bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactivation of hepatitis B virus in a patient with adult T‐cell leukemia–lymphoma receiving the anti‐CC chemokine receptor 4 antibody mogamulizumab
Authors: Nakano Nobuaki , Kusumoto Shigeru , Tanaka Yasuhito , Ishida Takashi , Takeuchi Shogo , Takatsuka Yoshifusa , Akinaga Shiro , Mizokami Masashi , Ueda Ryuzo , Utsunomiya Atae
Published: March 2013

The introduction of molecularly targeted drugs has increased the risk of reactivation of hepatitis B virus (HBV), which is a potentially fatal complication following anticancer chemotherapy even in patients who have previously resolved their HBV infection. CC chemokine receptor 4 (CCR4) has been identified as a novel molecular target in antibody therapy for patients with adult T‐cell leukemia–lymphoma (ATL) and peripheral T‐cell lymphoma, and the humanized anti‐CCR4 monoclonal antibody mogamulizumab has been developed. We reported HBV reactivation of an ATL patient with previously resolved HBV infection after mogamulizumab treatment in a dose‐finding study for this antibody. Our retrospective analysis using preserved samples also revealed the detailed kinetics of HBV DNA levels before and just after HBV reactivation.
Effect of Kampo extracts on urinary stone formation: An experimental investigation
Authors: Nishihata Masaya , Kohjimoto Yasuo , Hara Isao
Published: March 2013

Objective

To examine the effects of Kampo extracts on the process of urinary stone formation.

Methods

A total of 14 Kampo extracts (10 μg/mL) were examined in vitro by assessing whether they could inhibit two critical steps in the early process of calcium oxalate stone formation, namely crystal aggregation and crystal adhesion to the renal tubular epithelium of Madin–Darby canine kidney cells. The inhibitory effect of the extracts on stone formation was examined by using a rat model.

Results

Sanshishi and Takusha showed a strong inhibitory effect on the calcium oxalate monohydrate crystal aggregation (84.5% and 64.2%, respectively) and on the crystal adhesion to Madin–Darby canine kidney cells (88.2% and 54.6%, respectively). As pretreatment of Madin–Darby canine kidney cells with these two Kampo extracts did not show any inhibitory effect on crystal adhesion, they were considered to mainly affect the crystal surface to block crystal adhesion to Madin–Darby canine kidney cells. Gorin‐san, containing both Sanshishi and Takusha, showed significantly stronger inhibitory activities at lower concentrations compared with Chorei‐to, which contains Takusha. Finally, Sanshishi showed a prophylactic effect on calcium oxalate crystal deposition in the rat model.

Conclusions

These findings suggest that Gorin‐san, which contains Sanshishi and Takusha, might be used for the prophylaxis of urolithiasis in humans.
Economic growth and inequality in Singapore: The case for a minimum wage
Authors: Hui Weng Tat
Published: March 2013

In the context of Singapore's ageing population, the employment of large numbers of low‐skilled foreign workers is proving to be a major challenge to inclusive growth because of the stagnation of low‐wage workers' incomes. In order to address this problem, the author makes the case for introducing a minimum wage to complement existing in‐work benefit schemes. After addressing the commonly voiced objections to a minimum wage system, he suggests ways in which a minimum wage could be implemented in Singapore. New measures to enhance the social safety net and foster more sustainable economic growth are also proposed.
Adjuvant breast radiotherapy using a simultaneous integrated boost: Clinical and dosimetric perspectives
Authors: Alford Simone L. , Prassas Georgina N. , Vogelesang Cathy R. , Leggett Heather J. , Hamilton Chris S.
Published: March 2013

Introduction

We sought to assess the cosmetic outcomes and the proportion of patients with late radiotherapy toxicity in a group of women with early‐stage breast cancer treated with breast‐conserving surgery (BCS) and adjuvant radiotherapy using a simultaneous integrated boost (SIB) technique.

Methods and Materials

Female patients with early‐stage breast cancer (pT1‐2 N0‐1) treated with BCS and radiotherapy using an SIB technique were identified retrospectively from the departmental database. Radiotherapy consisted of 45 Gy in 25 fractions delivered to the whole breast with a simultaneous forward‐planned conformal boost to the tumour bed of 60 Gy in 25 fractions. Demographic data, as well as prospectively collected measures of toxicity and cosmesis, were recorded and analysed.

Results

Fifty‐five eligible patients were treated between 2009 and 2011. The median age was 61 years (range, 31 to 81 years). Median follow‐up was 13.3 months. Late toxicities (including oedema, pigmentation, telangiectasia, fibrosis, osteonecrosis and pain) were graded using Common Terminology Criteria for Adverse Events v3.0 criteria. Grade 0, 1 and 2 toxicities were assigned to 52.8%, 43.4% and 3.8% of patients, respectively. There were no cases of grade 3 or greater toxicity. Ninety‐eight per cent had a good or excellent cosmetic outcome based on independent assessment by both the patient and physician. One patient developed a second primary contralateral breast cancer. There were no cases of local recurrence.

Conclusion

The use of a conformal SIB technique is proposed as a mode of delivering adjuvant radiotherapy in early‐stage breast cancer. This schedule is convenient for the patient given the shortened overall treatment time. Additionally, the SIB technique seems to be well tolerated, with minimal toxicity and acceptable cosmetic outcomes. Finally, there are dosimetric benefits with respect to target coverage and reduction of dose and dose per fraction to organs at risk.
A randomized controlled trial of a self‐management psychosocial intervention for men with prostate cancer and their partners: a study protocol
Authors: McCaughan Eilis , Prue Gillian , McSorley Oonagh , Northouse Laurel , Schafenacker Ann , Parahoo Kader
Published: March 2013

Background

Little is known about interventions to help men and their partners cope with the after effects of prostate cancer treatment. The lack of in‐depth descriptions of the intervention content is hindering the identification of which intervention (or component of an intervention) works.

Aim

To describe the development and evaluation of the content of a self‐management psychosocial intervention for men with prostate cancer and their partners.

Design

A feasibility randomized controlled trial including structure, process, and outcome analysis.

Methods

This 9‐week intervention commences on completion of treatment and consists of three group and two telephone sessions. The intervention focuses on symptom management, sexual dysfunction, uncertainty management, positive thinking and couple communication. Forty‐eight couples will be assigned to either the intervention or a control group receiving usual care. Participants will be assessed at baseline, immediately postintervention and at 1 and 6 months postintervention. Outcome measures for patients and caregivers include self‐efficacy, quality of life, symptom distress, uncertainty, benefits of illness, health behaviour, and measures of couple communication and support. An additional caregiver assessment will be completed by the partner.

Discussion

The main purpose of this feasibility study is to investigate the acceptability of the CONNECT programme to men with prostate cancer and their partners and to gain feedback from the participants and facilitators to make changes to and enhance the programme. Reasons why men do not want to participate will be collated to enhance recruitment in the future. We will also test recruitment strategies, randomization procedures, and the acceptability of the questionnaires. Ethical approval granted December 2010.
A systematic review of the effectiveness of advanced practice nurses in long‐term care
Authors: Donald Faith , Martin‐Misener Ruth , Carter Nancy , Donald Erin E. , Kaasalainen Sharon , Wickson‐Griffiths Abigail , Lloyd Monique , Akhtar‐Danesh Noori , DiCenso Alba
Published: March 2013

Aim

To report quantitative evidence of the effectiveness of advanced practice nursing roles, clinical nurse specialists and nurse practitioners, in meeting the healthcare needs of older adults living in long‐term care residential settings.

Background

Although studies have examined the effectiveness of advanced practice nurses in this setting, a systematic review of this evidence has not been conducted.

Design

Quantitative systematic review.

Data sources

Twelve electronic databases were searched (1966–2010); leaders in the field were contacted; and personal files, reference lists, pertinent journals, and websites were searched for prospective studies with a comparison group.

Review methods

Studies that met inclusion criteria were reviewed for quality, using a modified version of the Cochrane Effective Practice and Organisation of Care Review Group risk of bias assessment criteria.

Results

Four prospective studies conducted in the USA and reported in 15 papers were included. Long‐term care settings with advanced practice nurses had lower rates of depression, urinary incontinence, pressure ulcers, restraint use, and aggressive behaviours; more residents who experienced improvements in meeting personal goals; and family members who expressed more satisfaction with medical services.

Conclusion

Advanced practice nurses are associated with improvements in several measures of health status and behaviours of older adults in long‐term care settings and in family satisfaction. Further exploration is needed to determine the effect of advanced practice nurses on health services use; resident satisfaction with care and quality of life; and the skills, quality of care, and job satisfaction of healthcare staff.
A Prospective Randomized Single‐Center Study on the Risk of Asymptomatic Cerebral Lesions Comparing Irrigated Radiofrequency Current Ablation with the Cryoballoon and the Laser Balloon
Authors: SCHMIDT BORIS , GUNAWARDENE MELANIE , KRIEG DETLEF , BORDIGNON STEFANO , FÜRNKRANZ ALEXANDER , KULIKOGLU MEHMET , HERRMANN WILFRIED , CHUN K.R. JULIAN
Published: March 2013

Asymptomatic Cerebral Lesions in AF Ablation

Background

Asymptomatic cerebral lesions (ACL) may occur during atrial fibrillation (AF) ablation. We sought to compare the ACL incidence between 3 contemporary technologies: (1) irrigated radiofrequency current (RFC), (2) the single big cryoballoon (CB), and (3) the endoscopic laser‐balloon (LB) in a prospective randomized pilot study.

Methods and Results

Ninety‐nine patients were treated in 3 groups. Diffusion weighted MRI was acquired pre‐ (n = 20) and 24–48 h postablation (n = 99).

After ablation, new ACL were detected in 22% of patients without significant differences between groups (RFC 8/33; CB 6/33; LB 8/33; P = 0.8). The presence of hypertension was identified as the only independent predictor of ACL by univariate regression analysis.

During LB ablation, more ablation lesions (140 ± 19 vs 119 ± 18; P = 0.007) were applied during longer procedures (166 ± 36 vs 143 ± 32 min; P = 0.05) in patients with ACL. Univariate analysis revealed that a higher number of ablation lesions predicted ACL (P = 0.02).

Conclusion

In this prospective, randomized, single‐center pilot study, ablation technology did not influence the occurrence of ACL during AF ablation.
Four factor Research Awareness Scale for Nurses in Japanese: Instrument development study
Authors: Watanabe Yoshino , Oe Makoto , Takemura Yukie , Sasaki Minako , Onishi Mami , Kanda Katsuya , Sanada Hiromi
Published: March 2013

Aim

Research awareness is an important consideration necessary for providing superior nursing care. However, a gap exists between research and clinical practice. A major obstacle to integrating research into clinical practice is the absence of research awareness among nurses. Studies on research awareness have focused primarily on three factors: attitude, competence, and encouragement for conducting research. The Research Awareness Scale for Nurses (RASN) in Japanese incorporates a critical, yet generally overlooked fourth factor of flexible structure for research. The aim of this study was to develop a nursing research awareness scale that could be used to determine the reasons for the lack of interest in research among nurses and to help nursing administrators take steps to integrate research into clinical practice.

Methods

The RASN was developed and tested in three stages. An item pool for the scale was generated from a published work review and focus group interviews. The scale was then tested in a pilot study, and finally in a main study. Reliability and validity were examined by exploratory and confirmatory factor analysis, Cronbach's alpha, one‐way anova and correlation analysis.

Results

The RASN exhibited good validity in the four factor structure (“attitude”, “competence”, “encouragement”, and “flexible structure”). Cronbach's alpha exhibited good internal consistency. The RASN was significantly and positively correlated with research‐related education and activities.

Conclusion

The RASN had good internal consistency, content validity, discriminant validity, and construct validity. These findings demonstrate that the RASN is a useful instrument for evaluating approaches toward the integration of research into clinical practice.
Turkish patients' decision‐making process in seeking treatment for myocardial infarction
Authors: Yardimci Tuğba , Mert Hatice
Published: March 2013

Aim

The purpose of this study was to reveal how Turkish patients experiencing acute myocardial infarction (AMI) for the first time decide to seek medical treatment following the initiation of the symptoms.

Methods

This qualitative study was carried out by using the grounded theory. Data were collected in a university hospital cardiology clinic in Turkey between March 2009 and March 2010. The sample comprised 30 patients having experienced AMI for the first time. The data were collected by an in‐depth interview technique via a semistructured interview form. All of the interviews were recorded using a tape‐recorder.

Results

The median decision‐making time was 90 min. Two main themes emerged at the end of the study: “feeling of abnormality” and “thinking the situation is critical”. Deciding to seek medical help was found to be a process which emerges with the severity of symptoms, an inability to manage symptoms, fear, and extrinsic factors.

Conclusion

The results of this study show the importance of being aware of the symptoms when deciding to seek treatment. It is recommended to develop training programs about AMI symptoms and the importance of receiving early medical help by targeting society in general and the individuals with a diagnosis of coronary artery disease and their relatives in particular, and to organize awareness‐raising campaigns supported by the media.
Fishing for function – distinct roles of Bace1 and Bace2 in Zebrafish development
Authors: Walter Jochen
Published: March 2013

Read the full article ‘Loss of Bace2 in zebrafish affects melanocyte migration and is distinct from Bace1 knock out phenotypes’ on doi: 10.1111/jnc.12198.
Validation of an ELISA for urinary dopamine: applications in monitoring treatment of dopamine‐related disorders
Authors: Nichkova Mikaela , Wynveen Paul M. , Marc David T. , Huisman Han , Kellermann Gottfried H.
Published: March 2013

Dopamine is a catecholamine that serves as a neurotransmitter in the central and peripheral nervous system. Non‐invasive, reliable, and high‐throughput techniques for its quantification are needed to assess dysfunctions of the dopaminergic system and monitor therapies. We developed and validated a competitive ELISA for direct determination of dopamine in urine samples. The method provides high specificity, good accuracy, and precision (average inter‐assay variation < 12%). The analysis is not affected by general urinary components and structurally related drugs and metabolites. The correlation between ELISA and LC‐MS/MS analyses was very good (r = 0.986, n = 28). The reference range was 64–261 μg/g Cr (n = 64). Week‐to‐week biological variations of second morning urinary dopamine under free‐living conditions were 23.9% for within‐ and 35.5% for between‐subject variation (n = 10). The assay is applied in monitoring Parkinson's disease patients under different treatments. Urinary dopamine levels significantly increase in a dose‐dependent manner for Parkinson's disease patients under l‐DOPA treatment. The present ELISA provides a cost‐effective alternative to chromatographic methods to monitor patients receiving dopamine restoring treatment to ensure appropriate dosing and clinical efficacy. The method can be used in pathological research for the assessment of possible peripheral biological markers for disorders related to the dopaminergic system.
The Meaning of Evidence‐Based Management to Brazilian Senior Nurse Leaders
Authors: Spiri Wilza Carla , MacPhee Maura
Published: March 2013

Purpose

The study objective was to understand the meaning of evidence‐based management for senior nurse leaders in accredited, public hospitals in the State of Sao Paulo, Brazil.

Design and Method

A phenomenological approach was used to analyze interviews conducted with 10 senior nurse leaders between August 2011 and March 2012. The analytic method was developed by the Brazilian phenomenologist, Martins.

Findings

Senior nurse leaders described how they critically appraise many sources of evidence when making managerial decisions. They emphasized the importance of working with their teams to locally adapt and evaluate best evidence associated with managerial decision making and organizational innovations. Their statements also demonstrated how they use evidence‐based management to support the adoption of evidence‐based practices. They did not, however, provide specific strategies for seeking out and obtaining evidence. Notable challenges were traditional cultures and rigid bureaucracies, while major facilitators included accreditation, teamwork, and shared decision making.

Conclusions

Evidence‐based management necessitates a continuous process of locating, implementing, and evaluating evidence. In this study leaders provided multiple, concrete examples of all these processes except seeking out and locating evidence. They also gave examples of other leadership skills associated with successful adoption of evidence‐based practice and management, particularly interdisciplinary teamwork and shared decision making.

Clinical Relevance

This study demonstrates senior nurse leaders’ awareness and utilization of evidence‐based management. The study also suggests what aspects of evidence‐based management need further development, such as more active identification of potential, new organizational innovations.
Effects of herbal supplements on the bioactivation of chemotherapeutic agents
Authors: Gorman Gregory S , Coward Lori , Darby Adrienne , Rasberry Bethany
Published: March 2013

Objectives

The aim of this study was to investigate the impact of commercially available, over-the-counter herbal supplements (St John's wort, black cohosh and ginger root extract) on the metabolic activation of tamoxifen and irinotecan.

Methods

Co-incubation of each drug and supplement combination over a range of concentrations was conducted in human liver microsomes and the decrease in the rate of active metabolite formation was monitored using high-performance liquid chromatography tandem mass spectrometry. Data was analysed using non-linear regression analysis and Dixon plots to determine the dominant mechanism of inhibition and to estimate the Ki and IC50 values of the commercial supplements.

Key findings

The data suggest that black cohosh was the strongest inhibitor tested in this study for both CYP450 and carboxyesterase mediated biotransformation of tamoxifen and irinotecan, respectively, to their active metabolites. St John's wort was a stronger inhibitor compared with ginger root extract for tamoxifen (CYP mediated pathway), while ginger root extract was a stronger inhibitor compared with St John's wort for the carboxyesterase mediated pathway.

Conclusions

Commercially available supplements are widely used by patients and their potential impact on the efficacy of the chemotherapy is often unknown. The clinical significance of these results needs to be evaluated in a comprehensive clinical trial.
Coupling biorelevant dissolution methods with physiologically based pharmacokinetic modelling to forecast in-vivo performance of solid oral dosage forms
Authors: Otsuka Keiichi , Shono Yasushi , Dressman Jennifer
Published: March 2013

Objectives

To summarize the basis for and progress with the development of in-vitro–in-silico–in-vivo (IV-IS-IV) relationships for oral dosage forms using physiologically based pharmacokinetic (PBPK) modelling, with the focus on predicting the performance of solid oral dosage forms in humans.

Key findings

Various approaches to forecasting oral absorption have been reported to date. These range from simple dissolution tests, through biorelevant dissolution testing and laboratory simulations of the gastrointestinal (GI) tract, to the use of PBPK modelling to predict oral drug absorption based on the physicochemical parameters of the drug substance. Although each of these approaches can be useful for qualitative predictions, forecasting oral absorption on a quantitative basis with an individual approach is only possible for selected drug/dosage form combinations. By integrating biorelevant dissolution test results with the PBPK models, it has become possible to achieve quantitatively accurate as well as qualitative predictions of plasma profiles after oral dosing for both immediate and modified release formulations.

With further refinement of both the biorelevant dissolution testing methods and the PBPK models, it should be possible to expedite the development and regulatory approval of optimized dosage forms and dosing conditions.
Polyphenol compounds in the chicken/animal diet: from the past to the future
Authors: Surai P. F.
Published: March 2013

Animal feed provides a range of antioxidants that help the body building an integrated antioxidant system responsible for a prevention of damaging effects of free radicals and products of their metabolism. Vitamin E is considered to be the main chain‐breaking antioxidant located in the membranes and effectively protecting them against lipid peroxidation. Recently, various polyphenol compounds, especially flavonoids, have received substantial attention because of their antioxidant activities in various in vitro systems. However, it was shown that flavonoid compounds are poorly absorbed in the gut and their concentrations in target tissues are too low to perform an effective antioxidant defences. The aim of the present paper is to review existing evidence about possible roles of various plant extracts provided with the diet in animal/poultry nutrition with a specific emphasis to their antioxidant activities.
Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel
Authors: Kaminetsky Jed , Werner Michael , Fontenot Greg , Wiehle Ronald D.
Published: March 2013

Introduction

Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism.

Aim

Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone.

Main Outcome Measures

Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated.

Methods

This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone.

Results

After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334 × 106/mL range. The gel was ineffective in raising sperm counts above 20 × 106/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts.

Conclusions

Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.
Incidence of diabetes mellitus in a population‐based cohort of persons with chronic hepatitis B virus infection
Authors: Spradling P. R. , Simons B. , Narayanan M. , Xing J. , Homan C. , Bulkow L. , Cagle H. , Schraer C. D. , McMahon B. J.
Published: March 2013

To investigate the effect of hepatitis B virus (HBV) infection on the development of diabetes mellitus (DM), we compared DM incidence and characteristics of Alaska Native persons with and without HBV infection. From 1990 to 2010, there were 52 incident DM cases among 1309 persons with infection vs 4557 DM cases among 85 698 persons without infection (log‐rank test, P = 0.20). Compared to infected persons without DM, those with DM were significantly older (57.0 vs 47.4 years, P < 0.001) and had higher body mass index (34.5 vs 28.4 kg/m2, P < 0.001). Genotype, immune active disease and the presence of cirrhosis were not associated with DM. In this population‐based cohort with over 20 years of follow‐up, there was no effect of HBV infection on DM development.
Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients
Authors: Petta S. , Grimaudo S. , Marco V. D. , Scazzone C. , Macaluso F. S. , Cammà C. , Cabibi D. , Pipitone R. , Craxì A.
Published: March 2013

Lower 25‐hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome‐wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D‐binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy‐proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high‐pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.
Knowledge about infection is the only predictor of treatment in patients with chronic hepatitis C
Authors: Younossi Z. M. , Stepanova M. , Afendy M. , Lam B. P. , Mishra A.
Published: March 2013

HCV is the leading cause of cirrhosis and liver cancer in the U.S. The Center for Disease Control (CDC) has recently recommended ‘Birth Cohort Screening’ of the U.S. Adult population to reduce the future burden of undiagnosed HCV infections in the U.S. Our aim was to assess independent predictors of receiving treatment in a cohort of HCV‐infected patients. The Hepatitis C follow‐up questionnaires of the National Health and Nutrition Examination Surveys (NHANES) conducted from 2001 to 2010 were used. The NHANES participants who tested positive for HCV RNA were followed by CDC 6 months after initial testing with questions related to their awareness of their infection and history or intention to receive treatment. A total of 500 NHANES participants tested positive for HCV RNA and were targeted for follow‐up. Of these, only 203 had completed the follow‐up questionnaire (response rate of 40.6%). Of these, only 101 (50%) knew about their HCV positivity before NHANES, and from them, only 34 (17%) had received treatment. In multivariate analysis, prior knowledge about their HCV infection in HCV‐positive individuals was independently associated with receiving routine care from a doctor or HMO, with higher income, female gender, being in poor or fair health and not consuming excessive amounts of alcohol. On the other hand, the knowledge about HCV infection was the only independent predictor of receiving anti‐HCV treatment (odds ratio 6.14). Knowledge about having HCV infection is the only independent predictor of receiving treatment. Therefore, birth cohort screening of the U.S. General population could lead to wider identification of HCV and potentially better management of the future burden of HCV and its complications.
Participatory and evolutionary integrated lake basin management
Authors: Lin Hebin , Thornton Jeffrey A. , Slawski Thomas M.
Published: March 2013

This study discusses some fundamental institutional rationales to support the participatory approach of integrated lake basin management (ILBM). Based on five propositions for institutional change embodied within evolutionary economic thinking, an institutional change pathway (ICP) framework is constructed composed of eight institutional factors and four socioeconomic constraints. By merging the ILBM governance themes with the ICP institutional factors and socioeconomic constraints, an ILBM‐ICP matrix is developed. The ILBM‐ICP matrix indicates ILBM has focused on institutional factors of (i) opportunities, (ii) choices and (iii) incentives, with lesser emphasis on (iv) competition, (v) investment and (vi) payoff. For a more balanced institutional foundation for ILBM, incorporation of the financial mechanism of payments for improving ecosystem services at the watershed scale (PIES‐W) forms an effective complement to the ILBM concept. PIES‐W features the rationale of coordinating human stakeholders’ conservation services (CS) for improving ecosystem services with human stakeholders’ needs for ES as a basis for survival. This study calls upon the political and scientific communities to merge their visions and coordinate their actions in leading institutional improvement of ILBM so as to contribute to sustainable ecosystem governance.
Lakes, landscapes and locals: Pooling partnership resources to create sustainable lake catchments
Authors: Pinder John R.
Published: March 2013

The historical lack of classification and legislative control on lake quality has previously prevented these complex water bodies from being adequately protected until the European Water Framework Directive became operative. Their increasing importance for all their values and the sensitivity of many lakes to climate change, however, has heightened their profile. Their relative importance has recently been lifted further by the development of the ‘ecosystem services’ approach to recognize multiple values. This report discusses initiatives taken to address problems outside the legal frameworks, provides an analysis of the processes involved and outlines where improvements can be made and where the present arrangements are vulnerable. It identifies the need for all ‘players’ to have a common agenda and use a common language to aid consensus building and resource sharing. It also advocates that high‐quality communications are the key to community stewardship of lake catchments and education is the foundation for changing the initiatives driven by individual champions to a position where protection of lakes is, through a cultural shift or establishing a new paradigm of community responsibility in protecting vulnerable lakes, wetlands and their catchments.
Cryptic genetic and wing pattern diversity in a mimeticHeliconiusbutterfly
Authors: Hill R. I. , Gilbert L. E. , Kronforst M. R.
Published: March 2013

Despite rampant colour pattern diversity in South America,Heliconius eratoexhibits a ‘postman’ wing pattern throughout most of Central America. We examined genetic variation across the range ofH. erato, including dense sampling in Central America, and discovered a deep genetic break, centred on the mountain range that runs through Costa Rica. This break is characterized by a novel mitochondrial lineage, which is nearly fixed in northern Central America, that branches basal to all previously described mitochondrial diversity in the species. Strong genetic differentiation also appears in Z‐linked and autosomal markers, and it is further associated with a distinct, but subtle, shift in wing pattern phenotype. Comparison of clines in wing phenotype, mtDNAand nuclear markers indicate they are all centred on the mountains dividing Costa Rica, but that cline width differs among data sets. Phylogeographical analyses, accounting for this new diversity, rewrite our understanding of mimicry evolution in this system. For instance, these results suggest thatH. eratooriginated west of the Andes, perhaps in Central America, and as many as 1 million years before its co‐mimic,H. melpomene. Overall our data indicate that neutral genetic markers and colour pattern loci are congruent and converge on the same hypothesis—H. eratooriginated in northwest South America or Central America with a ‘postman’ phenotype and then radiated into the wealth of colour patterns present today.
Creatio Ex Nihilo Recovered
Authors: Burrell David B.
Published: March 2013

Creatio ex nihilo sounds like a philosophical teaching, but philosophy has been utterly unprepared to offer proper expression for an origination which presupposes nothing at all! Yet each of the Abrahamic faiths insists on such an origination, so it proved serendipitous when sufficient contact opened between these diverse religious traditions to allow thinkers to assist one another in what proved to be a shared task—and indeed gain assistance from others as well, as Sara Grant elucidates the sui generis relation between creatures and creator using Shankara's “non‐duality”. With Robert Dobie's help, we shall can find ourselves attaining mutual illumination from witnessing Meister Eckhart and Ibn ’Arabi struggle with the same conundrum, reminding us how we will invariably falsify this crucial relating if we insist on thinking of Creator and creatures as “two things”, inevitably yielding a creator who must be the “biggest of all”. Yet this witness of classical explorers from different traditions may embolden contemporary thinkers to try their hand as well.
Creation in Early Christian Polemical Literature: Irenaeus against the Gnostics and Athanasius against the Arians
Authors: Gavrilyuk Paul
Published: March 2013

The doctrine of creation out of nothing was conceptually sharpened as the Church Fathers engaged the cosmological views of their opponents. This article discusses the emergence of this doctrine in the second century, focusing on the polemic of Irenaeus against the Gnostics. For Irenaeus, creatio ex nihilo was already a part of the “rule of truth,” which provided a hermeneutical key to the scriptures. Irenaeus also used rational arguments to show that Gnostic cosmologies obscured, rather than explained the origins of the world. A different challenge arose in the fourth century, when Arius began to teach that the Son was created out of nothing, thereby treating the divine act of the generation of the Son analogously to the creating of the world. Athanasius of Alexandria introduced an important distinction by correlating the eternal generation of the Son with the divine essence and the creation of the world with the will of the Father.
Creatio ex nihilo and the Divine Ideas in Aquinas: How fair is Bulgakov's critique?
Authors: Hughes John
Published: March 2013

In this article I engage with Sergei Bulgakov's “sophiological” critique of Aquinas's account of creatio ex nihilo and the divine ideas. Bulgakov claims that Aquinas's account is insufficiently Trinitarian, too influenced by pagan philosophy, and as such separates the divine will and intellect in such a way as to introduce arbitrariness and instrumentality into the relationship between the divine ideas and creation. I argue that it is inaccurate to characterise Aquinas's account of creation and the divine ideas as pagan or non‐Trinitarian; instead, following Augustine, Aquinas understands the divine ideas as essential to a thoroughly Trinitarian understanding of creation which is necessary to avoid reducing creation to impersonal necessary emanation on the one hand, or an arbitrary act of will on the other. However, I concede that, at times, Aquinas's account of the ideas of things which are never created may have opened the door to later more voluntarist and possibilist views.
Creation Ex Nihilo as Mixed Metaphor
Authors: Tanner Kathryn
Published: March 2013

This article makes the following three programmatic points. First, an understanding of divine transcendence, prominent in Christian theology's apophatic strain, developed in tandem, both historically and logically, with ideas about creation that eventuated in a creation ex nihilo viewpoint. Such an account of divine transcendence, second, fosters an account of creation (and a general understanding of the God/world relationship) that typically mixes both natural and personalistic images and categories. The loss of such an account of transcendence since the early modern period, I suggest thirdly and in conclusion, is therefore responsible in great part for the dualistic, mutually exclusive alternation between a deistic, interventionist God and pan(en)theism so common in modern Christian thought.
“Love is also a lover of life”: creatio ex nihilo and creaturely goodness
Authors: Webster John
Published: March 2013

Christian teaching about creation out of nothing appears to evacuate creatures of intrinsic worth. A theological‐spiritual response to this anxiety outlines the elements of the doctrine: (1) understanding creation requires the direction of intelligence by divine instruction; (2) God alone is cause of being to other beings, by his power, will and goodness; (3) the act of creation is ineffable, instantaneous, without movement, supereminent, and without material cause; (4) created things have being by divine gift; (5) the relation of creator and creatures is mixed, the creator not being constituted by creatures. Does this entail a metaphysics of creaturely privation in which creatures are permanently indigent? The creator is benevolent and, with no self‐interest, gives life, and so moves creatures to activity that the non‐reciprocal character of the creator‐creature relation is not malign but the principle of creaturely perfection.
disciplining bodies, disciplining objects: Museum Guards and the Museu Etnológico Português (1893–1929)
Authors: Lillios Katina T.
Published: March 2013

This article takes a microhistorical approach to the creation of a national museum by exploring the everyday practices of museum guards in the early history of the Museu Etnológico Português, now known as the Museu Nacional de Arqueologia, in Lisbon, Portugal. Using documentary sources such as letters, museum regulations, and notes, I explore the agency of the museum's first guards by identifying the ways they both enacted the prescribed behaviors of the museum and also challenged and transgressed these ideals, thereby shaping the cultural space of the museum. I suggest that guards, in the early years of the museum, functioned primarily as agents for marking social boundaries and as sites where transformations in the Portuguese social order were contested and, only secondarily, as individuals charged with protecting the security of objects. [Portugal, museum guards, microhistory, agency, national museums]
Intravenous ghrelin accelerates postoperative gastric emptying and time to first bowel movement in humans
Authors: Falkén Y. , Webb D.‐L. , Abraham‐Nordling M. , Kressner U. , Hellström P. M. , Näslund E.
Published: March 2013

Background

Ghrelin has been shown to stimulate gastric emptying in healthy humans and patients with delayed gastric emptying. The aim of this study is to assess the effect of ghrelin on gastric emptying on day 2 after open colorectal surgery.

Methods

Twenty‐four patients (mean age 69.2 ± 1.4, BMI 25.8 ± 0.8 kg m−2) were randomized to saline or ghrelin infusion (15 pmol kg−1 min−1) during 3 h before and on day 2 after open colorectal surgery. Of these, 20 were assessed both before and after surgery. At start of infusion, a liquid meal (480 kcal, 200 mL) was administered together with 1.5 g acetaminophen. Plasma was obtained at regular intervals together with visual analogue scales for hunger, satiety and nausea. Acetaminophen was analyzed as a marker of gastric emptying. Plasma glucose, insulin, acyl‐ghrelin, glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinoptrophic peptide (GIP), pancreatic polypeptide and peptide YY (PYY) were analyzed.

Key Results

Gastric emptying was faster during ghrelin infusion compared to saline before and after surgery (P < 0.02). In addition, plasma glucose was increased (P < 0.05). With ghrelin infusion, plasma insulin was unchanged except for lower values postoperatively (P < 0.05). Ghrelin did not alter plasma concentrations of gut peptides. After surgery, ghrelin shortened the time to first bowel movement compared to saline (2.1 ± 0.3 vs 3.5 ± 0.4 days, P = 0.02).

Conclusions & Inferences

A 3‐h ghrelin infusion increased the gastric emptying rate and hastened the time to first bowel movement after surgery. Ghrelin/ghrelin receptor agonists have a therapeutic potential in postoperative ileus; Karolinska Clinical Trial Registry nr CT20110084.
Activity‐dependent development of tactile and nociceptive spinal cord circuits
Authors: Koch Stephanie C. , Fitzgerald Maria
Published: March 2013

Developing brain circuits are shaped by postnatal sensory experience, but little is known about this process at the level of the spinal cord. Here we review the mechanisms by which cutaneous sensory input drives the maturation of spinal sensory circuits. Newborn animals are highly sensitive to tactile input and dorsal horn circuits are dominated by low threshold A fiber inputs. We show that this arises from the absence of the functional, targeted glycinergic inhibition of tactile activity that emerges only in the second week of life. Selective block of afferent C fibers in postnatal week 2 delays the maturation of glycinergic inhibition and maintains dorsal horn circuits in a neonatal state. We propose that in the newborn strong tactile A fiber input facilitates activity‐dependent synaptic strengthening in the dorsal horn, but that this ends with the arrival of nociceptive C fiber spinal input that drives the maturation of targeted glycinergic inhibition.
Neurotransmitters and synaptic components in the Merkel cell–neurite complex, a gentle‐touch receptor
Authors: Maksimovic Srdjan , Baba Yoshichika , Lumpkin Ellen A.
Published: March 2013

Merkel cells are an enigmatic group of rare cells found in the skin of vertebrates. Most make contacts with somatosensory afferents to form Merkel cell–neurite complexes, which are gentle‐touch receptors that initiate slowly adapting type I responses. The function of Merkel cells within the complex remains debated despite decades of research. Numerous anatomical studies demonstrate that Merkel cells form synaptic‐like contacts with sensory afferent terminals. Moreover, recent molecular analysis reveals that Merkel cells express dozens of presynaptic molecules that are essential for synaptic vesicle release in neurons. Merkel cells also produce a host of neuroactive substances that can act as fast excitatory neurotransmitters or neuromodulators. Here, we review the major neurotransmitters found in Merkel cells and discuss these findings in relation to the potential function of Merkel cells in touch reception.
Accelerating locomotor recovery after incomplete spinal injury
Authors: Hillen Brian K. , Abbas James J. , Jung Ranu
Published: March 2013

A traumatic spinal injury can destroy cells, irreparably damage axons, and trigger a cascade of biochemical responses that increase the extent of injury. Although damaged central nervous system axons do not regrow well naturally, the distributed nature of the nervous system and its capacity to adapt provide opportunities for recovery of function. It is apparent that activity‐dependent plasticity plays a role in this recovery and that the endogenous response to injury heightens the capacity for recovery for at least several weeks postinjury. To restore locomotor function, researchers have investigated the use of treadmill‐based training, robots, and electrical stimulation to tap into adaptive activity‐dependent processes. The current challenge is to maximize the degree of functional recovery. This manuscript reviews the endogenous neural system response to injury, and reviews data and presents novel analyses of these from a rat model of contusion injury that demonstrates how a targeted intervention can accelerate recovery, presumably by engaging processes that underlie activity‐dependent plasticity.
Neuronal correlates of the dominant role of GABAergic transmission in the developing mouse locomotor circuitry
Authors: Ziskind‐Conhaim Lea
Published: March 2013

GABA and glycine are the primary fast inhibitory neurotransmitters in the mammalian spinal cord, but they differ in their regulatory functions, balancing neuronal excitation in the locomotor circuitry in the mammalian spinal cord. This review focuses on the unique role of GABAergic transmission during the assembly of the locomotor circuitry, from early embryonic stages when GABAA receptor–activated membrane depolarizations increase network excitation, to the period of early postnatal development, when GABAergic inhibition plays a primary role in coordinating the patterns of locomotor‐like motor activity. To gain insight into the mechanisms that underlie the dominant contribution of GABAergic transmission to network activity during that period, we examined the morphological and electrophysiological properties of a subpopulation of GABAergic commissural interneurons that fit well with their putative function as integrated components of the rhythm‐coordinating networks in the mouse spinal cord.