bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased levels of circulating DNA in patients with systemic autoimmune diseases: A possible marker of disease activity in Sjögren’s syndrome
Authors: Bartoloni E , Ludovini V , Alunno A , Pistola L , Bistoni O , Crinò L , Gerli R
Published: May 2011

High levels of serum and/or plasma circulating DNA (cDNA) have been described in patients with systemic autoimmune diseases (SADs). However, the role of this molecule has not been clarified. Our aim was to evaluate plasma cDNA levels in 48 systemic lupus erythematosus (SLE) and 44 primary Sjögren’s syndrome (SS) patients, as compared with healthy and rheumatoid arthritis (RA) subjects, and to analyse their correlation with disease activity, disease damage and clinical manifestations. Plasma DNA was extracted using Qiagen columns and quantified by real-time quantitative PCR. Disease activity and damage were evaluated in both diseases by analysis of clinical and laboratory findings. Our results showed that plasma cDNA levels were significantly higher in patients with SS (mean ± SE: 32.0 ± 7.3 ng/ml) and with SLE (35.0 ± 9.0 ng/ml) than in controls (5.1 ± 1.1 ng/ml) ( p < 0.0001 for both). Disease activity index correlated with cDNA levels in SS ( p = 0.02), but not in SLE, and SS subjects with active disease displayed significantly higher cDNA levels with respect to inactive patients ( p < 0.05). No correlation was found between plasma cDNA levels and disease damage indexes in either SLE or SS. These results indicate that increased plasma cDNA levels can been demonstrated in SLE and in SS patients with respect to healthy subjects. Interestingly, although cDNA levels did not correlate with indexes of disease damage in these disorders, a significant correlation between cDNA concentrations and disease activity was observed in SS, but not in SLE, suggesting a possible role of cDNA as non-invasive marker of disease activity. The different results obtained in these SADs may be explained by distinct disease pathogenesis or the influence of immunosuppressive and corticosteroid therapy that, unlike in SS, is usually employed in SLE.
Volatility of World Soybean Prices, Import Tariffs and Poverty in Indonesia
Authors: Dartanto Teguh , Usman
Published: May 2011

High volatility of world soybean prices have caused uncertainty and vulnerability particularly in net-importer countries like Indonesia. This study aims to measure the impact on poverty in Indonesia of volatility in the world price and import tariffs of soybeans. By applying a computable general equilibrium (CGE)-microsimulation approach and the endogenous poverty line, it was shown that the dramatic volatility of world soybean prices during 2007–09 had a significant effect on increasing poverty in Indonesia. The simulation result showed that a 40 per cent increase in world price raises the head count index by 0.204 per cent which equals 427,971. However, zero import tariffs implemented by the government through regulation 01/PMK.011/2008 in response to high world prices could not perfectly absorb the negative impact of increasing world soybeans price on poverty. Zero import tariffs would be effective in protecting the poor in Indonesia if the world soybean price increase was not more than 10 per cent. Moreover, protection in the agricultural sector, such as raising import tariffs, intended to help agricultural producers will have the reverse effect of raising the head count index.
Trade Performance of SEZs in India
Authors: Tantri Malini L.
Published: May 2011

The performance of seven conventional Indian special economic zones (SEZs) at the disaggregate level is analysed within the framework of the zone-trade performance index, for the period between 1986–87 and 2007–08. The analysis reveals variations in performance across zones as well as within the zones over the reference period. The variations in performance are found to be statistically significant as well. The zones specifically located in economically developed states performed better than the zones in other states. This reveals the pressing problem of regional disparities finding reflection in the SEZs structure and calls for policy intervention. Further, zones are found to be equally sensitive to external economic fluctuations. On the positive side, the introduction of the SEZs policy in 2000–01 has had a favourable impact on the performance of these enclaves.
Parents’ Experiences Following Children’s Moderate to Severe Traumatic Brain Injury
Authors: Roscigno Cecelia I. , Swanson Kristen M.
Published: May 2011

Little is understood about parents’ experiences following children’s moderate to severe traumatic brain injury (TBI). Using descriptive phenomenology, we explored common experiences of parents whose children were diagnosed with moderate to severe TBI. Parents from across the United States ( N = 42, from 37 families) participated in two semistructured interviews (~ 90 minutes in length and 12 to 15 months apart) in the first 5 years following children’s TBI. First interviews were in person. Second interviews, done in person or by phone, facilitated updating parents’ experiences and garnering their critique of the descriptive model. Parent themes were (a) grateful to still have my child, (b) grieving for the child I knew, (c) running on nerves, and (d) grappling to get what my child and family need. Parents reported cultural barriers because of others’ misunderstandings. More qualitative inquiry is needed to understand how the knowledge, attitudes, beliefs, and culture-based expectations of others influence parents’ interactions and the family’s adjustment and well-being.
Major Depressive Disorder in Persons Exposed to Trauma: Relationship Between Emotional Intelligence and Social Support
Authors: Kwako Laura E. , Szanton Sarah J. , Saligan Leorey N. , Gill Jessica M.
Published: May 2011

BACKGROUND: Traumatic events are often linked to the onset of major depressive disorder (MDD) and for the increase of nonremittance of symptoms; however, psychological factors that contribute to the relationship between trauma and chronic depression are not well defined. OBJECTIVE: The objective of this study is to determine if emotional intelligence (EI) and social support differ in traumatized depressed patients when compared with controls. METHOD: The present study examines two psychosocial factors that may contribute to this link: EI and social support. Participants who experienced a trauma and had current MDD ( n = 38) were compared with nontraumatized healthy controls ( n = 40). RESULTS: Traumatized depressed participants exhibited lower total EI, because of reductions in strategic EI ability, as well as lower levels of social support compared with the control group. CONCLUSIONS: EI and social support were significantly correlated. These findings suggest that EI may be a novel target for intervention to prevent and treat MDD.
The Brief Cognitive-Behavioral COPE Intervention for Depressed Adolescents: Outcomes and Feasibility of Delivery in 30-Minute Outpatient Visits
Authors: Lusk Pamela , Melnyk Bernadette Mazurek
Published: May 2011

BACKGROUND: Despite a U.S. prevalence of 9%, less than 25% of depressed adolescents receive treatment because of time constraints in clinical practice and lack of mental health providers available to deliver it. OBJECTIVE: To assess the feasibility and effects of a brief manualized seven-session cognitive—behavioral skills building intervention entitled COPE (Creating Opportunities for Personal Empowerment) delivered to 15 depressed adolescents in routine 30-minute mental health medication management outpatient visits. STUDY DESIGN: A preexperimental one group pre- and posttest design was used. RESULTS: Adolescents reported significant decreases in depression, anxiety, anger, and destructive behavior as well as increases in self-concept and personal beliefs about managing negative emotions. Evaluations indicated that COPE was a positive experience for teens and parents. CONCLUSION: COPE is a promising brief cognitive—behavior therapy—based intervention that can be delivered within 30-minute individual outpatient visits. With this intervention, advanced practice nurses can work with practice time limitations and still provide evidence-based treatment for depressed teens.
Tridimensional Personalities and Polymorphism of Dopamine D2 Receptor Among Heroin Addicts
Authors: Teh Lay K. , Izuddin Abu F. , M. H. Fazleen H. , Zakaria Zainul A. , Salleh Mohd. Zaki
Published: May 2011

Background: Drug addiction is a multifactorial disorder. Researchers have posited that an individual’s inherited behavioral propensity or temperament contributes to the disorder by shaping a personality strongly linked with the risk of drug abuse. Further, they hypothesize that the polymorphism of dopamine D2 receptor increases the susceptibility to and severity of addiction. We, therefore, investigated possible associations between dopamine D2 receptor (DRD2) and personality traits among intravenous heroin addicts. Methods: We assessed 93 intravenous heroin addicts and controls using Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) and the Tridimensional Personality Questionnaire (TPQ). We confirmed drug-dependence status using a questionnaire based on DSM-IV criteria. We extracted DNA from the subjects’ whole blood and genotyped it for DRD2 allelic variants. Results: Genotype analysis showed a significantly higher frequency for the TaqIA polymorphism among the addicts (69.9%) compared to control subjects (42.6%; Fisher’s exact χ2, p < .05). We observed no significant differences for other variants between the addicts and controls. The addicts had higher scores for novelty seeking (NS) and harm avoidance (HA) personality traits but lower scores for reward dependence (RD) when compared to control subjects. Limitation: The environmental cues are different for the addicts, and the healthy university students we used as controls. We recommend that researchers employ a gene-environment interaction approach to study factors associated with addictive behaviors in future studies. Conclusion: Taq1A may be implicated for an increased vulnerability to addiction. Screening of this marker might be useful for identifying individuals at risk of addiction.
Nocturnal Sleep–Wake Parameters of Adolescents at Home Following Cancer Chemotherapy
Authors: Walker Amy J. , Johnson Kyle P. , Miaskowski Christine , Gedaly-Duff Vivian
Published: May 2011

Purpose: The purpose of this descriptive, longitudinal study was to describe objective nocturnal sleep–wake parameters of adolescents at home after receiving chemotherapy in the hospital or outpatient clinic and explore differences in sleep variables by age, gender, and corticosteroid use. Methods: We collected 7 days of wrist actigraphy and sleep diary data from 48 adolescents (10–19 years) who were receiving cancer chemotherapy for a primary or secondary cancer or a relapse. The actigraphic sleep variables included rest interval (i.e., time in bed), sleep onset, sleep offset, sleep duration, total sleep time (TST), wake after sleep onset (WASO), and %WASO. Results: Of the 48 adolescents, 38 had at least five nights of scored actigraphy and were included in analyses. Older (13–18 years) adolescents went to bed later and had fewer minutes of TST than younger adolescents (10–12 years). Exploratory analyses revealed no differences between adolescents who were taking oral corticosteroids (i.e., prednisone, dexamethasone) and those who were not or between males and females. Conclusion: These adolescents had sleep durations that met or exceeded the recommended sleep duration for their age groups but experienced significant WASO. Further research is needed to estimate sleep needs of adolescents during chemotherapy and determine factors that contribute to nocturnal wake-time so that targeted interventions can be designed to improve sleep quality.
The conditioned eyeblink reflex: a potential tool for the detection of cerebellar dysfunction in multiple sclerosis
Authors: Rampello Liborio , Casolla Barbara , Rampello Luigi , Pignatelli Marco , Battaglia Giuseppe , Gradini Roberto , Orzi Francesco , Nicoletti Ferdinando
Published: May 2011

The delayed conditioned eyeblink reflex, in which an individual learns to close the eyelid in response to a conditioned stimulus (e.g. a tone) relies entirely on the functional integrity of a cerebellar motor circuitry that involves the contingent activation of Purkinje cells by parallel and climbing fibres. Molecular changes that disrupt the function of this circuitry, in particular a loss of type-1 metabotropic glutamate receptors (mGlu1 receptors), occur in Purkinje cells of patients with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis as a result of neuroinflammation. mGlu1 receptors are required for cerebellar motor learning associated with the conditioned eyeblink reflex. We propose that the delayed paradigm of the eyeblink conditioning might be particularly valuable for the detection of subtle abnormalities of cerebellar motor learning that are clinically silent and are not associated with demyelinating lesions or axonal damage. In addition, the test might have predictive value following a clinically isolated syndrome, and might be helpful for the evaluation of the efficacy of drug treatment in multiple sclerosis.
Evaluation of an adjustment group forpeople with multiple sclerosis and lowmood: a randomized controlled trial
Authors: Lincoln Nadina B , Yuill Faye , Holmes Jessica , Drummond Avril ER , Constantinescu Cris S , Armstrong Sarah , Phillips Ceri
Published: May 2011

Background: Mood problems affect many people with multiple sclerosis (MS). The aim was to evaluate the effectiveness of a group treatment based on cognitive behavioural principles.

Methods: People with MS were screened on the General Health Questionnaire 12 (GHQ-12) and Hospital Anxiety and Depression Scale (HAD). Those identified with low mood were invited to take part in a randomized trial comparing the effect of attending an adjustment group with a waiting list control. Patients allocated to the adjustment group received six 2 h group treatment sessions. Outcomes were assessed 4 and 8 months after randomization, blind to group allocation.

Results: Of the 311 patients identified, 221 (71%) met the criteria for low mood and 151 (68%) agreed to take part. Hierarchical regression analyses were conducted to compare the two groups, correcting for baseline mood and disability. At 4 months, group allocation alone was a significant predictor of the primary outcome measure, the GHQ-12. At 8 months, group allocation alone was no longer a significant predictor for GHQ-12 scores, but it was when baseline GHQ-12 and Guy’s Neurological Disability Scale scores were controlled for. Comparison of the area under the curve revealed significant differences between the groups for GHQ-12 ( p = 0.003), HAD Anxiety ( p = 0.013), HAD Depression ( p = 0.004), Beck Depression Inventory ( p = 0.001), MS Self-efficacy ( p = 0.037) and MS Impact Scale Psychological ( p = 0.012).

Conclusion: Patients receiving treatment were less distressed and had less depression and anxiety. There was some evidence of improved self-efficacy and a reduction of the impact of MS on people’s lives.
A Comparative Study of Visuals in the Urban Landscapes of Tokyo and London
Authors: Yamada-Rice Dylan
Published: May 2011

This visual essay provides an overview of a comparative study of visuals in the urban landscapes of Tokyo and London, using Google Street View to make these comparisons. The data were analysed using Visual Content Analysis and colour coding. The findings are that Tokyo has a higher density and diversity of visuals at a wider range of heights. Visual and written communication also appear to be confined to more separately definable spaces with more equal weighting in the use of written and visual modes.
Red socks and purple rain: the political uses of colour in late apartheid South Africa
Authors: Archer Arlene , Stent Stacey
Published: May 2011

This article explores the extent to which colour functions as an independent mode in a particular context and explores the culturally produced regularities in the uses of colour in this context. Drawing on a Hallidayan metafunctional view of text, we look at how colour instantiated systems of knowledge and belief (ideational function) and social relations and identities (interpersonal function) in South Africa during the last decade of the apartheid government. In this type of repressive socio-political context, colour was a less policed mode, and thus had different affordances to images and the verbal modes. We argue that colour can function as an independent mode under certain conditions, such as stringent press restrictions, where the use of colour in a range of media (clothing, flags, posters) can play a crucial role in communicating.
Cartoon drawing as a means of accessing what students know about HIV/AIDS: an alternative method
Authors: Mutonyi Harriet , Kendrick Maureen E.
Published: May 2011

Combating the spread of HIV/AIDS in Uganda has involved massive public education campaigns. One of the challenges of these campaigns has always involved the need to simultaneously respect and transcend cultural taboos around direct discussions about sexuality and sexual issues, particularly among youth. Research consistently shows that drawing, as a means of investigating what students know, has the potential to reveal students’ perceptions of given concepts and provides an alternative to predominantly language-based methods. Visual methods, however, have rarely been taken up in research on students’ sexual health and HIV/AIDS knowledge. This interpretive case study examines the use of cartoon drawing as a unique tool for understanding Ugandan secondary students’ conceptions of HIV/ AIDS, particularly concepts that are not directly discussed culturally.
From leadership-as-practice to leaderful practice
Authors: Raelin Joe
Published: May 2011

Consistent with views that see leadership emerging from social practices rather than from the external mind, this paper contributes to an emerging movement in leadership studies known as ‘leadership-as-practice’ (L-A-P). This movement looks for leadership in its music and activity rather than in the traits and heroics of individual actors. The article distinguishes L-A-P from the individualistic approach by explaining its intersection with its dualistic counterpart, theory; with the agency—structure problem; and with relationality and meaning in organizations. It calls for a modification in classic approaches to research methodology and to leadership development. L-A-P is advised to consider its natural affinity with democratic participation through leaderful practices that systematically privilege the co-creation of social organization.
Alexander Pope and The Rape of the Lock – Conciliation or Judgment?
Authors: Watkins Dawn
Published: May 2011

The focus of this article is The Rape of the Lock, written by Alexander Pope (1688–1744). The poem was first published in 1712 but was further revised and expanded by Pope, prior to its publication in the first edition of Pope’s collected works in 1717. The opening lines of the poem

What dire offence from am’rous causes springs, What mighty contests rise from trivial things (Canto I.1–2)

point to its ostensible purpose as an instrument of reconciliation; its epic treatment of a matter so trivial as the stealing of a lock of hair being designed to “laugh together” the once friendly but now hostile families of the offender and the offended. Although the conciliatory intent of the poem remains a popular assumption, scholars have strongly disputed this view, arguing instead that the anecdotal reporting of a family feud provided Pope with a most welcome and timely poetic opportunity.

Pope was a Roman Catholic and because of the recusancy laws that existed throughout his lifetime all the conventional means by which he could hope to influence society were closed to him. However, this article argues that it was through the establishment of his reputation as a poet that Pope was able to gain authority and respect far beyond the confines of the Catholic community. Further, and via an alignment with views that dispute the traditional, positivist approach to the definition of legal judgment, the article suggests a reading of The Rape of the Lock as an instrument of judgment. The epic treatment of an insignificant dispute both operates to ridicule the trivial concerns of Pope’s immediate society, and allows for a wider questioning of the social and political issues of the period.
Breach! The Law’s Jouissance in Miéville’s The City & The City
Authors: Hourigan Daniel
Published: May 2011

This article critically examines the construction of law in China Miéville’s weird detective narrative The City & The City (2009). The discussion charts the excesses of law’s embodiment in Detective Tyador Borlú of the Besźel policzai with and against the primordial natural law discourse of the Law of Breach, and carefully examines the ways that this Law interdicts the common law in both parts of the fictional split city Besźel-Ul Qoma. Using the psychoanalytic concept of jouissance, this article unveils some of the modulations of authority presented by the novel’s unusual arrangement of politics, common law, and natural law.
The ‘dangerous other’ in maximum-security prisons
Authors: Drake Deborah
Published: May 2011

Drawing on data from maximum-security prisons in England, this article explores the way the representation of criminals as ‘dangerous others’ manifests in prison discourse and practice. Following Bourdieu, it is argued that within the ‘habitus of maximum-security’, prison staff become somewhat predisposed to seeing prisoners as essentialized, ‘dangerous others’ who are not ‘like us’, a perspective that is also reinforced in popular and tabloid print media outside the prison walls. The strength of these representations coupled with the habitus of maximum-security thus constrains possibilities for alternative representations of prisoners labelled as ‘dangerous others’ or for alternative ways of structuring the ethos and conditions of maximum-security prisons.
Current concepts in Graves’ disease
Authors: Girgis Christian M. , Champion Bernard L. , Wall Jack R.
Published: May 2011

Graves’ disease is the most common cause of hyperthyroidism in the developed world. It is caused by an immune defect in genetically susceptible individuals in whom the production of unique antibodies results in thyroid hormone excess and glandular hyperplasia. When unrecognized, Graves’ disease impacts negatively on quality of life and poses serious risks of psychosis, tachyarrhythmia and cardiac failure. Beyond the thyroid, Graves’ disease has diverse soft-tissue effects that reflect its systemic autoimmune nature. Thyroid eye disease is the most common of these manifestations and is important to recognise given its risk to vision and potential to deteriorate in response to radioactive iodine ablation. In this review we discuss the investigation and management of Graves’ disease, the recent controversy regarding the hepatotoxicity of propylthiouracil and the emergence of novel small-molecule thyroid-stimulating hormone (TSH) receptor ligands as potential targets in the treatment of Graves’ disease.
Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML
Authors: Scandura Joseph M. , Roboz Gail J. , Moh Michelle , Morawa Ewelina , Brenet Fabienne , Bose J. Robi , Villegas Luis , Gergis Usama S. , Mayer Sebastian A. , Ippoliti Cindy M. , Curcio Tania J. , Ritchie Ellen K. , Feldman Eric J.
Published: May 2011

We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m2 by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m2 for 7 days) and daunorubicin (60 mg/m2 × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34+ bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876.
High-affinity memory B cells induced by conjugate vaccines against weak tumor antigens are vulnerable to nonconjugated antigen
Authors: Savelyeva Natalia , Shipton Michael , Suchacki Amy , Babbage Gavin , Stevenson Freda K.
Published: May 2011

Induction of antibody-mediated immunity against hematologic malignancies requires CD4+ T-cell help, but weak tumor antigens generally fail to induce adequate T-cell responses, or to overcome tolerance. Conjugate vaccines can harness alternative help to activate responses, but memory B cells may then be exposed to leaking tumor-derived antigen without CD4+ T-cell support. We showed previously using lymphoma-derived idiotypic antigen that exposure to “helpless” antigen silences the majority of memory IgG+ B cells. Transfer experiments now indicate that silencing is permanent. In marked contrast to IgG, most coexisting IgM+ memory B cells exposed to “helpless” antigen survive. Confirmation in a hapten (NP) model allowed measurement of affinity, revealing this, rather than isotype, as the determinant of survival. IgM+ B cells had Ig variable region gene usage similar to IgG but with fewer somatic mutations. Survival of memory B cells appears variably controlled by affinity for antigen, allowing a minority of low affinity IgG+, but most IgM+, memory B cells to escape deletion in the absence of T-cell help. The latter remain, but the majority fail to undergo isotype switch. These findings could apply to other tumor antigens and are relevant for vaccination strategies aimed to induce long-term antibody.
How I treat primary CNS lymphoma
Authors: Ferreri Andrés J. M.
Published: May 2011

Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials. Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials.
New methods to measure residues coevolution in proteins
Authors: Gao Hongyun , Dou Yongchao , Yang Jialiang , Wang Jun
Published: May 2011

Background

The covariation of two sites in a protein is often used as the degree of their coevolution. To quantify the covariation many methods have been developed and most of them are based on residues position-specific frequencies by using the mutual information (MI) model.

Results

In the paper, we proposed several new measures to incorporate new biological constraints in quantifying the covariation. The first measure is the mutual information with the amino acid background distribution (MIB), which incorporates the amino acid background distribution into the marginal distribution of the MI model. The modification is made to remove the effect of amino acid evolutionary pressure in measuring covariation. The second measure is the mutual information of residues physicochemical properties (MIP), which is used to measure the covariation of physicochemical properties of two sites. The third measure called MIBP is proposed by applying residues physicochemical properties into the MIB model. Moreover, scores of our new measures are applied to a robust indicator conn(k) in finding the covariation signal of each site.

Conclusions

We find that incorporating amino acid background distribution is effective in removing the effect of evolutionary pressure of amino acids. Thus the MIB measure describes more biological background information for the coevolution of residues. Besides, our analysis also reveals that the covariation of physicochemical properties is a new aspect of coevolution information.
NCACO-score: An effective main-chain dependent scoring function for structure modeling
Authors: Tian Liqing , Wu Aiping , Cao Yang , Dong Xiaoxi , Hu Yun , Jiang Taijiao
Published: May 2011

Background

Development of effective scoring functions is a critical component to the success of protein structure modeling. Previously, many efforts have been dedicated to the development of scoring functions. Despite these efforts, development of an effective scoring function that can achieve both good accuracy and fast speed still presents a grand challenge.

Results

Based on a coarse-grained representation of a protein structure by using only four main-chain atoms: N, Cα, C and O, we develop a knowledge-based scoring function, called NCACO-score, that integrates different structural information to rapidly model protein structure from sequence. In testing on the Decoys'R'Us sets, we found that NCACO-score can effectively recognize native conformers from their decoys. Furthermore, we demonstrate that NCACO-score can effectively guide fragment assembly for protein structure prediction, which has achieved a good performance in building the structure models for hard targets from CASP8 in terms of both accuracy and speed.

Conclusions

Although NCACO-score is developed based on a coarse-grained model, it is able to discriminate native conformers from decoy conformers with high accuracy. NCACO is a very effective scoring function for structure modeling.
How the psychosocial context of clinical trials differs from usual care: A qualitative study of acupuncture patients
Authors: Barlow Fiona , Scott Clare , Coghlan Beverly , Lee Philippa , White Peter , Lewith George T , Bishop Felicity L
Published: May 2011

Background

Qualitative studies of participants' experiences in randomised clinical trials (RCTs) suggest that the psychosocial context of treatment in RCTs may be quite different to the psychosocial context of treatment in usual practice. This is important, as the psychosocial context of treatment is known to influence patient outcomes in chronic illness. Few studies have directly compared the psychosocial context of treatment across RCTs and usual practice. In this study, we explored differences in psychosocial context between RCT and usual practice settings, using acupuncture as our model.

Methods

We undertook a secondary analysis of existing qualitative interviews with 54 patients. 27 were drawn from a study of western and traditional acupuncture in usual practice (for a range of painful conditions). 27 were drawn from a qualitative study nested in an RCT of western acupuncture for osteoarthritis of the hip or knee. We used qualitative analysis software to facilitate an inductive thematic analysis in which we identified three main themes.

Results

In usual practice, starting acupuncture was more likely to be embedded in an active and ongoing search for pain relief, whereas in the RCT starting acupuncture was opportunistic. Usual practice patients reported few uncertainties and these had minimal consequences for them. In the RCT, patients experienced considerable uncertainties about their treatment and its effectiveness, and were particularly concerned about whether they were receiving real (or fake) acupuncture. Patients stopped acupuncture only at the end of the fixed course of treatment in the RCT, which was similar to those receiving acupuncture in the public sector National Health Service (NHS). In comparison, private sector patients re-evaluated and re-negotiated treatments particularly when starting to use acupuncture.

Conclusions

Differences in psychosocial context between RCTs and usual practice could reduce the impact of acupuncture in RCT settings and/or lead to under-reporting of benefit by patients in trials. New trial designs that ensure participants' experiences are similar to usual practice should minimise differences in psychosocial context and help attenuate these potentially confounding effects.
High-dose daptomycin and fosfomycin treatment of a patient with endocarditis caused by daptomycin-nonsusceptible Staphylococcus aureus: Case report
Authors: Chen Liang-Yu , Huang Cheng-Hsiung , Kuo Shu-Chen , Hsiao Chen-Yuan , Lin Mei-Lin , Wang Fu-Der , Fung Chang-Phone
Published: May 2011

Background

Emergence of daptomycin-nonsusceptible (DNS) Staphylococcus aureus is a dreadful problem in the treatment of endocarditis. Few current therapeutic agents are effective for treating infections caused by DNS S. aureus.

Case presentation

We describe the emergence of DNS S. aureus. in a patient with implantable cardioverter-defibrillator (ICD) device -related endocarditis who was priorily treated with daptomycin. Metastatic dissemination as osteomyelitis further complicated the management of endocarditis. The dilemma was successfully managed by surgical removal of the ICD device and combination antimicrobial therapy with high-dose daptomycin and fosfomycin.

Conclusions

Surgical removal of intracardiac devices remains an important adjunctive measure in the treatment of endocarditis. Our case suggests that combination therapy is more favorable than single-agent therapy for infections caused by DNS S. aureus.
Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior
Authors: Hedan Benoit , Thomas Rachael , Motsinger-Reif Alison , Abadie Jerome , Andre Catherine , Cullen John , Breen Matthew
Published: May 2011

Background

Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology.

Methods

Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed.

Results

Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis.

Conclusions

The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model for the human counterpart, providing additional evidence towards elucidation of the pathophysiological and genetic mechanisms associated with histiocytic malignancies. Extrapolation of data derived from canine histiocytic disorders to human histiocytic proliferation may help to further our understanding of the propagation and cancerization of histiocytic cells, contributing to development of new and effective therapeutic modalities for both species.
Asking the right questions: developing evidence-based strategies for treating HIV in women and children
Authors: Karim Quarraisha Abdool , Banegura Anchilla , Cahn Pedro , Christie Celia DC , Dintruff Robert , Distel Manuel , Hankins Catherine , Hellmann Nicholas , Katabira Elly , Lehrman Sandra , Montaner Julio , Purdon Scott , Rooney James F , Wood Robin , Heidari Shirin
Published: May 2011

In July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highly active antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults and children, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO's new recommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatment alone will increase the number of treatment-eligible people by 50% or more.

Scaling up access to HIV treatment is revealing important gaps in our understanding of how best to provide for all those in need. This knowledge gap is especially significant in developing countries, where women and children comprise a majority of those living with HIV infection. Given the magnitude and significance of these populations, the International AIDS Society, through its Industry Liaison Forum, prioritized HIV treatment and prophylaxis of women and children. In March 2010, the International AIDS Society and 15 partners launched a Consensus Statement outlining priority areas in which a relative lack of knowledge impedes delivery of optimal prevention of mother to child transmission (PMTCT) and treatment to women and children.

The Consensus Statement, "Asking the Right Questions: Advancing an HIV Research Agenda for Women and Children", makes a special appeal for a more gender-sensitive approach to HIV research at all stages, from conception to design and implementation. It particularly emphasizes research to enhance the understanding of sex-based differences and paediatric needs in treatment uptake and response. In addition to clinical issues, the statement focuses on programmatic research that facilitates access and adherence to antiretroviral regimens. Better coordination of HIV management with sexual and reproductive healthcare delivery is one such approach.

We discuss here our knowledge gaps concerning effective, safe PMTCT and treatment for women and children in light of the expansion envisioned by WHO's revised guidelines. The guideline's new goals present an opportunity for advancing the women and children's agenda outlined in the Consensus Statement.
An open source web application for the surveillance and prevention of the impacts on public health of extreme meteorological events: the SUPREME system
Authors: Toutant Steve , Gosselin Pierre , Bélanger Diane , Bustinza Ray , Rivest Sonia
Published: May 2011

Background

Every year, many deaths or health problems are directly linked to heat waves. Consequently, numerous jurisdictions around the world have developed intervention plans that are employed during extreme heat events; beyond their emergency sections, these plans generally include preventive measures to be implemented each year. Over the last five years, local and regional information systems have been implemented in a few Canadian cities for surveillance purposes. However, until recently, no such systems existed at the provincial level. In the context of the Government of Quebec's 2006-2012 Action Plan on Climate Change, a real-time integrated system for the surveillance and monitoring of extreme heat events has been implemented on a provincial level. The system is a component of a broader approach that would also monitor the public health impacts of all types of extreme meteorological events.

Results

After conducting a detailed needs analysis, the Quebec National Institute for Public Health developed and implemented an integrated web application leveraging open source software for the real-time Surveillance and Prevention of the impacts of Extreme Meteorological Events on public health, called the SUPREME system. Its first field use involved heat waves. This decision-support system is based on open source software and is composed of four modules: (1) data acquisition and integration, (2) risk analysis and alerts, (3), cartographic application, and (4) information dissemination - climate change and health portal. The system is available to health specialists through a secure web information portal and provides access to weather forecasts, historic and real-time indicators (including deaths and hospital admissions), alerts and various cartographic data used for conducting prevention activities and launching emergency measures.

Conclusions

The SUPREME system was implemented and used during the summer of 2010. It served as an important decision-making tool during the July 2010 heat wave in the province of Quebec, Canada. Planned improvements for 2011 include the integration of data related to other risk factors for other extreme events to the system. The next steps will be to provide access to the application to other groups of specialists that are involved in the prevention, monitoring, or analysis of extreme meteorological events and their effects on community health and well-being.
Improving Detection Accuracy of Lung Cancer Serum Proteomic Profiling via Two-Stage Training Process
Authors: Hsu Pei-Sung , Wang Yu-Shan , Huang Su-Chen , Lin Yi-Hsien , Chang Chih-Chia , Tsang Yuk-Wah , Jiang Jiunn-Song , Kao Shang-Jyh , Uen Wu-Ching , Chi Kwan-Hwa
Published: May 2011

Background

Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) is a frequently used technique for cancer biomarker research. The specificity of biomarkers detected by SELDI can be influenced by concomitant inflammation. This study aimed to increase detection accuracy using a two-stage analysis process.

Methods

Sera from 118 lung cancer patients, 72 healthy individuals, and 31 patients with inflammatory disease were randomly divided into training and testing groups by 3:2 ratio. In the training group, the traditional method of using SELDI profile analysis to directly distinguish lung cancer patients from sera was used. The two-stage analysis of distinguishing the healthy people and non-healthy patients (1st-stage) and then differentiating cancer patients from inflammatory disease patients (2nd-stage) to minimize the influence of inflammation was validated in the test group.

Results

In the test group, the one-stage method had 87.2% sensitivity, 37.5% specificity, and 64.4% accuracy. The two-stage method had lower sensitivity (> 70.1%) but statistically higher specificity (80%) and accuracy (74.7%). The predominantly expressed protein peak at 11480 Da was the primary splitter regardless of one- or two-stage analysis. This peak was suspected to be SAA (Serum Amyloid A) due to the similar m/z countered around this area. This hypothesis was further tested using an SAA ELISA assay.

Conclusions

Inflammatory disease can severely interfere with the detection accuracy of SELDI profiles for lung cancer. Using a two-stage training process will improve the specificity and accuracy of detecting lung cancer.
Thickness-dependent optimization of Er3+ light emission from silicon-rich silicon oxide thin films
Authors: Cueff Sébastien , Labbé Christophe , Jambois Olivier , Garrido Blas , Portier Xavier , Rizk Richard
Published: May 2011

This study investigates the influence of the film thickness on the silicon-excess-mediated sensitization of Erbium ions in Si-rich silica. The Er3+ photoluminescence at 1.5 μm, normalized to the film thickness, was found five times larger for films 1 μm-thick than that from 50-nm-thick films intended for electrically driven devices. The origin of this difference is shared by changes in the local density of optical states and depth-dependent interferences, and by limited formation of Si-based sensitizers in "thin" films, probably because of the prevailing high stress. More Si excess has significantly increased the emission from "thin" films, up to ten times. This paves the way to the realization of highly efficient electrically excited devices.
Standardized positive controls for detection of norovirus by reverse transcription PCR
Authors: Lee Sung-Geun , Lee Soe-Hyun , Park Seung-Won , Suh Chang-Il , Jheong Weon-Hwa , Oh SeHwan , Paik Soon-Young
Published: May 2011

Background

Norovirus is one of the most common causes of nonbacterial gastroenteritis in humans. Rapid spread by contaminated food and person-to-person transmission through the fecal-oral route are characteristics of norovirus epidemiology and result in high morbidity in vulnerable patient populations. Therefore, detection of norovirus is a major public health concern. Currently, the most common method for detecting and differentiating among norovirus strains in clinical and environmental samples is reverse transcription PCR (RT-PCR). Standardized positive controls used in RT-PCR assays to detect norovirus are designed to overcome the problem of false-negative results due to PCR inhibitors and suboptimal reaction conditions.

Results

In the current study, four types of RNA transcripts were produced from plasmids: norovirus GI-5 and GII-4 capsid regions with human rotavirus (VP7 gene derived) fragment insertions, and norovirus GI-6 and GII-4 capsid regions with hepatitis A virus (VP1/P2A gene derived) fragment insertions. These size-distinguishable products were used as positive controls under the RT-PCR assay conditions used to detect NoV in stool and groundwater samples. Their reliability and reproducibility was confirmed by multiple sets of experiments.

Conclusions

These standardized products may contribute to the reliable and accurate diagnosis by RT-PCR of norovirus outbreaks, when conducted by laboratories located in different regions.