bluuebunny/crossref_metadata_2025 huggingface dataset:
Are recent graduates enough prepared to perform obstetric skills in their rural and compulsory year? A study from Ecuador
Authors: Sánchez del Hierro Galo , Remmen Roy , Verhoeven Veronique , Van Royen Paul , Hendrickx Kristin
Published: August 2014

Objectives

The aim of this study was to assess the possible mismatch of obstetrical skills between the training offered in Ecuadorian medical schools and the tasks required for compulsory rural service.

Setting

Primary care, rural health centres in Southern Ecuador.

Participants

A total of 92 recent graduated medical doctors during their compulsory rural year.

Primary and secondary outcomes measures

A web-based survey was developed with 21 obstetrical skills. The questionnaire was sent to all rural doctors who work in Loja province, Southern Ecuador, at the Ministry of Health (n=92).

We measured two categories

‘importance of skills in rural practice’ with a five-point Likert-type scale (1= strongly disagree; 5= strongly agree); and ‘clerkship experience’ using a nominal scale divided in five levels: level 1 (not seen, not performed) to level 5 (performed 10 times or more). Spearman's rank correlation coefficient (r) was used to observe associations.

Results

A negative correlation was found in the skills: ‘episiotomy and repair’, ‘umbilical vein catheterisation’, ‘speculum examination’, ‘evaluation of cervical dilation during active labour’, ‘neonatal resuscitation’ and ‘vacuum-assisted vaginal delivery’. For instance ‘Episiotomy and repair’ is important (strongly agree and agree) to 100% of respondents, but in practice, only 38.9% of rural doctors performed the task three times and 8.3% only once during the internship, similar pattern is seen in the others.

Conclusions

In this study we have noted the gap between the medical needs of populations in rural areas and training provided during the clerkship experiences of physicians during their rural service year. It is imperative to ensure that rural doctors are appropriately trained and skilled in the performance of routine obstetrical duties. This will help to decrease perinatal morbidity and mortality in rural Ecuador.
DESIGN OF A FULLY INTEGRATED 2.4 GHz FREQUENCY PLL SYNTHESIZER FOR ZigBee TRANSCEIVER APPLICATION
Authors: LI DI , YANG YINTANG , ZHOU DUAN , LI YANI , WU XIAOPENG
Published: August 2014

A 2.4-GHz fully integrated frequency synthesizer is presented in this paper for Low-IF ZigBee (IEEE802.15.4) transceiver applications. The frequency synthesizer meets the system requirement of 2.4–2.4835 GHz frequency range with a frequency resolution of 5 MHz. The automatic-amplitude control (AAC) technique is employed for the voltage-controlled oscillator (VCO) which helps to optimize the output amplitude of the VCO over voltage, process and temperature variations. The chip has been fabricated in a 0.18 μm complementary metal oxide semiconductor (CMOS) process using a single poly layer, four metal layers and metal–insulator–metal (MIM) capacitors. The synthesized has a current dissipation of 4.7 mA from a 1.8 V power supply and occupies an area of 1 mm2 × 0.85 mm2. Measurement results show that the phase noise are -82 dBc/Hz–100 kHz offset and -109 dBc/Hz–1 MHz offset respectively.
Differentiability of spectral functions for nearly stable processes and large deviations
Authors: Tawara Yoshihiro , Tsuchida Kaneharu
Published: August 2014

We consider the differentiability of a spectral function generated by a Lévy process M with characteristic exponent |ξ|αl(|ξ|2), where l(x) is a slowly varying function at ∞. As an application, we obtain the large deviation principle for positive continuous additive functionals of M. Finally, we show that the exponent l(x) = ( log (1 + x))β/2 (0 < β < 2 - α) is an example for which our theorem is applicable.
Crowdsourced Monolingual Translation
Authors: Hu Chang , Resnik Philip , Bederson Benjamin B.
Published: August 2014

An enormous potential exists for solving certain classes of computational problems through rich collaboration among crowds of humans supported by computers. Solutions to these problems used to involve human professionals, who are expensive to hire or difficult to find. Despite significant advances, fully automatic systems still have much room for improvement. Recent research has involved recruiting large crowds of skilled humans (“crowdsourcing”), but crowdsourcing solutions are still restricted by the availability of those skilled human participants. With translation, for example, professional translators incur a high cost and are not always available; machine translation systems have been greatly improved recently but still can only provide passable translation; and crowdsourced translation is limited by the availability of bilingual humans.

This article describes crowdsourced monolingual translation, where monolingual translation is translation performed by monolingual people. Crowdsourced monolingual translation is a collaborative form of translation performed by two crowds of people who speak the source or the target language, respectively, with machine translation as the mediating device.

This article describes a general protocol to handle crowdsourced monolingual translation and analyzes three systems that implemented the protocol. These systems were studied in various settings and were found to supply significant improvement in quality over both machine translation and monolingual editing of machine translation output (“postediting”).
DRoP
Authors: Huffaker Bradley , Fomenkov Marina , claffy kc
Published: August 2014

In this paper we focus on geolocating Internet routers, using a methodology for extracting and decoding geography-related strings from fully qualified domain names (hostnames). We first compiled an extensive dictionary associating geographic strings (e.g., airport codes) with geophysical locations. We then searched a large set of router hostnames for these strings, assuming each autonomous naming domain uses geographic hints consistently within that domain. We used topology and performance data continually collected by our global measurement infrastructure to discern whether a given hint appears to co-locate different hostnames in which it is found. Finally, we generalized geolocation hints into domain-specific rule sets. We generated a total of 1,711 rules covering 1,398 different domains and validated them using domain-specific ground truth we gathered for six domains. Unlike previous efforts which relied on labor-intensive domain-specific manual analysis, we automate our process for inferring the domain specific heuristics, substantially advancing the state-of-the-art of methods for geolocating Internet resources.
XIA
Authors: Naylor David , Mukerjee Matthew K. , Agyapong Patrick , Grandl Robert , Kang Ruogu , Machado Michel , Brown Stephanie , Doucette Cody , Hsiao Hsu-Chun , Han Dongsu , Kim Tiffany Hyun-Jin , Lim Hyeontaek , Ovon Carol , Zhou Dong , Lee Soo Bum , Lin Yue-Hsun , Stuart Colleen , Barrett Daniel , Akella Aditya , Andersen David , Byers John , Dabbish Laura , Kaminsky Michael , Kiesler Sara , Peha Jon , Perrig Adrian , Seshan Srinivasan , Sirbu Marvin , Steenkiste Peter
Published: August 2014

Motivated by limitations in today's host-centric IP network, recent studies have proposed clean-slate network architectures centered around alternate first-class principals, such as content, services, or users. However, muchlike the host-centric IP design, elevating one principal type above others hinders communication between other principals and inhibits the network's capability to evolve. This paper presents the eXpressive Internet Architecture (XIA), an architecture with native support for multiple principals and the ability to evolve its functionality to accommodate new, as yet unforeseen, principals over time. We present the results of our ongoing research motivated by and building on the XIA architecture, ranging from topics at the physical level (``how fast can XIA go'') up through to the user level.
P4
Authors: Bosshart Pat , Daly Dan , Gibb Glen , Izzard Martin , McKeown Nick , Rexford Jennifer , Schlesinger Cole , Talayco Dan , Vahdat Amin , Varghese George , Walker David
Published: August 2014

P4 is a high-level language for programming protocol-independent packet processors. P4 works in conjunction with SDN control protocols like OpenFlow. In its current form, OpenFlow explicitly specifies protocol headers on which it operates. This set has grown from 12 to 41 fields in a few years, increasing the complexity of the specification while still not providing the flexibility to add new headers. In this paper we propose P4 as a strawman proposal for how OpenFlow should evolve in the future. We have three goals: (1) Reconfigurability in the field: Programmers should be able to change the way switches process packets once they are deployed. (2) Protocol independence: Switches should not be tied to any specific network protocols. (3) Target independence: Programmers should be able to describe packet-processing functionality independently of the specifics of the underlying hardware. As an example, we describe how to use P4 to configure a switch to add a new hierarchical label.
CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T-cell Checkpoint Immunotherapy in Pancreatic Cancer Models
Authors: Zhu Yu , Knolhoff Brett L. , Meyer Melissa A. , Nywening Timothy M. , West Brian L. , Luo Jingqin , Wang-Gillam Andrea , Goedegebuure S. Peter , Linehan David C. , DeNardo David G.
Published: August 2014

Cancer immunotherapy generally offers limited clinical benefit without coordinated strategies to mitigate the immunosuppressive nature of the tumor microenvironment. Critical drivers of immune escape in the tumor microenvironment include tumor-associated macrophages and myeloid-derived suppressor cells, which not only mediate immune suppression, but also promote metastatic dissemination and impart resistance to cytotoxic therapies. Thus, strategies to ablate the effects of these myeloid cell populations may offer great therapeutic potential. In this report, we demonstrate in a mouse model of pancreatic ductal adenocarcinoma (PDAC) that inhibiting signaling by the myeloid growth factor receptor CSF1R can functionally reprogram macrophage responses that enhance antigen presentation and productive antitumor T-cell responses. Investigations of this response revealed that CSF1R blockade also upregulated T-cell checkpoint molecules, including PDL1 and CTLA4, thereby restraining beneficial therapeutic effects. We found that PD1 and CTLA4 antagonists showed limited efficacy as single agents to restrain PDAC growth, but that combining these agents with CSF1R blockade potently elicited tumor regressions, even in larger established tumors. Taken together, our findings provide a rationale to reprogram immunosuppressive myeloid cell populations in the tumor microenvironment under conditions that can significantly empower the therapeutic effects of checkpoint-based immunotherapeutics. Cancer Res; 74(18); 5057–69. ©2014 AACR.
Serum 25-Hydroxyvitamin D Concentrations and Risk of Prostate Cancer: Results from the Prostate Cancer Prevention Trial
Authors: Schenk Jeannette M. , Till Cathee A. , Tangen Catherine M. , Goodman Phyllis J. , Song Xiaoling , Torkko Kathleen C. , Kristal Alan R. , Peters Ulrike , Neuhouser Marian L.
Published: August 2014

Background: Epidemiologic studies have reported inconsistent associations of vitamin D and prostate cancer risk; however, few have adequately controlled for detection bias related to prostate-specific antigen (PSA) screening, and the results of many studies may be affected by occult prostate cancers among controls.

Methods: Data for this nested case–control analysis (n = 1,695 cases/1,682 controls) are from the Prostate Cancer Prevention Trial. Baseline serum was analyzed for 25-hydroxyvitamin D [25(OH)D]. The presence or absence of cancer was subsequently determined by prostate biopsy. Polytomous logistic regression models were used to estimate associations of 25(OH)D with risk of total, Gleason 2–6, Gleason 7, and Gleason 8–10 prostate cancer. Results are presented for placebo and finasteride arms separately and combined.

Results: There were no associations of serum 25(OH)D with total prostate cancer risk. For Gleason 2–6 cancers, results were inconsistent across treatment arms with a suggestion of increased risk in the placebo arm only; however, there was no dose–response relationship. For Gleason 8–10 prostate cancers, 25(OH)D concentrations were associated with a linear decrease in risk among combined treatment arms [quartile 4 vs. 1: OR, 0.55; 95% confidence interval (CI), 0.32–0.94; Ptrend = 0.04]. These findings were somewhat stronger among men ≥65 versus 55–64 years at baseline (quartile 4 vs. 1: OR, 0.40; 95% CI, 0.18–0.88 vs. OR, 0.73; 95% CI, 0.35–1.52, respectively; Pinteraction = 0.52).

Conclusions: Higher serum 25(OH)D may modestly increase risk of Gleason 2–6 disease and more substantially reduce risk of Gleason 8–10 prostate cancer.

Impact: Vitamin D may have different effects for different stages of prostate cancers. Cancer Epidemiol Biomarkers Prev; 23(8); 1484–93. ©2014 AACR.
Calpain-Mediated Integrin Deregulation as a Novel Mode of Action for the Anticancer Gallium Compound KP46
Authors: Jungwirth Ute , Gojo Johannes , Tuder Theresa , Walko Gernot , Holcmann Martin , Schöfl Thomas , Nowikovsky Karin , Wilfinger Nastasia , Schoonhoven Sushilla , Kowol Christian R. , Lemmens-Gruber Rosa , Heffeter Petra , Keppler Bernhard K. , Berger Walter
Published: August 2014

On the basis of enhanced tumor accumulation and bone affinity, gallium compounds are under development as anticancer and antimetastatic agents. In this study, we analyzed molecular targets of one of the lead anticancer gallium complexes [KP46, Tris(8-quinolinolato)gallium(III)] focusing on colon and lung cancer. Within a few hours, KP46 treatment at low micromolar concentrations induced cell body contraction and loss of adhesion followed by prompt cell decomposition. This rapid KP46-induced cell death lacked classic apoptotic features and was insensitive toward a pan–caspase inhibitor. Surprisingly, however, it was accompanied by upregulation of proapoptotic Bcl-2 family members. Furthermore, a Bax- but not a p53-knockout HCT-116 subline exhibited significant KP46 resistance. Rapid KP46-induced detachment was accompanied by downregulation of focal adhesion proteins, including several integrin subunits. Loss of integrin-β1 and talin plasma membrane localization corresponded to reduced binding of RGD (Arg–Gly–Asp) peptides to KP46-treated cells. Accordingly, KP46-induced cell death and destabilization of integrins were enhanced by culture on collagen type I, a major integrin ligand. In contrast, KP46-mediated adhesion defects were partially rescued by Mg2+ ions, promoting integrin-mediated cell adhesion. Focal adhesion dynamics are regulated by calpains via cleavage of multiple cell adhesion molecules. Cotreatment with the cell-permeable calpain inhibitor PD150606 diminished KP46-mediated integrin destabilization and rapid cell death induction. KP46 treatment distinctly inhibited HCT-116 colon cancer xenograft in vivo by causing reduced integrin plasma membrane localization, tissue disintegration, and intense tumor necrosis. This study identifies integrin deregulation via a calpain-mediated mechanism as a novel mode of action for the anticancer gallium compound KP46. Mol Cancer Ther; 13(10); 2436–49. ©2014 AACR.
Nanolipolee-007, a Novel Nanoparticle-Based Drug Containing Leelamine for the Treatment of Melanoma
Authors: Gowda Raghavendra , Madhunapantula SubbaRao V. , Sharma Arati , Kuzu Omer F. , Robertson Gavin P.
Published: August 2014

Malignant melanoma is a difficult cancer to treat due to the rapid development of resistance to drugs targeting single proteins. One response to this observation is to identify single pharmacologic agents that, due to a unique mechanism of action, simultaneously target multiple key pathways involved in melanoma development. Leelamine has been identified as functioning in this manner but has poor bioavailability in animals and causes lethality when administered intravenously. Therefore, a nanoliposomal-based delivery system has been developed, called Nanolipolee-007, which stably loads 60% of the compound. The nanoparticle was as effective at killing melanoma cells as leelamine dissolved in DMSO and was more effective at killing cultured melanoma compared with normal cells. Mechanistically, Nanolipolee-007 inhibited PI3K/Akt, STAT3, and MAPK signaling mediated through inhibition of cholesterol transport. Nanolipolee-007 inhibited the growth of preexisting xenografted melanoma tumors by an average of 64% by decreasing cellular proliferation, reducing tumor vascularization, and increasing cellular apoptosis, with negligible toxicity. Thus, a unique clinically viable nanoparticle-based drug has been developed containing leelamine for the treatment of melanoma that acts by inhibiting the activity of major signaling pathways regulating the development of this disease. Mol Cancer Ther; 13(10); 2328–40. ©2014 AACR.
Informal Transactions with the Police
Authors: Voorhoeve Maaike
Published: August 2014

This article examines the intersection between, on the one hand, informal transactions with the police and, on the other, ‘sex crimes.’ Although prohibited by law, informal transactions have not been eradicated from the dealing between the police and civilians in Tunisia. Such transactions take place in case people have violated the law, but also, as this paper shows, when people have committed a ‘crime’ that is not described by legislation. In these cases, extra-legislative, informal norms are at play in two ways: the informal norm prescribing ‘paying off’ the police officer, and the informal norm prohibiting a certain dealing between the sexes. By describing the workings of such transactions in detail, this article presents an insight in what Blundo and De Sardan call the ‘état du quotidien’ in Tunisia under the authoritarian regime.
A new variety of Musa balbisiana Colla (Musaceae) from South India
Authors: JOE ALFRED , SREEJITH P. E. , SABU MAMIYIL
Published: August 2014

Musa balbisiana var. elavazhai, a new variety from South India is described here. A detailed description and photographs are provided for the easy identification of the variety.
Two new species of Syrphidae (Diptera) from Chukotka (Northern Russian Far East)
Authors: BARKALOV ANATOLIJ V. , MUTIN VALERIJ A.
Published: August 2014

Two new species, Platycheirus beringiensis sp. n. and Cheilosia chukotana sp. n., are described from Chukotka (northern part of Russian Far East). The new Platycheirus is close to Platycheirus immarginatus (Zetterstedt), but differing by the following characters: fore tibia with a black stripe on posterior side; mid-femur without fine black curved hairs directed to the base of the femur; mid-tibia without long anteroventral hairs; abdomen black with fine brownish lustre on tergites. The new Cheilosia species is close to Ch. semifasciata Becker, but differs by its characteristic sharply raised central knob, and by lack of transversal stripe and indentation in anterior third of frons.
The Political Resource Curse
Authors: Wiens David , Poast Paul , Clark William Roberts
Published: August 2014

Extant theoretical work on the political resource curse implies that dependence on resource revenues should decrease autocracies’ likelihood of democratizing but not necessarily affect democracies’ chances of survival. Yet most previous empirical studies estimate models that are ill-suited to address this claim. We improve upon previous studies, estimating a dynamic logit model using data from 166 countries, covering the period from 1816 to 2006. We find that an increase in resource dependence decreases an autocracy’s likelihood of being democratic over both the short term and long term but has no appreciable effect on democracies’ likelihood of persisting.
Big Data and Small: Collaborations between ethnographers and data scientists
Authors: Ford Heather
Published: August 2014

In the past three years, Heather Ford—an ethnographer and now a PhD student—has worked on ad hoc collaborative projects around Wikipedia sources with two data scientists from Minnesota, Dave Musicant and Shilad Sen. In this essay, she talks about how the three met, how they worked together, and what they gained from the experience. Three themes became apparent through their collaboration: that data scientists and ethnographers have much in common, that their skills are complementary, and that discovering the data together rather than compartmentalizing research activities was key to their success.
Nanotubular oxide layers and hydroxyapatite coatings on ‘Ti–13Zr–13Nb’ alloy
Authors: Zieliński A. , Antoniuk P. , Krzysztofowicz K.
Published: August 2014

The presented research was aimed to determine the mechanical properties of the nanotubular oxide layer covered with hydroxyapatite coating. The Ti–13Zr–13Nb alloy was oxidised in 1M phosphoric acid with an addition of 0·5% HF for HF solution at 20 V voltage. The electrochemically assisted deposition of hydroxyapatite was performed at cyclic polarisation in NH4H2PO4 and CaCl2 solution at 80°C. The mechanical properties were determined by nanoindentation, nanocreep and nanoscratch tests. The surface examinations were made with the light, scanning electron and atomic force microscopes. The measurements showed the significant difference between an oxide layer and nanotubular oxide coated with hydroxyapatite. The observed differences may be explained by an appearance of mechanically strong oxide layer, to which the ceramic hydroxyapatite layer is not tightly bound. The obtained results suggest that the nanotubular oxide layers should be covered with nanohydroxyapatite coatings, which would come inside the nanotubes resulting in better adhesion.
Fatigue strength of USP treated ASTM CA6NM for hydraulic turbine runner
Authors: Arakawa J. , Kakuta M. , Hayashi Y. , Tanegashima R. , Akebono H. , Kato M. , Sugeta A.
Published: August 2014

In order to investigate the effect of an ultrasonic shot peening (USP) treatment on the fatigue characteristics of structural materials for hydroelectric facilities, plane bending fatigue tests were carried out using USP treated ASTM CA6NM stainless cast steel. The results showed that the fatigue limit of the USP material was approximately 60% higher than that of the untreated material. Haigh's diagram evaluation suggested that an increase in crack initiation resistance associated with the high hardness and compressive residual stress by USP treatment was the main reason for the improvement in fatigue strength. Furthermore, the simulation of fatigue crack propagation implied that compressive residual stress leads to a low crack propagation rate compared with the untreated material. Consequently, it is clear that the USP treatment is an effective process for improving the fatigue properties of CA6NM.
Study of multilayer ZnO/Al doped ZnO nanostructured thin films
Authors: Rahman A. , Jayaganthan R. , Sharma J. V. N.
Published: August 2014

Single layer (ZnO, ZnS and Al doped ZnO film), double layer (ZnO/Al doped ZnO film) and triple layer films (ZnO/Al doped ZnO/ZnO and ZnO/Al doped ZnO/ZnS film) were deposited on sodalime glass substrate by electroless process. Wet deposited thin films were dried in air and subsequently annealed in a muffle furnace in air atmosphere at 500°C for 2 h. Significant characteristics of the thin films, such as crystallinity, surface roughness, as well as the optical properties in a large spectral range between 300 and 800 nm were analysed. Average grain size of the films was found 40–90 nm. The obtained sample of triple layer film of ZnO/Al doped ZnO/ZnS exhibits best, optimum optical characteristics, i.e. intermediate range of absorbance of spectra, lowest value of photoluminescence intensity, and has minimum recombination of electron–hole pairs. Triple layer film of ZnO/Al doped ZnO/ZnS is suitable in place of CdS/Al doped ZnO multilayer film as a transparent substrate in dye-sensitised solar cell.
Microstructure, mechanical and tribological properties of TaCN composite films
Authors: Yu L. H. , Huang T. , Xu J. H.
Published: August 2014

Tantalum and carbon nitride films, with varied power of the carbon target were synthesised by multi-target magnetron sputtering. The microstructure, mechanical and tribological properties of TaCN films were investigated by X-ray diffraction, Fourier transform infrared spectroscopy, atomic force microscopy, scanning electron microscopy, nano-indentation, nano-scratch, and a high temperature ball-on-disc tribometer. X-ray diffraction reveals that these films exhibit face centred cubic and base centred orthorhombic crystal structures, regardless of the power of the carbon target. At 50 W, the hardness, critical loads for cohesive failure ( Lc1) and critical loads for adhesive failure ( Lc2) of these films reach a maximum, 28·6 GPa, 4·52 N and 8·1 N, respectively, while at 80 W, the lowest average friction coefficient and wear rate of TaCN films are obtained, measured as 0·36 and 2·91×10−7 mm2 N−1, respectively.
Preparation of CuO nanostructures coating on copper as supercapacitor materials
Authors: Momeni M. M. , Nazari Z. , Kazempour A. , Hakimiyan M. , Mirhoseini S. M.
Published: August 2014

Copper oxide nanostructures with diverse morphology were prepared using Cu foil as substrate via a solution route. The as grown copper oxide nanostructures were characterised using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy analysis. The XRD and FTIR analysis confirm the formation of copper oxide. Scanning electron microscopy analysis shows the formation of hierarchical structures of copper oxide with different morphologies. Application of the prepared copper oxide was evaluated as supercapacitive material in 1M Na2SO4 solution using cyclic voltammetry (CV). The specific capacitance has been calculated using CV curves. It has been found that the pseudo-capacitor performance of copper oxide can be tuned via employing different samples.
Preparation and corrosion resistance of ZnO/CeO2 composite films
Authors: Wang D. Y. , Lin Z. F. , Li X. B. , Cheng W. H. , Fu Y. B. , Xu L. K.
Published: August 2014

Zinc oxide/cerium oxide (ZnO/CeO2) composite films were fabricated on zinc surfaces by electrochemical oxidation at different current densities. Scanning electron microscopy and X-ray photoelectron spectroscopy were used to investigate the surface compositions and morphologies of the films. Corrosion resistance was analysed using polarisation curves, open-circuit potential and electrochemical impedance spectroscopy. The X-ray photoelectron spectra showed that the films were composed of ZnO and CeO2. Evaluation of corrosion revealed that the samples with composite films had lower corrosion rates. On the basis of these findings, ZnO/CeO2 composites have potential as anticorrosion films for zinc.
Ser70 phosphorylation of Bcl-2 by selective tyrosine nitration of PP2A-B56δ stabilizes its antiapoptotic activity
Authors: Low Ivan Cherh Chiet , Loh Thomas , Huang Yiqing , Virshup David M. , Pervaiz Shazib
Published: August 2014

Key Points

O2− modifies B56δ at Y289 to block the PP2A holoenzyme assembly. This results in S70 Bcl-2 phosphorylation and promotes tumor chemoresistance. Primary lymphomas with low SOD1 have high B56δ tyrosine nitration and S70pBcl-2.
Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes
Authors: Schiller Benjamin J , Chodankar Rajas , Watson Lisa C , Stallcup Michael R , Yamamoto Keith R
Published: August 2014

Background

Glucocorticoid receptor (GR) is a hormone-activated, DNA-binding transcriptional regulatory factor that controls inflammation, metabolism, stress responses, and other physiological processes. In vitro, GR binds as an inverted dimer to a motif consisting of two imperfectly palindromic 6 bp half sites separated by 3 bp spacers. In vivo, GR employs different patterns of functional surfaces of GR to regulate different target genes. The relationships between GR genomic binding and functional surface utilization have not been defined.

Results

We find that A477T, a GR mutant that disrupts the dimerization interface, differs from wild-type GRα in binding and regulation of target genes. Genomic regions strongly occupied by A477T are enriched for a novel half site motif. In vitro, GRα binds half sites as a monomer. Through the overlap between GRα- and A477T-bound regions, we identify GRα-bound regions containing only half sites. We further identify GR target genes linked with half sites and not with the full motif.

Conclusions

Genomic regions bound by GR differ in underlying DNA sequence motifs and in the GR functional surfaces employed for regulation. Identification of GR binding regions that selectively utilize particular GR surfaces may discriminate sub-motifs, including the half site motif, that favor those surfaces. This approach may contribute to predictive models for GR activity and therapy.
Kaleidoscope
Authors: Tracy Derek K. , Joyce Dan W. , Shergill Sukhwinder S.
Published: August 2014

Drugs and violence are often observed as bedfellows; both have been associated with psychosis but the nature and timing of their relationships remains unclear. As part of the UK Prisoner Cohort Study, Keers et al prospectively followed up 967 prisoners convicted of sexual or violent offences (about a quarter of whom had a psychotic illness) in the community after release. Schizophrenia was associated with greater rates of violence, but the risk was mediated by untreated psychosis or when presenting with persecutory delusions – and no other definable psychopathology. Interestingly, drug-induced psychosis did not increase the risk of violence per se, once the substance misuse itself was accounted for. Does treatment have an impact on risk of violence in a population-based sample of patients with psychosis? Fazel et al demonstrated reductions in violent crime in patients during the time they were prescribed antipsychotics. Interestingly, the rates of violent crime were also reduced in patients with bipolar disorder who received mood stabilisers. Therefore, in addition to the effects of antipsychotics and mood stabilisers on relapse rates, their potential effects on violence and crime could be used to make decisions about management for these groups of patients. There is a clearer need for the appropriate treatment of prisoners with psychotic illnesses if their risk of violence is to be moderated. Cannabis is one of the most commonly used social drugs worldwide; it increases risk of psychosis, but there has been little to offer pharmacologically to those dependent upon this most prevalent illicit drug, and various trials of mood stabilisers, antidepressants and α2 adrenergic agonists have generally been disappointing. Allsop et al evaluated the novel cannabis extract nabiximols, containing cannabidiol – which has been shown to attenuate paranoia and euphoria – and tetrahydrocannabinol, delivered as a buccal spray. The active drug group showed statistically significant benefits in reduced withdrawal irritability, depression and cravings and remained longer in treatment. However, both placebo and drug groups showed reduced cannabis use at follow-up, with placebo being as effective as nabiximols in promoting longer-term cessation.
‘Schizophrenia is a dirty word’: service users' experiences of receiving a diagnosis of schizophrenia
Authors: Howe Lorna , Tickle Anna , Brown Ian
Published: August 2014

Aims and method

To explore service users' experiences of receiving a diagnosis of schizophrenia and the stigma associated with the diagnostic label. Seven participants were interviewed about their perceptions of these experiences. Interviews were analysed using interpretative phenomenological analysis.

Results

Five superordinate themes resulted from the analysis: (1) avoidance of the diagnosis of schizophrenia; (2) stigma and diagnostic labels; (3) lack of understanding of schizophrenia; (4) managing stigma to maintain normality; (5) being ‘schizophrenic’. These, together with their subthemes, highlighted avoidance of the term schizophrenia by participants and use of alternative terms by professionals, which limited opportunities for understanding the label and challenging associated stigma. Participants strived to maintain normality despite potential stigma.

Clinical implications

There is a need to address the process of giving a diagnosis as a phenomenon of consequence within its own terms. Implications relate to how professionals deliver and discuss the diagnosis of schizophrenia.
The College reply to Francis misses the big question: a commentary on OP92
Authors: Cox John , Gray Alison
Published: August 2014

The College has recently published an occasional paper in response to the Francis inquiry into the care at Mid Staffordshire NHS Foundation Trust. We consider that it overlooks one key question implicit in the inquiry's recommendations: ‘Is the business model of care fit for purpose?’ We question whether the business model in its present form is appropriate for the delivery of healthcare. We suggest there is a need for greater conceptual clarity with regard to the nature of compassionate care and the meaning of person-centred medicine. We recommend that a broader moral and ethical framework is considered not only for psychiatry, but for all healthcare provision which would transcend specialty and Royal College boundaries.
Nonlinear Pricing of Storable Goods
Authors: Hendel Igal , Lizzeri Alessandro , Roketskiy Nikita
Published: August 2014

This paper develops a model of nonlinear pricing of storable goods. We show that storability imposes novel constraints on a monopolist's ability to extract surplus. We then show that the attempt to relax these constraints can generate cyclical patterns in pricing and sales, even when consumers are homogeneous. Thus, the model provides a novel explanation for sales that does not rely on discriminating heterogeneous consumers. Enriching the model to allow for buyer heterogeneity in storage technology delivers the prediction that larger bundles are more likely to be on sale. (JEL D11, D42, L12)
An Economic Theory of the Evolutionary Emergence of Property Rights
Authors: Eswaran Mukesh , Neary Hugh M.
Published: August 2014

We model the emergence of an innate, biological sense of property rights where resource scarcity and output contestability reign. Preferences evolve such that, in evolutionarily stable equilibrium, an object is valued more by an individual who possesses it, or has produced it, than if he is neither possessor nor producer. In a distributional contest for the object, the possessor/producer will devote more effort to retaining it than an interloper will to expropriating it. Asymmetry in preferences for an object between possessor/producer and interloper, and consequent asymmetry of efforts defending or expropriating it, constitute our concept of innate property rights. (JEL C73, D11, P14)
Resisting Moral Wiggle Room: How Robust Is Reciprocal Behavior?
Authors: van der Weele Joël J. , Kulisa Julija , Kosfeld Michael , Friebel Guido
Published: August 2014

We provide the second mover in a trust game and a moonlighting game with an excuse for not reciprocating. While this type of manipulation has been shown to strongly reduce giving in the dictator game, we find that the availability of the excuse has no effect on the incidence of reciprocal behavior in these games. Our results cast doubt on the generalizability of previous dictator game findings and suggest that image concerns are not a key driver of reciprocal behavior. (JEL C72, D64, Z13)
The Effects of Regulation in the Presence of Multiple Unpriced Externalities: Evidence from the Transportation Sector
Authors: Bento Antonio , Kaffine Daniel , Roth Kevin , Zaragoza-Watkins Matthew
Published: August 2014

In transportation systems with unpriced congestion, allowing single-occupant low-emission vehicles in high-occupancy vehicle (HOV) lanes to encourage their adoption exacerbates congestion costs for carpoolers. The resulting welfare effects of the policy are negative, with environmental benefits overwhelmingly dominated by the increased congestion costs. Exploiting the introduction of the Clean Air Vehicle Stickers policy in California with a regression discontinuity design, our results imply a best-case cost of $124 per ton of reductions in greenhouse gases, $606,000 per ton of nitrogen oxides reduction, and $505,000 per ton of hydrocarbon reduction, exceeding those of other options readily available to policymakers. (JEL D62, L51, L62, Q51, Q54, R41, R48)
Under Pressure: Job Security, Resource Allocation, and Productivity in Schools under No Child Left Behind
Authors: Reback Randall , Rockoff Jonah , Schwartz Heather L.
Published: August 2014

We conduct the first nationwide study of incentives under the No Child Left Behind (NCLB) Act, which requires states to punish schools failing to meet target passing rates on students' standardized exams. States' idiosyncratic policies created variation in the risk of failure among very similar schools in different states, which we use to identify effects of accountability pressure. We find NCLB lowers teachers' perceptions of job security, shifts time towards specialist teachers in high-stakes subjects and away from whole-class instruction, and has positive or neutral effects on students' enjoyment of learning and achievement in reading, math, and science. (JEL H52, H75, I21, I28, J45)
Efficiency Analysis of Cournot Competition in Service Industries with Congestion
Authors: Perakis Georgia , Sun Wei
Published: August 2014

We consider Cournot competition in the presence of congestion effects. Our model consists of several service providers with differentiated services, each competing for users who are sensitive to both price and congestion. We distinguish two types of congestion effects, depending on whether spillover costs exist, that is, where one service provider's congestion cost increases with the other providers' output level. We quantify the efficiency of an unregulated oligopoly with respect to the optimal social welfare with tight upper and lower bounds. We show that, when there is no spillover, the welfare loss in an unregulated oligopoly is limited to 25% of the social optimum, even in the presence of highly convex costs. On the other hand, when spillover cost is present, there does not exist a constant lower bound on the efficiency of an unregulated oligopoly, even with affine cost. We show that the efficiency depends on the relative magnitude between the marginal spillover cost and the marginal benefit to consumers.

This paper was accepted by Christian Terwiesch, operations management.
Functional outcome and quality of life after the surgical treatment for diffuse-type giant-cell tumour around the knee
Authors: van der Heijden L. , Mastboom M. J. L. , Dijkstra P. D. S. , van de Sande M. A. J.
Published: August 2014

We retrospectively reviewed 30 patients with a diffuse-type giant-cell tumour (Dt-GCT) (previously known as pigmented villonodular synovitis) around the knee in order to assess the influence of the type of surgery on the functional outcome and quality of life (QOL). Between 1980 and 2001, 15 of these tumours had been treated primarily at our tertiary referral centre and 15 had been referred from elsewhere with recurrent lesions.

The mean follow-up was 64 months (24 to 393). Functional outcome and QOL were assessed with range of movement and the Knee injury and Osteoarthritis Outcome Score (KOOS), the Musculoskeletal Tumour Society (MSTS) score, the Toronto Extremity Salvage Score (TESS) and the SF-36 questionnaire. There was recurrence in four of 14 patients treated initially by open synovectomy. Local control was achieved after a second operation in 13 of 14 (93%). Recurrence occurred in 15 of 16 patients treated initially by arthroscopic synovectomy. These patients underwent a mean of 1.8 arthroscopies (one to eight) before open synovectomy. This achieved local control in 8 of 15 (53%) after the first synovectomy and in 12 of 15 (80%) after two. The functional outcome and QOL of patients who had undergone primary arthroscopic synovectomy and its attendant subsequent surgical procedures were compared with those who had had a primary open synovectomy using the following measures: range of movement (114º versus 127º; p = 0.03); KOOS (48 versus 71; p = 0.003); MSTS (19 versus 24; p = 0.02); TESS (75 versus 86; p = 0.03); and SF-36 (62 versus 80; p = 0.01).

Those who had undergone open synovectomy needed fewer subsequent operations. Most patients who had been referred with a recurrence had undergone an initial arthroscopic synovectomy followed by multiple further synovectomies. At the final follow-up of eight years (2 to 32), these patients had impaired function and QOL compared with those who had undergone open synovectomy initially.

We conclude that the natural history of Dt-GCT in patients who are treated by arthroscopic synovectomy has an unfavourable outcome, and that primary open synovectomy should be undertaken to prevent recurrence or residual disease.

Cite this article: Bone Joint J 2014; 96-B:1111–18.
Predictors of failure for cephalomedullary nailing of proximal femoral fractures
Authors: Kashigar A. , Vincent A. , Gunton M. J. , Backstein D. , Safir O. , Kuzyk P. R. T.
Published: August 2014

The purpose of this study was to identify factors that predict implant cut-out after cephalomedullary nailing of intertrochanteric and subtrochanteric hip fractures, and to test the significance of calcar referenced tip-apex distance (CalTAD) as a predictor for cut-out.

We retrospectively reviewed 170 consecutive fractures that had undergone cephalomedullary nailing. Of these, 77 met the inclusion criteria of a non-pathological fracture with a minimum of 80 days radiological follow-up (mean 408 days; 81 days to 4.9 years). The overall cut-out rate was 13% (10/77).

The significant parameters in the univariate analysis were tip-apex distance (TAD) (p <  0.001), CalTAD (p = 0.001), cervical angle difference (p = 0.004), and lag screw placement in the anteroposterior (AP) view (Parker’s ratio index) (p = 0.003). Non-significant parameters were age (p = 0.325), gender (p = 1.000), fracture side (p = 0.507), fracture type (AO classification) (p = 0.381), Singh Osteoporosis Index (p = 0.575), lag screw placement in the lateral view (p = 0.123), and reduction quality (modified Baumgaertner’s method) (p = 0.575). In the multivariate analysis, CalTAD was the only significant measurement (p = 0.001). CalTAD had almost perfect inter-observer reliability (interclass correlation coefficient (ICC) 0.901).

Our data provide the first reported clinical evidence that CalTAD is a predictor of cut-out. The finding of CalTAD as the only significant parameter in the multivariate analysis, along with the univariate significance of Parker’s ratio index in the AP view, suggest that inferior placement of the lag screw is preferable to reduce the rate of cut-out.

Cite this article: Bone Joint J 2014; 96-B:1029–34.
A systematic review and meta-analysis of the topical administration of tranexamic acid in total hip and knee replacement
Authors: Alshryda S. , Sukeik M. , Sarda P. , Blenkinsopp J. , Haddad F. S. , Mason J. M.
Published: August 2014

Intravenous tranexamic acid (TXA) has been shown to be effective in reducing blood loss and the need for transfusion after joint replacement. Recently, there has been interest in applying it topically before the closure of surgical wounds. This has the advantages of ease of application, maximum concentration at the site of bleeding, minimising its systemic absorption and, consequently, concerns about possible side-effects.

We conducted a systematic review and meta-analysis which included 14 randomised controlled trials (11 in knee replacement, two in hip replacement and one in both) which investigated the effect of topical TXA on blood loss and rates of transfusion. Topical TXA significantly reduced the rate of blood transfusion (total knee replacement: risk ratio (RR) 4.51; 95% confidence interval (CI): 3.02 to 6.72; p < 0.001 (nine trials, I2 = 0%); total hip replacement: RR 2.56; 95% CI: 1.32 to 4.97, p = 0.004 (one trial)). The rate of thromboembolic events with topical TXA were similar to those found with a placebo. Indirect comparison of placebo-controlled trials of topical and intravenous TXA indicates that topical administration is superior to the intravenous route.

In conclusion, topical TXA is an effective and safe method of reducing the need for blood transfusion after total knee and hip replacement. Further research is required to find its optimum dose for topical use.

Cite this article: Bone Joint J 2014;96-B:1005–15.
Ethical standards for orthopaedic surgeons
Authors: Benson M. , Boehler N. , Szendroi M. , Zagra L. , Puget† J.
Published: August 2014

This paper offers a summary of the ethical guide for the European orthopaedic community; the full report will be published in the EFORT Journal.

Cite this article: Bone Joint J 2014;96-B:1130–2.
Modafinil: Parkinson Disease–Related Somnolence
Authors: Generali Joyce A. , Cada Dennis J.
Published: August 2014

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu .
Searching and Thinking About Searching JSTOR
Authors: Gitelman Lisa
Published: August 2014

Digital resources are helping to change the ways scholars and students work, but they must also be helping to shape the work that gets done. Taking JSTOR as an example, we might ask about the discursive power of the database. How is using an online resource for research acceding to unnoticed assumptions that underlie the construction of that resource?
A conformational switch in collybistin determines the differentiation of inhibitory postsynapses
Authors: Soykan Tolga , Schneeberger Daniela , Tria Giancarlo , Buechner Claudia , Bader Nicole , Svergun Dmitri , Tessmer Ingrid , Poulopoulos Alexandros , Papadopoulos Theofilos , Varoqueaux Frédérique , Schindelin Hermann , Brose Nils
Published: August 2014

The formation of neuronal synapses and the dynamic regulation of their efficacy depend on the assembly of the postsynaptic neurotransmitter receptor apparatus. Receptor recruitment to inhibitory GABAergic and glycinergic synapses is controlled by the scaffold protein gephyrin and the adaptor protein collybistin. We derived new insights into the structure of collybistin and used these to design biochemical, cell biological, and genetic analyses of collybistin function. Our data define a collybistin‐based protein interaction network that controls the gephyrin content of inhibitory postsynapses. Within this network, collybistin can adopt open/active and closed/inactive conformations to act as a switchable adaptor that links gephyrin to plasma membrane phosphoinositides. This function of collybistin is regulated by binding of the adhesion protein neuroligin‐2, which stabilizes the open/active conformation of collybistin at the postsynaptic plasma membrane by competing with an intramolecular interaction in collybistin that favors the closed/inactive conformation. By linking trans‐synaptic neuroligin‐dependent adhesion and phosphoinositide signaling with gephyrin recruitment, the collybistin‐based regulatory switch mechanism represents an integrating regulatory node in the formation and function of inhibitory postsynapses.