bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a Theory of Counter-Modernity: Rethinking Zygmunt Bauman’s Holocaust Writings
Authors: Cannon Bob
Published: May 2014

This article defends the normative legitimacy of modernity from postmodern attempts to implicate modernity in oppressive social practices; Zygmunt Bauman’s Holocaust writings are an extreme example of such attempts. To discredit modernity Bauman renders the Holocaust a rational enterprise analogous to a modern factory system, dispassionately perpetrated by banal bureaucrats, such as Eichmann. Following Bauman, the identification of the Holocaust with modern mass production has become a standard trope of mainstream sociology, culminating in its identification with McDonald’s. However, this obscures the sadistic brutality of the Holocaust, the ideological zeal of perpetrators and the counter-modern norms that drove it. Although Bauman is widely considered a progressive thinker, his Holocaust writings bear the stamp of Heidegger’s regressive critique of modernity. A theory of counter-modernity not only provides a more accurate account of the Holocaust; it also restores the legitimacy of modern norms upon which a progressive critique of genocide rests.
Synthesis of polystyrene nanolatexes via emulsion polymerization using sodium dodecyl sulfonate as the emulsifier
Authors: Yang Liyan , Ke Yangchuan
Published: May 2014

Polystyrene (PS) nanolatexes were successfully prepared via emulsion polymerization using sodium dodecyl sulfonate as the emulsifier. The effects of emulsifier concentration, initiator concentration, polymerization reaction time, and polymerization reaction temperature on particle size and size distribution of PS colloidal spheres were investigated, respectively. The particle size of the diluted polymer emulsion was about 20 nm, as determined by laser scattering. These obtained PS particles were also characterized using Fourier transform infrared spectroscopy and scanning electron microscopy.
Synthesis and properties of main-chain oligomeric benzoxazine precursor containing cyclotriphosphazene units
Authors: Tan Zhi-Wei , Wu Xiong , Zhang Min , Qiu Jin-Jun , Liu Cheng-Mei
Published: May 2014

A linear oligobenzoxazine precursor with cyclotriphosphazene ring was prepared through the Schiff base route. The resulting polymers showed higher molecular weight and better thermal stability than those from the traditional Mannich polycondensation method. The oligomeric benzoxazine precursor can form a high-quality transparent yellow film; however, it was fragile after being cured. In order to identify the effect of end groups on the cured polymer, an aniline-capped polymer was prepared by the same Schiff base method and then was changed into a benzoxazine end group. The results indicated that the uncapped polymer exhibited higher stability than the capped polymer. This can be ascribed to different chemical structures resulting from different end groups.
The influence of processing aids on the properties of poly (arylene sulfide sulfone)
Authors: Kong Yu , Huang Guangshun , Zhang Gang , Wang Xiaojun , Long Shengru , Yang Jie
Published: May 2014

Zinc acetate (ZnAc) and diphenyl sulfone were used as melt stabilizer and plasticizer to improve the stability and flowability of poly (arylene sulfide sulfone) (PASS) during the melt processing. The effects of these processing aids on rheological, mechanical, dynamic mechanical, and thermal properties of PASS and their compatibility with the polymer matrix were investigated. Both capillary rheometer and parallel plate rheometer measurements showed that the processing aids could significantly improve stability and mobility of PASS melts, especially the compounding aid. Dynamic mechanical analysis and tensile test indicated that diphenyl suflone increased the stiffness of pure PASS at lower temperature ( T < Tg) and showed effectual plasticizing effects at higher temperature ( T > Tg), and ZnAc decreased the stiffness and Tg of pure PASS. The compatibility and thermal performance of PASS with diphenyl sulfone or ZnAc were also discussed.
Slug velocity measurement using acoustic emission technology
Authors: Alssayh Muammer , Addali Abdulmajid , Mba David , El-Alej Mohamed Essid
Published: May 2014

Two-phase flow is a common phenomenon that exists in the petroleum and chemical engineering industrial fields. An important feature employed to describe two-phase flow is the flow regime which varies depending on the individual velocities of the components within the two-phase flow. One of these regimes, the slug regime, can create significant pressure fluctuations that compromise the integrity of the transporting structure (pipes, separators, etc). This is in addition to other unwanted effects such as flooding at the receiving end, an increase in deposits of hydrates and corrosion. Under such circumstances, the detection of the slug and its associated characteristics are vitally important to the operator. This experimental study looks into the application of acoustic emission (AE) technology for detecting slug velocity in two phase (gas/liquid) flow. It is concluded that the slug velocity can be determined with AE sensors. The results were validated by using Ultrasound Transit Time technique and there was a good agreement between the two techniques at low gas void fraction.
Long-term outcome in Japanese patients with lupus nephritis
Authors: Kono M , Yasuda S , Kato M , Kanetsuka Y , Kurita T , Fujieda Y , Otomo K , Horita T , Oba K , Kondo M , Mukai M , Yanai M , Fukasawa Y , Atsumi T
Published: May 2014

The objective of this study was to clarify the long-term outcome in patients with lupus nephritis (LN) according to the International Society of Nephrology and Renal Pathology Society classification. This retrospective analysis comprised 186 Japanese patients given a diagnosis of LN by renal specimen with a mean observation period of 12 years. Primary end point was defined as death or end-stage renal disease, and standardized mortality ratios were calculated. Five patients presented with histopathological class I, 62 with II, 21 with III or III+V, 73 with IV or IV+V and 25 with V. Fourteen deaths occurred, corresponding to an overall standardized mortality ratio of 3.59 (95% confidence interval 2.02–5.81, p < 0.0001). Kaplan-Meier analysis revealed a 10-year overall survival of 95.7%. Nephrotic proteinuria (≥3.5 g/day) at baseline was identified as an independent poor prognostic factor for overall survival in Cox regression analysis. Kaplan-Meier analysis revealed a 10-year renal survival as 94.3%. Male gender and nephrotic proteinuria at baseline were identified as independent poor prognostic factors for renal survival in Cox regression analysis. In conclusion, LN was associated with a 3.59-fold increase in mortality compared with the general population. Male gender and nephrotic proteinuria were predictive for poor renal outcome.
Securing circulation pharmaceutically: Antiviral stockpiling and pandemic preparedness in the European Union
Authors: Elbe Stefan , Roemer-Mahler Anne , Long Christopher
Published: May 2014

Governments in Europe and around the world amassed vast pharmaceutical stockpiles in anticipation of a potentially catastrophic influenza pandemic. Yet the comparatively ‘mild’ course of the 2009 H1N1 pandemic provoked considerable public controversy around those stockpiles, leading to questions about their cost–benefit profile and the commercial interests allegedly shaping their creation, as well as around their scientific evidence base. So, how did governments come to view pharmaceutical stockpiling as such an indispensable element of pandemic preparedness planning? What are the underlying security rationalities that rapidly rendered antivirals such a desirable option for government planners? Drawing upon an in-depth reading of Foucault’s notion of a ‘crisis of circulation’, this article argues that the rise of pharmaceutical stockpiling across Europe is integral to a governmental rationality of political rule that continuously seeks to anticipate myriad circulatory threats to the welfare of populations – including to their overall levels of health. Novel antiviral medications such as Tamiflu are such an attractive policy option because they could enable governments to rapidly modulate dangerous levels of (viral) circulation during a pandemic, albeit without disrupting all the other circulatory systems crucial for maintaining population welfare. Antiviral stockpiles, in other words, promise nothing less than a pharmaceutical securing of circulation itself.
Sir Harold Ridley (1906–2001): televising and filming ophthalmic surgery and eye examinations
Authors: Emsley Elizabeth
Published: May 2014

Sir Harold Ridley is well known for his pioneering intraocular lens implantation surgery. He also had a significant commitment to the televising and filming of surgery. In his 1950 Television in Ophthalmology paper, Ridley describes the techniques he used to capture his surgery in monochrome and later in full colour for audiences at St Thomas' Hospital.
Pietro Manni (1778–1839) and the care of the apparently dead in the Age of Positivism
Authors: Cascella Marco
Published: May 2014

When can a man be declared ‘really dead’? Being able to determine whether an individual’s life has ended or not implies two important considerations, whether we can resuscitate him and avoid premature burial, the fear of which is termed ‘taphophobia’. By the end of the 18th century, several scientists were involved in the study of apparent death and resuscitation. Pietro Manni was an obstetrician who, affected by his brother’s death and his inability to help him, devoted himself to the study of apparent death, which became his aim in life. His Practical handbook for the care of the apparently dead is a detailed essay on resuscitation with a precise arrangement of topics – ventilation, tracheostomy, electricity and asphyxia in newborns – organised into chapters and paragraphs that resemble current texts on resuscitation.
Detection of crack formation and stress distribution for carbon fiber–reinforced polymer specimens through triboluminescent-based imaging
Authors: Aich Nirupam , Kim Eunho , ElBatanouny Mohamed , Plazas-Tuttle Jaime , Yang Jinkyu , Ziehl Paul , Saleh Navid B
Published: May 2014

This article demonstrates the ability of surface-coated triboluminescent materials to detect damage in carbon fiber–reinforced polymer specimens. An experimental protocol was developed to test the efficiency of the triboluminescent-based diagnostic method using carbon fiber–reinforced polymer coupons under combined bending–compression conditions. Luminescence, emitted from the triboluminescent coatings under quasi-static loading, was detected by capturing digital images. We employed image processing software to quantify change in luminescence as a function of triboluminescent concentration. We observed that 10%, 20%, and 30% triboluminescent coating resulted in 25.3, 27.9, and 40.4 (arbitrary units) total luminescence, respectively, which shows a positive correlation of triboluminescent concentration with luminescence. Finite element simulation was also performed to understand the stress and strain distribution and to aid in understanding and correlating light emission regions on the carbon fiber–reinforced polymer coupons under bending deformation. This work represents a step toward the development of a robust technology that employs triboluminescent materials for early damage detection, consistent with theoretical predictions of damage occurrence.
Modeling and analysis of Lamb wave propagation in a beam under lead zirconate titanate actuation and sensing
Authors: Venugopal Vishnu Prasad , Wang Gang
Published: May 2014

Lead zirconate titanate actuators and sensors have been the widely used in Lamb wave–based damage detection applications. The excitation frequency, waveform, and wave propagation characteristics should be comprehensively considered to effectively conduct diagnosis of incipient forms of damage. In this article, we investigate Lamb wave propagation in a beam under lead zirconate titanate actuation/sensing, in which the lead zirconate titanate effects are included. First, mathematical models are developed to account for both unimorph (i.e. sensor mode) and bimorph (i.e. actuator mode) configurations. The Timoshenko beam theory is adopted for both base beam and lead zirconate titanate layers to accommodate high-frequency responses. Second, the fully coupled electromechanical governing equations are determined and solved in an analytical form to formulate the spectral finite element model. Finally, parametric studies are carried out to determine the optimal actuation frequency, sensor size, actuator, and sensor placement. Our spectral finite element model predictions are validated by the experimental data and results in the literature. The application of spectral finite element model in the Lamb wave–based damage detection is demonstrated as well. In summary, the newly developed spectral finite element model provides an analytical framework in which to predict Lamb wave propagation under lead zirconate titanate actuation and sensing, as well as to develop new interrogation schemes.
Motivating Quality
Authors: Mackiewicz Jo
Published: May 2014

This study examines the type of edit that amateur editors called Advisors used in their comments on Epinions.com product reviews and the extent to which their editing-related comments might have motivated reviewers to revise and update their reviews. Advisors made substantive-type suggestions most frequently, but for the most part, reviews that received editing-related comments were not updated more often than were those with nonediting-related comments. Unlike professional editors, Advisors lack gatekeeping control that compels writers to revise their work, but as companies recognize the value of quality user-generated content, they may use amateur editors more often, perhaps in conjunction with professional technical editors.
The Role of Social Distress, Political Affiliation, and Education in Measuring Punitive Attitudes
Authors: Gideon Lior , Sherman-Oren Ayala
Published: May 2014

The purpose of this study is to examine the different factors that shape and facilitate punitive attitudes among Israeli public. Punitive attitudes were examined in respect to several demographic and environmental variables such as gender, level of religiosity, level of education, political affiliation, and victimization. In addition, social distress in respect to the political climate of the country was taken into consideration to examine the effect of “historical” events on results reliability. Using a random selection, a sample of 471 Israeli respondents was examined at two different time periods (Wave I: 2008–2009 and Wave II: 2011). Results of the current study indicate that demographic characteristics as well as social distress are related to the manifestation of punitive attitudes among Israelis, and thus the study demonstrates the different factors that affect public attitudes toward crime and punishment in the Israeli context. Results are discussed in regard to policy, and recommendations are made for future studies.
Does Attending Worship Mitigate Racial/Ethnic Discrimination in Influencing Health Behaviors? Results From an Analysis of the California Health Interview Survey
Authors: Caldwell Julia T. , Takahashi Lois M.
Published: May 2014

Existing research suggests that religious institutions play a significant role in improving the health of communities, particularly those coping with racial and ethnic discrimination. Using the California Health Interview Survey, this article examines the relationship of self-reported experiences of racial/ethnic discrimination, worship attendance, and several health behaviors. Supporting existing research, higher self-reported racial/ethnic discrimination is associated with worse health behaviors. Logistic regression models indicate that the odds of engaging in healthy lifestyle behaviors significantly increase for those who report attending worship, compared with those who do not attend worship, with variations by race/ethnicity. Worship attendance moderates the association between discrimination and binge drinking, but does not moderate the association for smoking, walking, or being obese. Findings suggest that religious attendance plays an important role in the health and well-being of all population groups. More research is needed to ascertain the reasons why attending worship may have the ability to mitigate the relationship between racial/ethnic discrimination and health.
Tribological behavior of in-situ (Cr, Mo)/Fe3Al-20 wt.%Al2O3 composites at elevated temperatures
Authors: Bai Yaping , Xing Jiandong , He Yuanyuan , Liu Zhen , Huang Qian , Ma Shengqiang , Gao Yimin
Published: May 2014

Dry-sliding tribological performance of in-situ Fe3Al-20 wt.%Al2O3, (4 wt.%Cr)/Fe3Al-20 wt.%Al2O3, and (4 wt.%Cr, 5 wt.%Mo)/Fe3Al-20 wt.%Al2O3 composites, produced by mechanically induced self-propagating mechanism and plasma-activated sintering, was investigated against Inconel718 from 25℃ to 800℃ under air/argon atmosphere. It can be found that (4 wt.%Cr, 5 wt.%Mo)/Fe3Al-20 wt.%Al2O3 composite exhibits more excellent comprehensive tribological properties with the friction coefficient decrease nearly 67% compared to Fe3Al-20 wt.%Al2O3 composite above 350℃ due to the balance between strength and lubricity. At 800℃, the dominant wear mechanism is oxidation wear under air condition, whereas under argon atmosphere, the actual wear mechanism is mainly transferred to microploughing.
Cross-gender communication in a Saudi Arabian Internet discussion forum
Authors: Madini Abeer Ahmed , de Nooy Juliana
Published: May 2014

The possibility of relatively anonymous communication involving no physical proximity means that Internet discussion forums offer opportunities for cross-gender communication that do not necessarily violate Saudi Arabian rules for behavior. This article studies participation in a public discussion forum for expatriate Saudi students. Building on a previous article that established the extent to which participants disclose their gender in the forum, it investigates the extent to which participants take advantage of the opportunity for mixed communication online, their attitudes towards it, and their reactions when it occurs. It analyzes in detail the cross-gender exchanges that occur in the corpus, together with remarks made by participants about this issue, in order to determine the circumstances under which mixed communication is seen as appropriate in this forum.
Value propositions
Authors: Frow Pennie , McColl-Kennedy Janet R. , Hilton Toni , Davidson Anthony , Payne Adrian , Brozovic Danilo
Published: May 2014

Despite significant interest in value propositions, there is limited agreement about their nature and role. Moreover, there is little understanding of their application to today’s increasingly interconnected and networked world. The purpose of this article is to explore the nature of value propositions, extending prior conceptualisations by taking a service ecosystem perspective. Following a critical review of the extant literature in service science on value propositions, value co-creation, service-dominant logic and networks and drawing on six metaphors that provide insights into the nature of value propositions, we develop a new conceptualisation. The role of value propositions is then explored in terms of resource offerings between actors within micro, meso and macro levels of service ecosystems. We illustrate these perspectives with two real-world exemplars. We describe the role of value propositions in an ecosystem as a shaper of resource offerings. Finally, we provide five key premises and outline a research agenda.
Ethnic minority, young onset, rare dementia type, depression: A case study of a Muslim male accessing UK dementia health and social care services
Authors: Regan Jemma L
Published: May 2014

A case study comprised of formal interviews, formal observations and informal discussions investigated the motivations and experiences accessing dementia care health and social care services for a Muslim, Pakistani male with dementia. Motivations derived from ‘desperation’ and an inability to access support from family or religious community. Experiences of accessing services were mostly negative. Dementia services were ill-informed about how to support persons with young onset dementia, with pre-existing mental health conditions, from an ethnic minority. Education and training to remove barriers to all dementia care services is required for persons with dementia, their families and within dementia services and religious communities.
Copper nanoparticles loaded cellulose-g-poly acrylic acid fibers with antibacterial properties
Authors: Bajpai SK , Das Pratima , Soni Bhawna
Published: May 2014

In this work, poly(acrylic acid) has been grafted onto cotton fibers through the free radical initiated polymerization and the resulting fibers have been characterized by Fourier transform infrared, thermogravimetric analysis, and scanning electron microscopy analysis. The grafted fibers have been loaded with copper nanoparticles using in situ approach. The Transmission Electron Microscopy (TEM) analysis of Cu nanoparticles revealed that almost 45% of the particles had a diameter range of 60–80 nm. The copper nanoparticles loaded fibers show slow release of Cu(II) ions, extended over a period of around 50 h. The release of Cu(II) ions followed a second-order kinetic model successfully. The fibers also exhibited an excellent antibacterial action against model bacteria Escherichia coli as tested by zone of inhibition method.
Modification of polyglycolic acid and poly lactic-co-glycolic acid fibers by ultrasonic treatment for enhancing hydrophilicity and cytocompatibility
Authors: Wang Biqiao , Zhang Peihua , Song Weiping , Zhao Li , He Chenguang
Published: May 2014

Ultrasonic modification was used as a simply-operated and efficient method for improving the hydrophilicity and cytocompatibility of polyglycolic acid (PGA) and poly lactic-co-glycolic acid (PLGA, lactide:glycolic acid (LA:GA) = 10:90) fibers, and maintaining the tensile property at the same time. The fibers were pre-treated ultrasonically by dipping in the mixed solution composed of absolute ethyl alcohol and polyphosphoric acid (PPA) (volume ratio 1:1) at 250 W ultrasonic power for 6 min. Scanning electron microscopy was used to observe the surface morphology of PGA and PLGA fiber before and after modification. Fourier transform infrared spectroscopy was used to investigate the change of fiber chemical composition. X-ray diffraction and differential scanning calorimetry analysis showed that the crystalline degree of modified PGA and PLGA fibers decreased. The results of tensile test indicated that compared to that before modification, the breaking strength of modified PLGA increased, while the breaking strength of PGA fiber remained unchanged. The water contact angle of modified fiber was lower than that of unmodified fiber, showing higher hydrophilicity. The cell proliferation assay indicated that fibroblast cells attached and proliferated better on the modified fiber, which means the modified fibers possess good cytocompatibility. These results suggested that ultrasonic modification is an easy-operated and efficient method and the modified PGA and PLGA fibers could be useful in the biomedical textiles field.
Inadvertent subclavian artery cannulation and options for management
Authors: Mousa Albeir Y , Abu-Halimah Shadi , Nanjundappa Aravinda , AbuRahma Ali F
Published: May 2014

Central line placement is an integral part of our daily routine and although it is necessary in a select group of patients, serious complications may occur in up to 10% of cases. Inadvertent placement in the subclavian artery is considered to be one of the most challenging complications to the vascular specialist, which is mainly due to its deep anatomical location. Several endovascular options are available and should be tailored to fit each scenario. Herein, we present different approaches for the management of three cases of inadvertent subclavian artery cannulation. The first patient was treated with a covered stent, the second with prolonged balloon inflation, and the third with a closure device.
Water transport parameters of autoclaved aerated concrete: Experimental assessment of different modeling approaches
Authors: Korecký Tomáš , Keppert Martin , Maděra Jiří , Černý Robert
Published: May 2014

The water-permeability, moisture-diffusivity, and sorptivity concepts of modeling liquid water transport in porous building materials are analyzed. An overall assessment of the particular models is performed using the moisture profiles measured for two types of autoclaved aerated concrete. The water-permeability and moisture-diffusivity modeling approaches are found suitable from a point of view of accuracy of moisture-transport simulation but they have certain limitations. While the water-permeability concept is advisable for compact materials, the moisture-diffusivity concept should be preferred for materials with a high water penetration rate. Therefore, a combination of both these approaches in a single laboratory is beneficial. The sorptivity concept, on the other hand, can be recommended for a basic assessment of water transport capabilities of building materials only.
Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer: latest evidence and clinical implications
Authors: Pernas Simon Sonia
Published: May 2014

Neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer is exactly the paradigm of targeted therapy and a suitable setting to develop and test rapidly novel therapies in early stages. Moreover, neoadjuvant approaches provide a significant source of tumour tissue to identify molecular heterogeneity and potential predictive biomarkers of response. The addition of trastuzumab to primary chemotherapy revolutionized the treatment of this tumour subtype, increasing pathological complete response rate (pCR) that, even with its limitations, has also been shown to be an early marker of survival in HER2-positive disease. HER2-positive breast cancer is a biological heterogeneous disease with different characteristics and clinical outcomes. Multiple promising anti-HER2 drugs with nonoverlapping mechanisms of action have recently been developed. Combined administration of two different HER2-targeted agents, that is, trastuzumab with lapatinib or pertuzumab, and primary chemotherapy shows enhanced antitumour activity, with an increase in pCR to values never reached in the past. Moreover, results of recent studies show that the combination of targeted therapy alone (dual HER2 blockade with or without endocrine therapy) also has activity in a substantial percentage of patients, eradicating HER2-positive tumours without chemotherapy and with a favourable toxicity profile. It is still necessary to be able to select the appropriate group of patients who can avoid chemotherapy (approximately 25%), and to establish robust predictive biomarkers of response or resistance to the anti-HER2 approach. Neoadjuvant therapy represents an enormous step forward in HER2-positive breast cancer. The results of the most relevant neoadjuvant studies and latest evidence are described in this review, though new questions have emerged.
Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes
Authors: Scully Marie , Thomas Mari , Underwood Mary , Watson Henry , Langley Katherine , Camilleri Raymond S. , Clark Amanda , Creagh Desmond , Rayment Rachel , Mcdonald Vickie , Roy Ashok , Evans Gillian , McGuckin Siobhan , Ni Ainle Fionnuala , Maclean Rhona , Lester William , Nash Michael , Scott Rosemary , O Brien Patrick ,   collaborators of the UK TTP Registry
Published: May 2014

Key Points

In women presenting with an initial diagnosis of TTP during pregnancy, cTTP was more common than acquired TTP. Active monitoring and management during pregnancy results in positive pregnancy outcomes.
Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study
Authors: Abrahamsson Anna , Albertsson-Lindblad Alexandra , Brown Peter N. , Baumgartner-Wennerholm Stefanie , Pedersen Lars M. , D’Amore Francesco , Nilsson-Ehle Herman , Jensen Paw , Pedersen Michael , Geisler Christian H. , Jerkeman Mats
Published: May 2014

Key Points

Rituximab and autologous stem cell transplantation are both independently associated with improved overall survival in mantle cell lymphoma. Male gender is an independent negative prognostic factor in mantle cell lymphoma.
Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia
Authors: Treon Steven P. , Tripsas Christina K. , Meid Kirsten , Kanan Sandra , Sheehy Patricia , Chuma Stacey , Xu Lian , Cao Yang , Yang Guang , Liu Xia , Patterson Christopher J. , Warren Diane , Hunter Zachary R. , Turnbull Barry , Ghobrial Irene M. , Castillo Jorge J.
Published: May 2014

Key Points

Carfilzomib, rituximab, and dexamethasone (CaRD) produce overall and CR/VGPR responses in 87% and 36% of frontline WM patients, respectively. CaRD activity was not impacted by MYD88 and CXCR4 mutations and represents a neuropathy-sparing option for treating WM patients.
Prevalence of gastrointestinal stromal tumour (GIST) in the United Kingdom at different therapeutic lines: an epidemiologic model
Authors: Starczewska Amelio Justyna M , Cid Ruzafa Javier , Desai Kamal , Tzivelekis Spiros , Muston Dominic , Khalid Javaria Mona , Ashman Philip , Maguire Andrew
Published: May 2014

Background

The prevalence of patients with gastrointestinal stromal tumourgst (GIST) who fail currently available treatments imatinib and sunitinib (third-line treatment-eligible GIST) is unknown, but is expected to be below an ultra-orphan disease threshold of 2/100,000 population used in England and Wales. Our study was designed to estimate the prevalence and absolute number of UK patients with unresectable/metastatic GIST at first-, second- and eventually third-line treatment.

Methods

Our open population model estimates the probability that the prevalence of UK third-line treatment-eligible GIST patients will remain under the ultra-orphan disease threshold. Model parameters for incidence, proportion of unresectable/metastatic disease and survival estimates for GIST patients were obtained from a targeted literature review and a UK cancer register. The robustness of the results was checked through differing scenarios taking extreme values of the input parameters.

Results

The base-case scenario estimated a prevalence of third-line treatment-eligible GIST of 1/100,000 and a prevalence count of 598 with a 99.9% likelihood of being below the ultra-orphan disease threshold. The extreme scenarios, one-way and probabilistic sensitivity analyses and threshold analysis confirmed the robustness of these results.

Conclusions

The prevalence of third-line treatment-eligible GIST is very low and highly likely below the ultra-orphan disease threshold.
Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells
Authors: Hirschi Benjamin , Gallmeier Eike , Ziesch Andreas , Marschall Maximilian , Kolligs Frank T
Published: May 2014

Background

Colorectal cancers carrying the B-Raf V600E-mutation are associated with a poor prognosis. The purpose of this study was to identify B-RafV600E-mediated traits of cancer cells in a genetic in vitro model and to assess the selective sensitization of B-RafV600E-mutant cancer cells towards therapeutic agents.

Methods

Somatic cell gene targeting was used to generate subclones of the colorectal cancer cell line RKO containing either wild-type or V600E-mutant B-Raf kinase. Cell-biologic analyses were performed in order to link cancer cell traits to the BRAF-mutant genotype. Subsequently, the corresponding tumor cell clones were characterized pharmacogenetically to identify therapeutic agents exhibiting selective sensitivity in B-RafV600E-mutant cells.

Results

Genetic targeting of mutant BRAF resulted in restoration of sensitivity to serum starvation-induced apoptosis and efficiently inhibited cell proliferation in the absence of growth factors. Among tested agents, the B-Raf inhibitor dabrafenib was found to induce a strong V600E-dependent shift in cell viability. In contrast, no differential sensitizing effect was observed for conventional chemotherapeutic agents (mitomycin C, oxaliplatin, paclitaxel, etoposide, 5-fluorouracil), nor for the targeted agents cetuximab, sorafenib, vemurafenib, RAF265, or for inhibition of PI3 kinase. Treatment with dabrafenib efficiently inhibited phosphorylation of the B-Raf downstream targets Mek 1/2 and Erk 1/2.

Conclusion

Mutant BRAF alleles mediate self-sufficiency of growth signals and serum starvation-induced resistance to apoptosis. Targeting of the BRAF mutation leads to a loss of these hallmarks of cancer. Dabrafenib selectively inhibits cell viability in B-RafV600E mutant cancer cells.
Secondary bile acids: an underrecognized cause of colon cancer
Authors: Ajouz Hana , Mukherji Deborah , Shamseddine Ali
Published: May 2014

Bile acids were first proposed as carcinogens in 1939. Since then, accumulated evidence has linked exposure of cells of the gastrointestinal tract to repeated high physiologic levels of bile acids as an important risk factor for gastrointestinal cancers. High exposure to bile acids may occur in a number of settings, but most importantly, is prevalent among individuals who have a high dietary fat intake.

A rapid effect on cells of high bile acid exposure is the generation of reactive oxygen species and reactive nitrogen species, disruption of the cell membrane and mitochondria, induction of DNA damage, mutation and apoptosis, and development of reduced apoptosis capability upon chronic exposure. Here, we review the substantial evidence of the mechanism of secondary bile acids and their role in colon cancer.
Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study
Authors: Kura Aminu Umar , Cheah Pike-See , Hussein Mohd Zobir , Hassan Zurina , Tengku Azmi Tengku Ibrahim , Hussein Nor Fuzina , Fakurazi Sharida
Published: May 2014

Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.
Generalized MMSE beamforming for multicell MIMO systems with random user geometry and channel feedback latency
Authors: Sohn Illsoo , Lee Hyoungjoo , Lee Kwang Bok
Published: May 2014

In this paper, we propose a generalized minimum mean square error (MMSE) beamforming for downlink multicell multiple-input multiple-output (MIMO) systems with local BS cooperations. Unlike the previous beamforming strategies which have been designed for an idealized multicell MIMO system model, we consider a complicated but realistic multicell MIMO system model. Our realistic multicell MIMO system model captures (i) different average SNRs of users due to random geometrical distribution of users within cells, (ii) channel feedback latency due to air propagation time and signal processing time, and (iii) different channel aging effects for intracell channel information and intercell channel information due to an additional backhaul latency during the exchange of information between pairs of neighboring cells. The key novelty of this paper is that we derive the closed-form beamforming expressions of the generalized MMSE beamforming using convex optimization technique. The closed-form beamforming expression gives insights on how the geometry of users and channel feedback latency affect the construction of optimal beamforming vectors. Numerical results verify that the proposed generalized MMSE beamforming outperforms previous beamforming strategies in both BER and average throughput performances.
Occurrence of Vibrio and Salmonella species in mussels (Mytilus galloprovincialis) collected along the Moroccan Atlantic coast
Authors: Mannas Hasna , Mimouni Rachida , Chaouqy Noureddine , Hamadi Fatima , Martinez-Urtaza Jaime
Published: May 2014

This study reports the occurrence of different Vibrio and Salmonella species in 52 samples of Mytilus galloprovincialis collected from four sites along the Atlantic coast between Agadir and Essaouira (Anza, Cap Ghir, Imssouane and Essaouira). The level of Escherichia coli (E. coli) was also determined to evaluate the degree of microbial pollution in the investigated areas. In this study three methods were used : AFNOR NF EN ISO 6579 V08-013 for Salmonella spp., the provisional method routinely used by several laboratories (Institut Pasteur, Paris,…) for Vibrio cholerae and Vibrio parahaemolyticus in the seafood, and the most probable number method (MPN) using Norm ISO/TS 16649–3 (2005) for E. coli. The most frequently isolated Vibrios were Vibrio alginolyticus (90.4% of samples), followed by V. cholerae non O1 non O139 (15.4%) and V. parahaemolyticus (7.7%). Salmonella spp. was found in 15% of the samples. The number of E. coli ranged between 0.2/100 g and 1.8 103 /100 g of mussel soft tissues. This study indicates the potential sanitary risk associated with the presence of pathogenic bacteria in cultivated mussels in the two populous regions of southern Morocco, where shellfish production and maritime tourism are important to the local economy.
Coral calcification under daily oxygen saturation and pH dynamics reveals the important role of oxygen
Authors: Wijgerde Tim , Silva Catarina I. F. , Scherders Vera , van Bleijswijk Judith , Osinga Ronald
Published: May 2014

Coral reefs are essential to many nations, and are currently in global decline. Although climate models predict decreases in seawater pH (∼0.3 units) and oxygen saturation (∼5 percentage points), these are exceeded by the current daily pH and oxygen fluctuations on many reefs (pH 7.8–8.7 and 27–241% O2 saturation). We investigated the effect of oxygen and pH fluctuations on coral calcification in the laboratory using the model species Acropora millepora. Light calcification rates were greatly enhanced (+178%) by increased seawater pH, but only at normoxia; hyperoxia completely negated this positive effect. Dark calcification rates were significantly inhibited (51–75%) at hypoxia, whereas pH had no effect. Our preliminary results suggest that within the current oxygen and pH range, oxygen has substantial control over coral growth, whereas the role of pH is limited. This has implications for reef formation in this era of rapid climate change, which is accompanied by a decrease in seawater oxygen saturation owing to higher water temperatures and coastal eutrophication.
Metabolism and mis-metabolism of the neuropathological signature protein TDP-43
Authors: Huang Chi-Chen , Bose Jayarama Krishnan , Majumder Pritha , Lee Kuen-Haur , Huang Jen-Tse Joseph , Huang Jeffrey K. , Shen Che-Kun James
Published: May 2014

TDP-43 is a pathological signature protein of neurodegenerative diseases with TDP-43 proteinopathies including FTLD-TDP and ALS-TDP. These TDP-43 proteinopathies are characterized with cytoplasmic insoluble TDP-43(+) aggregates in the diseased cells, the formation of which requires the seeding of TDP-25 fragment generated by caspase cleavage of TDP-43. We have investigated the metabolism and mis-metabolism of TDP-43 in cultured cells and found that the endogenous and exogenously over-expressed TDP-43 are degraded not only by ubiquitin proteasome system (UPS) and macroautophagy (MA), but also by the chaperone-mediated autophagy (CMA) mediated through interaction between Hsc70 and ubiquitinated TDP-43. Furthermore, proteolytic cleavage of TDP-43 by caspase(s) is a necessary intermediate step for degradation of a majority of the TDP-43 protein, with the TDP-25/TDP-35 fragments being the main substrates. Finally, we have determined the threshold level of the TDP-25 fragment that is necessary for formation of the cytosolic TDP-43(+) aggregates in cells containing the full-length TDP-43 at an elevated level close to that found in patients with TDP-43 proteinopathies. A comprehensive model of the metabolism and mis-metabolism of TDP-43 in relation to these findings is presented.
NF-κB determines axonal re- and degeneration by cell-specific balance of RelA and p50 subunits in the adult CNS
Authors: Haenold Ronny , Weih Falk , Herrmann Karl-Heinz , Schmidt Karl-Friedrich , Krempler Katja , Engelmann Christian , Nave Klaus-Armin , Reichenbach Jürgen R. , Löwel Sigrid , Witte Otto W. , Kretz Alexandra
Published: May 2014

NF-κB is dually involved in neurogenesis and brain pathology. Here, we addressed its role in adult axoneogenesis by generating mutations of RelA and p50 heterodimers of canonical NF-κB. In addition to activation in astrocytes, optic nerve axonotmesis caused a hitherto unrecognized RelA induction in growth inhibitory oligodendrocytes. Intraretinally, RelA was induced in severed retinal ganglion cells and inferred in bystander Muller glia. Cell type-specific deletion of transactivating RelA in neurons and/or macroglia considerably stimulated axonal regeneration in a distinct and synergistic pattern. In contrast, deletion of the p50 suppressor subunit promoted spontaneous and post-injury Wallerian degeneration. Growth effects mediated by RelA deletion paralleled a downregulation of growth inhibitory Cdh1 and upregulation of the endogenous Cdh1 suppressor EMI1. Pro-degenerative loss of p50, however, stabilized retinal Cdh1. In vitro, RelA deletion elicited opposing, pro-regenerative shifts in active nuclear and inactive cytoplasmic moieties of Cdh1 and Id2. The involvement of NF-κB and cell cycle regulators such as Cdh1 in regenerative processes of non-replicative neurons presents novel options regarding how molecular reprograming might be executed to stimulate adult axoneogenesis and treat CNS axonopathies.
Ribosome-omics of the human ribosome
Authors: Gupta Varun , Warner Jonathan R.
Published: May 2014

The torrent of RNA-seq data becoming available not only furnishes an overview of the entire transcriptome but also provides tools to focus on specific areas of interest. Our focus on the synthesis of ribosomes asked whether the abundance of mRNAs encoding ribosomal proteins (RPs) matched the equimolar need for the RPs in the assembly of ribosomes. We were at first surprised to find, in the mapping data of ENCODE and other sources, that there were nearly 100-fold differences in the level of the mRNAs encoding the different RPs. However, after correcting for the mapping ambiguities introduced by the presence of more than 2000 pseudogenes derived from RP mRNAs, we show that for 80%–90% of the RP genes, the molar ratio of mRNAs varies less than threefold, with little tissue specificity. Nevertheless, since the RPs are needed in equimolar amounts, there must be sluggish or regulated translation of the more abundant RP mRNAs and/or substantial turnover of unused RPs. In addition, seven of the RPs have subsidiary genes, three of which are pseudogenes that have been “rescued” by the introduction of promoters and/or upstream introns. Several of these are transcribed in a tissue-specific manner, e.g., RPL10L in testis and RPL3L in muscle, leading to potential variation in ribosome structure from one tissue to another. Of the 376 introns in the RP genes, a single one is alternatively spliced in a tissue-specific manner.
Time to get to know you
Authors: Barber Jenny
Published: May 2014

In the concluding part of her series, Sue Griffin explains why careful observation is key to treating each child as an individual and ensuring that inclusive practice underpins all aspects of nursery life
A great routine to get into
Authors: Bennetts Veronica
Published: May 2014

Dance not only provides fun physical activity for children, it also develops confidence – even in those who may not seem natural performers. Use Macmillan's new fundraising campaign as a springboard to get dancing.
Inside a rainforest
Authors: Chalmers Debbie
Published: May 2014

Children can gain knowledge and understanding of climate change, conservation, endangered species and the environment during the early years, through learning about rainforests and the creatures who live in them.
From the base to the tip
Authors: Davies Alison
Published: May 2014

This series of activities based on the symbolism of different shapes concludes with the triangle. From a Celtic Triskele to Egyptian pyramids, mountains to pine trees; there are manmade and natural versions all around.
Woolly ideas win!
Authors: Garner Lynne
Published: May 2014

Wool and yarn crafts are great for developing children's hand control and motor skills, using a cheap resource to create something quite impressive. Lynne Garner explains finger knitting, weaving and pom-pom making.
Turn over a new leaf
Authors: White Hilary
Published: May 2014

You might have tried leaf printing but what about leaf pounding to dye fabric, using leaves as a painting canvas instead of paper or creating natural necklaces? Hilary White shares these and many more ideas.