New media applications such as social networking sites are understood as important evolutions for queer youth. These media and communication technologies allow teenagers to transgress their everyday life places and connect with other queer teens. Moreover, social media websites could also be used for real political activism such as publicly sharing coming out videos on YouTube. Despite these increased opportunities for self-reflexive storytelling on digital media platforms, their everyday use and popularity also bring particular complexities in the everyday lives of young people. Talking to 51 youngsters between 13 and 19 years old in focus groups, this paper inquires how young audiences discursively constructed meanings on intimate storytelling practices such as interpreting intimate stories, reflecting on their own and other peers' intimate storytelling practices. Specifically focusing on how they relate to intimate storytelling practices of gay peers, this paper identified particular challenges for queer youth who transgress the heteronormative when being active on popular social media. The increasing mediatization of intimate youth cultures brings challenges for queer teenagers, which relate to authenticity, (self-) surveillance and fear of imagined audiences.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8psNg
via IFTTT
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 16 Δεκεμβρίου 2015
The discursive construction of gay teenagers in times of mediatization: youth's reflections on intimate storytelling, queer shame and realness in popular social media places
Declining maternal mortality in the face of persistently high HIV prevalence in a middle-income country
Objective: To estimate maternal mortality ratio (MMR) and determine maternal death causes and trends in Greater Soweto, Johannesburg, South Africa. Design: Cross-sectional study. Setting: Chris Hani Baragwanath Maternity Hospital (CHBMH) in Greater Soweto. Population: Maternal deaths at CHBMH. Methods: Record review of maternal deaths from 1997 to 2012, using hospital death records, with denominator data from the district health information system and the hospital. Main outcome measures: Maternal mortality ratio per 100000 live births, and causes of death classified as in the South African confidential enquiries. Results: There were 479 deaths, with a peak MMR of 139 in 2004 and a decline to 86 in 2012. Of 332 women tested, 245 (74%) were HIV-infected. Nonpregnancy-related infection (40%) was the most frequent cause of death, followed by hypertension (16%) and obstetric haemorrhage (13%). HIV infection rates in these groups were 92%, 30% and 61%, respectively. Previous caesarean section was associated with obstetric haemorrhage death (odds ratio [OR] 3.2, 95% confidence interval [95% CI] 1.7-6.0), maternal age 35years with hypertension death (OR 2.2, 95% CI 1.2-3.7) and antenatal anaemia with nonpregnancy-related infection death (OR 4.0, 95% CI 2.3-6.9), compared with other causes of death. Conclusion: There is evidence of a decline in MMR since HIV treatment for pregnant women was introduced in 2004. Previous caesarean section, advanced maternal age, and anaemia were associated with death from obstetric haemorrhage, hypertensive disorders of pregnancy and nonpregnancy-related infections, respectively. MMR may be further reduced with accelerated initiation of HIV treatment during pregnancy.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8ppBa
via IFTTT
Film policy, national identity and period adaptations in Flanders during the 1970s and 1980s
During the 1970s and 1980s, 'period adaptations,' or period films based on the Flemish literary patrimony, were the most prominent and prestigious genre of film production in Flanders, the northern, Dutch-speaking region of Belgium. Connecting the observation that official film policy largely determines Flemish film production with the dominant interpretation of period adaptations in Flemish cultural and national terms, these films are often seen as the product of an official Flemish film policy strategy. Drawing on original archival research and interviews with policy actors and film-makers, this article offers a detailed historical account of the Flemish film support process behind the allocation of official film funds for period adaptations and how the national question was involved. Contrary to common assumptions, this film support process was a very complex and often ambiguous one, whereby Flemish cultural nationalist concerns could work both to the advantage and to the disadvantage of period adaptation projects. While the Minister of Culture's advisory board (the film commission) took a key role within this process, the agency of a variety of other actors (most notably Flemish public television and film producers) should also be taken into consideration.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1m6HlBI
via IFTTT
A cross-cultural approach to Brokeback Mountain (1997 & 2005)
In her article "A Cross-Cultural Approach to Brokeback Mountain" Jono Van Belle draws on insights from film theory and cultural narratology in order to analyse Annie Proulx's short story "Brokeback Mountain" and its filmic adaptation by Ang Lee. Van Belle's analysis is about how culturally different worldviews play a role in the construction of meaning by audience and she links the different narrative levels of semantics, genre typology, and worldviews in the short story and the film to the scholarship of the story. Further, Van Belle argues that worldviews and the problematics of gayness represented in "Brokeback Mountain" and its filmic adaptation would gain insight following in-depth research by comparative analyses between Eastern and Western epistemologies.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8prZE
via IFTTT
Youth and intimate media cultures: gender, sexuality, relationships, and desire as storytelling practices in social networking sites
This paper investigates how young people give meaning to gender, sexuality, relationships, and desire in the popular social networking site (SNS) Netlog. In arguing how SNSs are important spaces for intimate politics, the extent to which Netlog is a space that allows contestations of intimate stories and a voicing of difference is questioned. These intimate stories should be understood as self-representational media practices; young people make sense of their intimate stories in SNSs through media cultures. Media cultures reflect how audiences and SNS institutions make sense of intimacy. This paper concludes that intimate stories as media practices in the SNS Netlog are structured around creativity, anonymity, authenticity, performativity, bricolage and intertextuality. The intimate storytelling practices focusing on creativity, anonymity, bricolage and intertextuality are particularly significant for a diversity of intimacies to proliferate.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1m6HmWh
via IFTTT
(Non-) invasive mapping of cortical language areas
The precise localization of eloquent cortex is crucial for planning the extent and exact location of cortical resection in neurosurgical settings. While all brain areas are of functional importance, the term "eloquent" brain region refers to structures where damage can result in severe neurological symptoms that significantly affect the patient's functional outcome and quality of life. Presurgical functional mapping has become an essential tool to avoid neurological impairment after surgical resection in patients with focal epilepsy or resectable tumors.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1T1eidH
via IFTTT
Cholesterol Oxidase
Recombinant Cholesterol Oxidase belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with oxygen as acceptor. This enzyme participates in bile acid biosynthesis.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8eYNK
via IFTTT
XPF cell line
The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5 incision made during nucleotide excision repair. This complex is a structure specific contact us: contact@creative-biogene.com Tel: 5166698109 Visit: http://ift.tt/1I8eYxu...
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1ZbnC2b
via IFTTT
Isotopically labeled Peptides
Stable Isotope Labeled MS Peptide Standard contact us: contact@creative-proteomics.com Tel: 5166698109 Visit: http://ift.tt/1I8eYxj
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1ZbnAY8
via IFTTT
Automatic Mechanisms for Social Attention Are Culturally Penetrable
Abstract
Are mechanisms for social attention influenced by culture? Evidence that social attention is triggered automatically by bottom-up gaze cues and is uninfluenced by top-down verbal instructions may suggest it operates in the same way everywhere. Yet considerations from evolutionary and cultural psychology suggest that specific aspects of one's cultural background may have consequence for the way mechanisms for social attention develop and operate. In more interdependent cultures, the scope of social attention may be broader, focusing on more individuals and relations between those individuals. We administered a multi-gaze cueing task requiring participants to fixate a foreground face flanked by background faces and measured shifts in attention using eye tracking. For European Americans, gaze cueing did not depend on the direction of background gaze cues, suggesting foreground gaze alone drives automatic attention shifting; for East Asians, cueing patterns differed depending on whether the foreground cue matched or mismatched background cues, suggesting foreground and background gaze information were integrated. These results demonstrate that cultural background influences the social attention system by shifting it into a narrow or broad mode of operation and, importantly, provides evidence challenging the assumption that mechanisms underlying automatic social attention are necessarily rigid and impenetrable to culture.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8nbl6
via IFTTT
Language Use and Coalition Formation in Multiparty Negotiations
Abstract
The alignment of bargaining positions is crucial to a successful negotiation. Prior research has shown that similarity in language use is indicative of the conceptual alignment of interlocutors. We use latent semantic analysis to explore how the similarity of language use between negotiating parties develops over the course of a three-party negotiation. Results show that parties that reach an agreement show a gradual increase in language similarity over the course of the negotiation. Furthermore, reaching the most financially efficient outcome is dependent on similarity in language use between the parties that have the most to gain from such an outcome.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NwIbPs
via IFTTT
Mechanisms of Reference Frame Selection in Spatial Term Use: Computational and Empirical Studies
Abstract
Previous studies have shown that multiple reference frames are available and compete for selection during the use of spatial terms such as "above." However, the mechanisms that underlie the selection process are poorly understood. In the current paper we present two experiments and a comparison of three computational models of selection to shed further light on the nature of reference frame selection. The three models are drawn from different areas of human cognition, and we assess whether they may be applied to a reference frame selection by examining their ability to account for both existing and new empirical data comprising acceptance rates, response times, and response time distributions. These three models are the competitive shunting model (Schultheis, ), the leaky competing accumulator (LCA) model (Usher & McClelland, ), and a lexical selection model (Howard, Nickels, Coltheart, & Cole-Virtue, ). Model simulations show that only the LCA model satisfactorily accounts for the empirical observations. The key properties of this model that seem to drive its success are its bounded linear activation function, its number and type of processing stages, and its use of decay. Uncovering these critical properties has important implications for our understanding not only of spatial term use, in particular, but also of conflict and selection in human cognition more generally.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8nb4M
via IFTTT
The cerebro-cerebellum: Could it be loci of forward models?
Publication date: Available online 15 December 2015
Source:Neuroscience Research
Author(s): Takahiro Ishikawa, Saeka Tomatsu, Jun Izawa, Shinji Kakei
It is widely accepted that the cerebellum acquires and maintain internal models for motor control. An internal model simulates mapping between a set of causes and effects. There are two candidates of cerebellar internal models, forward models and inverse models. A forward model transforms a motor command into a prediction of the sensory consequences of a movement. In contrast, an inverse model inverts the information flow of the forward model. Despite the clearly different formulations of the two internal models, it is still controversial whether the cerebro-cerebellum, the phylogenetically newer part of the cerebellum, provides inverse models or forward models for voluntary limb movements or other higher brain functions. In this article, we review physiological and morphological evidence that suggests the existence in the cerebro-cerebellum of a forward model for limb movement. We will also discuss how the characteristic input-output organization of the cerebro-cerebellum may contribute to forward models for non-motor higher brain functions.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1mnpQNZ
via IFTTT
Impulsivity in cocaine-dependent individuals with and without attention-deficit/hyperactivity disorder
Background: Cocaine-dependent individuals (CDI) display increased impulsivity. Despite its multi- factorial nature however, most studies in CDI have treated impulsivity monolithically. Moreover, the impact of attention-deficit/hyperactivity disorder (ADHD) has often not been taken into account. This study investigates whether CDI+ADHD differ from CDI without an ADHD diagnosis and healthy controls (HC) on several impulsivity measures. Methods : 34 CDI, 25 CDI+ADHD and 28 HC participated in this study. Trait impulsivity was assessed with the motor, attentional and non-planning subscales of the Barratt Impulsiveness Scale (BIS-11). Neurocognitive dimensions of impulsivity were examined with the stop signal task (SST), delay discounting task (DDT) and information sampling task (IST). Results : Relative to HC, both CDI and CDI+ADHD scored higher on all BIS-11 subscales, required more time to inhibit their responses (SST) and sampled less information before making a decision (IST). Greater discounting of delayed rewards (DDT) was only found among CDI+ADHD. Compared to CDI without ADHD, CDI+ADHD scored higher on the BIS-11 non-planning and total scale and showed higher discounting rates. Conclusion : CDI score higher on several indices of impulsivity relative to HC, regardless of whether they have concomitant ADHD. CDI+ADHD are specifically characterized by a lack of future orientation compared to CDI without ADHD.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1O5dGze
via IFTTT
Strange bedfellows?: big business meets small farmer
Population growth and urbanization cause an increased demand for food distributed through modern food supply chains, dominated by a handful of large international agri-businesses. Primary production, quite contrarily, is dominated by hundreds of millions of small-scale farmers in developing countries. Although big business and small-scale farmers might seem to be strange bedfellows, there are numerous situations in which they already form economic relationships. In the doctoral thesis, the focus lies on a peculiar subset of relationships, so-called inclusive business models, which consists of for-profit buying relationships with small-scale farmers in which the firm states to care about the well-being of the farmer. The thesis contains four papers. Two papers analyse the organisational structure of the economic relationship between firms and small-scale farmers. One paper takes a critical look at an often used way to measure the well-being of small-scale farmers: a food security indicator. The final paper is on coffee certification, a well-known example of an inclusive business model, and looks at its impact on the set of activities farmers rely on to make a living.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1O5dGiJ
via IFTTT
Treatment satisfaction and quality of support in outpatient substitution treatment: opiate users' experiences and perspectives
Aims: Patient-reported outcomes have become an important source of information to guide service provision. Although opiate substitution treatment (OST) is an evidence-based and widely available intervention for opiate dependent individuals, evaluation studies have primarily focused on objective outcome indicators rather than on clients' perspectives and personal experiences. This study aims to assess opiate users' satisfaction with various aspects of substitution treatment and their subjective experiences and expectations regarding the provision of psychosocial support. Methods: The study sample consisted of 77 opiate- dependent individuals who had been involved in OST for at least three months in some cities in Belgium. Qualitative interviews were used to explore clients' subjective experiences, in addition to some quantitative measures. Findings: About half of the respondents recently received some form of psychosocial support and they were generally satisfied about these services. However, the number of persons who wanted psychosocial support clearly outnumbered those actually receiving these services. Respondents stressed the importance of building trusting relationships with OST staff. Also, the need for more flexible and individualised support was emphasised. Conclusions: Compared with other stakeholders' perspectives or traditional outcome indicators, service users' subjective experiences shed an alternative light on the impact of opiate dependence and OST on individuals' daily lives. This information should be incorporated in individual treatment planning and when designing and evaluating OST services.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1P7pmXA
via IFTTT
Keep an eye on your friends, even when you don’t know them”: Drug use and harm reduction in the Goa trance scene in Belgium
Aims: The high prevalence of illegal drug use among rave party attendees and the emerging Goa trance scene in Belgium are the main impetus for assessing perceived harm reduction strategies among Goa party visitors. Insights into this question can contribute to our understanding of contemporary underground drug cultures and help to identify potential pathways for targeted interventions in (underground) music scenes such as Goa trance. Methods: Following pilot observations at Goa parties, in-depth interviews were conducted with 19 Belgian Goa party attendees. Respondents were recruited by snowball sampling. Findings: Their insiders' perspectives revealed that solidarity is still apparent and is an important variable in minimizing drug-related harm. Furthermore, controlled drug consumption is employed to minimize harm, such as buying drugs from trusted people, trying to keep drug use limited to weekends, respecting one's own limits, and always providing help and support to people in need. Conclusions: The combination of introducing communitarian and neo-liberal values into harm reduction strategies might challenge public health workers. Approaching drug users as active citizens and useful resources may lead the way to innovative harm reduction strategies. Evaluating enabling resources in settings where drug use occurs, will provide additional pathways to harm reduction policies and programs.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1P7pkyY
via IFTTT
Design and systematic study of imidazole based DNAzymes: an integrated NMR and molecular dynamics approach
Proteins are known as the workhorses of the cell and fulfill numerous tasks essential for the cell's survival. One of the most important tasks is their involvement in catalysis. From a thermodynamic point of view, this is made possible by the stabilisation of the transition state, a high-energy reaction state between reactants and products. This stabilization is made possible due to a combination of a wide variety of chemical functionalities inherent to the twenty amino acid building blocks. This variety observed with proteins stands in sharp contrast to the limited structural diversity of DNA and RNA. These biomolecules are optimized for hydrogen bonding and the formation of complementary, predictable helix-like structures. It thus seemed highly unlikely DNA and RNA could ever fulfill the same catalytic functions as proteins. The discovery and subsequent development of natural and synthetic catalytic RNA and DNA (deoxy)ribozymes has overturned this belief. Mainly identified by means of in vitro selection and evolution experiments, RNA/DNA-based catalysts employ a variety of catalytic mechanisms. Nevertheless, despite the numerous successes of the top-down in vitro approach, structural insight in how these RNA- and DNAzymes ultimately achieve catalysis is still lacking and can be considered as one of the main drawbacks for their further development. Inspired by these developments and limitations, the current research project aims to develop DNA-based hydrolases via a more bottom-up approach. Here the stable and predictable nature of the DNA duplex is employed to position one or more imidazole-bearing thymine nucleotide building blocks (TIm) using standard phosphoramidite solid phase chemistry. Via systematic studies using UV-VIS thermal melting experiments, NMR and molecular dynamics simulations, the mutual impact of the modification and the DNA scaffold could be identified. This approach was applied in two major systematic studies focussing on both single and multiple TIm modified DNA systems. In case of the single modified systems a so-called pKaH-regulating motif (figure) has been uncovered where the imidazole modification at position n in the DNA duplex engages in a persistent hydrogen bond interaction with the carbonyl groups of guanine bases at positions n+1 and n+2 residing in the DNA major groove. This interaction in turn contributes in a significant thermal stabilisation of ±6°C and increase of over 1 pKaH unit with respect to other non-interacting modified systems. In addition to its identity and overall features, the possible sequential permutations of this motif were explored as well. Given that a single TIm functionality alone is unlikely to generate any meaningful catalytic activity, the second systematic study focused on the mutual impact of multiple imidazole residues residing in the same system, both in the presence and absence of the interaction motif. Furthermore these systems allowed to confirm that the motif is tolerated when multiple imidazoles are present and relative positioning of the pKaH-regulating motif with respect to the non-interacting imidazole allows to regulate the pKaH value of the second non-interacting imidazole functionality within certain limits as well. The observations and guidelines obtained during these studies should allow to gradually develop more intricate systems that are ultimately able to cleave ester and/or amide bonds in a stereo selective fashion.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1P7pmH1
via IFTTT
Restless Legs Syndrome
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1lOSJ5O
via IFTTT
A Compartmentalized Profibrotic Immune Response Characterizes Pericardial Tuberculosis, Irrespective of HIV-1 Infection
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1lOSJ5D
via IFTTT
Personalizing Therapy in Idiopathic Pulmonary Fibrosis: A Glimpse of the Future?
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NwH81S
via IFTTT
Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials
American Journal of Respiratory and Critical Care Medicine, Volume 192, Issue 12, Page 1416-1419, December 15, 2015.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NwH81I
via IFTTT
Pulmonary Venous Varix
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NwH6an
via IFTTT
Dyspnea: Don’t Just Look, Ask!
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NwH6a7
via IFTTT
Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
American Journal of Respiratory and Critical Care Medicine, Volume 192, Issue 12, Page 1462-1474, December 15, 2015.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NwH5TJ
via IFTTT
Scientometrics Portal Launched to Celebrate 10 Years of Applied Ontology
IOS Press is proud to announce the Applied Ontology scientometrics installation in celebration of the journal's 10th anniversary. The portal allows users to visually explore how Applied Ontology has changed and grown in the last decade. The installation is developed by the STKO Lab at the University of California, Santa Barbara.
Scientometrics play an increasingly important role in facilitating the understanding of different research fields as well as research topics within them. The installation has deployed modules based on linked data of published articles in Applied Ontology of the last 10 years. Various modules explore where the authors come from, how they collaborate and how the topics within the field of applied ontology developed over the years. An overview per author shows details of their work published in Applied Ontology.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TPmzBo
via IFTTT
Expanding the clinical spectrum of the “HDAC8-phenotype” – Implications for molecular diagnostics, counselling and risk prediction
Abstract
Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of eleven patients carrying ten distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features.
The phenotype of our patients is very broad whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients.
Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counselling and risk prediction.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Yg8SlD
via IFTTT
Refining the continuum of CFTR-associated disorders in the era of newborn screening
Abstract
Clinical heterogeneity in cystic fibrosis (CF) often causes diagnostic uncertainty in infants without symptoms and in older patients with milder phenotypes. We performed a cross-sectional evaluation of a comprehensive set of clinical and laboratory descriptors in a physician-defined cohort (N=376; Children's Hospital of Wisconsin and the American Family Children's Hospital CF centers in Milwaukee and Madison, Wisconsin, USA) to determine the robustness of categorizing CF (N=300), cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (N=19), and CFTR related (CRMS) metabolic syndrome (N=57) according to current consensus guidelines. Outcome measures included patient demographics, clinical measures, sweat chloride levels, CFTR genotype, age at diagnosis, airway microbiology, pancreatic function, infection, and nutritional status. The CF cohort had a significantly higher median sweat chloride level (105 mmol/L) than CFTR-related disorder patients (43 mmol/L) and CFTR-related metabolic syndrome patients (35 mmol/L; p≤0.001). Patient groups significantly differed in pancreatic sufficiency, immunoreactive trypsinogen levels, sweat chloride values, genotype, and positive Pseudomonas aeruginosa cultures (p≤0.001). An automated classification algorithm using recursive partitioning demonstrated concordance between physician diagnoses and consensus guidelines. Our analysis suggests that integrating clinical information with sweat chloride levels, CFTR genotype, and pancreatic sufficiency provides a context for continued longitudinal monitoring of patients for personalized and effective treatment.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Yg8QdC
via IFTTT
A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma
Head and neck squamous cell carcinoma (HNSCC) causes a significant morbidity worldwide with the incidence of approximately 550,000 cases per year [1]. The most common risk factors are tobacco use and human papillomavirus (HPV) infection [2,3]. At diagnosis, a majority of patients present with locally advanced disease, but patients with HPV-positive HNSCC have a more favorable survival compared to patients with HPV-negative HNSCC [4–6]. However, there is a clear interaction between tobacco use and HPV-related carcinogenesis reflected by the worse survival of patients with HPV-positive HNSCC and smoking history compared to non-smokers [6,7].
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Np7zJ1
via IFTTT
A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma
Cetuximab is an anti-epidermal growth factor receptor (EGFR/ErbB) antibody whose efficacy in treating relapsed/metastatic head and neck squamous cell carcinomas (R/M HNSCC) is limited by inherent or acquired resistance [1]. Epithelial-to-mesenchymal transition (EMT) has been hypothesized as a possible cause for drug resistance and worse prognosis in HNSCC [2–4]. The Hedgehog signaling pathway (HhP) has been implicated in EMT [5]. In the HhP the sonic hedgehog (SHH) ligand activates a signaling cascade that leads to glioma-associated oncogene family zinc finger 1 (GLI1) expression, which in turn modulates numerous cancer target genes [5,6].
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1lORlQp
via IFTTT
C/EBPα negatively regulates SIRT7 expression via recruiting HDAC3 to the upstream- promoter of hepatocellular carcinoma cells
Publication date: Available online 15 December 2015
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Gui-fen Liu, Jian-yi Lv, Yan-jun Zhang, Lang-xi Zhang, Guo-dong Lu, Ze-jun Xie, Mo-bin Cheng, Yu-fei Shen, Ye Zhang
Mammalian Sirtuin proteins (SIRTs) are homologs of yeast Sir2, and characterized as class III histone deacetylases of NAD+ dependence. Unlike their lower counterparts that directly involved in the extending of lifespan, mammalian SIRTs are mainly function in metabolism and cellular homeostasis, among them, SIRT7 is the least understood. SIRT7 is localized in nucleus and rich in nucleoli associated with RNA polymerase I, and correlated with cell proliferation. In contrast, SIRT7 has recently been demonstrated to specifically deacetylate H3K18ac in the chromatin, and in most cases represses proliferation. Although MicroRNA as miR-125b has been reported to down-regulate SIRT7 by binding to its 3'UTR, however, how SIRT7 gene is regulated remains unclear. Here, we identified the transcription initiation site of human SIRT7 gene at the upstream 23rd A nucleotide respective to the translational codon, and the SIRT7 is a TATA-less and initiator-less gene. The sequences in the upstream region between -256 and -129bp are identical with important functions in the three species detected. A C/EBPα responding element is found that binds both C/EBPα and C/EBPβ in vitro. We showed TSA induced SIRT7 gene transcription and only the HDAC3, but not its catalytic domain depleted mutant, interacted with C/EBPα to occupy the C/EBPα element and repressed SIRT7 gene in the hepatocellular carcinoma cells. To our knowledge, this is the first report on the regulation mechanism of SIRT7 gene, in which, HDAC3 collaborated with C/EBPα to occupy its responding element in the upstream region of SIRT7 gene and repressed its expression in human cells.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1I8kqQQ
via IFTTT
Controlling Material Reactivity Using Architecture
3D printing methods are used to generate reactive material architectures. Several geometric parameters are observed to influence the resultant flame propagation velocity, indicating that the architecture can be utilized to control reactivity. Two different architectures, channels and hurdles, are generated, and thin films of thermite are deposited onto the surface. The architecture offers an additional route to control, at will, the energy release rate in reactive composite materials.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/226Dp4Y
via IFTTT
N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]- 1-carboxamide: a promising positron emission tomography ligand for fatty acid amide hydrolase
Publication date: Available online 15 December 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Yoko Shimoda, Masayuki Fujinaga, Akiko Hatori, Joji Yui, Yiding Zhang, Nobuki Nengaki, Yusuke Kurihara, Tomoteru Yamasaki, Lin Xie, Katsushi Kumata, Hideki Ishii, Ming-Rong Zhang
To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]- 1-carboxamide ([11C]DFMC, [11C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1 nM) for FAAH. [11C]1 was synthesized by C-11C coupling reaction of arylboronic ester 2 with [11C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [11C]1 was obtained with a radiochemical yield of 20 ± 10% (based on [11C]CO2, decay-corrected, n = 10) and specific activity of 48–166 GBq/μmol. After the injection of [11C]1 in mice, high uptake of radioactivity (> 2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for [11C]1 revealed high uptakes in the cerebellar nucleus (SUV = 2.4) and frontal cortex (SUV = 2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30 min after the radioligand injection. The present results indicate that [11C]1 is a promising PET ligand for imaging of FAAH in living brain.
Graphical abstract
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Mgrx4u
via IFTTT
Allosteric inhibitors of Coxsackie virus A24 RNA polymerase
Publication date: Available online 15 December 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Catherine H. Schein, Diane Rowold, Kyung H. Choi
Coxsackie virus A24 (CVA24), a causative agent of acute hemorrhagic conjunctivitis, is a prototype of enterovirus (EV) species C. The RNA polymerase (3Dpol) of CVA24 can uridylylate the viral peptide linked to the -genome (VPg) from distantly related EV, and is thus, a good model for studying this reaction. Once UMP is bound, VPgpU primes RNA elongation. Structural and mutation data have identified a conserved binding surface for VPg on the RNA polymerase (3Dpol), located about 20Å from the active site. Here, computational docking of over 60,000 small compounds was used to select those with the lowest (best) specific binding energies (BE) for this allosteric site. Compounds with varying structures and low BE were assayed for their effect on formation of VPgU by CVA24-3Dpol. Two compounds with the lowest specific BE for the site inhibited both uridylylation and formation of VPgpolyU at 10-20 μM. These small molecules can be used to probe the role of this allosteric site in polymerase function, and may be the basis for novel antiviral compounds.
Graphical abstract
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1MgrwO9
via IFTTT
Role of Second Transplantation for Children With Acute Myeloid Leukemia Following Posttransplantation Relapse
Background
In children with acute myeloid leukemia (AML), hematopoietic stem cell transplantation (HSCT) in first remission is indicated for patients with a relatively high risk of relapse. Second HSCT is a curative option; however, few reports have been published about a second HSCT in children for AML with posttransplantation relapse.
Procedure
Using the database provided by the Japanese Society of Hematopoietic Cell Transplantation, we analyzed 46 children with AML who underwent a second allogeneic HSCT after achieving a second remission.
Results
The median duration from the first to second HSCT was 20 months, and the source of the second HSCT was related bone marrow (BM) in 22, related peripheral blood in 6, unrelated BM in 14, and unrelated cord blood in 4 patients. Twenty-five children eventually died of the following causes: progressive disease in 14 and transplant-related toxicities in 9. The 5-year overall survival rate was 41.7 ± 7.7%. An interval of less than 24 months between the first and second HSCT was a significant poor prognostic factor.
Conclusions
Children with AML who experience a relapse after HSCT in first remission have a good chance of survival with a second HSCT if a second remission is achieved.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Np5vAN
via IFTTT
Exchange Transfusion and Leukapheresis in Pediatric Patients with AML With High Risk of Early Death by Bleeding and Leukostasis
Background
The risk of early death (ED) by bleeding/leukostasis is high in patients with AML with hyperleukocytosis (>100,000/μl). Within the pediatric AML-BFM (Berlin-Frankfurt-Münster) 98/04 studies, emergency strategies for these children included exchange transfusion (ET) or leukapheresis (LPh). Risk factors for ED and interventions performed were analyzed.
Patients
Two hundred thirty-eight of 1,251 (19%) patients with AML presented with hyperleukocytosis; 23 of 1,251 (1.8%) patients died of bleeding/leukostasis.
Results
ED due to bleeding/leukostasis was highest at white blood cell (WBC) count >200,000/μl (14.3%). ED rates were even higher (20%) in patients with FAB (French-American-British) M4/M5 and hyperleukocytosis >200,000/μl. Patients with WBC >200,000/μl did slightly better with ET/LPh compared to those without ET/LPh (ED rate 7.5% vs. 21.2%, P = 0.055). Multivariate WBC >200,000/μl was of strongest prognostic significance for ED (P(χ2) <0.0001).
Conclusion
Our data confirm the high risk of bleeding/leukostasis in patients with hyperleukocytosis. ET/LPh shows a trend toward reduced ED rate due to bleeding/leukostasis and is recommended at WBC >200,000/μl, and in FAB M4/M5 even at lower WBC.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Np5vAy
via IFTTT
Experimental and numerical investigations of the influence of cracks on mass diffusion in mortar and concrete
Even though it was intensely studied in the last decades, chloride ingress into cracked concrete and its influence on reinforced concrete (RC) structures with cracks is still not sufficiently understood, due to its complexity. Along the years, different testing methods were adopted by researchers in order to study the influence of different factors: crack characteristics, environmental parameters, concrete properties and mitigating mechanisms on chloride penetration in cracked concrete. Due to their many advantages, a great interest has been shown in developing a numerical model that can accurately predict chloride penetration into concrete by taking into consideration several aspects of the transport mechanisms of chloride. Still, very limited investigation of the influence of chloride diffusion on samples with real cracks can be found in literature. In this thesis an attempt was made to develop a numerical model that can accurately simulate chloride penetration in structures with real cracks. Chapter 1 presents the introduction, underlining the motivation and the background of the present research project. General information about chloride penetration in concrete is presented such as the service life of a RC structure, the critical chloride value and corrosion mechanisms are presented. Also an outline of the thesis is presented. In chapter 2 a brief review of both the experimental and numerical information found in literature regarding chloride ingress in uncracked and cracked concrete is provided. First, several crack preparation methods are presented, followed by the description of the most common experimental methods used to determine chloride penetration in concrete: migration tests and diffusion tests. The main chloride transport mechanisms are then given and briefly discussed. Also the influence of different parameters (crack width, crack depth, water-to-binder ratio, cement content and cement type, and loading conditions) and mitigating mechanisms on chloride penetration in cracked concrete are presented. Finally, a description of the various numerical and modelling techniques found in literature analysing the two or three- dimensional aspects of chloride ingress in cracked concrete taking into account its different transport mechanisms is provided. Chapter 3 deals with the experimental part of the research. First, an overview of the experimental part is provided. In order to study the influence of real cracks on the chloride penetration in RC structures, 40 cores with 100 mm diameter were drilled from different locations from a previously loaded RC slab, manufactured with a concrete class C30/37 with a maximum size of aggregate of 14 mm. The samples where then prepared to meet the requirements specified in the standard NT BUILD 492 (1999) for the non-steady state migration test (100 mm diameter and 50 mm thickness). Based on their characteristics, the 40 samples were then grouped in four main categories: samples without cracks and without rebars (S), samples with cracks and without rebars (SC), samples without cracks and with rebars (SR), samples with cracks and with rebars (SCR). For each particular sample, geometric characteristics (crack width, crack tortuosity and roughness, rebar position) have been determined, and the position of the carbonation front was also detected. In addition to crack width measurements along the top and bottom surfaces, each core was vertically sectioned in different locations, perpendicular to the surface crack. The crack profile through the specimen's thickness was studied and the crack width through the sample was determined. In order to experimentally determine the chloride ingress, a non-steady state migration test was performed (NT BUILD 492, 1999) and both the chloride penetration profile and the migration coefficient were determined for each sample. Based on the experimental data it was found that the presence of cracks has a significant influence on chloride ingress, increasing it, but also that chloride penetration is significantly affected by the characteristics of the concrete on the exposed surface. The surface layer of concrete affects the transport characteristics of the material and can enhance the chloride ingress. Also, although a more complex study must be performed, based on the available data, it was found that carbonation influences the chloride front and decreases significantly the chloride concentration. Even though having a limited number of replicas, a statistical analysis at a confidence level of 95% was realized in order to investigate the possible influence of crack width on chloride ingress, but no statistically significant influence was found within the range considered. Chapter 4 presents a numerical model that can realistically simulate chloride ingress in uncracked and cracked concrete. Initially, a 2D model was developed to simulate chloride transport on mortar samples with artificial cracks (notches), with different widths and depths, using the Abaqus/Standard software based on the finite element method (FEM) using the mass diffusion tool. The algorithm for solving mass diffusion equations in Abaqus is described. The numerical results obtained were compared to the experimental ones and a good agreement between them was found, showing the validity of the proposed model. Also, from these simulations it was found that within the parameter range considered the chloride transport property of concrete is not influenced by the considered crack widths, but only by the crack depths. Furthermore, it was also concluded that chloride penetration depth has a reduced sensitivity to changes in the diffusion coefficient, when simulating chloride diffusion. A 3D model was then used to simulate chloride ingress in the uncracked and cracked samples used in the experimental part previously described. It must be mentioned that as in the case of the 2D model presented above, the model parameters such as the diffusion coefficient D, the initial chloride concentration c and the applied chloride concentration C, were determined experimentally and were used as simulation parameters. Chloride ingress was simulated in uncracked concrete (reference samples type S) and afterwards it was simulated on cracked concrete (Sample 4-of type SC with cracks and without rebars). When comparing the numerical results with the experimental ones, good agreement was found. Also, this chapter presents a 3D model of each sample used in the experimental part, with regards to the individual geometrical characteristics of each sample, including the crack pattern and rebar position. In chapter 5, final conclusions, personal contributions and some suggestions of further research are presented
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Np5vk2
via IFTTT