bluuebunny/crossref_metadata_2025 huggingface dataset:
Double stapled haemorrhoidopexy for haemorrhoidal prolapse: indications, feasibility and safety
Authors: Stuto A. , Favero A. , Cerullo G. , Braini A. , Narisetty P. , Tosolini G.
Published: February 2012

Aim  Selected patients with haemorrhoidal prolapse undergoing double stapled anopexy with the procedure for prolapse and haemorrhoids (PPH03) were studied.

Method  Between March 2007 and March 2010, 235 patients referred with haemorrhoids were included in the study. Patients with obstructed defaecation were excluded. At surgery intraoperative evaluation for double stapled anopexy was carried out based on the criteria of prolapse occupying half or more of the anal circumference and redundant prolapsed tissue determined by the circular anal dilator. Patients fulfilling these criteria were submitted for double stapled anopexy with the PPH03 stapler. All clinical and operative data were recorded in a prospectively maintained database.

Results  Among the 142 patients with haemorrhoidal prolapse having surgery 91 had a single and 51 a double stapled technique. The mean operative time was 34.8 min with no major or minor intraoperative complications. Recurrence at 48 months was 1.9% and the mean satisfaction score was 8.9.

Conclusion  The double stapled PPH03 technique in selected cases was as safe and effective as a single stapling technique with a lower incidence of recurrence over a medium‐term follow‐up.
Orobothriurus (Scorpiones: Bothriuridae) phylogeny, Andean biogeography, and the relative importance of genitalic and somatic characters
Authors: Mattoni Camilo I. , Ochoa José A. , Ojanguren Affilastro Andrés A. , Prendini Lorenzo
Published: February 2012

Mattoni, C.I., Ochoa, J.A., Ojanguren Affilastro, A.A. & Prendini, L. (2012) Orobothriurus (Scorpiones: Bothriuridae) phylogeny, Andean biogeography, and the relative importance of genitalic and somatic characters. —Zoologica Scripta, 41, 160–176.

The genus Orobothriurus Maury, 1976 (Bothriuridae Simon, 1880) displays an Andean pattern of distribution, most of its species occurring at high altitudes (over 2000–2500 m to a maximum altitude record of 4910 m) from central Peru to Argentina. The recent discovery of several new species and the uncertain phylogenetic position of Orobothriurus lourencoi Ojanguren Affilastro, 2003, required a reanalysis of Orobothriurus phylogeny. Thirty bothriurid taxa, including all species of Orobothriurus and Pachakutej Ochoa, 2004, were scored for 65 morphological characters and analysed with parsimony under equal and implied weighting. The resulting topology justifies the establishment of a new genus, RumikiruOjanguren Affilastro et al., in press, for O. lourencoi and a closely related, new species, Rumikiru atacamaOjanguren Affilastro et al., in press. It also offers new insights about the phylogeny and biogeography of Orobothriurus and related genera. Characters from the male genitalia (i.e. hemispermatophore), comprising approximately 26% of the morphological matrix, were found to be less homoplastic than those from somatic morphology, contradicting suggestions that genitalia are uninformative or potentially misleading in phylogenetic studies.
Conversion rates of abstracts presented at the Urological Society of Australia and New Zealand (USANZ) Annual Scientific Meeting into full‐text journal articles
Authors: Yoon Peter D. , Chalasani Venu , Woo Henry H.
Published: February 2012

What's known on the subject? and What does the study add?

It is well known that the transition of a presented abstract in a scientific meeting to a journal article improves the quality of the meeting and prevents an abstract being incorporated into meta‐analyses or practice guidelines without proper appraisal.

This is the first analysis of USANZ Annual Scientific Meeting abstracts’ conversion to full publication. With relatively low publication rates compared to other international meetings, this review identifies the need for mechanisms to encourage USANZ researchers to convert their abstracts into published articles.

The numbers and characteristics of the abstracts presented at the Annual Scientific Meetings (ASM) of the Urological Society of Australia and New Zealand (USANZ) that are converted to peer‐reviewed publications have not previously been analysed and published. We undertook a review of all abstracts presented at the USANZ ASM from 2005 to 2009. A PubMed search was performed between 15 June and 15 July 2012, using a search algorithm to identify the full‐text publications of the presented abstracts. Correlation between abstract characteristics and publication rate was then examined to distinguish the predictors for publications. Of 614 abstracts that were presented at USANZ ASM between 2005 and 2009, 183 papers were published, giving a publication rate of 29.80%. The papers were predominantly published in urological journals and were more likely to be published if they were presented by an international author or were retrospective studies or if basic science research. The mean (SD) time to publication was 14.46 (13.89) months and the mean Impact Factor of journals where papers were published was 2.90. The overall publication rate was relatively low compared with other urological meetings held in America and Europe. USANZ has a challenge of encouraging higher‐quality research from the authors to further enhance its publication rate and consequently the calibre of the meeting itself.
Assessment tools of energy balance‐related behaviours used in European obesity prevention strategies: review of studies during preschool
Authors: Mouratidou T. , Mesana M. I. , Manios Y. , Koletzko B. , Chinapaw M. J. M. , De Bourdeaudhuij I. , Socha P. , Iotova V. , Moreno L. A. ,   ToyBox‐study group
Published: February 2012

Valid and reliable measures of energy balance‐related behaviours are required when evaluating the effectiveness of public health interventions aiming at prevention of childhood obesity. A structured descriptive review was performed to appraise food intake, physical activity and sedentary behaviour assessment tools used in obesity intervention strategies targeting mainly preschool children across Europe. In total, 25 papers are described, addressing energy balance‐related behaviours as study outcomes and targeting individuals or clusters of individuals at school‐ or home‐based environment. Parentally reported food records and 24‐h recalls were commonly used to assess food intake. Subjective levels of physical activity and sedentary behaviour were commonly accessed via parentally reported questionnaires. Accelerometry was used to obtain objective measures of physical activity. Insufficient evidence of tool evaluation was provided. When feasible, food records and accelerometry are recommended as the most appropriate methods to assess food intake in young children. Sedentary behaviour could be assessed via questionnaires that include key indicators of sedentarism and are able to differentiate individual practices. The choice of methodology for the assessment of specific intervention effects should be equally balanced between required accuracy levels and feasibility, and be guided by the intervention targets.
A systematic approach for the development of a kindergarten‐based intervention for the prevention of obesity in preschool age children: the ToyBox‐study
Authors: Manios Y. , Grammatikaki E. , Androutsos O. , Chinapaw M. J. M. , Gibson E. L. , Buijs G. , Iotova V. , Socha P. , Annemans L. , Wildgruber A. , Mouratidou T. , Yngve A. , Duvinage K. , de Bourdeaudhuij I. ,   ToyBox‐study group
Published: February 2012

The increasing childhood obesity epidemic calls for appropriate measures and effective policies to be applied early in life. Large‐scale socioecological frameworks providing a holistic multifactorial and cost‐effective approach necessary to support obesity prevention initiatives in this age are however currently missing. To address this missing link, ToyBox‐study aims to build and evaluate a cost‐effective kindergarten‐based, family‐involved intervention scheme to prevent obesity in early childhood, which could potentially be expanded on a pan‐European scale. A multidisciplinary team of researchers from 10 countries have joined forces and will work to realize this according to a systematic stepwise approach that combines the use of the PRECEDE‐PROCEED model and intervention mapping protocol. ToyBox‐study will conduct systematic and narrative reviews, secondary data analyses, focus group research and societal assessment to design, implement and evaluate outcome, impact, process and cost effectiveness of the intervention. This is the first time that such a holistic approach has been used on a pan‐European scale to promote healthy weight and healthy energy balance‐related behaviours for the prevention of early childhood obesity. The results of ToyBox‐study will be disseminated among key stakeholders including researchers, policy makers, practitioners and the general population.
The Development of Entrepreneurial Leadership: The Role of Human, Social and Institutional Capital
Authors: Leitch Claire M. , McMullan Christel , Harrison Richard T.
Published: February 2012

This paper contributes to the literature on entrepreneurial leadership development. Leadership studies are characterized by an increasing emphasis given to an individual leader's social and organizational domain. Within the context of human capital and social capital theory, the paper reflects on the emergence of a social capital theory of leadership development. Using a retrospective, interpretivist research method, the authors present the experience of a cohort of business leaders on an executive development programme to uncover the everydayness of leadership development in practice. Specifically, they explore how entrepreneurial leadership develops as a social process and what the role of social capital is in this. The findings suggest that the enhancement of leaders’ human capital only occurred through their development of social capital. There is not, as extant literature suggests, a clear separation between leader development and leadership development. Further, the analysis implies that the social capital theory of leadership is limited in the context of the entrepreneurial small firm, and the authors propose that it should be expanded to incorporate institutional capital, that is, the formal structures and organizations which enhance the role of social capital and go beyond enriching the human capital stock of individual leaders.
Towards a Real Sustainable Agri‐food Security and Food Policy: Beyond the Ecological Fallacies?
Authors: MARSDEN TERRY
Published: February 2012

The recent rises in food prices represent the ‘tip of the iceberg’ and a ‘canary in the mine’ moment for world agriculture. They are underlain by a continuing ‘race to the bottom’ and speculative process whereby systems of resource production and exploitation are continuing to rely upon ‘infinite supply’ assumptions and narrow technological solutions to ‘feeding the world’. I argue here that these conditions are leading to a dominant policy framing that tends to marginalise diverse and place‐based agro‐ecological systems by creating a new legitimacy for bio‐economic rather than eco‐economic solutions. Government and policy‐making bodies need to redefine and widen their approaches to agriculture and agri‐food in ways that recognise its social, cultural, political and spatially diverse contribution in a post‐carbon world.
Voting on Electoral Reform: A Comparative Perspective on the Alternative Vote Referendum in the United Kingdom
Authors: QVORTRUP MATT
Published: February 2012

Referendums on electoral systems are relatively rare. In most countries changes to the electoral system are enacted through the legislatures. The British referendum in May 2011 is thus one of the rare examples. In this article it is shown that the apparently idiosyncratic factors in the referendum were consistent with general trends identified in other referendums. While the media focused on the harshness of the campaign, the referendum also resulted in surprising coalitions between long‐term foes, thus suggesting that the referendum contributed to cross‐party cooperation rarely seen in a majoritarian system like that of Great Britain.
A Convolution Estimator for the Density of Nonlinear Regression Observations
Authors: STØVE BÅRD , TJØSTHEIM DAG
Published: February 2012

Abstract.  The problem of estimating an unknown density function has been widely studied. In this article, we present a convolution estimator for the density of the responses in a nonlinear heterogenous regression model. The rate of convergence for the mean square error of the convolution estimator is of order n−1 under certain regularity conditions. This is faster than the rate for the kernel density method. We derive explicit expressions for the asymptotic variance and the bias of the new estimator, and further a data‐driven bandwidth selector is proposed. We conduct simulation experiments to check the finite sample properties, and the convolution estimator performs substantially better than the kernel density estimator for well‐behaved noise densities.
Estimating the Conditional Error Distribution in Non‐parametric Regression
Authors: KIWITT SEBASTIAN , NEUMEYER NATALIE
Published: February 2012

Abstract.  We consider a general non‐parametric regression model, where the distribution of the error, given the covariate, is modelled by a conditional distribution function. For the estimation, a kernel approach as well as the (kernel based) empirical likelihood method are discussed. The latter method allows for incorporation of additional information on the error distribution into the estimation. We show weak convergence of the corresponding empirical processes to Gaussian processes and compare both approaches in asymptotic theory and by means of a simulation study.
Political Modernity and Secularization: Thoughts from the Japanese Eighteenth and Nineteenth Centuries
Authors: PARAMORE KIRI
Published: February 2012

Although some politics and international relations discourses continue to maintain that there is a causal link between secularism and political modernity, religious studies, anthropology, and history research over the past decade has been rather merciless in debunking this idea as one of the tropes of Western imperialism. This article considers at how Japanese political thinkers of the eighteenth and nineteenth centuries engaged this trope, and how that engagement contributed to the particular relationship between religion and governance that emerged in the modern Japanese empire (1868–1945). The article argues that developments in the Confucian political thought of the Tokugawa shogunate (1603–1868), particularly in the works of Ogyū Sorai (1666–1728) and Aizawa Seishisai (1792–1863), contributed significantly to the capacity of Japanese thinkers and politicians to creatively engage the role of religion in Western imperialism during the nineteenth and twentieth centuries.
Sacred Topography and Social Memory: Religious Change and the Landscape in Early Modern Britain and Ireland1
Authors: WALSHAM ALEXANDRA
Published: February 2012

This article analyses the relationship between the tumultuous religious changes of the sixteenth and seventeenth centuries and the landscape of the British Isles. It examines the immediate impact and long‐term cultural repercussions of the Protestant and Catholic Reformations on perceptions of and practices associated with the natural world and physical environment, as well as the influence exerted by intellectual and cultural trends associated with developments in science, medicine, and antiquarianism. Reformed theology fundamentally undermined traditional assumptions about the presence of the sacred in the material universe, but the religious ruptures of the era were tempered and complicated by elements of continuity and movements of counter‐reaction. Springs, trees, stones, and other notable topographical landmarks retained powerful religious resonances after the Reformation. Potent reminders of the pre‐Reformation past, they also provided a stimulus to the making of new myths and legends and acted as catalysts of the transformation of social memory.
Photostabilization of ascorbic acid with citric acid, tartaric acid and boric acid in cream formulations
Authors: Ahmad I. , Ali Sheraz M. , Ahmed S. , Shad Z. , Vaid F. H. M.
Published: February 2012

Synopsis

This study involves the evaluation of the effect of certain stabilizers, that is, citric acid (CT), tartaric acid (TA) and boric acid (BA) on the degradation of ascorbic acid (AH2) in oil‐in‐water cream formulations exposed to the UV light and stored in the dark. The apparent first‐order rate constants (0.34–0.95 × 10−3 min−1 in light, 0.38–1.24 × 10−2 day−1 in dark) for the degradation reactions in the presence of the stabilizers have been determined. These rate constants have been used to derive the second‐order rate constants (0.26–1.45 × 10−2 M−1 min−1 in light, 3.75–8.50 × 10−3 M−1 day−1 in dark) for the interaction of AH2 and the individual stabilizers. These stabilizers are effective in causing the inhibition of the rate of degradation of AH2 both in the light and in the dark. The inhibitory effect of the stabilizers is in the order of CT > TA > BA. The rate of degradation of AH2 in the presence of these stabilizers in the light is about 120 times higher than that in the dark. This could be explained on the basis of the deactivation of AH2‐excited triplet state by CT and TA and by the inhibition of AH2 degradation through complex formation with BA. AH2 leads to the formation of dehydroascorbic acid (A) by chemical and photooxidation in cream formulations.
Spectrofluorescence of skin and hair
Authors: McMullen R. L. , Chen S. , Moore* D. J.
Published: February 2012

Synopsis

There are numerous chromophores present throughout the strata of human skin, which present many challenges and opportunities to probe molecular events. Fluorescence spectroscopy is principally employed to identify important biochemical components of the skin including endogenous tryptophan, tyrosine, pepsin‐digestible collagen cross‐links, collagenase‐digestible collagen cross‐links, NADH, etc. Over the last 15 years, many advances in instrument technology have been introduced allowing for much faster data acquisition with spectrofluorometers. As a result, a series of spectrofluorescence emission scans can be generated for a range of excitation wavelengths, or vice versa (excitation scans for a range of emission wavelengths), quickly to generate excitation–emission matrices. In this work, we constructed an endogenous fingerprint of fluorescent compounds present in skin, hair and nail tissues by employing a range of excitation wavelengths from 270 to 450 nm with a resolution of 2 nm. As a result, we generated surface plots of fluorescence emission as a function of excitation and emission wavelengths. From these data, we identified the predominant fluorescent chromophores in each tissue. We examined several sources of skin including in vivo human and ex vivo pig, sheep, goat and cow skin. We also analysed various types of mature hair characterized by the degree of melanin content. These analyses provided us with a fundamental understanding of the effects of melanin distribution in hair fibres and aided with the identification of fluorophores present in hair.
European Union Meets South Korea: Bureaucratic Interests, Exporter Discrimination and the Negotiations of Trade Agreements*
Authors: ELSIG MANFRED , DUPONT CÉDRIC
Published: February 2012

Who in the European Union drives the process of pursuing bilateral trade negotiations? In contrast to societal explanations, this article develops a novel argument as to how the European Commission manages the process and uses its position in strategic ways to pursue its interests. Rooted in principal–agent theory, the article discusses agent preferences and theorizes the conditions under which the agent sets specific focal points and interacts strategically with principals and third parties. The argument is discussed with case study evidence drawn from the first trade agreement concluded and ratified since the EU Commission announced its new strategy in 2006: the EU–South Korea trade agreement.
Cocaine decreases expression of neurogranin via alterations in thyroid receptor/retinoid X receptor signaling
Authors: Kovalevich Jane , Corley Gladys , Yen William , Kim Jae , Rawls Scott M. , Langford Dianne
Published: February 2012

J. Neurochem. (2012) 121, 302–313.

Mounting evidence suggests a potential link between cocaine abuse, disruptions in hypothalamic‐pituitary‐thyroid axis signaling, and neuroplasticity, but molecular mechanisms remain unknown. Neurogranin (Ng) is a gene containing a thyroid hormone‐responsive element within its first intron that is involved in synaptic plasticity. Transcriptional activation requires heterodimerization of thyroid hormone receptor (TR) and retinoid X receptor (RXR) bound by their respective ligands, tri‐iodothryonine and 9‐cis‐retinoic acid (9‐cis‐RA), and subsequent binding of this complex to the thyroid hormone‐responsive element of the Ng gene. In this study, the effects of chronic cocaine abuse on Ng expression in euthyroid and hypothyroid mice were assessed. In cocaine‐treated mice, decreased Ng expression was observed in the absence of changes in levels of thyroid hormones or other hypothalamic‐pituitary‐thyroid signaling factors. Therefore, we hypothesized that cocaine decreases Ng expression via alterations in 9‐cis‐RA availability and TR/RXR signaling. In support of this hypothesis, RXR‐γ was significantly decreased in brains of cocaine‐treated mice while CYP26A1, the main enzyme responsible for neuronal RA degradation, was significantly increased. Results from this study provide the first evidence for a direct effect of cocaine abuse on TR/RXR signaling, RA metabolism, and transcriptional regulation of Ng, a gene essential for adult neuroplasticity.
The multiobjective multidimensional knapsack problem: a survey and a new approach
Authors: Lust Thibaut , Teghem Jacques
Published: February 2012

The knapsack problem (KP) and its multidimensional version (MKP) are basic problems in combinatorial optimization. In this paper, we consider their multiobjective extension (MOKP and MOMKP), for which the aim is to obtain or approximate the set of efficient solutions. In the first step, we classify and briefly describe the existing works that are essentially based on the use of metaheuristics. In the second step, we propose the adaptation of the two‐phase Pareto local search (2PPLS) to the resolution of the MOMKP. With this aim, we use a very large scale neighborhood in the second phase of the method, that is the PLS. We compare our results with state‐of‐the‐art results and show that the results we obtained were never reached before by heuristics for biobjective instances. Finally, we consider the extension to three‐objective instances.
The Effect ofHIFA Waiver Expansions on Uninsurance Rates in Adult  Populations
Authors: Atherly Adam , Dowd Bryan E. , Coulam Robert F. , Guy Gery
Published: February 2012

Research Objective

To evaluate the effect of theHealthInsuranceFlexibility andAccountability (HIFA) demonstrations on the rate of uninsured. The policy purpose of theHIFAdemonstrations is to encourage “new comprehensive state approaches” that will increase the number of insured.HIFAinterventions include changes in benefit packages, eligibility rules for public programs, and state subsidization of private health insurance premiums. Some states emphasized private insurance (premium assistance), whereas others placed greater emphasis on expanded eligibility for public insurance.

Data Sources/Study Setting

Data were drawn from theCurrentPopulationSurvey from 2000 to 2007. The target populations for theHIFAwaiver demonstrations consisted of individuals who were eligible for theHIFAwaiver demonstrations in demonstration states.

Study Design

The estimation approach was a probit model using a difference‐in‐differences approach.

Principal Findings

In states that fully implemented theirHIFAwaiver,HIFAincreased the rate of insurance coverage by 6.4 percentage points on average in the targeted adult population, suggesting that approximately 118,848 adults gained health insurance due toHIFA. TotalHIFAadult enrollment in the six states studied was 280,739. The effect size varied by state, with Maine having the largest effect and Illinois the smallest. The results were robust to different specifications of the control group.

Conclusions

Our findings suggest that public insurance initiatives that provide states with flexibility regarding eligibility and plan design are a viable policy approach to reducing uninsurance rates.
Organizational Characteristics of High‐ and Low‐Performing Anticoagulation Clinics in the Veterans Health Administration
Authors: Rose Adam J. , Petrakis Beth Ann , Callahan Patricia , Mambourg Scott , Patel Dimple , Hylek Elaine M. , Bokhour Barbara G.
Published: February 2012

Objective

Anticoagulation clinics (ACCs) can improve anticoagulation control and prevent adverse events. However, ACCs vary widely in their performance on anticoagulation control. Our objective was to compare the organization and management of top‐performing with that of bottom‐performing ACCs.

Data Sources/Study Setting

Three high outlier and three low outlier ACCs in the Veterans Health Administration (VA).

Study Design

Site visits with qualitative data collection and analysis.

Data Collection/Extraction Methods

We conducted semi‐structured interviews with ACC staff regarding work flow, staffing, organization, and quality assurance efforts. We also observed ACC operations and collected documents, such as the clinic protocol. We used grounded thematic analysis to examine site‐level factors associated with high and low outlier status.

Principal Findings

High outlier sites were characterized by (1) adequate (pharmacist) staffing and effective use of (nonpharmacist) support personnel; (2) innovation to standardize clinical practice around evidence‐based guidelines; (3) the presence of a quality champion for the ACC; (4) higher staff qualifications; (5) a climate of ongoing group learning; and (6) internal efforts to measure performance. Although high outliers had all of these features, no low outlier had more than two of them.

Conclusions

The top‐performing ACCs in the VA system shared six relatively recognizable characteristics. Efforts to improve performance should focus on these domains.
A Comparison of Two Approaches to Increasing Access to Care: Expanding Coverage versus Increasing Physician Fees
Authors: White Chapin
Published: February 2012

Objective

To compare the effects of a coverage expansion versus a Medicaid physician fee increase on children's utilization of physician services.

Primary Data Source

National Health Interview Survey (1997–2009).

Study Design

We use the Children's Health Insurance Program, enacted in 1997, as a natural experiment, and we performed a panel data regression analysis using the state‐year as the unit of observation. Outcomes include physician visits per child per year and the following indicators of access to primary care: whether the child saw a physician, pediatrician, or visited an ER in the last year, and whether the parents reported experiencing a non‐cost‐related access problem. We analyzed these outcomes among all children, and separately among socioeconomic status (SES) quartiles defined based on family income and parents' education.

Principal Findings

Children's Health Insurance Program had a major impact on the extent and nature of children's insurance coverage. However, it is not associated with any change in the aggregate quantity of physician services, and its associations with indicators of access are mixed. Increases in physician fees are associated with broad‐based improvements in indicators of access.

Conclusions

The findings suggest that (1) coverage expansions, even if they substantially reduce patient cost sharing, do not necessarily increase physician utilization, and (2) increasing the generosity of provider payments in public programs can improve access among low‐SES children, and, through spillover effects, increase higher‐SES children as well.
Investor Information Demand: Evidence from Google Searches Around Earnings Announcements
Authors: DRAKE MICHAEL S. , ROULSTONE DARREN T. , THORNOCK JACOB R.
Published: February 2012

The objective of this study is to investigate factors that influence investor information demand around earnings announcements and to provide insights into how variation in information demand impacts the capital market response to earnings. The Internet is one channel through which public information is disseminated to investors and we propose that one way that investors express their demand for public information is via Google searches. We find that abnormal Google search increases about two weeks prior to the earnings announcement, spikes markedly at the announcement, and continues at high levels for a period after the announcement. This finding suggests that information diffusion is not instantaneous with the release of the earnings information, but rather is spread over a period surrounding the announcement. We also find that information demand is positively associated with media attention and news, and is negatively associated with investor distraction. When investors search for more information in the days just prior to the announcement, preannouncement price and volume changes reflect more of the upcoming earnings news and there is less of a price and volume response when the news is announced. This result suggests that, when investors demand more information about a firm, the information content of the earnings announcement is partially preempted.
The Influence of Elections on the Accounting Choices of Governmental Entities
Authors: KIDO NOLAN , PETACCHI REINING , WEBER JOSEPH
Published: February 2012

This paper investigates whether gubernatorial elections affect state governments’ accounting choices. We identify two accounts, the compensated absence liability account and the unfunded pension liability account, which provide incumbent gubernatorial candidates with flexibility for manipulation. We find that, in an election year, the liability associated with compensated absences and unfunded pension liabilities are both systematically lower. We also find that the variation in these employment‐related liabilities is correlated with proxies for the incumbent's incentives and ability to manipulate their accounting reports. Jointly, these results suggest that state governments manipulate accounting numbers to present a healthier financial picture in an election year.
Regional quantification of muscarinic acetylcholine receptors and β‐adrenoceptors in human airways
Authors: Ikeda T , Anisuzzaman ASM , Yoshiki H , Sasaki M , Koshiji T , Uwada J , Nishimune A , Itoh H , Muramatsu I
Published: February 2012

BACKGROUND AND PURPOSE Muscarinic acetylcholine receptors (mAChRs) and β‐adrenoceptors in the airways and lungs are clinically important in chronic obstructive pulmonary disease (COPD) and asthma. However, the quantitative and qualitative estimation of these receptors by radioligand binding approaches in human airways has not yet been reported because of tissue limitations.

EXPERIMENTAL APPROACH The regional distribution and relative proportion of mAChR and β‐adrenoceptor subtypes were evaluated in human bronchus and lung parenchyma by a tissue segment binding method with [3H]‐N‐methylscopolamine ([3H]‐NMS) for mAChRs and [3H]‐CGP‐12,177 for β‐adrenoceptors. Functional responses to carbachol and isoprenaline were also analysed in the bronchus.

KEY RESULTS The M3 subtype predominantly occurred in the bronchus, but the density decreased from the segmental to subsegmental bronchus, and was absent in lung parenchyma. On the other hand, the M1 subtype occurred in the lung only, and the M2 subtype was distributed ubiquitously in the bronchus and lungs. β2‐adrenoceptors were increased along the airways, and their densities in the subsegmental bronchus and lung parenchyma were approximately twofold higher than those of mAChRs in the same region. β1‐adrenoceptors were also detected in lung parenchyma but not in the bronchus. The muscarinic contractions and adrenoceptor relaxations in both bronchial regions were mediated through M3‐mAChRs and β2‐adrenoceptors, respectively.

CONCLUSIONS AND IMPLICATIONS From the present radioligand binding approach with intact tissue segments, we constructed a distribution map of mAChRs and β‐adrenoceptors in human bronchus and lung parenchyma for the first time, providing important evidence for future pharmacotherapy and new drug development for respiratory disorders.
The omega‐3 polyunsaturated fatty acid eicosapentaenoic acid inhibits mouse MC‐26 colorectal cancer cell liver metastasis via inhibition of PGE2‐dependent cell motility
Authors: Hawcroft G , Volpato M , Marston G , Ingram N , Perry SL , Cockbain AJ , Race AD , Munarini A , Belluzzi A , Loadman PM , Coletta PL , Hull MA
Published: February 2012

BACKGROUND AND PURPOSE

The omega‐3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) has antineoplastic activity at early stages of colorectal carcinogenesis, relevant to chemoprevention of colorectal cancer (CRC). We tested the hypothesis that EPA also has anti‐CRC activity at later stages of colorectal carcinogenesis, relevant to treatment of metastatic CRC, via modulation of E‐type PG synthesis.

EXPERIMENTAL APPROACH

A BALB/c mouse model, in which intrasplenic injection of syngeneic MC‐26 mouse CRC cells leads to development of liver metastases, was used. Dietary EPA was administered in the free fatty acid (FFA) form for 2 weeks before and after ultrasound‐guided intrasplenic injection of 1 × 106 MC‐26 cells (n= 16 each group).

KEY RESULTS

Treatment with 5% (w w‐1) EPA‐FFA was associated with a reduced MC‐26 mouse CRC cell liver tumour burden compared with control animals (median liver weight 1.03 g vs. 1.62 g; P < 0.034). Administration of 5% EPA‐FFA was also linked to a significant increase in tumour EPA incorporation and lower intratumoural PGE2 levels (with concomitant increased production of PGE3). Liver tumours from 5% EPA‐FFA‐ treated mice demonstrated decreased 5‐bromo‐2‐deoxyuridine‐positive CRC cell proliferation and reduced phosphorylated ERK 1/2 expression at the invasive edge of tumours. A concentration‐dependent reduction in MC‐26 CRC cell Transwell® migration following EPA‐FFA treatment (50–200 µM) in vitro was rescued by exogenous PGE2 (10 µM) and PGE1‐alcohol (1 µM).

CONCLUSIONS AND IMPLICATIONS

EPA‐FFA inhibits MC‐26 CRC cell liver metastasis. EPA incorporation is associated with a ‘PGE2 to PGE3 switch’ in liver tumours. Inhibition of PGE2‐EP4 receptor‐dependent CRC cell motility probably contributes to the antineoplastic activity of EPA.
Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP
Authors: Kusuhara Hiroyuki , Furuie Hidetoshi , Inano Akihiro , Sunagawa Akihiro , Yamada Saiko , Wu Chunyong , Fukizawa Shinya , Morimoto Nozomi , Ieiri Ichiro , Morishita Mariko , Sumita Kiminobu , Mayahara Hiroshi , Fujita Takuya , Maeda Kazuya , Sugiyama Yuichi
Published: February 2012

BACKGROUND AND PURPOSE An ATP‐binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans.

EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP‐dependent sulphasalazine uptake by hBCRP‐expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild‐type and Bcrp(–/–) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 µg) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1.

KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (Ki 0.70 ± 0.41 µM). Curcumin increased the area under the curve (AUC)0–8 of plasma sulphasalazine eightfold in wild‐type mice at 300 and 400 mg·kg−1, but not in Bcrp(–/–) mice. Curcumin increased AUC0–24 of plasma sulphasalazine 2.0‐fold at microdoses and 3.2‐fold at therapeutic doses in humans. Non‐linearity of the dose–exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (Km 1.7 ± 0.3 µM). Its linear index (dose/Km) at the therapeutic dose was high and may saturate OATP2B1.

CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non‐linearity in the dose–exposure relationship of sulphasalazine.
Processes of annual moraine formation at a temperate alpine valley glacier: insights into glacier dynamics and climatic controls
Authors: Lukas Sven
Published: February 2012

This paper presents the first detailed sedimentological study of annual moraines formed by an alpine valley glacier. The moraines have been forming since at least AD 1980 by a subsidiary lobe of Gornergletscher, Switzerland that advances up a reverse bedrock slope. They reach heights of 0.5–1.5 m, widths of up to 6 m and lengths of up to several hundreds of metres. Sediments in these moraines are composed of proglacial outwash and debris flow units; subglacial traction till is absent entirely. Based on four representative sections, three genetic process combinations have been identified: (i) inefficient bulldozing of a gently sloping ice margin transfers proglacial sediments onto the ice, causing differential ablation and dead‐ice incorporation upon retreat; (ii) terrestrial ice‐contact fans are formed by the dumping of englacial and supraglacial material from point sources such as englacial conduit fills; debris flows and associated fluvial sediments are stacked against a temporarily stationary margin at the start, and deformed during glacier advance in the remainder, of the accumulation season; (iii) a steep ice margin without supraglacial input leads to efficient bulldozing and deformation of pre‐existing foreland sediments by wholesale folding. Ice‐surface slope appears to be a key control on the type of process responsible for moraine formation in any given place and year. The second and third modes result in stable and higher moraines that have a higher preservation potential than those containing dead ice. Analysis of the spacing and climatic records at Gornergletscher reveals that winter temperature controls marginal retreat and hence moraine formation. However, any climatic signal is complicated by other factors, most notably the presence of a reverse bedrock slope, so that the extraction of a clear climatic signal is not straightforward. This study highlights the complexity of annual moraine formation in high‐mountain environments and suggests avenues for further research.
Efficacy of the ketogenic diet: Which epilepsies respond?
Authors: Thammongkol Sasipa , Vears Danya F. , Bicknell‐Royle Jillian , Nation Judy , Draffin Kellie , Stewart Karen G. , Scheffer Ingrid E. , Mackay Mark T.
Published: February 2012

We report the efficacy of the ketogenic diet in refractory epilepsies focusing on outcomes with regard to epilepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty‐four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbohydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) classification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty‐nine (48%) of 61 patients were responders at 3 months. Two children became seizure‐free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epilepsy of infancy, childhood absence epilepsy, focal epilepsy, epilepsy with myoclonic‐atonic seizures, and Dravet syndrome. Children with lissencephaly and hypoxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syndrome is an important factor in decisions about timing of initiation of the ketogenic diet.
Modulation of Somatosensory Profiles by Spinal Cord Stimulation in Primary Raynaud′s Syndrome
Authors: Münster Tino , Tiebel Nils , Seyer Hendrikus , Maihöfner Christian
Published: February 2012

Background and Goal: Spinal cord stimulation (SCS) is an effective antinociceptive treatment for various neuropathic pain syndromes. Apart from antinociceptive action, it may modulate overall somatosensory perception. This case report targets the question of whether SCS may alter quantitative sensory testing (QST) in a patient with primary Raynaud′s syndrome.

Materials and Methods: We report on a 44‐year‐old female patient with primary Raynaud′s syndrome who had SCS via cervical and lumbar electrodes. QST was performed in a standardized manner assessing cold detection threshold (CDT) and warm detection threshold (WDT), cold pain threshold (CPT) and heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT) thresholds, and vibration detection threshold (VDT) and pressure pain thresholds (PPT). We tested at the dorsum of the right/left hand of the patient with engaged and disengaged SCS. Test results were compared with a control group of 80 subjects.

Results: Without SCS, the patient showed a sensory decrease in CDT, MDT, MPT, and VDT. SCS influenced the perception of cold, warm, and tactile detection thresholds, whereby CDT, WDT, and VDT were impaired and MDT was improved.

Conclusion: SCS significantly modulated the somatosensory profile in a patient with primary Raynaud′s syndrome. These effects were pronounced in qualities involving Aβ, C, and A∂ nerve fibers. Further investigations may help to understand the mechanisms of action of SCS.
Use and Costs of Prescription Medications and Alternative Treatments in Patients with Osteoarthritis and Chronic Low Back Pain in Community‐Based Settings
Authors: Gore Mugdha , Tai Kei‐Sing , Sadosky Alesia , Leslie Douglas , Stacey Brett R.
Published: February 2012

Objective:  To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP).

Methods:  The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain‐related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008.

Results:  Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti‐inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs.

Conclusions:  Patients with OA and CLBP used a variety of pain‐related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.
The clinical relevance of persistent recombinant immunoblot assay–indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling
Authors: Makuria Addisalem T. , Raghuraman Sukanya , Burbelo Peter D. , Cantilena Cathy C. , Allison Robert D. , Gibble Joan , Rehermann Barbara , Alter Harvey J.
Published: February 2012

BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti‐HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA‐indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti‐HCV–positive blood donors.

STUDY DESIGN AND METHODS: Donor demographics, exposure history, and humoral and cell‐mediated immunity (CMI) were compared in 15 RIBA‐indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti‐HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon‐γ enzyme‐linked immunosorbent spot assay.

RESULTS: In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA‐indeterminate subjects. CMI responses in RIBA‐indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA‐indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA‐indeterminate donors were older than the other groups.

CONCLUSION: The CMI and LIPS results suggest that persistent RIBA‐indeterminate reactions represent waning anti‐HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long‐term HCV‐recovered subjects.