bluuebunny/crossref_metadata_2025 huggingface dataset:
CaMKIIδ and cardiomyocyte Ca2+ signalling new perspectives on splice variant targeting
Authors: Bell James R , Raaijmakers Antonia JA , Janssens Johannes V , Delbridge Lea MD
Published: September 2015

Control of cardiomyocyte cytosolic Ca2+ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca2+, Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca2+ channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca2+ levels promote the binding of a Ca2+/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca2+ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδB in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδC. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδB, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca2+ uptake and maintain cytosolic Ca2+ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.
Audit Pricing for Strategic Alliances: An Incomplete Contract Perspective
Authors: Demirkan Sebahattin , Zhou Nan
Published: September 2015

We study the pricing of audit services for strategic alliances, a governance structure involving an incomplete contract between separate firms. Since incomplete contracts do not specify all future contingencies, we expect that the nonverifiability of information and potential agency behavior in alliances increase audit complexity, resulting in higher audit fees. Our findings support this prediction. We then separate strategic alliances into joint ventures and contractual alliances, as the latter involve more complexity. We find that our audit fee results are largely driven by contractual alliances. We perform additional tests to rule out the concern that our audit fee results might be attributable to the impact of strategic alliances on distress risk, audit risk, or control risk. Contrary to the distress risk argument, we find that auditors arelesslikely to issue going‐concern modified opinions when there is an increase in strategic alliances. Contrary to the audit risk argument, we find that an increase in strategic alliances is unrelated to the likelihood of financial misstatements. Contrary to the control risk argument, we find that an increase in strategic alliances is unrelated to internal control weakness opinions.
CEO Overconfidence and Stock Price Crash Risk
Authors: Kim Jeong‐Bon , Wang Zheng , Zhang Liandong
Published: September 2015

This study examines the association between chief executive officer (CEO) overconfidence and future stock price crash risk. Overconfident managers overestimate the returns to their investment projects and misperceive negative net present value (NPV) projects as value creating. They also tend to ignore or explain away privately observed negative feedback. As a result, negative NPV projects are kept for too long and their bad performance accumulates, which can lead to stock price crashes. Using a large sample of firms for the period 1993–2010, we find that firms with overconfident CEOs have higher stock price crash risk than firms with nonoverconfident CEOs. The impact of managerial overconfidence on crash risk is more pronounced when the CEO is more dominant in the top management team and when there are greater differences of opinion among investors. Finally, it appears that the effect of CEO overconfidence on crash risk is less pronounced for firms with more conservative accounting policies.
Two new types of allergens from the cockroach, Periplaneta americana
Authors: Fang Y. , Long C. , Bai X. , Liu W. , Rong M. , Lai R. , An S.
Published: September 2015

Periplaneta americana cockroach is an important source of inhalant indoor allergen resource, and there are more than twenty IgE‐binding components identified in P. americana, but only nine allergens were characterized. Our knowledge about cockroach allergens remains poor. In this work, two novel allergen proteins Per a 11 (alpha‐amylase) and Per a 12 (chitinase) with molecular weight around 55 and 45 kDa, respectively, were purified and characterized from the midgut of cockroaches. Their primary sequences were determined by Edman degradation, mass spectrometry, and cDNA cloning. Sera from 39 and 30 of 47 (83.0% and 63.8%) patients reacted to Per a 11 and Per a 12 on immunoblots, respectively. The allergenicity of Per a 11 and Per a 12 was further confirmed by competitive ELISA, basophil activation test (BAT), and skin prick test (SPT). They appear to be of importance for the allergic reactions induced by cockroach and have a potential for component‐based diagnosis of allergy.
Synthesis, In vitro and Docking Studies of New Flavone Ethers as α‐Glucosidase Inhibitors
Authors: Imran Syahrul , Taha Muhammad , Ismail Nor Hadiani , Kashif Syed Muhammad , Rahim Fazal , Jamil Waqas , Wahab Habibah , Khan Khalid Mohammed
Published: September 2015

We report herein the synthesis, α‐glucosidase inhibition and docking studies for a series of 3–15 new flavones. A simple nucleophilic substitution reaction takes place between 3′hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3′hydroxyflavone (2) and the newly synthesized flavones (3–15) were being evaluated for their ability to inhibit activity of α‐glucosidase. Compounds 2, 3, 5, 7–10 and 13 showed good inhibitory activity with IC50 values ranging between 1.26 and 36.44 μm as compared to acarbose (IC50 = 38.25 ± 0.12 μm). Compounds 5 (5.45 ± 0.08 μm), 7 (1.26 ± 0.01 μm) and 8 (8.66 ± 0.08 μm) showed excellent inhibitory activity, and this may be due to trifluoromethyl substitution that is common for these compounds. Compound 7, a 2,5‐trifluoromethyl‐substituted compound, recorded the highest inhibition activity, and it is thirty times better than the standard drug. Docking studies for compound 7 suggest that both trifluoromethyl substituents are well positioned in a binding pocket surrounded by Phe300, Phe177, Phe157, Ala278, Asp68, Tyr71 and Asp214. The ability of compound 7 to interact with Tyr71 and Phe177 is extremely significant as they are found to be important for substrates recognition by α‐glucosidase.
Effects of dextromethorphan as add‐on to sitagliptin on blood glucose and serum insulin concentrations in individuals with type 2 diabetes mellitus: a randomized, placebo‐controlled, double‐blinded, multiple crossover, single‐dose clinical trial
Authors: Marquard J. , Stirban A. , Schliess F. , Sievers F. , Welters A. , Otter S. , Fischer A. , Wnendt S. , Meissner T. , Heise T. , Lammert E.
Published: September 2015

In this clinical trial, we investigated the blood glucose (BG)‐lowering effects of 30, 60 and 90 mg dextromethorphan (DXM) as well as 100 mg sitagliptin alone versus combinations of DXM and sitagliptin during an oral glucose tolerance test (OGTT) in 20 men with T2DM. The combination of 60 mg DXM plus 100 mg sitagliptin was observed to have the strongest effect in the OGTT. It lowered maximum BG concentrations and increased the baseline‐adjusted area under the curve for serum insulin concentrations in the first 30 min of the OGTT (mean ± standard deviation 240 ± 47 mg/dl and 8.1 ± 6.1 mU/l/h, respectively) to a significantly larger extent than did 100 mg sitagliptin alone (254 ± 50 mg/dl and 5.8 ± 2.5 mU/l/h, respectively; p < 0.05) and placebo (272 ± 49 mg/dl and 3.9 ± 3.0 mU/l/h, respectively; p < 0.001). All study drugs were well tolerated, alone and in combination, without serious adverse events or hypoglycaemia. Long‐term clinical trials are now warranted to investigate the potential of the combination of 30 or 60 mg DXM and dipeptidyl peptidase‐4 inhibitors in the treatment of individuals with T2DM, in particular as preclinical studies have identified the β‐cell protective properties of DXM.
Management of apposing, full‐thickness tracheal perforations in two horses
Authors: Gillen A. , Munsterman A. , Pinto N. , Caldwell F. , Wooldridge A. , Cuming R. , Hanson R.
Published: September 2015

Two horses, one 15‐year‐old Arabian gelding and one 10‐year‐old Quarter Horse gelding, presented with a history of marked subcutaneous emphysema. The first case exhibited no external wound, although there was a depression noted on the ventral neck. The second case had a laceration on the ventral aspect of the neck over the trachea. Endoscopic examination revealed both horses to have concurrent dorsal and ventral perforations of the trachea. The horses were managed by placing a short, cuffed, J‐shaped tracheostomy tube in the ventral perforation, while the dorsal perforation healed. The dorsal perforation in the first horse was allowed to heal by second intention, whereas sutures were placed in the dorsal perforation in the second case to reduce the healing time. Both horses were maintained on oral antimicrobial and nonsteroidal anti‐inflammatory medications throughout treatment. The dorsal perforation healed after 13 days in the first horse, and 22 days in the second horse. The ventral perforation healed in both horses by second intention following tracheostomy removal, giving a cosmetically acceptable result. In addition to facilitating tracheal healing, the tracheostomy tubes prevented the progression of subcutaneous emphysema, and promoted its resolution.
Temporary right recurrent laryngeal neuropathy in a horse associated with a left prosthetic laryngoplasty procedure
Authors: Canada N. C. , McNally T. P. , Slone D. E. , Clark C. K.
Published: September 2015

Right recurrent laryngeal neuropathy (RLN) is an uncommon, acquired disease for which the aetiology can frequently be diagnosed. Numerous aetiologies have been proposed for right‐sidedRLNwhich comprises 2% of all cases ofRLN. In this report we discuss the clinical course, treatment and outcome following right‐sided laryngeal paralysis as a complication of left‐sided prosthetic laryngoplasty in a horse. To the authors' knowledge, this is the first report of such a surgical complication.
Contrast radiography in the equine orthopaedic case
Authors: Barker W. H. J.
Published: September 2015

Routine contrast radiography has a valuable role in equine orthopaedics, providing additional information to standard radiography. However, ultrasonography provides additional information with respect to soft tissue pathology not appreciable when using contrast radiography alone, particularly in the investigation of synovial sepsis, ligament and tendon pathology, and osteochondral defects. The benefits of contrast media in more advanced imaging modalities such as computed tomography are just being recognised clinically.
Granulosa cell tumours in the mare: A review of 52 cases
Authors: Sherlock C. E. , Lott‐Ellis K. , Bergren A. , Withers J. M. , Fews D. , Mair T. S.
Published: September 2015

Granulosa cell tumour (GCT) is reported to be the most common ovarian neoplasm in the mare. A multicentre retrospective study evaluating the medical records of horses undergoing ovariectomy for treatment of aGCTwas undertaken, documenting the presenting clinicopathological features, treatment and outcome. Follow‐up information was obtained by telephone questionnaire. Fifty‐two mares were included. Most presented with behavioural/reproductive abnormalities, including stallion‐like behaviour (50%), aggression (31%), prolonged oestrus or nymphomania (19%), and persistent anoestrus (8%). Most (93%) affected ovaries had a multilocular appearance when examined ultrasonographically. Only 60% of horses with histopathologically confirmedGCTs demonstrated elevations in serum inhibin concentrations. Twenty‐five percent of horses had histopathologically confirmed bilateralGCTs. Ninety‐four percent of horses that underwent ovariectomy were discharged from the hospital. Standing laparoscopic ovariectomies had a lower complication rate (34%) than other surgical methods. Long‐term complications were uncommon (11%). In conclusion, histopathologically confirmedGCTs can occur in the presence of normal serum inhibin concentrations. The high prevalence of bilateralGCTs indicates that thorough evaluation of the contralateral ovary is necessary. Surgical ovariectomy for treatment ofGCTs has favourable short‐ and long‐term outcomes. Standing laparoscopic ovariectomy may be associated with a lower complication rate than other surgical methods.
Saphenous vein graft aneurysm fistula formation causing right heart failure: an unusual presentation
Authors: Boon K. J. , Arshad M. A. , Singh H. , Lainchbury J. G. , Blake J. W. H.
Published: September 2015

Saphenous vein graft aneurysm (SVG) formation after coronary artery bypass grafting is a rare complication of the surgery. We present a case of a 68‐year‐old man with an unusual presentation of such an aneurysm. Thirty‐four years after his initial bypass surgery, the patient presented with a fistula formation into his right atrium from a vein graft aneurysm. Late aneurysm formation is thought to occur secondary to atherosclerotic degeneration of the SVG with background hypertension and dyslipidaemia accelerating the process. Diagnostic modalities used to investigate SVG aneurysms include computed tomography, transthoracic echocardiogram, magnetic resonance imaging and cardiac catheterisation. Aneurysms with fistula formation historically require aggressive surgical intervention. Resection of the aneurysm with subsequent revascularisation if required is the surgical norm. SVG aneurysm with fistula formation into a cardiac chamber is a rare complication of coronary artery bypass grafting (CABG), which can occur with atypical presenting symptoms. Physicians should keep in mind the possibility of this occurring in post‐CABG patients presenting with heart failure and a new murmur.
Growth and Distribution in Heterodox Models with Managers and Financiers
Authors: Krishna Dutt Amitava
Published: September 2015

Heterodox models of income distribution and growth generally have two classes: workers and capitalists. However, recent discussions of inequality have drawn attention to changes in income distribution due to wage inequality and to an increase in the income and wealth of the top income group. To take these changes into account, this paper uses a simple two‐group framework to develop simple classical‐Marxian and post‐Keynesian‐Kaleckian models, in which one group consists of production workers who also own capital and another group consists of managers and financiers, as well as traditional capitalists, to analyze the determinants and growth implications of distributional changes.
The bifurcation of the cyanogenic glucoside and glucosinolate biosynthetic pathways
Authors: Clausen Mette , Kannangara Rubini M. , Olsen Carl E. , Blomstedt Cecilia K. , Gleadow Roslyn M. , Jørgensen Kirsten , Bak Søren , Motawie Mohammed S. , Møller Birger Lindberg
Published: September 2015

The biosynthetic pathway for the cyanogenic glucoside dhurrin in sorghum has previously been shown to involve the sequential production of (E)‐ and (Z)‐p‐hydroxyphenylacetaldoxime. In this study we used microsomes prepared from wild‐type and mutant sorghum or transiently transformed Nicotiana benthamiana to demonstrate that CYP79A1 catalyzes conversion of tyrosine to (E)‐p‐hydroxyphenylacetaldoxime whereas CYP71E1 catalyzes conversion of (E)‐p‐hydroxyphenylacetaldoxime into the corresponding geometrical Z‐isomer as required for its dehydration into a nitrile, the next intermediate in cyanogenic glucoside synthesis. Glucosinolate biosynthesis is also initiated by the action of a CYP79 family enzyme, but the next enzyme involved belongs to the CYP83 family. We demonstrate that CYP83B1 from Arabidopsis thaliana cannot convert the (E)‐p‐hydroxyphenylacetaldoxime to the (Z)‐isomer, which blocks the route towards cyanogenic glucoside synthesis. Instead CYP83B1 catalyzes the conversion of the (E)‐p‐hydroxyphenylacetaldoxime into an S‐alkyl‐thiohydroximate with retention of the configuration of the E‐oxime intermediate in the final glucosinolate core structure. Numerous microbial plant pathogens are able to detoxify Z‐oximes but not E‐oximes. The CYP79‐derived E‐oximes may play an important role in plant defense.
ZmZHOUPI, an endosperm‐specific basic helix–loop–helix transcription factor involved in maize seed development
Authors: Grimault Aurélie , Gendrot Ghislaine , Chamot Sophy , Widiez Thomas , Rabillé Hervé , Gérentes Marie‐France , Creff Audrey , Thévenin Johanne , Dubreucq Bertrand , Ingram Gwyneth C. , Rogowsky Peter M. , Depège‐Fargeix Nathalie
Published: September 2015

In angiosperm seeds the embryo is embedded within the endosperm, which is in turn enveloped by the seed coat, making inter‐compartmental communication essential for coordinated seed growth. In this context the basic helix–loop–helix domain transcription factor AtZHOUPI (AtZOU) fulfils a key role in both the lysis of the transient endosperm and in embryo cuticle formation in Arabidopsis thaliana. In maize (Zea mays), a cereal with a persistent endosperm, a single gene, ZmZOU, falls into the same phylogenetic clade as AtZOU. Its expression is limited to the endosperm where it peaks during the filling stage. In ZmZOU‐RNA interference knock‐down lines embryo size is slightly reduced and the embryonic suspensor and the adjacent embryo surrounding region show retarded breakdown. Ectopic expression of ZmZOU reduces stomatal number, possibly due to inappropriate protein interactions. ZmZOU forms functional heterodimers with AtICE/AtSCREAM and the closely related maize proteins ZmICEb and ZmICEc, but its interaction is more efficient with the ZmICEa protein, which shows sequence divergence and only has close homologues in other monocotyledonous species. Consistent with the observation that these complexes can trans‐activate target gene promoters from Arabidopsis, ZmZOU partially complements the Atzou‐4 mutant. However, structural, trans‐activation and gene expression data support the hypothesis that ZmZOU and ZmICEa may have coevolved to form a functional complex unique to monocot seeds. This divergence may explain the reduced functionality of ZmZOU in Arabidopsis, and reflect functional specificities which are unique to the monocotyledon lineage.
Dynamic spectrin/ankyrin-G microdomains promote lateral membrane assembly by opposing endocytosis
Authors: Jenkins Paul M. , He Meng , Bennett Vann
Published: September 2015

Locally dynamic micrometer-scale domains based on spectrin and ankyrin-G determine membrane identity by preventing endocytosis.
Near-IR squaraine dye–loaded gated periodic mesoporous organosilica for photo-oxidation of phenol in a continuous-flow device
Authors: Borah Parijat , Sreejith Sivaramapanicker , Anees Palapuravan , Menon Nishanth Venugopal , Kang Yuejun , Ajayaghosh Ayyappanpillai , Zhao Yanli
Published: September 2015

A study of dye-loaded organosilica for photo-oxidation.
Meta-analysis of the Effects of Sanitizing Treatments on Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes Inactivation in Fresh Produce
Authors: Prado-Silva Leonardo , Cadavez Vasco , Gonzales-Barron Ursula , Rezende Ana Carolina B. , Sant'Ana Anderson S.
Published: September 2015

The aim of this study was to perform a meta-analysis of the effects of sanitizing treatments of fresh produce on
Salmonella
spp.,
Escherichia coli
O157:H7, and
Listeria monocytogenes
. From 55 primary studies found to report on such effects, 40 were selected based on specific criteria, leading to more than 1,000 data on mean log reductions of these three bacterial pathogens impairing the safety of fresh produce. Data were partitioned to build three meta-analytical models that could allow the assessment of differences in mean log reductions among pathogens, fresh produce, and sanitizers. Moderating variables assessed in the meta-analytical models included type of fresh produce, type of sanitizer, concentration, and treatment time and temperature. Further, a proposal was done to classify the sanitizers according to bactericidal efficacy by means of a meta-analytical dendrogram. The results indicated that both time and temperature significantly affected the mean log reductions of the sanitizing treatment (
P
< 0.0001). In general, sanitizer treatments led to lower mean log reductions when applied to leafy greens (for example, 0.68 log reductions [0.00 to 1.37] achieved in lettuce) compared to other, nonleafy vegetables (for example, 3.04 mean log reductions [2.32 to 3.76] obtained for carrots). Among the pathogens,
E. coli
O157:H7 was more resistant to ozone (1.6 mean log reductions), while
L. monocytogenes
and
Salmonella
presented high resistance to organic acids, such as citric acid, acetic acid, and lactic acid (∼3.0 mean log reductions). With regard to the sanitizers, it has been found that slightly acidic electrolyzed water, acidified sodium chlorite, and the gaseous chlorine dioxide clustered together, indicating that they possessed the strongest bactericidal effect. The results reported seem to be an important achievement for advancing the global understanding of the effectiveness of sanitizers for microbial safety of fresh produce.
Membrane-Associated Glucose-Methanol-Choline Oxidoreductase Family Enzymes PhcC and PhcD Are Essential for Enantioselective Catabolism of Dehydrodiconiferyl Alcohol
Authors: Takahashi Kenji , Hirose Yusaku , Kamimura Naofumi , Hishiyama Shojiro , Hara Hirofumi , Araki Takuma , Kasai Daisuke , Kajita Shinya , Katayama Yoshihiro , Fukuda Masao , Masai Eiji
Published: September 2015

Sphingobium
sp. strain SYK-6 is able to degrade various lignin-derived biaryls, including a phenylcoumaran-type compound, dehydrodiconiferyl alcohol (DCA). In SYK-6 cells, the alcohol group of the B-ring side chain of DCA is initially oxidized to the carboxyl group to generate 3-(2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl) acrylic acid (DCA-C). Next, the alcohol group of the A-ring side chain of DCA-C is oxidized to the carboxyl group, and then the resulting metabolite is catabolized through vanillin and 5-formylferulate. In this study, the genes involved in the conversion of DCA-C were identified and characterized. The DCA-C oxidation activities in SYK-6 were enhanced in the presence of flavin adenine dinucleotide and an artificial electron acceptor and were induced ca. 1.6-fold when the cells were grown with DCA. Based on these observations, SLG_09480 (
phcC
) and SLG_09500 (
phcD
), encoding glucose-methanol-choline oxidoreductase family proteins, were presumed to encode DCA-C oxidases. Analyses of
phcC
and
phcD
mutants indicated that PhcC and PhcD are essential for the conversion of (+)-DCA-C and (−)-DCA-C, respectively. When
phcC
and
phcD
were expressed in SYK-6 and
Escherichia coli
, the gene products were mainly observed in their membrane fractions. The membrane fractions of
E. coli
that expressed
phcC
and
phcD
catalyzed the specific conversion of DCA-C into the corresponding carboxyl derivatives. In the oxidation of DCA-C, PhcC and PhcD effectively utilized ubiquinone derivatives as electron acceptors. Furthermore, the transcription of a putative cytochrome
c
gene was significantly induced in SYK-6 grown with DCA. The DCA-C oxidation catalyzed by membrane-associated PhcC and PhcD appears to be coupled to the respiratory chain.
Assistive technologies for ageing populations in six low-income and middle-income countries: a systematic review
Authors: Marasinghe Keshini Madara , Lapitan Jostacio Moreno , Ross Alex
Published: September 2015

Despite the benefits derived from the use of assistive technologies (AT), some parts of the world have minimal or no access to AT. In many low-income and middle-income countries (LMIC), only 5–15% of people who require AT have access to them. Rapid demographic changes will exacerbate this situation as populations over 60 years of age, as well as functional limitations among older populations, in LMIC are expected to be higher than in high-income countries in the coming years. Given both these trends, AT are likely to be in high demand and provide many benefits to respond to challenges related to healthy and productive ageing. Multiple databases were searched for English literature. Three groups of keywords were combined: those relating to AT, ageing population and LMIC selected for this study, namely Brazil, Cambodia, Egypt, India, Turkey and Zimbabwe. These countries are expected to see the most rapid growth in the 65 and above population in the coming years. Results indicate that all countries had AT designed for older adults with existing impairment and disability, but had limited AT that are designed to prevent impairment and disability among older adults who do not currently have any disabilities. All countries have ratified the UN Convention on the Rights of Persons with Disabilities. The findings conclude that AT for ageing populations have received some attention in LMIC as attested by the limited literature results. Analysis of review findings indicate the need for a comprehensive, integrated health and social system approach to increase the current availability of AT for ageing populations in LMIC. These would entail, yet not be limited to, work on: (1) promoting initiatives for low-cost AT; (2) awareness raising and capacity building on AT; (3) bridging the gap between AT policy and practice; and (4) fostering targeted research on AT.
Long-term effect of physical activity on health-related quality of life among menopausal women: a 4-year follow-up study to a randomised controlled trial
Authors: Mansikkamäki Kirsi , Raitanen Jani , Nygård Clas-Håkan , Tomás Eija , Rutanen Reetta , Luoto Riitta
Published: September 2015

Objectives

The aim of the study was to explore the long-term effects of physical activity intervention on quality of life (QoL) 4 years after an original randomised controlled trial (RCT).

Design

Cohort study after an RCT.

Setting

95 of the 159 women from the original RCT participated in weight, height and waist circumference measurements, performed the UKK 2 km Walk Test and completed the SF-36 Health Survey questionnaire. Multilevel mixed regression models were performed in order to compare the original and current group in an RCT setting.

Participants

There were 159 participants in the original RCT; 2.5 years later, 102 of the women responded to a questionnaire and 4-year after the trial, there were 95 respondents. The inclusion criteria in the original RCT were: being symptomatic, experiencing daily hot flushes, age between 40 and 63 years, not using hormone therapy now or in the past 3 months, sedentary lifestyle and having last menstruated 3–36 months earlier.

Main outcome measure

Health-related QoL as measured with the SF-36 instrument.

Results

Women in the intervention group had a significantly higher probability of improved physical functioning (OR 1.41; 95% CI 1.00 to 1.99) as compared with women in the control group. In addition, women in the intervention group had higher odds of good role functioning (OR 1.21; 95% CI 0.88 to 1.67), physical health (OR 1.33; 95% CI 0.96 to 1.84) and general health (OR 1.14; 95% CI 0.81 to 1.62), relative to women in the control group, although the differences did not reach statistical significance.

Conclusions

Women in the intervention group showed positive long-term effects on physical and mental dimensions of QoL after 4 years.

Trial registration number

ISRCTN54690027.
Confirmation of suboptimal protocols in spinal immobilisation?
Authors: Dixon Mark , O'Halloran Joseph , Hannigan Ailish , Keenan Scott , Cummins Niamh M
Published: September 2015

Background

Spinal immobilisation during extrication of patients in road traffic collisions is routinely used despite the lack of evidence for this practice. In a previous proof of concept study (n=1), we recorded up to four times more cervical spine movement during extrication using conventional techniques than self-controlled extrication.

Objective

The objective of this study was to establish, using biomechanical analysis which technique provides the minimal deviation of the cervical spine from the neutral in-line position during extrication from a vehicle in a larger sample of variable age, height and mass.

Methods

A crew of two paramedics and four fire-fighters extricated 16 immobilised participants from a vehicle using six techniques for each participant. Participants were marked with biomechanical sensors and relative movement between the sensors was captured via high-speed infrared motion analysis cameras. A three-dimensional mathematical model was developed and a repeated-measures analysis of variance was used to compare movement across extrication techniques.

Results

Controlled self-extrication without a collar resulted in a mean movement of 13.33° from the neutral in-line position of the cervical spine compared to a mean movement of 18.84° during one of the equipment-aided extrications. Two equipment-aided techniques had significantly higher movement (p<0.05) than other techniques. Both height (p=0.003) and mass (p=0.02) of the participants were significant independent predictors of movement.

Conclusions

These data support the findings of the proof of concept study, for haemodynamically stable patients controlled self-extrication causes less movement of the cervical spine than extrications performed using traditional prehospital rescue equipment.
Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198
Authors: Molenaar Remco J. , Botman Dennis , Smits Myrthe A. , Hira Vashendriya V. , van Lith Sanne A. , Stap Jan , Henneman Peter , Khurshed Mohammed , Lenting Krissie , Mul Adri N. , Dimitrakopoulou Dionysia , van Drunen Cornelis M. , Hoebe Ron A. , Radivoyevitch Tomas , Wilmink Johanna W. , Maciejewski Jaroslaw P. , Vandertop W. Peter , Leenders William P. , Bleeker Fonnet E. , van Noorden Cornelis J.
Published: September 2015

Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1R132H, a structural alteration that leads to catalysis of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. In this study, we present evidence that small-molecule inhibitors of IDH1R132H that are being developed for cancer therapy may pose risks with coadministration of radiotherapy. Cancer cells heterozygous for the IDH1R132H mutation exhibited less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there were higher levels of reactive oxygen species, DNA double-strand breaks, and cell death compared with IDH1 wild-type cells. These effects were reversed by the IDH1R132H inhibitor AGI-5198. Exposure of IDH1 wild-type cells to D-2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivity. Mechanistic investigations revealed that the radiosensitivity of heterozygous cells was independent of the well-described DNA hypermethylation phenotype in IDH1-mutated cancers. Thus, our results argue that altered oxidative stress responses are a plausible mechanism to understand the radiosensitivity of IDH1-mutated cancer cells. Further, they offer an explanation for the relatively longer survival of patients with IDH1-mutated tumors, and they imply that administration of IDH1R132H inhibitors in these patients may limit irradiation efficacy in this setting. Cancer Res; 75(22); 4790–802. ©2015 AACR.
Generation of a Mouse Model of Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System through Combined Deletion of Snf5 and p53
Authors: Ng Jessica M.Y. , Martinez Daniel , Marsh Eric D. , Zhang Zhe , Rappaport Eric , Santi Mariarita , Curran Tom
Published: September 2015

Malignant rhabdoid tumors arise in several anatomic locations and are associated with poor outcomes. In the brain, these tumors are known as atypical teratoid/rhabdoid tumors (AT/RT). While genetically engineered models for malignant rhabdoid tumors exist, none of them recapitulate AT/RT, for which preclinical models remain lacking. In the majority of AT/RT, LOH occurs at the genetic locus SNF5 (Ini1/BAF47/Smarcb1), which functions as a subunit of the SWI/SNF chromatin-remodeling complex and a tumor suppressor in familial and sporadic malignant rhabdoid tumors. Therefore, we generated mice in which Snf5 was ablated specifically in nestin-positive and/or glial fibrillary acid protein (GFAP)-positive progenitor cells of the developing central nervous system (CNS). Snf5 ablation in nestin-positive cells resulted in early lethality that could not be rescued by loss of p53. However, Snf5 ablation in GFAP-positive cells caused a neurodegenerative phenotype exacerbated by p53 loss. Notably, these double mutants exhibited AT/RT development, associated with an earlier failure in granule neuron migration in the cerebellum, reduced neuronal projections in the hippocampus, degeneration of the corpus callosum, and ataxia and seizures. Gene expression analysis confirmed that the tumors that arose in Snf5/p53 mutant mice were distinct from other neural tumors and most closely resembled human AT/RT. Our findings uncover a novel role for Snf5 in oligodendrocyte generation and survival, and they offer evidence of the first genetically engineered mouse model for AT/RT in the CNS. Cancer Res; 75(21); 4629–39. ©2015 AACR.
A TDO2-AhR Signaling Axis Facilitates Anoikis Resistance and Metastasis in Triple-Negative Breast Cancer
Authors: D'Amato Nicholas C. , Rogers Thomas J. , Gordon Michael A. , Greene Lisa I. , Cochrane Dawn R. , Spoelstra Nicole S. , Nemkov Travis G. , D'Alessandro Angelo , Hansen Kirk C. , Richer Jennifer K.
Published: September 2015

The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates of metastasis after diagnosis, relative to estrogen-positive breast cancers, but while TNBC cells are relatively more resistant to anoikis, the mechanisms involved are unclear. Through gene expression and metabolomic profiling of TNBC cells in forced suspension culture, we identified a molecular pathway critical for anchorage-independent cell survival. TNBC cells in suspension upregulated multiple genes in the kynurenine pathway of tryptophan catabolism, including the enzyme tryptophan 2,3-dioxygenase (TDO2), in an NF-κB–dependent manner. Kynurenine production mediated by TDO2 in TNBC cells was sufficient to activate aryl hydrocarbon receptor (AhR), an endogenous kynurenine receptor. Notably, pharmacologic inhibition or genetic attenuation of TDO2 or AhR increased cellular sensitivity to anoikis, and also reduced proliferation, migration, and invasion of TNBC cells. In vivo, TDO2 inhibitor–treated TNBC cells inhibited colonization of the lung, suggesting that TDO2 enhanced metastatic capacity. In clinical specimens of TNBC, elevated expression of TDO2 was associated with increased disease grade, estrogen receptor–negative status, and shorter overall survival. Our results define an NF-κB–regulated signaling axis that promotes anoikis resistance, suggest functional connections with inflammatory modulation by the kynurenine pathway, and highlight TDO2 as an attractive target for treatment of this aggressive breast cancer subtype. Cancer Res; 75(21); 4651–64. ©2015 AACR.
Zum Herkunftsort des Simon Magus
Authors: Scholten Clemens
Published: September 2015

The hometown of Simon Magus must not be a village in Samaria, but is perhaps the place of the old town of the Philistines Gittha in Idumaea.
Negotiating with Rebels
Authors: Heger Lindsay L. , Jung Danielle F.
Published: September 2015

When rebels provide social services, do they have more leverage negotiating the terms of a peace deal? The literature suggests service-providing groups may, on average, have a wider base of support and a more centralized organizational structure. We argue that these features deter potential spoilers from breaking away from the organization during negotiation processes. This, in turn, makes governments more willing to enter negotiations since the threat from spoilers is smaller. Thus, compared to nonproviders, service-providing rebels are more likely to engage in negotiations and these processes are likely to be more stable. This article analyzes these propositions by gathering service provision data on nearly 400 rebel groups and their involvement in and behavior during peace talks. It also serves as an introduction to a larger project about the implications of rebel service provision on conflict outcomes.
Fitness-scaling adaptive genetic algorithm with local search for solving the Multiple Depot Vehicle Routing Problem
Authors: Wang Shuihua , Lu Zeyuan , Wei Ling , Ji Genlin , Yang Jiquan
Published: September 2015

The multi-depot vehicle routing problem is a well-known non-deterministic polynomial-time hard combinatorial optimization problem, which is crucial for transportation and logistics systems. We proposed a novel fitness-scaling adaptive genetic algorithm with local search (FISAGALS). The fitness-scaling technique converts the raw fitness value to a new value that is suitable for selection. The adaptive rates strategy changes the crossover and mutation probabilities depending on the fitness value. The local search mechanism exploits the problem space in a more efficient way. The experiments employed 33 benchmark problems. Results showed the proposed FISAGALS is superior to the standard genetic algorithm, simulated annealing, tabu search, and particle swarm optimization in terms of success instances and computation time. Furthermore, FISAGALS performs better than parallel iterated tabu search (PITS) and fuzzy logic guided genetic algorithm (FLGA), and marginally worse than ILS-RVND-SP in terms of the maximum gap. It performs faster than PITS and ILS-RVND-SP (a combination of iterated local search framework [ILS], a variable neighborhood descent with random neighborhood ordering [RVND] and the the set partitioning [SP] model) and slower than FLGA. In summary, FISAGALS is a competitive method with state-of-the-art algorithms.
Facebook habits among adolescents
Authors: Öncü Semiral
Published: September 2015

Facebook is the most popular social network in most nations and in Turkey. It is argued that it can involve insecure behavior in adolescents. Teenagers in Turkey are to receive tablet computers nationwide through the FATIH project. Personal availability is likely to impact Internet and Facebook habits. Also, with lack of social support, teens might more intensely engage in Facebook. This study identifies teens who are more likely to perform less secure Facebook activities. A survey was conducted on 4,261 middle and high school students in Turkey. Logistic regressions were run to predict the likelihood of Facebook-related behaviors. Results showed that teens who perceive support from significant others, males, metropolitans, and teens who have more tablet computer opportunities, competencies and beliefs were more likely to engage in risky activities. Family support significantly reduced the likelihood of risky behaviors. Results call for promoting family support and monitoring tablet computer habits. Teens should be educated about social network threats and privacy.
Adaptive natural killer cell response to cytomegalovirus and disability progression in multiple sclerosis
Authors: Martínez-Rodríguez Jose E , Cobo-Calvo Alvaro , Villar Luisa M , Munteis Elvira , Blanco Yolanda , Rasal Raquel , Vera Andrea , Muntasell Aura , Alvarez-Lafuente Roberto , Saiz Albert , Alvarez-Cermeño Jose C , Martínez-Yélamos Sergio , Roquer Jaume , López-Botet Miguel
Published: September 2015

Background:

Human cytomegalovirus (HCMV) causes a highly prevalent infection which may have a multifaceted impact on chronic inflammatory disorders. However, its potential influence in multiple sclerosis (MS) remains controversial. The HCMV-host interaction may induce an adaptive reconfiguration of the natural killer (NK) cell compartment, whose hallmark is a persistent expansion of peripheral NKG2C+ NK-cells.

Objective:

The purpose of this study was to evaluate whether the HCMV-driven NKG2C+ NK-cell expansion is related to the MS clinical course.

Methods:

Multicentre analysis of NKG2C expression and genotype according to HCMV serostatus and time of assignment of irreversible disability scores in 246 MS patients prospectively followed up in our institutions.

Results:

NKG2C expression was unrelated to disease-modifying drugs, remained stable under steady-state conditions, and was higher in HCMV(+) NKG2C+/+ homozygous individuals. NKG2C+ NK-cell expansion in HCMV(+) patients, as compared to HCMV(+) or HCMV(–) patients with lower NKG2C+ NK-cells proportions, conferred a lower risk of progression in Cox regression analysis (Expanded Disability Status Scale (EDSS)>3.0, hazard ratio (HR)=0.33, 95% confidence interval (CI) 0.15–0.71, p=0.005; EDSS>5.5, HR=0.23, 95% CI 0.07-0.74, p=0.014). Neither HCMV serostatus nor NKG2C genotype appeared to be related to disability progression.

Conclusions:

HCMV may exert a beneficial influence on MS, decreasing the risk of disability progression in those patients displaying a virus-driven NKG2C+ NK-cell expansion.
Social justice and Internet technology
Authors: Christians Clifford G
Published: September 2015

This essay is the honorary “Steve Jones Internet Research Lecture” for 2015, presented at the International Communication Association meetings in San Juan, Puerto Rico on 23 May 2015. Internet technology is understood in social terms not just as tools. As a social/cultural phenomenon, the new media’s core ethical norm arguably becomes social justice. The global dynamics of the Internet system requires an international definition of justice as intrinsic worthiness, rather than the standard idea of justice as right-order legality determined by nation-state conventions. This understanding of justice is defended against relativism which claims that values are culture specific.
Judgments of Responsibility Versus Accountability
Authors: Brees Jeremy , Martinko Mark J.
Published: September 2015

We proposed and found that employees’ judgments of responsibility and accountability are distinct but positively related constructs. Using attribution theory for responsibility judgments and lay dispositionalism for accountability judgments, we hypothesized that employees hold others more responsible (i.e., causal) and accountable (i.e., punishable) than they hold themselves for the same workplace mistakes. Independent mean differences within a sample of 286 working adults revealed that people held others more responsible but not more accountable than they held themselves. Post hoc analyses revealed a counterintuitive finding. Counter to what theory would predict, as workplace mistake seriousness increased the variation between self-judgement and other-judgment decreased. Implications and future directions for accountability research are discussed.
The NYU Osteoporosis Model of Care Experience
Authors: Saxena Amit , Honig Stephen , Rivera Sonja , Pean Christian A. , Egol Kenneth A.
Published: September 2015

Introduction:

Participants who sustain a fragility fracture are at increased risk for subsequent fractures. Despite the consequences of recurrent fractures, bone mineral density (BMD) testing and treatment rates for osteoporosis after a fracture remain low. The New York University (NYU) Langone Osteoporosis Model of Care was developed to identify women at increased risk for recurrent fractures and to reduce the rates of subsequent fracture through patient and physician education.

Methods:

Women aged 50 years and older who had a fracture and received their care at NYU affiliated hospitals were contacted via mail after discharge. Participants were provided educational materials explaining decreased bone strength and its possible relationship to their fracture and were asked to complete a questionnaire. One year postfracture, participants were sent follow-up questionnaires requesting their most recent fracture treatment and BMD information. Educational material was also provided to the treating orthopedic surgeons.

Results:

Overall, 524 patients were contacted and 210 (40%) enrolled. By the end of 24 months, 92 participants completed their 1-year questionnaire (44% of the enrollees). Forty-two (46%) participants had undergone new BMD testing and 37 (40%) were receiving antiresorptive medications, including 6 (6%) who had not been prescribed these medications before enrolling in the program.

Conclusions:

The Osteoporosis Model of Care is a simple and cost-effective educational program, which improved comprehensive fracture care in an actual clinical setting. Patient enrollment remains a challenge in implementing the program. Our program highlights difficulties in providing community-dwelling participants with appropriate postfracture care. With increasing concern among the public regarding the use of bone strengthening medications and continued low postfracture treatment rates, educating patients with high fracture risk is critical to reducing the rate of subsequent fracture. Our Model of Care Program demonstrates both the success and limitations of a postfracture educational approach using discharge diagnosis data to identify patients with fracture.
Microstructure and mechanical properties of underwater friction taper plug weld on X65 steel with carbon and stainless steel plugs
Authors: Yin Y. , Yang X. , Cui L. , Cao J. , Xu W.
Published: September 2015

Underwater friction taper plug welding for X65 pipeline steel was performed using Q345 structural steel and 316L stainless steel plugs. Weld microstructures, defects formation and mechanical properties were investigated. Using Q345 plugs can produce defect free and overmatching welded joints whose impact toughness was also favourable. Lower bainite and lath martensite in the weld zone resulted in high hardness with maximum value up to 418 HV10. Using 316L plugs can significantly reduce weld zone hardness due to austenite dominated microstructure. Microcracks can easily emerge at and may propagate along γ–δ phase boundaries to form macrocracks. Intermittent cracks were found along the bonding interface of all the 316L plug welds, which should be caused by the relief of the residual stress.
HIV and the role of the HCA: raising awareness and breaking stigma
Authors: Bard Brigette
Published: September 2015

In the UK, 107 800 people have human immunodeficiency virus (HIV) and of these, some 26 400 are unaware they have contracted the virus. The symptoms of HIV are often invisible for years and, due mainly to misinformation and stigma, people who have contracted HIV do not come forward for testing and treatment, perhaps because they do not fully understand how the virus is transmitted or that they could have been exposed to it.

Healthcare assistants (HCAs) and assistant practitioners (APs) have a vital role to play in discussing HIV with patients and colleagues openly and honestly, raising awareness of HIV, educating communities and patients on the facts about HIV, discussing HIV testing options available with patients, if appropriate, and raising awareness about how advances in treatments have meant, as we like to say, HIV is no longer a death sentence.