials of a double‐ and single‐legged drop jumps.

Main Outcome Measurements

Dynamic knee valgus was measured as the distance between knee joints during the landing phase of the double‐leg drop jumps. Medial knee displacement was the outcome considered during the landing phase of the single‐leg drop jumps. For both drop jump tasks, neuromuscular recruitment was evaluated through rectified normalized electromyographic activity of the quadriceps and hamstrings (amplitude and latency), and quadriceps/hamstrings electromyographic co‐contraction ratio.

Results

Although the SG‐ACLr group demonstrated a tendency toward a greater dynamic knee valgus during both drop jumps, these differences did not reach statistical significance. EMG data revealed different neuromuscular strategies for each group, depending on the specific jump.

Conclusions

These findings suggest that women with SG‐ACLr have a tendency toward greater dynamic knee valgus that could predispose to additional knee injuries. Rehabilitation specialists need to be aware of existing kinematic and neuromuscular deficiencies years after SG‐ACLr. Taking this into consideration will aid in prescribing appropriate interventions designed to prevent re‐injury.
Sensory and Motor Thresholds of Transcutaneous Electrical Stimulation Are Influenced by Gender and Age
Authors: de Jesus Guirro Rinaldo Roberto , de Oliveira Guirro Elaine Caldeira , de Sousa Natanael Teixeira Alves
Published: July 2014

Background

Transcutaneous electrical stimulation (ES) is a therapeutic procedure used in rehabilitation. However, the effectiveness of it depends on sensory responses to pain and motor control in neuromuscular recruitment, considering the differences related to gender and age of the subjects treated, as well as the intensity and frequency of ES.

Objective

To determine the threshold of sensory perception (TSP) and the threshold of motor response (TMR) in young and elderly individuals of both genders.

Design

Randomized controlled clinical trial.

Setting

General community.

Participants

Eighty volunteers with no history of systemic diseases were selected to participate in the study: 40 men and 40 women were subdivided by convenience sampling and age group into young male and female (age 21.6 ± 2.4 years) groups as well as into elderly female and male groups (age 72.6 ± 6.1 years).

Interventions

The participants received electrical stimulation (ES) at 5 and 50 Hz, with pulse durations of 20, 100, 400, 1000, and 3000 μs applied on the flexor muscle bellies of the wrist and fingers.

Main Outcome Measures

TSP was identified as the first sensation of increased current intensity and TMR as the minimum muscle contraction detected. The results were submitted to analysis of variance, followed by the Tukey's test, with a significance level of 5%.

Results

TSP was lower than TMR for all pulse durations, regardless of gender and age. In women, TSP was lower than that in young and elderly men at both frequencies. However, TSP was higher in elderly subjects than in younger subjects at 50 Hz for both genders. Age also affected the TMR, presenting higher thresholds in elderly subjects of both genders at 50 Hz; however the same occurred only in male subjects at 5 Hz.

Conclusion

Age and gender interfere directly with ES. These variables should be considered during rehabilitation because they indicate that electrical stimulation in elderly women should be carefully performed, as they have lower thresholds than elderly men when polarized currents are used, and there is a risk of skin lesion because of their high thresholds.
ANNUITIZATION BEHAVIOR: TAX INCENTIVES VS. PRODUCT DESIGN
Authors: Kling Alexander , Richter Andreas , Ruß Jochen
Published: July 2014

We analyze and compare the impact of tax incentives and of introducing enhanced annuities on annuitization behavior considering heterogeneity among the insured. We find that tax incentives for annuitization result in a significant increase of the portion of people who should annuitize and also an increase of the insurer's profit since less healthy individuals also annuitize, i.e. adverse selection is reduced. However, the problem that different insured receive a different value for money is even increased by tax incentives. If enhanced annuities are introduced, the percentage of insured who should annuitize further increases. Adverse selection is further reduced and the differences in value for money from annuitizing shrink.
Neo-Statecraft Theory, Historical Institutionalism and Institutional Change
Authors: James Toby S.
Published: July 2014

This article provides a critical examination of the contribution that statecraft theory, which has been subject to recent revision and development, makes to the literature on institutional change. It articulates an emergentneo-statecraft approach that offers an agent-led form of historical institutionalism. This overcomes the common criticism that historical institutionalists underplay the creative role of actors. The article also argues that the approach brings back into focus the imperatives of electoral politics as a source of institutional change and provides a macro theory of change which is also commonly missing from historical institutionalist work. It can therefore identify previously unnoticed sources of stability and change, especially in states with strong executives and top-down political cultures.