bluuebunny/crossref_metadata_2025 huggingface dataset:
Host DNA Damage Response Factors Localize to Merkel Cell Polyomavirus DNA Replication Sites To Support Efficient Viral DNA Replication
Authors: Tsang Sabrina H. , Wang Xin , Li Jing , Buck Christopher B. , You Jianxin
Published: January 2014

Accumulating evidence indicates a role for Merkel cell polyomavirus (MCPyV) in the development of Merkel cell carcinoma (MCC), making MCPyV the first polyomavirus to be clearly associated with human cancer. With the high prevalence of MCPyV infection and the increasing amount of MCC diagnosis, there is a need to better understand the virus and its oncogenic potential. In this study, we examined the relationship between the host DNA damage response (DDR) and MCPyV replication. We found that components of the ATM- and ATR-mediated DDR pathways accumulate in MCPyV large T antigen (LT)-positive nuclear foci in cells infected with native MCPyV virions. To further study MCPyV replication, we employed our previously established system, in which recombinant MCPyV episomal DNA is autonomously replicated in cultured cells. Similar to native MCPyV infection, where both MCPyV origin and LT are present, the host DDR machinery colocalized with LT in distinct nuclear foci. Immunofluorescence
in situ
hybridization and bromodeoxyuridine (BrdU) incorporation analysis showed that these DDR proteins and MCPyV LT in fact colocalized at the actively replicating MCPyV replication complexes, which were absent when a replication-defective LT mutant or an MCPyV-origin mutant was introduced in place of wild-type LT or wild-type viral origin. Inhibition of DDR kinases using chemical inhibitors and ATR/ATM small interfering RNA (siRNA) knockdown reduced MCPyV DNA replication without significantly affecting LT expression or the host cell cycle. This study demonstrates that these host DDR factors are important for MCPyV DNA replication, providing new insight into the host machinery involved in the MCPyV life cycle.

IMPORTANCE
MCPyV is the first polyomavirus to be clearly associated with human cancer. However, the MCPyV life cycle and its oncogenic mechanism remain poorly understood. In this report, we show that, in cells infected with native MCPyV virions, components of the ATM- and ATR-mediated DDR pathways accumulate in MCPyV LT-positive nuclear foci. Such a phenotype was recapitulated using our previously established system for visualizing MCPyV replication complexes in cells. By combining immunofluorescent staining, fluorescence
in situ
hybridization, and BrdU incorporation analysis, we demonstrate that DDR proteins are important for maintaining robust MCPyV DNA replication. This study not only provides the first look into the microscopic details of DDR factor/LT replication complexes at the MCPyV origin but also provides a platform for further studying the mechanistic role of host DDR factors in the MCPyV life cycle and virus-associated oncogenesis.
A Double-Mimetic Peptide Efficiently Neutralizes HIV-1 by Bridging the CD4- and Coreceptor-Binding Sites of gp120
Authors: Quinlan Brian D. , Joshi Vinita R. , Gardner Matthew R. , Ebrahimi Kourosh H. , Farzan Michael
Published: January 2014

The HIV-1 envelope glycoprotein binds cooperatively to its cellular receptor CD4 and a coreceptor, principally CXCR4 or CCR5. We have previously improved a natural amino-acid form of a scorpion toxin-derived CD4-mimetic peptide and in parallel generated sulfopeptide mimetics of the CCR5 amino terminus. Here we show that some fusions of these CCR5- and CD4-mimetic peptides, expressed as immunoadhesins, neutralize HIV-1 more efficiently than CD4-Fc or equimolar mixtures of immunoadhesin forms of each peptide. Specifically, double-mimetic peptides with linkers of 11 amino acids or greater, and with the CCR5-mimetic component preceding the CD4-mimetic component, were more efficient than constructs with shorter linkers or in a reverse orientation. The potency of these constructs derives from (i) their ability to simultaneously and cooperatively bind the CD4- and CCR5-binding sites of a single gp120 monomer of the HIV-1 envelope glycoprotein trimer and (ii) the ability of the CCR5-mimetic component to prevent the CD4-mimetic peptide from promoting infection when cellular CD4 is limiting. Thus, there is a significant advantage to simultaneously targeting both conserved regions of the HIV-1 envelope glycoprotein.

IMPORTANCE
This report describes a novel class of peptides that potently inhibit HIV-1 entry. These peptides simultaneously target the receptor- and coreceptor-binding sites of the HIV-1 envelope glycoprotein gp120. Peptides of this class overcome key limitations of inhibitors that target only one gp120 binding region and illustrate the utility of binding the sulfotyrosine-binding pockets of gp120.
Core Binding Factor Beta Plays a Critical Role by Facilitating the Assembly of the Vif-Cullin 5 E3 Ubiquitin Ligase
Authors: Fribourgh Jennifer L. , Nguyen Henry C. , Wolfe Leslie S. , DeWitt David C. , Zhang Wenyan , Yu Xiao-Fang , Rhoades Elizabeth , Xiong Yong
Published: January 2014

The HIV-1 virion infectivity factor (Vif) targets the cellular cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) for degradation via the host ubiquitin-proteasome pathway. Vif recruits a cellular E3 ubiquitin ligase to polyubiquitinate A3G/F. The activity of Vif critically depends on the cellular core binding factor beta (CBFβ). In this study, we investigated the Vif-CBFβ interaction and the role of CBFβ in the E3 ligase assembly. Vif-CBFβ interaction requires an extensive region of Vif spanning most of its amino terminus and zinc finger region, and cullin 5 (Cul5) binding enhances the stability of the Vif-CBFβ interaction. Our results further demonstrate that CBFβ plays a critical role in facilitating Cul5 binding to the Vif/elongin B/elongin C complex. Vif, with or without bound substrate, is unable to bind Cul5 in the absence of CBFβ. These studies support the notion that CBFβ serves as a molecular chaperone to facilitate Vif-E3 ligase assembly.

IMPORTANCE
The host antiviral restriction factors A3G/F inhibit viral replication. The HIV-1 protein Vif targets A3G/F for degradation. This immune evasion activity of Vif is dependent on the cellular factor CBFβ. Multiple regions of Vif are known to be important for Vif function, but the mechanisms are unclear. The studies described here provide important information about the Vif-CBFβ interaction interface and the function of CBFβ in E3 ligase assembly. In particular, our comprehensive Vif-CBFβ interface mapping results help to delineate the role of various Vif regions, determining if they are important for binding CBFβ or A3G/F. Furthermore, our studies reveal an important potential mechanism of CBFβ that has not been shown before. Our results suggest that CBFβ may serve as a molecular chaperone to enable Vif to adopt an appropriate conformation for interaction with the Cul5-based E3 ligase. This study advances our understanding of how CBFβ facilitates the Vif-mediated degradation of APOBEC3 proteins.
Evolutionarily Conserved Requirement for Core Binding Factor Beta in the Assembly of the Human Immunodeficiency Virus/Simian Immunodeficiency Virus Vif-Cullin 5-RING E3 Ubiquitin Ligase
Authors: Han Xue , Liang Weizi , Hua Deping , Zhou Xiaohong , Du Juan , Evans Sean L. , Gao Qimeng , Wang Hong , Viqueira Rachel , Wei Wei , Zhang Wenyan , Yu Xiao-Fang
Published: January 2014

The human immunodeficiency virus type 1 (HIV-1)-encoded virion infectivity factor (Vif) is required to inactivate the host restriction factor APOBEC3 by engaging Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-β) is a novel regulator of Vif-CRL5 function; as yet, its mechanism of regulation remains unclear. In the present study, we demonstrate that CBF-β promotion of Vif-CRL5 assembly is independent of its influence on Vif stability and is also a conserved feature of primate lentiviral Vif proteins. Furthermore, CBF-β is critical for the formation of the Vif-ElonginB/ElonginC-Cul5 core E3 ubiquitin ligase complex
in vitro
. CBF-β from diverse vertebrate species supported HIV-1 Vif function, indicating the conserved nature of Vif–CBF-β interfaces. Considering the importance of the interaction between Vif and CBF-β in viral CRL5 function, disrupting this interaction represents an attractive pharmacological intervention against HIV-1.

IMPORTANCE
HIV-1 encodes virion infectivity factor (Vif) to inactivate its host's antiviral APOBEC3 proteins. Vif triggers APOBEC3 degradation by forming Vif-Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-β) is a novel regulator of Vif-CRL5 function whose mechanism of regulation remains poorly defined. In the present study, we demonstrate that the promotion of Vif-CRL5 assembly by CBF-β can be separated from its influence on Vif stability. The promotion of Vif-CRL5 assembly, but not the influence on Vif stability, is conserved among primate lentiviral Vif proteins: we found that CBF-β from diverse vertebrate species supported HIV-1 Vif function. Considering the importance of the interaction between Vif and CBF-β in viral CRL5 function and HIV-1 replication, disrupting this interaction is an attractive strategy against HIV-1.
Acupuncture for Neuropathic Pain Due to Bortezomib in a Patient with Multiple Myeloma
Authors: Mandıroğlu Sibel , Çevik Cemal , Aylı Meltem
Published: January 2014

Multiple myeloma (MM) is characterised by an increase in plasma cells, particularly in the bone marrow but also in other organs and systems, and with the abnormal production of immunoglobulin. Bortezomib, a current treatment option, inhibits angiogenesis by proteasome inhibition and is known to be effective in the treatment of MM. Peripheral neuropathy (PN) is a common dose-related side effect of bortezomib in patients with MM. We describe a case of PN due to bortezomib treatment which responded dramatically to acupuncture treatment, enabling his bortezomib treatment to continue. The patient was a 74-year-old man with pain, numbness, tingling and weakness in his hands and feet after 22 days of bortezomib treatment given by the haematology clinic. His neuropathic pain score was 8/10. There were no autonomic symptoms. Electroneurophysiological testing confirmed sensorimotor PN. Acupuncture treatment was planned as his neuropathic pain continued. Acupuncture was administered bilaterally to ST36, SP6 and LI4 15 times (every other day in the first five sessions and then twice a week). The numbness, tingling and pain symptoms substantially decreased after the first two treatments. After the 15th session acupuncture treatment was continued once a month. At the end of the sixth month the neuropathic pain assessment score was 0/10. There was no side effect of acupuncture treatment. Acupuncture seems promising as a complementary medical treatment for neuropathic pain from bortezomib-induced PN. Clinical studies involving more cases and electrophysiological studies are necessary to investigate the effectiveness of acupuncture.
What explains worse patient experience in London? Evidence from secondary analysis of the Cancer Patient Experience Survey
Authors: Saunders Catherine L , Abel Gary A , Lyratzopoulos Georgios
Published: January 2014

Objective

To explore why patients with cancer treated by London hospitals report worse experiences of care compared with those treated in other English regions.

Design

Secondary analysis of the 2011/2012 National Cancer Patient Experience Survey (n=69 086).

Setting and participants

Patients with cancer treated by the English National Health Service (NHS) hospitals.

Main outcome measures

64 patient experience measures covering all aspects of cancer care (pre-diagnosis to discharge).

Methods

Using mixed effects logistic regression, we explored whether poorer scores in London hospitals could be explained by patient case-mix (age, gender, ethnicity and cancer type). Because patients referred to tertiary centres and/or with complex medical problems may report more critical experiences, we also explored whether the experiences reported in London may reflect higher concentration of teaching hospitals in the capital. Finally, using the data from the (general) Adult Inpatients Survey, we explored whether the extent of poorer experience reported by London patients was similar for respondents to either survey.

Results

For 52/64 questions, there was evidence of poorer experience in London, with the percentage of patients reporting a positive experience being lower compared with the rest of England by a median of 3.7% (IQR 2.5–5.4%). After case-mix adjustment there was still evidence for worse experience in London for 44/64 questions. In addition, adjusting for teaching hospital status made trivial difference to the case-mix-adjusted findings. There was evidence that London versus rest-of-England differences were greater for patients with cancer compared with (general) hospital inpatients for 10 of 16 questions in both the Cancer Patient Experience and the Adult Inpatients Surveys.

Conclusions

Patients with cancer treated by London hospitals report worse care experiences and by and large these differences are not explained by patient case-mix or teaching hospital status. Efforts to improve care in London should aim to meet patient expectations and improve care quality.
Temporal summation of pain and ultrasound Doppler activity as predictors of treatment response in patients with rheumatoid arthritis: protocol for the Frederiksberg hospitals Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study
Authors: Christensen Anton Wulf , Rifbjerg-Madsen Signe , Christensen Robin , Amris Kirstine , Taylor Peter C , Locht Henning , Ellegaard Karen , Torp-Pedersen Søren , Jespersen Anders , Bartels Else Marie , Danneskiold-Samsøe Bente , Bliddal Henning
Published: January 2014

Introduction

Chronic pain is common in rheumatoid arthritis (RA) and may still persist despite regression of objective signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in RA. Application of the disease activity score DAS28 can classify some patients with active RA solely based on a high tender joint count and poor patient global health score. In such cases, intensified treatment with anti-inflammatory drugs would be expected to yield poorer results than in cases with DAS28 elevation due to a high score for swollen joints and C reactive protein (CRP). Evaluation of central pain sensitisation in patients with few inflammatory indices may be a predictive tool regarding the effect of anti-inflammatory treatment. Computerised pneumatic cuff pressure algometry (CPA) is a method for assessing temporal summation (ie, degree of central sensitisation). The main objective of this study was to examine the prognostic values of pressure pain-induced temporal summation, ultrasound Doppler activity and the interaction between them in relation to treatment response (DAS28-CRP change) in patients with RA initiating any anti-inflammatory therapy.

Method and analysis

120 participants ≥18 years of age will be recruited. Furthermore, they must be either (1) diagnosed with RA, untreated with disease-modifying antirheumatic drugs for at least 6 months and about to initiate disease-modifying antirheumatic drug treatment or (2) about to begin or switch treatment with any biological drug for their RA. Data (clinical, imaging, blood samples, patient reported outcomes and CPA measurements) will be collected from each participant at baseline and after 4 months of anti-inflammatory treatment.

Ethics and dissemination

This study has been approved by the ethics committee for the Copenhagen region (H-4-2013-007). Dissemination will occur through presentations and publication in international peer-reviewed journals.
Improving the use of phlebotomy services in a paediatric inpatient setting
Authors: Pitchforth Jacqueline , Lemer Claire
Published: January 2014

The aim of this project was to improve the use of the current Paediatric Phlebotomy service. The main problem identified was the lack of a system to notify medical teams of unsuccessful blood requests. A phlebotomy process map was constructed to help analyse reasons why failure to notify occurred. Pre and post intervention audits were conducted using the number of unsuccessful blood requests notified as a baseline measurement. The initial intervention was modified based on feedback during the process. A 44% improvement in the number of unsuccessful blood requests notified and a potential cost savings of £6240 was demonstrated in the post-intervention audit. Further work is required as to whether these improvements can be increased, sustained and be cost effective.
Managing human factors in the assembly of the paediatric bronchoscope
Authors: Saxby Clair , Williams Richard
Published: January 2014

Foreign body aspiration in children is a life threatening event and prompt bronchoscopy and extraction is essential for their survival. During a recent paediatric airway emergency at Torbay hospital, Devon, the theatre staff were unable to assemble the paediatric bronchoscope. We therefore investigated methods to improve the efficiency and timeliness of the assembly of the paediatric bronchoscope.

To assess the current problem we asked ten theatre staff at random to assemble the paediatric bronchoscope. 70% of the staff were not able to assemble the paediatric bronchoscope. A prompt poster was developed as a visual aid to help demonstrate how to assemble the paediatric bronchoscope. Another ten theatre staff were asked to assemble the paediatric bronchoscope. Now all of the staff were able to assemble the paediatric bronchoscope.

The prompt poster enabled all the theatre staff tested to correctly assemble the paediatric bronchoscope and the average time taken was reduced. To further develop the service mandatory training sessions have been arranged to help theatre staff remain confident and continue to develop their skills and knowledge.
Improving weekend handover between junior doctors on medical and surgical wards
Authors: Bethune Rob , Campbell Kate , Rose Alex , Wassall Richard , Price Catherine , Siese Thomas , Finn Roisin , Whitaker Sean
Published: January 2014

Poor weekend handover has been implicated as one of the causes of observed higher mortality rates at weekends in UK hospitals. In a large teaching hospital we, a group of junior doctors, set about improving the quality and effectiveness of weekend handover. We used the Model for Improvement to implement a weekend handover sticker through an iterative process using multiple Plan/Do/Study/Act (PDSA) cycles. Over the 16 week study period the number of completed weekend tasks increased by 30% and the number of patients with a documented weekend handover increased by nearly 50%.

Junior doctors are well positioned to notice the quality and safety shortcomings within hospitals, and by using effective improvement methods they can improve these systems at little or no cost.
Fascia iliaca block for pain relief from proximal femoral fracture in the emergency department: a review of the literature
Authors: Chesters Adam , Atkinson Paul
Published: January 2014

Objectives

to determine the efficacy of the fascia iliaca block in providing analgesia to patients with a proximal femoral fracture in the emergency department.

Methods

EMBASE, PubMed, CINAHL and Google Scholar were searched. Free text keywords for population, intervention and outcome were identified to create a search string. The reference lists from articles identified in the primary electronic search were hand searched. Potentially eligible studies were identified based on review of the title and abstract. If eligibility was unclear from the title and abstract, the full text was examined. Randomised controlled trials comparing the fascia iliaca block with standard analgesia were included. A standardised appraisal of the methodological quality of the studies was performed.

Results

39 articles were identified, of which 13 were duplicates. Of the remaining 26, 15 were relevant to the question and suitable for further sorting. There was one conference poster presenting data, which were later published as an audit, and so was considered to be a duplicate. Of the 14 remaining papers, 2 were randomised controlled trials, 6 were cohort studies and 3 were reports of audit of practice. There were 3 abstracts of conference poster or paper submissions, which were descriptions of reviews or service development projects rather than primary studies. The two randomised controlled trials showed statistically significant superior or equal pain relief between the fascia iliaca block and other forms of acute pain relief.

Conclusions

the fascia iliaca block could have an important role in first-line pain control for patients presenting to the emergency department with a proximal femoral fracture. There is potential to reform the acute management of this common group of patients.
Anaemia in inflammatory bowel disease
Authors: Dibb Martyn , Subramanian Sreedhar
Published: January 2014

Anaemia is a common manifestation in inflammatory bowel disease (IBD) and impairs quality of life. Anaemia in IBD is typically caused by iron deficiency or anaemia of chronic disease. Treatment of iron deficiency with oral iron may lead to gastrointestinal intolerance though this may be related to the dose of iron replacement. New intravenous formulations have emerged which allow safe, rapid and effective correction of iron deficiency in IBD. In this article, we provide a review on the topic and cover recent progress in the field for the practicing gastroenterologist.
A prediction algorithm for first onset of major depression in the general population: development and validation
Authors: Wang JianLi , Sareen Jitender , Patten Scott , Bolton James , Schmitz Norbert , Birney Arden
Published: January 2014

Objective

Prediction algorithms are useful for making clinical decisions and for population health planning. However, such prediction algorithms for first onset of major depression do not exist. The objective of this study was to develop and validate a prediction algorithm for first onset of major depression in the general population.

Methods

Longitudinal study design with approximate 3-year follow-up. The study was based on data from a nationally representative sample of the US general population. A total of 28 059 individuals who participated in Waves 1 and 2 of the US National Epidemiologic Survey on Alcohol and Related Conditions and who had not had major depression at Wave 1 were included. The prediction algorithm was developed using logistic regression modelling in 21 813 participants from three census regions. The algorithm was validated in participants from the 4th census region (n=6246). Major depression occurred since Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions, assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule–diagnostic and statistical manual for mental disorders IV.

Results

A prediction algorithm containing 17 unique risk factors was developed. The algorithm had good discriminative power (C statistics=0.7538, 95% CI 0.7378 to 0.7699) and excellent calibration (F-adjusted test=1.00, p=0.448) with the weighted data. In the validation sample, the algorithm had a C statistic of 0.7259 and excellent calibration (Hosmer-Lemeshow χ2=3.41, p=0.906).

Conclusions

The developed prediction algorithm has good discrimination and calibration capacity. It can be used by clinicians, mental health policy-makers and service planners and the general public to predict future risk of having major depression. The application of the algorithm may lead to increased personalisation of treatment, better clinical decisions and more optimal mental health service planning.
Postwar environment and long-term mental health problems in former child soldiers in Northern Uganda: the WAYS study
Authors: Amone-P'Olak Kennedy , Stochl Jan , Ovuga Emilio , Abbott Rosemary , Meiser-Stedman Richard , Croudace Tim J , Jones Peter B
Published: January 2014

Background

War experiences (WE) and postwar environments (PWE) are associated with mental ill-health. The present study aims to investigate the pathways from WE and PWE to mental ill-health and to define opportunities for intervention through analysis of the war-affected youths study (WAYS) cohort study.

Method

WAYS is an ongoing study of a large cohort of former child soldiers being conducted in Uganda. Mental health problems, subjective WE and PWE contexts were assessed by local adaptations of internationally developed measures for use with former child soldiers at least 6 years after the end of the war. Structural equation modeling was used to test two mediation hypotheses: (1) the ‘trauma model’ in which WE directly influence long-term mental health and (2) the ‘psychosocial path’ in which WE influence long-term mental health through PWE stressors.

Results

WE were linked to depression/anxiety (β=0.15 (95% CI 0.01 to 0.30)) through PWE (accounting for 44% of the variance in the relationship between these variables) and to conduct problems (β=0.23 (95% CI 0.03 to 0.43); (accounting for 89% of the variance, ie, near complete mediation)). The direct relation between WE and depression/anxiety attenuated but remained statistically significant. For conduct problems, the direct relationship was no longer significant after accounting for PWE.

Conclusions

PWE are a key determinant of continued mental health problems in former child soldiers. Interventions to reduce long-term mental problems should address both PWE stressors (psychosocial model) and specialised mental healthcare (trauma model) and consider both models of intervention as complementary.
Accumulation of childhood poverty on young adult overweight or obese status: race/ethnicity and gender disparities
Authors: Hernandez Daphne C , Pressler Emily
Published: January 2014

Background

Childhood poverty is positively correlated with overweight status during childhood, adolescence and adulthood. Repeated exposure of childhood poverty could contribute to race/ethnicity and gender disparities in young adult overweight/obese (OV/OB) weight status.

Methods

Young adults born between 1980 and 1990 who participated in the Young Adult file of the 1979 National Longitudinal Study of Youth were examined (N=3901). The accumulation of childhood poverty is captured via poverty exposure from each survey year from the prenatal year through age 18 years. Body mass index was calculated and categorised into the reference criteria for adults outlined by the Center for Disease Control. Logistic regression models were stratified by race/ethnicity and included a term interacting poverty and gender, along with a number of covariates, including various longitudinal socioeconomic status measures and indicators for the intergenerational transmission of economic disadvantage and body weight.

Results

Reoccurring exposure to childhood poverty was positively related to OV/OB for white, black and Hispanic young adult women and inversely related for white young adult men. A direct relationship between the accumulation of childhood poverty and OV/OB was not found for black and Hispanic young adult men.

Conclusions

Helping families move out of poverty may improve the long-term health status of white, black and Hispanic female children as young adults. Community area interventions designed to change impoverished community environments and assist low-income families reduce family level correlates of poverty may help to reduce the weight disparities observed in young adulthood.
Heat illness in military populations: asking the right questions for research
Authors: Stacey Mike , Woods D , Ross D , Wilson D
Published: January 2014

Reports of death and injury in military populations due to exertional heat illness (EHI) and its most severe form, exertional heat stroke, date from antiquity. Yet, understanding of why one soldier may succumb to EHI, while those around him do not, is incomplete. This paper sets out research questions in support of the health of military populations who may experience exertional heat stress. The mechanisms by which excess body heat arises and is dissipated are outlined and the significance of core temperature measurement during exercise is discussed. Known risk factors for EHI are highlighted and new approaches for identifying individual vulnerability to EHI are introduced. A better understanding of the underlying pathophysiology may allow the effective use of biomarkers in future risk stratification and identification of EHI, allied to emerging genetic technologies. The thermal burden associated with states of dress and personal protection of Service personnel in their worldwide duties should be a focus of research as new equipment is introduced. At all times, the discerning use of existing guidance by Commanders on the ground will remain a mainstay of preventing EHI.
Heterogeneous practice patterns regarding antiplatelet medications for neuroendovascular stenting in the USA: a multicenter survey
Authors: Faught Ryan W F , Satti Sudhakar R , Hurst Robert W , Pukenas Bryan A , Smith Michelle Janine
Published: January 2014

Background

Adequate dual antiplatelet (AP) therapy is imperative when performing neurovascular stenting procedures. Currently, no consensus for the ideal AP regimen exists. Thus the present study aimed to gain a better understanding of real world practice AP patterns by surveying neurointerventional surgeons.

Methods

Survey links were emailed to 296 neurointerventional surgeons practicing in the USA, asking 51 questions including demographics, stent specific use, AP pre and post-medication, types of APs, point of care (POC) assessment, complications, and outcomes. Data were collected and analyzed using Research Electronic Data Capture (REDCap).

Results

74 participants responded; 56.8% were from academic centers. Participants treated an average of 5.5 aneurysms per month. They placed an average of 1.6 intracranial stents and 1.4 cervical stents per month. Mean number of pipeline embolization devices (PEDs) placed per year was 15.2. Heterogeneity existed regarding AP regimens; the most frequent included acetylsalicylic acid (ASA) 325 mg+Plavix 75 mg daily (for 7 days prior) and ASA 325 mg+Plavix 75 mg daily (for 5 days prior) for routine placement of intracranial and cervical stents, respectively. For emergency placement, ASA 325 mg+Plavix 600 mg (at time of surgery) was the most frequently used. 46.8% routinely used POC testing, most frequently VerifyNow (Accumetrics, San Diego, California, USA); the most common threshold determining a non-responder was <30% inhibition. 85.7% used POC for PED placement. Management changes based on POC testing were diverse.

Conclusions

The results highlight the heterogeneity of current practices regarding AP medication regimens during neurovascular stenting. Given its importance, evidence based protocols are imperative. Minimal literature exists focusing on neurovasculature, and therefore understanding current practice patterns represents a first step toward generating these protocols.
Recreational drug use in men who have sex with men (MSM) attending UK sexual health services is significantly higher than in non-MSM
Authors: Hunter L J , Dargan P I , Benzie A , White J A , Wood D M
Published: January 2014

Introduction

The aim of this study was to investigate the pattern of recreational drug use in patients attending a genitourinary medicine clinic, and to determine whether drug use was greater among men who have sex with men (MSM) patients, when compared to non-MSM male patients.

Methods

A questionnaire was given to all patients attending the genitourinary medicine clinics at two inner city teaching hospitals over 3 months (July to September 2011). The questionnaire was self-completed by patients while waiting to be seen by a clinician. Data were collected on age, gender, gender of sexual partner(s), and previous/current recreational drug use (type/frequency of drugs used). Only data from male respondents have been analysed in this paper.

Results

1328 questionnaires were completed. Of the male respondents (n=729), 475 (65.2%) were identified as non-MSM and 254 (34.8%) were identified as MSM. The mean±SD age of male respondents was 31±9 years years. Lifetime and last month use of mephedrone, ketamine, volatile nitrites (‘poppers’), sildenafil (Viagra), GHB, and GBL were all significantly higher in the MSM group compared to the non-MSM group. Lifetime use of cocaine powder, MDMA, amphetamine, and methamphetamine were also significantly higher in the MSM group; however, there was no significant difference in last month use of these drugs between MSM and non-MSM groups.

Conclusions

Both lifetime and last month use of most recreational drugs was more common in MSM, when compared to non-MSM males. Sexual health clinics may provide an opportunistic encounter to identify patterns of recreational drug use, explore motivations for use, and implement strategies to reduce harms related to drug use. This will require a multidisciplinary approach to address the psychosocial aspects of drug taking behaviours, in combination with healthcare professionals experienced in the management of recreational drug use.
A methodology for evaluating the effects of spalling on the structural capacity of reinforced concrete bridge girders
Authors: Luckai Jeffrey , Polak Maria Anna , Walbridge Scott
Published: January 2014

Corrosion of the reinforcing steel is a primary deterioration mechanism for reinforced concrete bridges. The spatial distribution of such spalling, relative to bar splices and laps, has not been considered in previous studies and may have a significant influence on structural capacity. In this paper, a modified area concept for considering this spalling is proposed. A methodology has been developed that employs this concept for the practical evaluation of existing bridges. It uses graphical spalling surveys, reinforcement layout information, and existing information regarding material and geometric properties as inputs for the flexural and shear analysis of deteriorated bridge girders. This methodology is easily adapted for full bridge analysis and to consider the effects of bar section loss and bond deterioration. A case study bridge is evaluated to show that this methodology offers a viable tool for the rapid assessment of spalled bridge girders to facilitate the prioritization of rehabilitation projects.
Production and characterization of Tm3+/Yb3+ codoped pedestal-type PbO–GeO2 waveguides
Authors: de Assumpção T.A.A. , Alvarado M.A. , Alayo M.I. , Kassab L.R.P.
Published: January 2014

This work explores the production and characterization of pedestal-type active waveguides based on PbO–GeO2 (PGO) thin films codoped with Tm3+/Yb3+ rare earth ions. Silicon wafers containing around 1.7 μm of SiO2 thickness were used as substrate, and the pedestal structure was obtained by conventional photolithography and plasma etching in a reactive ion etching reactor. Plasma etching procedures were made in steps to reduce roughness at the laterals and sidewalls of waveguides. Around 0.5 μm of Tm3+/Yb3+ codoped PGO thin film was obtained by radio frequency magnetron sputtering deposition after etching procedures. Results of scanning electron microscopy confirmed the waveguide pedestal profile. Optical propagation losses around 4, 5, and 20 dB/cm were observed at 1050, 633, and 543 nm, respectively, for waveguide width in the 30–100 μm range. Near field profiles at these wavelengths and also at 980 nm are also reported and confirmed the multimode coupling behavior. The present results corroborate the possibility of using Tm3+/Yb3+ codoped PGO thin films as active waveguides for photonic applications.
The oldest crust in the Ukrainian Shield – Eoarchaean U–Pb ages and Hf–Nd constraints from enderbites and metasediments
Authors: Claesson S. , Bibikova E. , Shumlyanskyy L. , Dhuime B. , Hawkesworth C. J.
Published: January 2014

The oldest crust in the Ukrainian Shield occurs in the Podolian and Azov domains, which both include Eoarchaean components. U–Pb age data for Dniestr–Bug enderbites, Podolian Domain, indicate that these are
c.
3.75 Ga old, and Lu–Hf isotope data indicate extraction from chondritic to mildly isotopically depleted sources with ɛ
Hf
up to
c.
+2. Nd model ages support their Eoarchaean age, while model ages for Dniestr–Bug metasedimentary gneisses indicate that these also include younger crustal material. Most of the Hf-age data for metasedimentary zircon from the Soroki greenstone belt, Azov Domain, reflects Eoarchaean primary crustal sources with chondritic to mildly depleted Hf isotope signatures at 3.75 Ga. A minor portion is derived from Mesoarchaean crust with a depleted ɛ
Hf
signature of
c.
+4 at 3.1 Ga. U–Pb zircon ages from Fedorivka greenstone belt metasediments are consistent with the Soroki age data, but also include a 2.7–2.9 Ga component. Nd whole rock model ages provide support for a younger crustal component in the latter. Both domains have been subject to Neoarchaean,
c.
2.8 Ga, and Palaeoproterozoic,
c.
2.0 Ga, metamorphism. The spatial distribution indicates that the Podolian and Azov domains evolved independently of each other before the amalgamation of the Ukrainian Shield.
Abundant sulphate in the Neoproterozoic ocean: implications of constant δ
34
S of barite in the Aberfeldy SEDEX deposits, Scottish Dalradian
Authors: Moles Norman R. , Boyce Adrian J. , Fallick Anthony E.
Published: January 2014

The timing and extent of ocean oxygenation is controversial. Proterozoic sulphur isotope datasets often show marked fluctuations over small stratigraphic intervals, suggesting that oceanic sulphate concentrations were much lower than modern values. A large accumulation of Neoproterozoic sulphate (>8 million tonnes preserved), as stratiform barite rock, is located in the Grampian Highlands near Aberfeldy. Diagenetic/metamorphic alteration has caused pronounced δ
34
S variations near bed margins. This aside, barite throughout the deposits shows a narrow range in δ
34
S, mean 36±1.5‰. We infer that this is representative of contemporaneous seawater sulphate, and that δ
34
S
seawater
was constant during deposition of a stratigraphical thickness >250 m of mostly fine-grained clastic sediments. Uniformity of δ
34
S
seawater
during barite precipitation, even in thick (>10 m) beds and with the co-occurrence of abundant sulphides incorporating bacteriogenically reduced sulphur, implies no limit to availability of seawater sulphate during hydrothermal exhalative events. Our data, combined with previous δ
34
S research on Dalradian metasediments, suggest a stability, abundance and constancy of ocean sulphate in the Neoproterozoic. This contrasts with isotopic data using trace sulphate in limestones. It appears that, around the time of the Marinoan glaciation (
c.
635 Ma), the ocean, although stratified at least locally, comprised a substantial reservoir of sulphate-bearing oxygenated seawater.
How to Understand Divergent Views on Bipolar Disorder in Youth
Authors: Carlson Gabrielle A. , Klein Daniel N.
Published: January 2014

There are two divergent viewpoints on the phenomenology and outcome of bipolar I (BP I) disorder in youth. Disparities evolved as unintended consequences from investigators' inconsistencies both in translating the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R, and DSM-IV criteria and in operationalizing them differently in their standardized assessments. Rates of conservatively diagnosed BP I are lower both in community studies of youths than in adults and from liberally defined BP I in youths. Rates of co-occurring attention-deficit hyperactivity disorder (ADHD) are lower in conservatively than liberally defined children and adolescents with BP I. Rates of both BP I and of ADHD are lower in offspring of BP I probands, and outcome more closely approximates that of adults with BP I in conservatively versus liberally defined children and teens with BP I. Both perspectives can claim evidence for reliability and validity that support their positions. However, the samples are so different that it is difficult to compare studies conducted from these different perspectives.
Advances in Cognitive Theory and Therapy: The Generic Cognitive Model
Authors: Beck Aaron T. , Haigh Emily A.P.
Published: January 2014

For over 50 years, Beck's cognitive model has provided an evidence-based way to conceptualize and treat psychological disorders. The generic cognitive model represents a set of common principles that can be applied across the spectrum of psychological disorders. The updated theoretical model provides a framework for addressing significant questions regarding the phenomenology of disorders not explained in previous iterations of the original model. New additions to the theory include continuity of adaptive and maladaptive function, dual information processing, energizing of schemas, and attentional focus. The model includes a theory of modes, an organization of schemas relevant to expectancies, self-evaluations, rules, and memories. A description of the new theoretical model is followed by a presentation of the corresponding applied model, which provides a template for conceptualizing a specific disorder and formulating a case. The focus on beliefs differentiates disorders and provides a target for treatment. A variety of interventions are described.
The Reliability of Clinical Diagnoses: State of the Art
Authors: Kraemer Helena Chmura
Published: January 2014

Reliability of clinical diagnosis is essential for good clinical decision making as well as productive clinical research. The current review emphasizes the distinction between a disorder and a diagnosis and between validity and reliability of diagnoses, and the relationships that exist between them. What is crucial is that reliable diagnoses are essential to establishing valid diagnoses. The present review discusses the theoretical background underlying the evaluation of diagnoses, possible designs of reliability studies, estimation of the reliability coefficient, the standards for assessment of reliability, and strategies for improving reliability without compromising validity.
Dirac Fermions in Solids: From High-Tc Cuprates and Graphene to Topological Insulators and Weyl Semimetals
Authors: Vafek Oskar , Vishwanath Ashvin
Published: January 2014

Understanding Dirac-like fermions has become an imperative in modern condensed matter sciences: All across the research frontier, from graphene to high Tc superconductors to the topological insulators and beyond, various electronic systems exhibit properties that can be well described by the Dirac equation. Such physics is no longer the exclusive domain of quantum field theories and other esoteric mathematical musings; instead, physics of real condensed matter systems is governed by such equations, and important materials science and practical implications hinge on our understanding of Dirac particles in two and three dimensions. Although the physics that gives rise to the massless Dirac fermions in each of the above-mentioned materials is different, the low-energy properties are governed by the same Dirac kinematics. The aim of this article is to review a selected cross-section of this vast field by highlighting the generalities and contrasting the specifics of several physical systems.
Low-Frequency Unsteadiness of Shock Wave/Turbulent Boundary Layer Interactions
Authors: Clemens Noel T. , Narayanaswamy Venkateswaran
Published: January 2014

Shock wave/boundary layer interactions occur in a wide range of supersonic internal and external flows, and often these interactions are associated with turbulent boundary layer separation. The resulting separated flow is associated with large-scale, low-frequency unsteadiness whose cause has been the subject of much attention and debate. In particular, some researchers have concluded that the source of low-frequency motions is in the upstream boundary layer, whereas others have argued for a downstream instability as the driving mechanism. Owing to substantial recent activity, we are close to developing a comprehensive understanding, albeit only in simplified flow configurations. A plausible model is that the interaction responds as a dynamical system that is forced by external disturbances. The low-frequency dynamics seem to be adequately described by a recently proposed shear layer entrainment-recharge mechanism. Upstream boundary layer fluctuations seem to be an important source of disturbances, but the evidence suggests that their impact is reduced with increasing size of the separated flow.
Impact of Diet on Human Intestinal Microbiota and Health
Authors: Salonen Anne , de Vos Willem M.
Published: January 2014

Our intestinal microbiota is involved in the breakdown and bioconversion of dietary and host components that are not degraded and taken up by our own digestive system. The end products generated by our microbiota fuel our enterocytes and support growth but also have signaling functions that generate systemic immune and metabolic responses. Due to the immense metabolic capacity of the intestinal microbiota and its relatively high plasticity, there is great interest in identifying dietary approaches that allow intentional and predictable modulation of the microbiota. In this article, we review the current insights on dietary influence on the human intestinal microbiota based on recent high-throughput molecular studies and interconnections with health. We focus especially on the emerging data that identify the amount and type of dietary fat as significant modulators of the colonic microbiota and its metabolic output.
Gastric Digestion In Vivo and In Vitro: How the Structural Aspects of Food Influence the Digestion Process
Authors: Bornhorst Gail M. , Paul Singh R.
Published: January 2014

Food digestion is crucial for sustaining life. Although it has been examined for more than 300 years, the basic principles are not entirely understood. Antral motility is well characterized, and current research is seeking to determine flow patterns generated by the stomach's peristaltic contractions. The rate of gastric emptying for solid and liquid meals has been determined according to variations in meal composition, energy content, and subject characteristics. The glycemic response has been measured for many carbohydrate foods and is altered by factors such as amount of processing, particle size, and starch structure. Similarly, ileal starch digestibility is altered by food and starch properties. Even though many foods have been studied according to their glycemic response, starch digestibility, and in vitro digestion kinetics, the rate-determining processes and underlying mechanisms remain to be established. The link between food properties, digestion processes, and final health outcomes must be strengthened for functional food optimization.
Nondestructive Measurement of Fruit and Vegetable Quality
Authors: Nicolaï Bart M. , Defraeye Thijs , De Ketelaere Bart , Herremans Els , Hertog Maarten L.A.T.M. , Saeys Wouter , Torricelli Alessandro , Vandendriessche Thomas , Verboven Pieter
Published: January 2014

We review nondestructive techniques for measuring internal and external quality attributes of fruit and vegetables, such as color, size and shape, flavor, texture, and absence of defects. The different techniques are organized according to their physical measurement principle. We first describe each technique and then list some examples. As many of these techniques rely on mathematical models and particular data processing methods, we discuss these where needed. We pay particular attention to techniques that can be implemented online in grading lines.