bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on the use of gonadotropin-releasing hormone antagonists in prostate cancer
Authors: Boccon-Gibod Laurent , van der Meulen Egbert , Persson Bo-Eric
Published: July 2011

Androgen deprivation therapy (ADT) is the main treatment approach in advanced prostate cancer and in recent years has primarily involved the use of gonadotropin-releasing hormone (GnRH) agonists. However, despite their efficacy, GnRH agonists have several drawbacks associated with their mode of action. These include an initial testosterone surge and testosterone microsurges on repeat administration. GnRH antagonists provide an alternative approach to ADT with a more direct mode of action that involves immediate blockade of GnRH receptors. Antagonists produce a more rapid suppression of testosterone (and prostate-specific antigen [PSA]) without a testosterone surge or microsurges and appear to offer an effective and well tolerated option for the hormonal treatment of prostate cancer. Comparisons with GnRH agonists have shown GnRH antagonists to be at least as effective in achieving and maintaining castrate testosterone levels in patients with prostate cancer. Furthermore, with antagonists, the lack of an initial testosterone surge (which may cause clinical flare) may allow more rapid relief of symptoms related to prostate cancer, avoid the need for concomitant antiandrogens to prevent clinical flare (so avoiding any antiandrogen-associated adverse events) and allow GnRH antagonist use in patients with high tumour burden and/or acute problems such as spinal cord compression. Although several antagonists have been investigated, only degarelix and abarelix are currently available for clinical use in prostate cancer. Currently, degarelix is the most extensively studied and widely available agent in this class. Degarelix is one of a newer generation of antagonists which, in a comprehensive and ongoing clinical development programme, has been shown to provide rapid, profound and sustained testosterone suppression without the systemic allergic reactions associated with earlier antagonists. This review examines the currently available data on GnRH antagonists in prostate cancer.
Some thoughts on the big and small matters of medieval geographical knowledge
Authors: Harvey David
Published: July 2011

Reflecting on the relationships between geography and the disciplines of history and archaeology, this commentary on Lilley's (2011) article questions a ‘periodised’ view of the world. Thinking through the nature of these disciplinary relations, and on notions of temporal scale, therefore, this short article seeks to make space for how geographers can engage with ‘medieval subject matters’ in new ways.
Applied policy research and critical human geography
Authors: Woods Michael , Gardner Graham
Published: July 2011

This paper discusses the relationship between applied policy research commissioned by the state and the development and maintenance of critical human geographies. In contrast with recent debates, which have centred on the relative status of human geography within policy circles, we focus on the often mundane and messy realities of undertaking policy research. The paper argues that applied policy research offers considerable potential for human geographers to pursue substantive and normative concerns, but can also place geographers in complex and demanding situations that present practical and ethical challenges. In such contexts, being ‘relevant’ in the manner demanded by policy actors while maintaining critical integrity necessitates a high degree of reflexivity, strategic calculation and tradeoffs between principles and pragmatism. The paper draws on our experience of undertaking contract research on parish and town councils for the UK government. We emphasize the opportunities and pitfalls represented by the internal differentiation of the state, the importance of active negotiation and compromise with clients and stakeholders, the mediating role played by the ‘evidence base’, the politics of expertise and the use of applied policy research as a platform for wider policy engagement. The paper concludes by calling for greater reflection on the realities of applied policy research.
Against dialogue
Authors: Allen Chris
Published: July 2011

This is a response to Woods and Gardner’s (2011) article which argues that geographers’ views on ‘policy research’ have been erroneously reduced to a ‘good’ / ‘bad’ dualism and that this has allowed ‘critical’ geographers to disengage from a dialogue about the potential that it offers for dialogue with policy makers. In this article I suggest that Woods and Gardner have put forward an argument that is based on a hermeneutics of trust which suggests that dialogue breeds ‘mutual understanding’ which, in turn, can provide a consensual basis for social progress. As such it considers the politics of cooperation but not the politics of scepticism and conflict in policy research. I argue that the experience of geographers shows that there are good reasons to be wary of policy research because it too often suppresses dissent and conflict. Thus a stand of hostility towards policy research is entirely legitimate but, more importantly, necessary in the interests of fostering a democratic debate in which conflict is brought out into the open.
Human geography, ideology and institutional normativity
Authors: Bailey Keiron , Grossardt Ted
Published: July 2011

In response to Woods and Gardner’s (2011) article we note a number of points of agreement. These include the need to engage and collaborate with formal institutional representatives and structures even under less than ideal conditions, for example involving our lack of ability to deliver meaningful products in accord with stated (rhetorical) aims. In this way, we may ensure presentation of data and methods that may be otherwise plausibly deniable. However, we would like to raise the question of how broader societal aims might be better identified and served, and of how we as human geographers might work within the often random, and sometimes contradictory, environment of the academic-industrial complex to encourage such progress. We outline examples from our experience on large-scale projects in contested domains which highlight the need for human geographers to maintain multiple positionalities within democratic systems.
Policy research as critical praxis
Authors: McGuirk Pauline
Published: July 2011

In responding to Woods and Gardner’s (2011) article, this piece positions policy research as a potentially rich site for critical praxis. It works through the possibilities around (i) negotiating the politics of policy research; (ii) the iterative and hybrid nature of policy research; and (iii) the internally differentiated nature of states. While remaining clear-eyed around the limits Woods and Gardner point to that shape collaborative work around policy, the article argues that policy research can be a site where the ethical and normative commitments of a critical agenda can be pursued. This requires that we recognise, first, policy research as a context for situated knowledge production within the complex social terrain of the state and, second, the performative and constitutive effects of knowledge.
Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1
Authors: Balusu Ramesh , Fiskus Warren , Rao Rekha , Chong Daniel G. , Nalluri Srilatha , Mudunuru Uma , Ma Hongwei , Chen Lei , Venkannagari Sreedhar , Ha Kyungsoo , Abhyankar Sunil , Williams Casey , McGuirk Joseph , Khoury Hanna Jean , Ustun Celalettin , Bhalla Kapil N.
Published: July 2011

Nucleophosmin 1 (NPM1) is an oligomeric, nucleolar phosphoprotein that functions as a molecular chaperone for both proteins and nucleic acids. NPM1 is mutated in approximately one-third of patients with AML. The mutant NPM1c+ contains a 4-base insert that results in extra C-terminal residues encoding a nuclear export signal, which causes NPM1c+ to be localized in the cytoplasm. Here, we determined the effects of targeting NPM1 in cultured and primary AML cells. Treatment with siRNA to NPM1 induced p53 and p21, decreased the percentage of cells in S-phase of the cell cycle, as well as induced differentiation of the AML OCI-AML3 cells that express both NPMc+ and unmutated NPM1. Notably, knockdown of NPM1 by shRNA abolished lethal AML phenotype induced by OCI-AML3 cells in NOD/SCID mice. Knockdown of NPM1 also sensitized OCI-AML3 to all-trans retinoic acid (ATRA) and cytarabine. Inhibition of NPM1 oligomerization by NSC348884 induced apoptosis and sensitized OCI-AML3 and primary AML cells expressing NPM1c+ to ATRA. This effect was significantly less in AML cells coexpressing FLT3-ITD, or in AML or normal CD34+ progenitor cells expressing wild-type NPM1. Thus, attenuating levels or oligomerization of NPM1 selectively induces apoptosis and sensitizes NPM1c+ expressing AML cells to treatment with ATRA and cytarabine.
Rescue of murine silica-induced lung injury and fibrosis by human embryonic stem cells
Authors: Spitalieri P. , Quitadamo M.C. , Orlandi A. , Guerra L. , Giardina E. , Casavola V. , Novelli G. , Saltini C. , Sangiuolo F.
Published: July 2011

Alveolar type II pneumocytes (ATII cells) are considered putative alveolar stem cells. Since no treatment is available to repair damaged epithelium and prevent lung fibrosis, novel approaches to induce regeneration of injured alveolar epithelium are desired.

The objective of this study was to assess both the capacity of human embryonic stem cells (HUES-3) to differentiatein vitrointo ATII cells and the ability of committed HUES-3 cells (HUES-3-ATII cells) to recoverin vivoa pulmonary fibrosis model obtained by silica-induced damage.

In vitrodifferentiated HUES-3-ATII cells displayed an alveolar phenotype characterised by multi-lamellar body and tight junction formation, by the expression of specific markers such as surfactant protein (SP)-B, SP-C and zonula occludens (ZO)-1 and the activity of cystic fibrosis transmembrane conductance regulator-mediated chloride ion transport.

After transplantation of HUES-3-ATII cells into silica-damaged mice, histological and biomolecular analyses revealed a significant reduction of inflammation and fibrosis markers along with lung function improvement, weight recovery and increased survival. The persistence of human SP-C, human nuclear antigen and human DNA in the engrafted lungs indicates that differentiated cells remained engrafted up to 10 weeks.

In conclusion, cell therapy using HUES-3 cells may be considered a promising approach to lung injury repair.
Airways changes related to air pollution exposure in wheezing children
Authors: Martins P.C. , Valente J. , Papoila A.L. , Caires I. , Araújo-Martins J. , Mata P. , Lopes M. , Torres S. , Rosado-Pinto J. , Borrego C. , Annesi-Maesano I. , Neuparth N.
Published: July 2011

In this study, we aimed to evaluate the relationship between individual total exposure to air pollution and airway changes in a group of 51 wheezing children.

Respiratory status was assessed four times (January 2006, June 2006, January 2007 and June 2007) during a 1-week period through a standardised questionnaire, spirometry, exhaled nitric oxide fraction and pH in exhaled breath condensate (EBC). Concentrations of particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10), O3, NO2and volatile organic compounds were estimated through direct measurements with anad hocdevice or air pollution modelling in the children's schools and at their homes in the same 4 weeks of the study. For each child, total exposure to the different air pollutants was estimated as a function of pollutant concentrations and daily activity patterns.

Increasing total exposure to PM10, NO2, benzene, toluene and ethylbenzene was significantly associated with a decrease of forced expiratory volume in 1 s (FEV1) and with an increase of change in FEV1. Increasing exposure to NO2and benzene was also related to a significant decrease of FEV1/forced vital capacity. Increasing exposure to PM10, NO2, benzene and ethylbenzene was associated with acidity of EBC.

This study suggests an association in wheezing children between airway changes and total exposure to air pollutants, as estimated by taking into account the concentration in the various microenvironments attended by the children.
Pulmonary manifestations of immunoglobulin G4-related sclerosing disease
Authors: Ryu J.H. , Sekiguchi H. , Yi E.S.
Published: July 2011

Immunoglobulin (Ig)G4-related sclerosing disease (ISD) (also called IgG4-related systemic disease, IgG4-related disease or hyper-IgG4 disease) is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4.

Although initial descriptions of this disorder focused on its pancreatic presentation (autoimmune pancreatitis), it has become apparent that ISD is a systemic disease with many facets. The lesion of ISD is characterised by lymphoplasmacytic inflammation, fibrosis, phlebitis and increased numbers of IgG4-positive plasma cells. The disease can either be localised to one or two organs, or be present with diffuse multi-organ disease. Furthermore, lesions in different organs can present simultaneously or metachronously. In the thorax, lesions associated with ISD have been described in the lung parenchyma, airways and pleura, as well as the mediastinum.

Data published to date suggest that ISD may account for a portion of various fibroinflammatory conditions of unknown cause encountered in the chest, including inflammatory pseudotumours, idiopathic interstitial pneumonias, fibrosing mediastinitis, inflammatory pleural lesions and, occasionally, airway disease.

Some aspects of pulmonary manifestations attributed to ISD remain controversial and additional studies are needed to clarify the relationship along with the increasing relevance of this disorder to pulmonary medicine.
Interferon release does not add discriminatory value to smear-negative HIV–tuberculosis algorithms
Authors: Rangaka M.X. , Gideon H.P. , Wilkinson K.A. , Pai M. , Mwansa-Kambafwile J. , Maartens G. , Glynn J.R. , Boulle A. , Fielding K. , Goliath R. , Titus R. , Mathee S. , Wilkinson R.J.
Published: July 2011

Clinical algorithms for evaluating HIV-infected individuals for tuberculosis (TB) prior to isoniazid preventive therapy (IPT) perform poorly, and interferon-γ release assays (IGRAs) have moderate accuracy for active TB. It is unclear whether, when used as adjunct tests, IGRAs add any clinical discriminatory value for active TB diagnosis in the pre-IPT assessment.

779 sputum smear-negative HIV-infected persons, established on or about to commence combined antiretroviral therapy (ART), were screened for TB prior to IPT. Stepwise multivariable logistic regression was used to develop clinical prediction models. The discriminatory ability was assessed by receiver operator characteristic area under the curve (AUC). QuantiFERON®-TB Gold in-tube (QFT-GIT) was evaluated.

The prevalence of smear-negative TB by culture was 6.4% (95% CI 4.9–8.4%). Used alone, QFT-GIT and the tuberculin skin test (TST) had comparable performance; the post-test probability of disease based on single negative tests was 3–4%. In a multivariable model, the QFT-GIT test did not improve the ability of a clinical algorithm, which included not taking ART, weight <60 kg, no prior history of TB, any one positive TB symptom/sign (cough ≥2 weeks) and CD4+ count <250 cells per mm3, to discriminate smear-negative culture-positive and -negative TB (72% to 74%; AUC comparison p=0.33). The TST marginally improved the discriminatory ability of the clinical model (to 77%, AUC comparison p=0.04).

QFT-GIT does not improve the discriminatory ability of current TB screening clinical algorithms used to evaluate HIV-infected individuals for TB ahead of preventive therapy. Evaluation of new TB diagnostics for clinical relevance should follow a multivariable process that goes beyond test accuracy.
TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls
Authors: Almstrand A-C. , Josefson M. , Bredberg A. , Lausmaa J. , Sjövall P. , Larsson P. , Olin A-C.
Published: July 2011

Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight–secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis.

Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS.

Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25versus0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups.

We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.
Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses
Authors: Li Daofeng , Zhang Yunqin , Hu Xiaona , Shen Xiaoye , Ma Lei , Su Zhen , Wang Tao , Dong Jiangli
Published: July 2011

Background

Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation.

Results

A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes.

Conclusion

Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants.
Development of a highly sensitive real-time one step RT-PCR combined complementary locked primer technology and conjugated minor groove binder probe
Authors: Hong JiYoung , Kang Byunghak , Kim Ahyoun , Hwang Seoyeon , Ahn Jinhee , Lee Sunhwa , Kim Jonghyen , Park Jae-Hak , Cheon Doo-Sung
Published: June 2011

Background

Enterovirus (EV) infections are commonly associated with encephalitis and meningitis. Detection of enteroviral RNA in clinical specimens has been demonstrated to improve the management of patients, by ruling out other causes of disease.

Method

To develop a sensitive and reliable assay for routine laboratory diagnosis, we developed a real-time one step reverse transcription polymerase chain reaction (RT-PCR) assay with minor groove binder probes and primers modified with complementary locked primer technology (TMC-PCR). We checked the sensitivity of the developed assay by comparing it to a previously published TaqMan probe real-time one-step RT-PCR (TTN-PCR) procedure using enteroviral isolates, Enterovirus Proficiency panels from Quality Control on Molecular Diagnostics (QCMD-2007), and clinical specimens from patients with suspected EV infections.

Results

One hundred clinical specimens from 158 suspected viral meningitis cases were determined to be positive by the TMC-PCR assay (63.29%), whereas only 60 were found to be positive by the TTN-PCR assay (37.97%). The positive and negative agreements between the TMC-PCR and TTN-PCR assays were 100% and 59.2%, respectively.

Conclusion

This data suggest that the TMC-PCR assay may be suitable for routine diagnostic screening from patient suspected EV infection.
Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer
Authors: Cheruvu Praveena , Metcalfe Su K , Metcalfe Justin , Chen Yuhchyau , Okunieff Paul , Milano Michael T
Published: July 2011

Background

Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC.

Methods

We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions.

Results

Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%).

Conclusion

Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed.
Sustained eradication of hepatitis C virus by low-dose long-term interferon therapy in a renal transplant recipient with dual infection with hepatitis B and C viruses: a case report
Authors: Chang Ming-Ling , Lai Ping-Chin , Yeh Chau-Ting
Published: June 2011

Introduction

Accelerated liver function deterioration has been recognized in renal transplant recipients infected with hepatitis C virus (HCV). Although combination therapy with interferon plus ribavirin has been established as the standard treatment for patients with chronic HCV, the high risk of allograft rejection associated with interferon therapy has greatly discouraged the clinical use of this regimen. In Asia, where chronic hepatitis B virus (HBV) is prevalent, dual infection with HBV and HCV poses an even greater challenge for clinical hepatologists.

Case presentation

In this article, we report the case of a 51-year-old Taiwanese man with dual infection with HBV and HCV prior to renal transplantation. Low-dose interferon (3 to 6 × 106 U/week) and ribavirin (100 mg/day to 200 mg/day) were prescribed following the reactivation of the man's HCV after renal transplantation. Additionally, lamivudine (100 mg/day) was administered concomitantly to prevent HBV reactivation. His initial serum HCV RNA concentration was 5.2 × 106 copies/mL (genotype 2a). After three and one-half years of antiviral therapy, his HCV was successfully eradicated without any episodes of allograft rejection. His serum HCV RNA remained negative six months after withdrawal from interferon and ribavirin treatment. His serum HBV DNA remained undetectable throughout the course of therapy.

Conclusion

Low-dose, long-term interferon therapy may achieve sustained eradication of HCV in the renal transplant recipient with dual infection with HBV and HCV.
Systematic Bias in Genomic Classification Due to Contaminating Non-neoplastic Tissue in Breast Tumor Samples
Authors: Elloumi Fathi , Hu Zhiyuan , Li Yan , Parker Joel S , Gulley Margaret L , Amos Keith D , Troester Melissa A
Published: July 2011

Background

Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification.

Methods

To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors.

Results

Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability.

Conclusions

Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.
Uptake of family planning methods and unplanned pregnancies among HIV‐infected individuals: a cross‐sectional survey among clients at HIV clinics in Uganda
Authors: Wanyenze Rhoda K , Tumwesigye Nazarius M , Kindyomunda Rosemary , Beyeza‐Kashesya Jolly , Atuyambe Lynn , Kansiime Apolo , Neema Stella , Ssali Francis , Akol Zainab , Mirembe Florence
Published: July 2011

Background

Prevention of unplanned pregnancies among HIV‐infected individuals is critical to the prevention of mother to child HIV transmission (PMTCT), but its potential has not been fully utilized by PMTCT programmes. The uptake of family planning methods among women in Uganda is low, with current use of family planning methods estimated at 24%, but available data has not been disaggregated by HIV status. The aim of this study was to assess the utilization of family planning and unintended pregnancies among HIV‐infected people in Uganda.

Methods

We conducted exit interviews with 1100 HIV‐infected individuals, including 441 men and 659 women, from 12 HIV clinics in three districts in Uganda to assess the uptake of family planning services, and unplanned pregnancies, among HIV‐infected people. We conducted multivariate analysis for predictors of current use of family planning among women who were married or in consensual union and were not pregnant at the time of the interview.

Results

One‐third (33%, 216) of the women reported being pregnant since their HIV diagnoses and 28% (123) of the men reported their partner being pregnant since their HIV diagnoses. Of these, 43% (105) said these pregnancies were not planned: 53% (80) among women compared with 26% (25) among men. Most respondents (58%; 640) reported that they were currently using family planning methods. Among women who were married or in consensual union and not pregnant, 80% (242) were currently using any family planning method and 68% were currently using modern family planning methods (excluding withdrawal, lactational amenorrhoea and rhythm). At multivariate analysis, women who did not discuss the number of children they wanted with their partners and those who did not disclose their HIV status to sexual partners were less likely to use modern family planning methods (adjusted OR 0.40, range 0.20‐0.81, and 0.30, range 0.10‐0.85, respectively).

Conclusions

The uptake of family planning among HIV‐infected individuals is fairly high. However, there are a large number of unplanned pregnancies. These findings highlight the need for strengthening of family planning services for HIV‐infected people.
Disease activity and low physical activity associate with number of hospital admissions and length of hospitalisation in patients with rheumatoid arthritis
Authors: Metsios George S , Stavropoulos-Kalinoglou Antonios , Treharne Gareth J , Nevill Alan M , Sandoo Aamer , Panoulas Vasileios F , Toms Tracey E , Koutedakis Yiannis , Kitas George D
Published: June 2011

Introduction

Substantial effort has been devoted for devising effective and safe interventions to reduce preventable hospital admissions in chronic disease patients. In rheumatoid arthritis (RA), identifying risk factors for admission has important health policy implications, but knowledge of which factors cause or prevent hospital admissions is currently lacking. We hypothesised that disease activity/severity and physical activity are major predictors for the need of hospitalisation in patients with RA.

Methods

A total of 244 RA patients were assessed for: physical activity (International Physical Activity Questionnaire), RA activity (C-reactive protein: CRP; disease activity score: DAS28) and disability (Health Assessment Questionnaire: HAQ). The number of hospital admissions and length of hospitalisation within a year from baseline assessment were collected prospectively.

Results

Disease activity and disability as well as levels of overall and vigorous physical activity levels correlated significantly with both the number of admissions and length of hospitalisation (P < 0.05); regression analyses revealed that only disease activity (DAS28) and physical activity were significant independent predictors of numbers of hospital admissions (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046)) and length of hospitalisation (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046). Sub-analysis of the data demonstrated that only 19% (n = 49) of patients engaged in recommended levels of physical activity.

Conclusions

This study provides evidence that physical activity along with disease activity are important predictors of the number of hospital admissions and length of hospitalisation in RA. The combination of lifestyle changes, particularly increased physical activity along with effective pharmacological therapy may improve multiple health outcomes as well as cost of care for RA patients.
Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two distinct paths to aneuploidy
Authors: Ozery-Flato Michal , Linhart Chaim , Trakhtenbrot Luba , Izraeli Shai , Shamir Ron
Published: June 2011

Background

Chromosomal aneuploidy, that is to say the gain or loss of chromosomes, is the most common abnormality in cancer. While certain aberrations, most commonly translocations, are known to be strongly associated with specific cancers and contribute to their formation, most aberrations appear to be non-specific and arbitrary, and do not have a clear effect. The understanding of chromosomal aneuploidy and its role in tumorigenesis is a fundamental open problem in cancer biology.

Results

We report on a systematic study of the characteristics of chromosomal aberrations in cancers, using over 15,000 karyotypes and 62 cancer classes in the Mitelman Database. Remarkably, we discovered a very high co-occurrence rate of chromosome gains with other chromosome gains, and of losses with losses. Gains and losses rarely show significant co-occurrence. This finding was consistent across cancer classes and was confirmed on an independent comparative genomic hybridization dataset of cancer samples. The results of our analysis are available for further investigation via an accompanying website.

Conclusions

The broad generality and the intricate characteristics of the dichotomy of aneuploidy, ranging across numerous tumor classes, are revealed here rigorously for the first time using statistical analyses of large-scale datasets. Our finding suggests that aneuploid cancer cells may use extra chromosome gain or loss events to restore a balance in their altered protein ratios, needed for maintaining their cellular fitness.
Cinemeducation in psychiatry
Authors: Dave Subodh , Tandon Kopal
Published: June 2011

Psychiatry has had a significant influence on both Hollywood and world cinema. In turn, psychiatrists' fascination with psychiatric themes in films has inspired scores of books and bibliographies about films and psychiatry. Advances in medical education have led to the development of core-competency-based curricula for both undergraduate and postgraduate students. Learning objectives underpin such competencies. However, teaching competencies in the workplace is hampered by practical and ethical issues, especially in the case of psychiatric patients. Medical educationalists have found films to be a useful teaching tool with their larger-than-life vivid portrayals. In this article we demonstrate, with examples, the use of films and discrete film clips to achieve specific learning objectives that can be incorporated easily into most undergraduate and postgraduate teaching programmes in psychiatry.
Treatment of the early stages of bipolar disorder
Authors: Elanjithara Thomas Elias , Frangou Sophia , McGuire Philip
Published: June 2011

For many patients with bipolar disorder there is a long delay between the onset of illness and receiving a diagnosis and the initiation of treatment. This may have an adverse effect on the clinical outcome. Early intervention in bipolar disorder has received less attention than in schizophrenia, and there are relatively few specialist services in this area. This article reviews the literature on the early detection of bipolar disorder and on the effectiveness of pharmacological, psychological and psychosocial interventions in the early phase of the disorder.
Article 8 of the Human Rights Act 1998 and intellectual disability
Authors: Curtice Martin , Crocombe Juli
Published: June 2011

Various UK reports have identified issues of poor health and social care for people with an intellectual disability. Such reports emphasise the vital importance of addressing human rights issues in the future to improve and address shortcomings in such care. Article 8 of the European Convention on Human Rights affords protection for private and family life, and applies irrespective of whether someone has the capacity to make such decisions affecting their life. This in particular is important for people with an intellectual disability. Compared with the rest of the Convention, there has been relatively more case law pertaining to Article 8. This review considers Article 8 case law involving people with an intellectual disability in the areas of community care, accommodation, day centres, lifting and hoisting, sexual relations, marriage and education. In doing so, it demonstrates the varied application and core principles for use of the Article in clinical practice and decision-making.
Fresh paradigms in psychotherapy for psychiatrists
Authors: Healy Kevin
Published: June 2011

The recent expansion of neuroscientific knowledge is changing the nature of psychotherapeutically competent psychiatric practice. For example, components of medical psychotherapy that optimise neuroplasticity and restructure and reinforce synaptic connections can bring about enduring therapeutic changes in patients' personal functioning, experience and behaviour. By renewing their connection to the advancements of neuroscience, psychiatrists in all specialties can build their identities as professionals and their skills as practitioners, making psychotherapeutic interventions more effective for their patients.
The case for early intervention in anorexia nervosa: theoretical
exploration of maintaining factors
Authors: Treasure Janet , Russell Gerald
Published: June 2011

Here we revisit and reinterpret the original study in which the so-called
‘Maudsley (London) model’ of family therapy was compared with individual
therapy for anorexia nervosa. Family therapy was more effective in
adolescents with a short duration of illness. However, this is only part of
the story. A later study describing the 5-year outcome contains important
information. Those adolescents randomised to family therapy achieved a
better outcome 5 years later. Moreover, the group with an onset in
adolescence but who had been ill for over 3 years had a poor response to
both family and individual therapy, suggesting that unless effective
treatment is given within the first 3 years of illness onset, the outcome is
poor. We examine other evidence supporting this conclusion and consider the
developmental and neurobiological factors that can account for this.
Detection of bipolar disorder
Authors: Young Allan H. , MacPherson Holly
Published: June 2011

Major depressive episodes are common in bipolar disorder, which consequently
may be misdiagnosed as major depressive disorder. Improved detection of
bipolar disorder rests upon better ascertainment of a history of hypomania.
Antidepressants are of dubious benefit in bipolar disorder and more accurate
diagnosis of depression would promote better treatment.
The Sexual Offences Act 2003 and people with mental disorders
Authors: Curtice Martin , Kelson Emma
Published: June 2011

The Sexual Offences Act 2003 repealed and revamped almost all of the existing statute law in relation to sexual offences. The purpose of this was to strengthen and modernise the law in this area. Incorporated within the Act were new and specific offences providing for ‘Offences against persons with a mental disorder impeding choice’ and offences involving ‘Inducement, threat or deception to procure sexual activity with a person with a mental disorder’. Psychiatrists may be involved in such cases to provide assessment and opinion as to whether the alleged victim had a mental disorder and because of this lacked the capacity to consent to sexual activity. Knowledge of the intricacies and implementation of these offences against people with mental disorder can aid clinicians who may be asked to provide expert written and oral evidence and opinion for court cases.
Snail2 controls mesodermal BMP/Wnt induction of neural crest
Authors: Shi Jianli , Severson Courtney , Yang Jianxia , Wedlich Doris , Klymkowsky Michael W.
Published: June 2011

The neural crest is an induced tissue that is unique to vertebrates. In the clawed frog Xenopus laevis, neural crest induction depends on signals secreted from the prospective dorsolateral mesodermal zone during gastrulation. The transcription factors Snail2 (Slug), Snail1 and Twist1 are expressed in this region. It is known that Snail2 and Twist1 are required for both mesoderm formation and neural crest induction. Using targeted blastomere injection, morpholino-based loss of function and explant studies, we show that: (1) Snail1 is also required for mesoderm and neural crest formation; (2) loss of snail1, snail2 or twist1 function in the C2/C3 lineage of 32-cell embryos blocks mesoderm formation, but neural crest is lost only in the case of snail2 loss of function; (3) snail2 mutant loss of neural crest involves mesoderm-derived secreted factors and can be rescued synergistically by bmp4 and wnt8 RNAs; and (4) loss of snail2 activity leads to changes in the RNA levels of a number of BMP and Wnt agonists and antagonists. Taken together, these results identify Snail2 as a key regulator of the signals involved in mesodermal induction of neural crest.
Negative Electron Transfer Dissociation Fourier Transform Mass Spectrometry of Glycosaminoglycan Carbohydrates
Authors: Leach Franklin E. , Wolff Jeremy J. , Xiao Zhongping , Ly Mellisa , Laremore Tatiana N. , Arungundram Sailaja , Al-Mafraji Kanar , Venot Andre , Boons Geert-Jan , Linhardt Robert J. , Amster I. Jonathan
Published: July 2011

Electron transfer through gas-phase ion–ion reactions has led to the widespread application of electron-based techniques once only capable in ion trapping mass spectrometers. Although any mass analyzer can, in theory, be coupled to an ion–ion reaction device (typically a 3-D ion trap), some systems of interest exceed the capabilities of most mass spectrometers. This case is particularly true in the structural characterization of glycosaminoglycan (GAG) oligosaccharides. To adequately characterize highly sulfated GAGs or oligosaccharides above the tetrasaccharide level, a high-resolution mass analyzer is required. To extend previous efforts on an ion trap mass spectrometer, negative electron transfer dissociation coupled with a Fourier transform ion cyclotron resonance mass spectrometer has been applied to increasingly sulfated heparan sulfate and heparin tetrasaccharides as well as a dermatan sulfate octasaccharide. Results similar to those obtained by electron detachment dissociation are observed.
Validation of the human chorionic gonadotropin immunoassay in cerebrospinal fluid for the diagnostic work-up of neurohypophyseal germinomas
Authors: González-Sánchez Víctor , Moreno-Pérez Oscar , Pellicer Pedro Sánchez , Sánchez-Ortiga Ruth , Guerra Rocío Alfayate , Dot Montserrat Mauri , Alfonso Antonio Miguel Picó
Published: July 2011

Background

The measurement of human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) is useful for the differential diagnosis of suprasellar lesions. However, the concentrations that prove diagnostic for neurohypophyseal germinoma have not been well defined. In addition, the immunoassays used for such measurements are the same as those applied in serum, and few studies have been performed regarding the validation of such techniques in CSF. The present study aims to apply the Elecsys® hCG + β immunoassay from Roche Diagnostics to measure hCG in CSF, as a useful tool in the diagnosis of neurohypophyseal germinomas in children and young adults.

Methods

Validation of the immunoassay involved calculation of the functional sensitivity and reference values for hCG in CSF in 35 controls in the absence of pregnancy, trophoblastic disease or tumour pathology. For the clinical application study, three patients diagnosed with neurohypophyseal germinoma have been reviewed.

Results

The functional sensitivity obtained was 0.4 IU/L. The reference values for hCG in CSF ranged from undetectable values to 0.7 IU/L. The hCG concentrations in CSF in the three studied patients, with confirmed diagnosis of neurohypophyseal germinoma, were 21.1, 32.6 and 23 IU/L, respectively.

Conclusions

The Elecsys® hCG + β immunoassay from Roche Diagnostics can be used to detect hCG in CSF with high precision. According to our results, CSF-hCG concentrations that exceed the established reference interval (undetectable values to 0.7 IU/L) in the presence of suprasellar lesions and hypophyseal stalk thickening must be considered pathological, establishing the need to exclude the presence of germinoma.
The CCR5-delta32 polymorphism as a model to study host adaptation against infectious diseases and to develop new treatment strategies
Authors: Hütter Gero , Ganepola Susanne
Published: June 2011

Humans respond differently toward exposure against pathogens and some individuals are completely resistant against transmission due to a genetically determined susceptibility. A rising number of such, so-called, host factors have been described during the last years, but their role for diagnostic or therapeutic application is still to be clarified. Here, we describe the biology of the chemokine receptor CCR5 and its polymorphism in the context of host adaptation and immune system function. Furthermore, the first clinical applications exploiting our knowledge of this chemokine receptor as a host factor are described.
Clinical manifestations of co-infection with malaria and leptospirosis
Authors: Gurjar Mohan , Saigal Saurabh , Baronia Arvind K , Azim Afzal , Poddar Banani , Singh Ratender K
Published: July 2011

Though both malaria and leptospirosis are frequent in the tropics, co-infections are under-recognized due to overlapping of clinical features. Here, we reviewed clinical manifestations of published co-infection along with our three cases. Out of a total of 18 patients, nine patients (50%) required ICU admission. Almost all patients had prodromal symptoms in the form of fever, headache and myalgia. Seven patients (37%) had altered sensorium, three patients (17%) had hypotension at admission, and 11 patients (61%) had acute kidney injury (AKI). Pulmonary manifestations in the form of pulmonary bleeding were present in four cases (22%). Three (17%) patients had acute lung injury/ acute respiratory distress syndrome. Almost 55% patients had DIC in the form of altered prothrombin time, activated partial thromboplastin time and low fibrinogen level. Four patients (22%) had subconjuctival suffusion, two of them had haematuria, while one presented with nasal bleeding. All patients had altered liver function tests. Of all the 18 patients, 17 (94%) survived, while one died.
Primary renal hydatidosis with associated macroscopic hydatiduria – a computed tomography urography diagnosis with pathological confirmation
Authors: Parashari Umesh C , Upadhyay Deepika , Khanduri Sachin , Qayyum Fareena Akbar , Bhadury Samarjit
Published: July 2011

Primary renal hydatid disease which involves any other organ is extremely rare. Cystic rupture into the pelvicalyceal system, causing hydatiduria, is pathognomonic of renal hydatidosis, although it is usually microscopic and is seen in only 10–20% of renal hydatidosis cases. Gross hydaturia is uncommon but is present in the case discussed below. We report an exceptionally rare case of primary renal hydatidosis associated with the rupture of the cyst into the pelvicalyceal system diagnosed primarily on the basis of computed tomography urography. The diagnosis was confirmed on a pathological and surgical basis.