bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychoanalytic and Musical Ambiguity: the Tritone in Gee, Officer Krupke
Authors: Jaffee Nagel Julie
Published: March 2010

The poignant and timeless Broadway musical West Side Story is viewed from the standpoint of taking musical forms as psychoanalytic data. The musical configuration of notes called the tritone (or diabolus in musica) is taken as a sonic metaphor expressing ambiguity both in musical vocabulary and in mental life. The tritone, which historically and harmonically represents instability, is heard throughout the score and emphasizes the intrapsychic, interpersonal, and social dramas that unfold within and between the two gangs in West Side Story. Particular emphasis is given to the comic but exceedingly sober song Gee, Officer Krupke. Bernstein’s sensitivity to the ambiguity and tension inherent in the tritone in West Side Story is conceptualized as an intersection of music theory and theories of mind; this perspective holds implications for clinical practice and transports psychoanalytic concepts from the couch to the Broadway stage and into the community to address the complexities of love, hate, aggression, prejudice, and violence. Ultimately, West Side Story cross-pollinates music and theater, as well as music and psychoanalytic concepts.
Plying the Steel: a Reconsideration of Surgical Metaphors in Psychoanalysis
Authors: Ivey Gavin
Published: March 2010

Among the metaphors that Freud used to describe psychoanalysis, the surgical is possibly the most deplored. It is considered an anachronistic remnant of a dubious medical ideology that psychoanalysis has largely renounced. However, while analysts today avoid surgical analogies, their patients continue to produce surgical fantasies about analytic treatment. This fact alone requires a serious consideration of the meanings that surgical metaphors have for them. A second reason for reconsidering the role of the surgical metaphor, from the analyst’s perspective, lies in its creative revival by W. R. Bion. Disregarding the shift away from surgical analogizing, Bion employed the metaphor to vividly portray various aspects of the analytic situation and the patient’s experience of them. A brief historical overview of the surgical metaphor in psychoanalysis is provided, followed by an account of the reasons for its demise and by a review of the criticisms that continue to be leveled at it. Bion’s use of surgical metaphors toward the end of his life is then explored. Finally, illustrations are given of the various ways in which patients use spontaneous surgical metaphors to depict transference and the analytic process. Though the analyst should not deliberately adopt surgical metaphors, it is important to remain open to these transference portrayals.
‘God’s Golden Acre for Children’: Pastoralism and Sense of Place in New Suburban Communities
Authors: Corcoran Mary P.
Published: March 2010

This paper is based on an empirical case study of four suburbs in the Dublin city hinterland. It is argued that pastoral ideology plays an active role in constituting these new suburbs and helps to inculcate a sense of place. This sense of place in turn helps to cement social embeddedness which acts as a bulwark against isolation and alienation. Pastoral ideology is invoked by suburbanites even when the pastoral dimension of the suburb is under threat or has disappeared. The village or ‘main street’ acts as an important anchor for new suburban residents as does the surrounding ‘rural’ landscape and their own collective memories. However, the study reveals a gap between how some newer suburbs are represented and imagined, and how they are experienced in everyday life. This raises questions about the long-term viability of suburbs that lack a sense of place.
The Right of Children to Free and Compulsory Education Act, 2009
Authors: Dubey Muchkund
Published: March 2010

Much of the discussion on the Right to Education Act, 2009 has ignored the point that the passage of such a law has actually missed an excellent opportunity to address the systemic and fundamental problems of school education in India. Whether it is the question of access to all in a definite time frame, or improving quality with concrete provision of funds, taking education out of the current state of persistent underfunding despite the longstanding commitment to provide 6 percent of the GDP for education, it failed to meet the vision behind the Constitutional amendment that made education a fundamental right in Article 21A. Besides, this law perpetuates the multi-layer discriminating school system in India and reduces the notion of education to functional literacy, excluding a vast number of children in the age group of 0 to 5 at the pre-primary level and 16 to 18 in the secondary level from the ambit of universal and compulsory education. In fact, several of the measures mentioned in the Act may be devices to distract attention from the systemic problems facing school education.
Comparison of Paper-and-Pencil Versus Web Administration of the Youth Risk Behavior Survey (YRBS): Risk Behavior Prevalence Estimates
Authors: Eaton Danice K. , Brener Nancy D. , Kann Laura , Denniston Maxine M. , McManus Tim , Kyle Tonja M. , Roberts Alice M. , Flint Katherine H. , Ross James G.
Published: March 2010

The authors examined whether paper-and-pencil and Web surveys administered in the school setting yield equivalent risk behavior prevalence estimates. Data were from a methods study conducted by the Centers for Disease Control and Prevention (CDC) in spring 2008. Intact classes of 9th- or 10th-grade students were assigned randomly to complete a survey via paper-and-pencil or Web. Data from 5,227 students were analyzed using logistic regression to identify associations of mode with reporting of 74 risk behaviors. Mode was associated with reporting of only 7 of the 74 risk behaviors. Results indicate prevalence estimates from paper-and-pencil and Web school-based surveys are generally equivalent.
Agency Characteristics and Changes in Home Health Quality After Home Health Compare
Authors: Jung Kyoungrae , Shea Dennis , Warner Candy
Published: March 2010

Objective: This study examines the association between home health agency characteristics and quality improvement in home health care after Home Health Compare (HHC), a public-reporting initiative in the Medicare program. Method: We examined the changes in seven quality measures reported in HHC from 2003 to 2007. We used a linear regression model to examine whether quality changes over time differed by agency characteristics. Results: We found improvements in quality after HHC in the indicators that measure patients’ ability to independently manage daily activities; however, the use of emergent care did not change, and hospitalization rates increased during the study period. Agencies with low quality at baseline, not-for-profit or hospital-based agencies, and agencies with longer Medicare tenure showed greater improvement for some quality measures than their counterparts. Discussion: There was large variation in the degree of quality improvement after HHC by quality indicators and by agency characteristics.
‘Curvy, hunky, kinky’: Using corpora as tools for critical analysis
Authors: Caldas-Coulthard Carmen Rosa , Moon Rosamund
Published: March 2010

This article, an expanded version of an oral presentation in 1999, uses corpus methodology as a research tool to investigate how social actors are classified in the public discourse of the media, with lexis as our point of entry. Our main focus is the nature of the labels which provide categorization, especially of gender relations. Our main claim is that uses of premodification associated with the two types of newspapers in Britain and their lexical choices produce differential judgmental stances that have social effects. In the first of two complementary studies, we discuss the adjective lexicon of the tabloid press in comparison with quality newspapers, with curvy, hunky and kinky as exemplars with respect to sexualization and the construction of gender. In our second study, we discuss adjectival premodification of man, woman, girl and boy in tabloids and broadsheets: our findings show that the media categorizes people through very specific points of view and values not always apparent to a non-critical reader. Collocational patterns undoubtedly reveal societal and sociolectal attitudes, especially in terms of stereotypes of gender, sexualization, age and behaviour. Our main aim, therefore, is to show that corpus studies can help to deconstruct hidden meanings and the asymmetrical ways people are represented in the press.
Disembodiment and cyberspace: Gendered discourses in female teenagers’ personal information disclosure
Authors: García Gómez Antonio
Published: March 2010

At present, cyberspace tends to occupy a growing part of the social realities of most teenagers. The present study suggests that personal weblogs collectively can be said to comprise a social institution which serves to foster and maintain a cult of femininity. In promoting a cult of femininity, these personal weblogs are not merely reflecting the female role in society; they are also supplying one source of definitions of, and socialization into, that role. The main business of this study is to engage with a fairly large amount of data and try to answer some basic questions about how personal weblogs open up a new context for female teenage identity construction. More precisely, this article analyses the different gendered discourses British and Spanish female teenagers live out when they narrate their current and former romantic relationships. The study suggests that these female teenagers’ self-concepts, floating free of corporeal experience, derive from a struggle between their social relational identity and their individual-based social identity.
The discursive construction of identity and power in the critical classroom: Implications for applied critical theories
Authors: Mayes Patricia
Published: March 2010

The role of teacher identity and micro-level interaction in the construction of power relations in the critical classroom is investigated. This study took place in an American university in an English composition program that had implemented ‘critical pedagogy’, an applied critical theory that has the goal of changing the traditional power relations between teachers and students. Analysis of the institutional context and the discursive construction of teachers’ identities revealed contradictions between this goal and some of the teaching practices and suggested that power was not effectively redistributed as intended. The findings suggest that applied critical theories are often too simplistic, assuming that power can be straightforwardly transferred from the ‘powerful’ to the ‘powerless’. It is argued that proponents of such theories have under-theorized the notion of power, overlooking the paradox of ideology, which points to the role of micro-level interaction in the construction of power relations.
Changing the Cultural View and Coverage of End-of-Life Care
Authors: DeFanti Thomas R.
Published: March 2010

Since the mid-60s, the trend has been for treatment to stand at the forefront of medicine and when death occurs, it is seen as a failure of intervention. Institutional deaths are far greater today for the elderly and terminally ill patients than prior to the Medicare era. The safety, comfort, desires, and mental/spiritual well-being of the patient (and their family) are often lost in the attempt to treat rather than comfort. The cost of end-of-life care continues to spiral out of control (along with the rest of health care costs), yet there has been very little impact on longevity in spite of all the technological advances. A change in attitude is needed to properly provide and pay for end-of-life care.
Thalidomide for the Control of Severe Paraneoplastic Pruritus Associated With Hodgkin’s Disease
Authors: Gonçalves Ferraz
Published: March 2010

A 22-year-old woman with nodular sclerosis type II Hodgkin lymphoma diagnosed in June 2001. She initially underwent chemotherapy with 6 cycles of ABVD (adriamycin, bleomycin, vincristine, dacarbazine) regimen, leading to clinical remission. As it relapsed, she was again treated with 2 different chemotherapy regimens. In November 2003, she underwent bone marrow autotransplantation, but it relapsed after 2 months. After that, she was treated with chemotherapy in monotherapy until November 2005. In December 2005, she was referred to palliative care. Her main symptom was very severe pruritus that interfered with all aspects of her life, making her scratch continuously and interfering in all aspects of her life. She was treated with loratadine, hydroxyzine, prednisolone, paroxetine, mirtazapine, cimetidine, and ondansetron, individually and in various combinations. She also underwent ultraviolet phototherapy. All trials failed and her pruritus remained at level 8 of 10 most of the time. In April 2006, she started on thalidomide, 200 mg at night. The pruritus significantly improved to a level of 3 of 10 but did not disappear completely. She was at last able to sleep properly at night. She remained with a low level of pruritus until her death in July 2008, at the same dose of thalidomide.
What Does It Mean to Be a Patient Research Partner? An Ethnodrama
Authors: Schipper Karen , Abma Tineke A. , van Zadelhoff Ezra , van de Griendt Joos , Nierse Christi , Widdershoven Guy A. M.
Published: March 2010

There is a trend in medical and health research to involve patients in the research process. A recent role is the patient acting as a research partner in a team of professionals. There are a few publications about these collaborations and the value of research partners. But is the research partner accepted as a credible knower? How can equality in the collaboration be reached? And how to handle tensions between the research partner’s personal agenda and the interests of and burdens on fellow patients? Finally there is the question of how the research influences the research partner’s self-perception. The purpose of this article is to investigate these epistemological, relational, ethical, and existential issues, while presenting an ethnodrama. In this drama, the personal narrative of the research partner, a person with a renal disease, unfolds in dialogue with her research mates, whose voices are also present in the text. The article is based on a health research agenda—setting process with the Kidney Association in the Netherlands.
Conceptualising social exclusion and lesbian, gay, bisexual, and transgender people: the implications for promoting equity in nursing policy and practice
Authors: Fish Julie
Published: March 2010

Since the early 1980s, there has been increasing recognition that the health of individuals and communities is affected by social disadvantage. Following the election of the New Labour Government in 1997, social exclusion became a key concept in UK policymaking. Social exclusion approaches consider health outcomes to be linked to living and working conditions rather than, primarily, to healthcare interventions. Social exclusion is thus an important concept for nursing scholarship for understanding how people’s life circumstances may have an impact on their health. This paper analyses some of the theoretical underpinnings which may lead to recognition of the concept of lesbian, gay, bisexual and trans (LGBT) social exclusion. The paper goes on to propose a model of the multidimensional aspects of lesbian, gay, bisexual and trans social exclusion drawing on research evidence of the social, political and global inequalities experienced by lesbian, gay, bisexual and trans people. In conclusion, it considers the implications for promoting health equity in nursing policy and practice.
Inhibition of endothelial cell activation by bHLH protein E2-2 and its impairment of angiogenesis
Authors: Tanaka Aya , Itoh Fumiko , Nishiyama Koichi , Takezawa Toshiaki , Kurihara Hiroki , Itoh Susumu , Kato Mitsuyasu
Published: March 2010

E2-2 belongs to the basic helix-loop-helix (bHLH) family of transcription factors. E2-2 associates with inhibitor of DNA binding (Id) 1, which is involved in angiogenesis. In this paper, we demonstrate that E2-2 interacts with Id1 and provide evidence that this interaction potentiates angiogenesis. Mutational analysis revealed that the HLH domain of E2-2 is required for the interaction with Id1 and vice versa. In addition, Id1 interfered with E2-2–mediated effects on luciferase reporter activities. Interestingly, injection of E2-2–expressing adenoviruses into Matrigel plugs implanted under the skin blocked in vivo angiogenesis. In contrast, the injection of Id1-expressing adenoviruses rescued E2-2–mediated inhibition of in vivo angiogenic reaction. Consistent with the results of the Matrigel plug assay, E2-2 could inhibit endothelial cell (EC) migration, network formation, and proliferation. On the other hand, knockdown of E2-2 in ECs increased EC migration. The blockade of EC migration by E2-2 was relieved by exogenous expression of Id1. We also demonstrated that E2-2 can perturb VEGFR2 expression via inhibition of VEGFR2 promoter activity. This study suggests that E2-2 can maintain EC quiescence and that Id1 can counter this effect.
Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth
Authors: Kreuels Benno , Kreuzberg Christina , Kobbe Robin , Ayim-Akonor Matilda , Apiah-Thompson Peter , Thompson Benedicta , Ehmen Christa , Adjei Samuel , Langefeld Iris , Adjei Ohene , May Jürgen
Published: March 2010

The high prevalence of hemoglobin S (HbS) in Africa and hemoglobin C (HbC) in parts of West Africa is caused by the strong protection against severe falciparum malaria during childhood. Much less is known about the effect of HbS and especially HbC on Plasmodium falciparum infection, uncomplicated malaria, and anemia. A total of 1070 children from the Ashanti Region, Ghana, were enrolled at the age of 3 months and visited monthly until 2 years of age. The effects of the β-globin genotype on the age-dependent incidence of malaria, levels of parasitemia, and hemoglobin as well as physical development were analyzed by population-averaged models. Infants with HbAS were protected from uncomplicated malaria (P < .005) and anemia (P < .001), had lower age-adjusted parasite densities (P < .001), and higher age-adjusted hemoglobin levels compared with children with the HbAA genotype (P = .004). In contrast, HbAC carriers had lower hemoglobin levels (P < .033) and were not protected against malaria or anemia. Notably, infants with HbAS were also significantly protected against stunting compared with carriers of HbAA or HbAC. This indicates differing mechanisms of protection against malaria of HbAS and HbAC and might help to understand why HbC is restricted to distinct areas of West Africa.
A parallel and incremental algorithm for efficient unique signature discovery on DNA databases
Authors: Lee Hsiao Ping , Sheu Tzu-Fang , Tang Chuan Yi
Published: March 2010

Background

DNA signatures are distinct short nucleotide sequences that provide valuable information that is used for various purposes, such as the design of Polymerase Chain Reaction primers and microarray experiments. Biologists usually use a discovery algorithm to find unique signatures from DNA databases, and then apply the signatures to microarray experiments. Such discovery algorithms require to set some input factors, such as signature length l and mismatch tolerance d, which affect the discovery results. However, suggestions about how to select proper factor values are rare, especially when an unfamiliar DNA database is used. In most cases, biologists typically select factor values based on experience, or even by guessing. If the discovered result is unsatisfactory, biologists change the input factors of the algorithm to obtain a new result. This process is repeated until a proper result is obtained. Implicit signatures under the discovery condition (l, d) are defined as the signatures of length ≤ l with mismatch tolerance ≥ d. A discovery algorithm that could discover all implicit signatures, such that those that meet the requirements concerning the results, would be more helpful than one that depends on trial and error. However, existing discovery algorithms do not address the need to discover all implicit signatures.

Results

This work proposes two discovery algorithms - the consecutive multiple discovery (CMD) algorithm and the parallel and incremental signature discovery (PISD) algorithm. The PISD algorithm is designed for efficiently discovering signatures under a certain discovery condition. The algorithm finds new results by using previously discovered results as candidates, rather than by using the whole database. The PISD algorithm further increases discovery efficiency by applying parallel computing. The CMD algorithm is designed to discover implicit signatures efficiently. It uses the PISD algorithm as a kernel routine to discover implicit signatures efficiently under every feasible discovery condition.

Conclusions

The proposed algorithms discover implicit signatures efficiently. The presented CMD algorithm has up to 97% less execution time than typical sequential discovery algorithms in the discovery of implicit signatures in experiments, when eight processing cores are used.
Nuclear variants of bone morphogenetic proteins
Authors: Felin Jenny E , Mayo Jaime L , Loos Trina J , Jensen J Daniel , Sperry Daniel K , Gaufin Stephanie L , Meinhart Christopher A , Moss Jennie B , Bridgewater Laura C
Published: March 2010

Background

Bone morphogenetic proteins (BMPs) contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts.

Results

In all three proteins, a bipartite nuclear localization signal (NLS) was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5) containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle.

Conclusions

The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.
Analysis of the genome content of Lactococcus garvieae by genomic interspecies microarray hybridization
Authors: Aguado-Urda Mónica , López-Campos Guillermo H , Fernández-Garayzábal José F , Martín-Sánchez Fernando , Gibello Alicia , Domínguez Lucas , Blanco María M
Published: March 2010

Background

Lactococcus garvieae is a bacterial pathogen that affects different animal species in addition to humans. Despite the widespread distribution and emerging clinical significance of L. garvieae in both veterinary and human medicine, there is almost a complete lack of knowledge about the genetic content of this microorganism. In the present study, the genomic content of L. garvieae CECT 4531 was analysed using bioinformatics tools and microarray-based comparative genomic hybridization (CGH) experiments. Lactococcus lactis subsp. lactis IL1403 and Streptococcus pneumoniae TIGR4 were used as reference microorganisms.

Results

The combination and integration of in silico analyses and in vitro CGH experiments, performed in comparison with the reference microorganisms, allowed establishment of an inter-species hybridization framework with a detection threshold based on a sequence similarity of ≥ 70%. With this threshold value, 267 genes were identified as having an analogue in L. garvieae, most of which (n = 258) have been documented for the first time in this pathogen. Most of the genes are related to ribosomal, sugar metabolism or energy conversion systems. Some of the identified genes, such as als and mycA, could be involved in the pathogenesis of L. garvieae infections.

Conclusions

In this study, we identified 267 genes that were potentially present in L. garvieae CECT 4531. Some of the identified genes could be involved in the pathogenesis of L. garvieae infections. These results provide the first insight into the genome content of L. garvieae.
Differential detection of nuclear envelope autoantibodies in primary biliary cirrhosis using routine and alternative methods
Authors: Tsangaridou Elena , Polioudaki Hara , Sfakianaki Rania , Samiotaki Martina , Tzardi Maria , Koulentaki Meri , Panayotou George , Kouroumalis Elias , Castanas Elias , Theodoropoulos Panayiotis A
Published: March 2010

Background

Detection of autoantibodies giving nuclear rim pattern by immunofluorescence (anti-nuclear envelope antibodies - ANEA) in sera from patients with primary biliary cirrhosis (PBC) is a useful tool for the diagnosis and prognosis of the disease. Differences in the prevalence of ANEA in PBC sera so far reported have been attributed to the methodology used for the detection as well as to ethnic/geographical variations. Therefore, we evaluated the prevalence of ANEA in sera of Greek patients with PBC by using methods widely used by clinical laboratories and a combination of techniques and materials.

Methods

We screened 103 sera by immunoblotting on nuclear envelopes and indirect immunofluorescence (IIF) using cells and purified nuclei. Reactivities against specific autoantigens were assessed using purified proteins, ELISA, immunoprecipitation and mass spectrometry.

Results

We found higher prevalence of ANEA when sera were assayed by IIF on purified nuclei or cultured cells (50%) compared to Hep2 commercially available slides (15%). Anti-gp210 antibodies were identified in 22.3% and 33% of sera using ELISA for the C-terminal of gp210 or both ELISA and immunoprecipitation, respectively. Immunoblotting on nuclear envelopes revealed that immunoreactivity for the 210 kDa zone is related to anti-gp210 antibodies (p < 0.0001). Moreover, we found that sera had antibodies for lamins A (6.8%), B (1%) and C (1%) and LBR (8.7%), whereas none at all had detectable anti-p62 antibodies.

Conclusions

The prevalence of ANEA or anti-gp210 antibodies is under-estimated in PBC sera which are analyzed by conventional commercially available IIF or ELISA, respectively. Therefore, new substrates for IIF and ELISA should be included by clinical laboratories in the analysis of ANEA in autoimmune sera.
Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy
Authors: Matsunaga Miki , Okamoto Yasumasa , Suzuki Shin-ichi , Kinoshita Akiko , Yoshimura Shinpei , Yoshino Atsuo , Kunisato Yoshihiko , Yamawaki Shigeto
Published: March 2010

Background

Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.

Methods

Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up.

Results

Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT.

Conclusions

These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.
University life and pandemic influenza: Attitudes and intended behaviour of staff and students towards pandemic (H1N1) 2009
Authors: Van Debbie , McLaws Mary-Louise , Crimmins Jacinta , MacIntyre C Raina , Seale Holly
Published: March 2010

Background

In a pandemic young adults are more likely to be infected, increasing the potential for Universities to be explosive disease outbreak centres. Outbreak management is essential to reduce the impact in both the institution and the surrounding community. Through the use of an online survey, we aimed to measure the perceptions and responses of staff and students towards pandemic (H1N1) 2009 at a major university in Sydney, Australia.

Methods

The survey was available online from 29 June to 30 September 2009. The sample included academic staff, general staff and students of the University.

Results

A total of 2882 surveys were completed. Nearly all respondents (99.6%, 2870/2882) were aware of the Australian pandemic situation and 64.2% (1851/2882) reported either "no anxiety" or "disinterest." Asian-born respondents were significantly (p < 0.001) more likely to believe that the pandemic was serious compared to respondents from other regions. 75.9% (2188/2882) of respondents had not made any lifestyle changes as a result of the pandemic. Most respondents had not adopted any specific behaviour change, and only 20.8% (600/2882) had adopted the simplest health behaviour, i.e. hand hygiene. Adoption of a specific behaviour change was linked to anxiety and Asian origin. Students were more likely to attend the university if unwell compared with staff members. Positive responses from students strongly indicate the potential for expanding online teaching and learning resources for continuing education in disaster settings. Willingness to receive the pandemic vaccine was associated with seasonal influenza vaccination uptake over the previous 3 years.

Conclusions

Responses to a pandemic are subject to change in its pre-, early and mid-outbreak stages. Lessons for these institutions in preparation for a second wave and future disease outbreaks include the need to promote positive public health behaviours amongst young people and students.
Replication methods and tools in high-throughput cultivation processes - recognizing potential variations of growth and product formation by on-line monitoring
Authors: Huber Robert , Palmen Thomas G , Ryk Nadine , Hillmer Anne-Kathrin , Luft Karina , Kensy Frank , Büchs Jochen
Published: March 2010

Background

High-throughput cultivations in microtiter plates are the method of choice to express proteins from recombinant clone libraries. Such processes typically include several steps, whereby some of them are linked by replication steps: transformation, plating, colony picking, preculture, main culture and induction. In this study, the effects of conventional replication methods and replication tools (8-channel pipette, 96-pin replicators: steel replicator with fixed or spring-loaded pins, plastic replicator with fixed pins) on growth kinetics of Escherichia coli SCS1 pQE-30 pSE111 were observed. Growth was monitored with the BioLector, an on-line monitoring technique for microtiter plates. Furthermore, the influence of these effects on product formation of Escherichia coli pRhotHi-2-EcFbFP was investigated. Finally, a high-throughput cultivation process was simulated with Corynebacterium glutamicum pEKEx2-phoD-GFP, beginning at the colony picking step.

Results

Applying different replication tools and methods for one single strain resulted in high time differences of growth of the slowest and fastest growing culture. The shortest time difference (0.3 h) was evaluated for the 96 cultures that were transferred with an 8-channel pipette from a thawed and mixed cryoculture and the longest time difference (6.9 h) for cultures that were transferred with a steel replicator with fixed pins from a frozen cryoculture. The on-line monitoring of a simulated high-throughput cultivation process revealed strong variances in growth kinetics and a twofold difference in product formation. Another experiment showed that varying growth kinetics, caused by varying initial biomass concentrations (OD600 of 0.0125 to 0.2) led to strongly varying product formation upon induction at a defined point of time.

Conclusions

To improve the reproducibility of high-throughput cultivation processes and the comparability between different applied cultures, it is strongly recommended to use automated or manual liquid handling stations or, alternatively, multi-channel pipettes. Because of their higher transfer volume and hence precision in comparison to pin replicators, they reduce the variance of initial biomass concentrations. With respect to the results obtained, other methods to increase the comparability between parallel cultivations by compensating differences in biomass concentrations are required, such as using autoinduction media, fed-batch operation of precultures or on-line monitoring in microtiter plates combined with automated liquid handling.
Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach
Authors: Parravicini Chiara , Abbracchio Maria P , Fantucci Piercarlo , Ranghino Graziella
Published: March 2010

Background

GPR17 is a hybrid G-protein-coupled receptor (GPCR) activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes (cysteinyl-LTs), and involved in brain damage and repair. Its exploitment as a target for novel neuro-reparative strategies depends on the elucidation of the molecular determinants driving binding of purinergic and leukotrienic ligands. Here, we applied docking and molecular dynamics simulations (MD) to analyse the binding and the forced unbinding of two GPR17 ligands (the endogenous purinergic agonist UDP and the leukotriene receptor antagonist pranlukast from both the wild-type (WT) receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I) to Ile.

Results

MD suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and extracellular loop (EL) 2. The driving interaction involves R255 and the UDP phosphate moiety. To support this hypothesis, steered MD experiments showed that the energy required to unbind UDP is higher for the WT receptor than for R255I. Three potential binding sites for pranlukast where instead found and analysed. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the WT receptor and the R255I receptor were found for the unbinding of pranlukast.

Conclusions

These data thus suggest that, in contrast to which has been hypothesized for nucleotides, the lack of the R255 residue doesn't affect the binding of pranlukast a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17.
EVITA: a tool for the early EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage
Authors: Püntmann Isabel , Schmacke Norbert , Melander Arne , Lindberg Gunnar , Mühlbauer Bernd
Published: March 2010

Background

New drugs are generally claimed to represent a therapeutic innovation. However, scientific evidence of a substantial clinical advantage is often lacking. This may be the result of using inadequate control groups or surrogate outcomes only in the clinical trials. In view of this, EVITA was developed as a user-friendly transparent tool for the early evaluation of the additional therapeutic value of a new drug.

Methods

EVITA does not evaluate a new compound per se but in an approved indication in comparison with existing therapeutic strategies. Placebo as a comparator is accepted only in the absence of an established therapy or if employed in an add-on strategy on top. The evaluation attributes rating points to the drug in question, taking into consideration both therapeutic benefit and risk profile. The compound scores positive points for superiority in efficiency and/or adverse effects as demonstrated in randomized controlled trials (RCTs), whilst negative points are awarded for inferiority and/or an unfavorable risk profile. The evaluation follows an algorithm considering the clinical relevance of the outcomes, the strength of the therapeutic effect and the number of RCTs performed. Categories for therapeutic aim and disease severity, although essential parts of the EVITA assessment, are attributed but do not influence the EVITA score which is presented as a color-coded bar graph. In case the available data were unsuitable for an EVITA calculation, a traffic-type yield sign is assigned instead to criticize such practice. The results are presented online http://www.evita-report.de together with all RCTs considered as well as the reasons for excluding a given RCT from the evaluation. This allows for immediate revision in response to justified criticism and simplifies the inclusion of new data.

Results

As examples, four compounds which received approval within the last years were evaluated for one of their clinical indications: lenalidomide, pioglitazone, bupropion and zoledronic acid. Only the first achieved an EVITA score above zero indicating therapeutic advantage.

Conclusions

The strength of EVITA appears to lie in its speedy assessment of the potential therapeutic advantage of a new drug for a given indication. At the same time, this approach draws attention to the typical deficits of data used for drug approval. EVITA is not intended to replace classical health technology assessment reports but rather serves as a screening tool in the sense of horizon scanning.
Perceptions of unmet healthcare needs: what do Punjabi and Chinese-speaking immigrants think? A qualitative study
Authors: Marshall Emily G , Wong Sabrina T , Haggerty Jeannie L , Levesque Jean-Fréderic
Published: March 2010

Background

Unmet healthcare needs - the difference between healthcare services deemed necessary to deal with a particular health problem and the actual services received - is commonly measured by the question, "During the past 12 months, was there ever a time when you felt that you needed healthcare, but you didn't receive it?" In 2003, unmet needs were reported by 10% of immigrants in Canada, yet, little is known specifically about Chinese- or Punjabi-speaking immigrants' perceptions and reporting of unmet needs. Our study examined: 1) How are unmet healthcare needs conceptualized among Chinese- and Punjabi-speaking immigrants? 2) Are their primary healthcare experiences related to their unmet healthcare needs?

Methods

Twelve focus groups (6 Chinese, 6 Punjabi; n = 78) were conducted in Chinese or Punjabi and socio-demographic and health data were collected. Thematic analysis of focus group data examined the perceptions of unmet needs and any relationship to primary healthcare experiences.

Results

Our analysis revealed two overarching themes: 1) defining an unmet healthcare need and 2) identifying an unmet need. Participants had unmet healthcare needs in relation to barriers to accessing care, their lack of health system literacy, and when the health system was less responsive than their expectations.

Conclusions

Asking whether someone ever had a time when they needed healthcare but did not receive it can either underestimate or overestimate unmet need. Measuring unmet need using single items is likely insufficient since more detail in a revised set of questions could begin to clarify whether the reporting of an unmet need was based on an expectation or a clinical need. Who defines what an unmet healthcare need is depends on the context (insured versus uninsured health services, experience in two or more healthcare systems versus experience in one healthcare system) and who is defining it (provider, patient, insurer).
Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy
Authors: Lewis Mark G , Norelli Sandro , Collins Matt , Barreca Maria Letizia , Iraci Nunzio , Chirullo Barbara , Yalley-Ogunro Jake , Greenhouse Jack , Titti Fausto , Garaci Enrico , Savarino Andrea
Published: March 2010

Background

In this study we successfully created a new approach to ART in SIVmac251 infected nonhuman primates. This drug regimen is entirely based on drugs affecting the pre-integration stages of replication and consists of only two nucleotidic/nucleosidic reverse transcriptase inhibitors (Nt/NRTIs) and raltegravir, a promising new drug belonging to the integrase strand transfer inhibitor (INSTI) class.

Results

In acutely infected human lymphoid CD4+T-cell lines MT-4 and CEMx174, SIVmac251 replication was efficiently inhibited by raltegravir, which showed an EC90in the low nanomolar range. This result was confirmed in primary macaque PBMCs and enriched CD4+T cell fractions.In vivomonotherapy with raltegravir for only ten days resulted in reproducible decreases in viral load in two different groups of animals. When emtricitabine (FTC) and tenofovir (PMPA) were added to treatment, undetectable viral load was reached in two weeks, and a parallel increase in CD4 counts was observed. In contrast, the levels of proviral DNA did not change significantly during the treatment period, thus showing persistence of this lentiviral reservoir during therapy.

Conclusions

In line with the high conservation of the three main amino acids Y143, Q148 and N155 (responsible for raltegravir binding) and molecular docking simulations showing similar binding modes of raltegravir at the SIVmac251 and HIV-1 IN active sites, raltegravir is capable of inhibiting SIVmac251 replication both in tissue culture andin vivo. This finding may help to develop effective ART regimens for the simian AIDS model entirely based on drugs adopted for treatment in humans. This ART-treated AIDS nonhuman primate model could be employed to find possible strategies for virus eradication from the body.
Insulin receptor signaling in the development of neuronal structure and function
Authors: Chiu Shu-Ling , Cline Hollis T
Published: March 2010

Sensory experience plays a crucial role in regulating neuronal shape and in developing synaptic contacts during brain formation. These features are required for a neuron to receive, integrate, and transmit signals within the neuronal network so that animals can adapt to the constant changing environment. Insulin receptor signaling, which has been extensively studied in peripheral organ systems such as liver, muscle and adipocyte, has recently been shown to play important roles in the central nervous system. Here we review the current understanding of the underlying mechanisms that regulate structural and functional aspects of circuit development, particularly with respect to the role of insulin receptor signaling in synaptic function and the development of dendritic arbor morphology. The potential link between insulin receptor signaling malfunction and neurological disorders will also be discussed.
Generation and analysis of expressed sequence tags from a cDNA library of the fruiting body of Ganoderma lucidum
Authors: Luo Hongmei , Sun Chao , Song Jingyuan , Lan Jin , Li Ying , Li Xiwen , Chen Shilin
Published: March 2010

Background

Little genomic or trancriptomic information on Ganoderma lucidum (Lingzhi) is known. This study aims to discover the transcripts involved in secondary metabolite biosynthesis and developmental regulation of G. lucidum using an expressed sequence tag (EST) library.

Methods

A cDNA library was constructed from the G. lucidum fruiting body. Its high-quality ESTs were assembled into unique sequences with contigs and singletons. The unique sequences were annotated according to sequence similarities to genes or proteins available in public databases. The detection of simple sequence repeats (SSRs) was preformed by online analysis.

Results

A total of 1,023 clones were randomly selected from the G. lucidum library and sequenced, yielding 879 high-quality ESTs. These ESTs showed similarities to a diverse range of genes. The sequences encoding squalene epoxidase (SE) and farnesyl-diphosphate synthase (FPS) were identified in this EST collection. Several candidate genes, such as hydrophobin, MOB2, profilin and PHO84 were detected for the first time in G. lucidum. Thirteen (13) potential SSR-motif microsatellite loci were also identified.

Conclusion

The present study demonstrates a successful application of EST analysis in the discovery of transcripts involved in the secondary metabolite biosynthesis and the developmental regulation of G. lucidum.
A case of pseudohyperkalemia in a patient presenting with leucocytosis and high potassium level: a Case Report
Authors: Kim Alice , Biteman Benjamin , Malik Umer F , Siddique Shahzad , Martin Mersadies R , Ali Syed A , Maboud Nadeem , Raja Sabiya , Zachry Alison , Mahmoud Ahmed
Published: March 2010

Pseudohyperkalemia can appear in a variety of settings and should be recognized early. Treatment of pseudohyperkalemia can lead to an inappropriate decrease of actual serum potassium levels which may lead to life threatening conditions. In the case presented, an 81-year-old male presented with massive leucocytosis and an extremely elevated potassium level. This case report emphasizes the importance of recognizing pseudohyperkalemia in a patient with a severely increased potassium and WBC level; such patients may be clinically asymptomatic or may have a normal ECG.