bluuebunny/crossref_metadata_2025 huggingface dataset:
Refining a Location Analysis Model Using a Mixed Methods Approach: Community Readiness as a Key Factor in Siting Rural Palliative Care Services
Authors: Crooks Valorie A. , Schuurman Nadine , Cinnamon Jonathan , Castleden Heather , Johnston Rory
Published: November 2010

Drawing on recent debates pointing to the value of mixed methods research in human geography, the authors revisit a quantitative location analysis model previously created to site palliative care services in rural British Columbia, Canada. The original quantitative model posited that population (i.e., number of residents in the community), isolation (i.e., travel time to existing specialized palliative care), and vulnerability (i.e., number of residents older than 65 years in the community) are three factors that must be accounted for when siting palliative care services in rural areas. Using qualitative interview data, the authors refine this model to include a newly identified factor: community readiness. They conclude with a discussion of the benefits of adopting a mixed methods approach to location analysis model development.
The impact of lifestyle modification in preventing or delaying the progression of type 2 diabetes mellitus among high-risk people in Jordan
Authors: Abujudeh Bashar A. , Abu Al Rub Raeda F. , Al-Faouri Ibrahim G. , Gharaibeh Muntaha K.
Published: November 2010

Purpose: To investigate (1) the effectiveness of educational interventions in reducing the risk for developing type 2 diabetes mellitus (DM) among Jordanian adults at high risk, and (2) whether levels of self-esteem and self-efficacy affect the responses of participants towards educational interventions in reducing risks for developing type 2 DM.

Design: A comparative experimental pretest–post-test control group design was used. One hundred and thirteen participants at high risk for developing type 2 DM were randomly assigned to a study group ( n = 57) and a control group ( n = 56) based on the matching technique according to the risk factors.

Methods: The participants in the study group received 12 educational sessions about healthy diet guidelines and five educational sessions about guidelines for moderately intense physical activity. Participants in the control group received general written information about diet and exercises, but no specific individualised interventions were offered to them.

Results: The risk of type 2 DM among the study group was reduced by 28%. The results also indicated that participants in the study group had significant reduction in their body weight, and body mass index, and fasting blood sugar level. Participants in the study group with higher self-esteem and self-efficacy levels before receiving interventions achieved lower weight loss comparing to those who had lower self-esteem and self-efficacy levels.

Implications: The findings of the present study confirmed that lifestyle interventions concerned with educational sessions about dietary behaviours and exercises illustrate promising results in preventing or delaying the risk of developing type 2 DM by modifying its risk factors.
Informativeness, Incentive Compensation, and the Choice of Inventory Buffer
Authors: Baiman Stanley , Netessine Serguei , Saouma Richard
Published: November 2010

ABSTRACT: Previous research in management accounting and economics has noted the potential for complementarities between the firm’s performance measurement system and its other organizational design choices. We add to this literature by studying how the informativeness and incentive properties of a performance metric can be influenced by one particular organizational design choice—the size of the firm’s inventory buffers. We model a manufacturing setting in which an agent manages a workstation that processes intermediate units. As intermediate units arrive, they are stored in an inventory buffer until the agent can process them. The buffer can hold a maximum number of intermediate units—its buffer size. The agent is compensated on the basis of his workstation’s throughput. We characterize the conditions under which reducing the inventory buffer enhances/degrades the informativeness of the performance metric and, hence, mitigates/exacerbates the agent’s incentive problem.
Determinants of Hedge Fund Internal Controls and Fees
Authors: Cassar Gavin , Gerakos Joseph
Published: November 2010

ABSTRACT: We investigate the determinants of hedge fund internal controls and their association with the fees that funds charge investors. Hedge funds are subject to minimal regulation. Hence, hedge fund managers voluntarily implement internal controls, and managers and investors freely contract on fees. We find that internal controls are stronger in funds with higher potential agency costs. Further, internal controls are stronger in funds domiciled in jurisdictions that provide investors with limited legal redress for fraud and financial misstatements. Short selling funds, however, are more likely to protect information about their investment positions by implementing weaker internal controls. With respect to fees, we find that the percentage of positive profits that the manager receives increases in the strength of the fund’s internal controls. Finally, removing the manager from setting and reporting the fund’s official net asset value, along with reputational incentives and monitoring by leverage providers, are all associated with lower likelihoods of future regulatory investigations of fraud and/or financial misstatement.
Once Bitten, Twice Shy: The Relation between Outcomes of Earnings Guidance and Management Guidance Strategy
Authors: Feng Mei , Koch Adam S.
Published: November 2010

ABSTRACT: We examine how management quarterly guidance strategy is affected by various outcomes from previously issued guidance. We find that managers are less likely to provide quarterly earnings guidance for a given year when past management forecasts have been overly optimistic, when past forecasts were unsuccessful at influencing analysts’ expectations, when past forecasts failed to reduce information asymmetry, and when past forecasts resulted in earnings disappointments. For firms that continue to give guidance, adverse prior outcomes also affect the precision of future guidance and the number of quarters within a year for which they give guidance.
An Empirical Analysis of Auditor Independence in the Banking Industry
Authors: Kanagaretnam Kiridaran , Krishnan Gopal V. , Lobo Gerald J.
Published: November 2010

ABSTRACT: We examine auditor independence in the banking industry by analyzing the relation between fees paid to auditors and the extent of earnings management through loan loss provisions (LLP). We also examine whether this relation differs across large banks whose managements are required under the Federal Deposit Insurance Corporation Improvement Act to evaluate internal control over financial reporting and whose auditors must attest to the effectiveness of such internal controls, and small banks that are not subject to those requirements. We find that unexpected auditor fees are unrelated to earnings management for large banks. For small banks, we find greater earnings management via under-provisioning of LLP by banks that pay higher unexpected total and nonaudit fees to the auditor. These results suggest that auditor fee dependence on the audit client is associated with earnings management via abnormal LLP and is a potential threat to auditor independence for small banks. Our findings are relevant to policymakers contemplating new regulations in light of the recent banking crisis.
Ethics and the Tax Profession: Restoring the Public Interest Focus
Authors: Stuebs Martin , Wilkinson Brett
Published: November 2010

ABSTRACT: Tax practice is an integral component of the public accounting profession. Although accountancy as a profession embraces a strong public interest notion, there is an inevitable tension in tax practice between serving the client and maintaining the integrity of the tax system. Resolving this tension necessitates an ethics-infused judgment process. Ethical failures over the past decade have weakened the tax profession and called into question the extent to which practitioners in fact operate in a manner consistent with the public interest. In this paper, we explore the fundamental causes of the ethical problems that have plagued the tax profession and provide a roadmap for reform of the tax profession. Using Cressey’s (1953) fraud triangle as a framework, we first examine the normative ideal for the tax profession. We then examine the recent tax shelter abuses perpetrated by the major public accounting firms and find results consistent with our expectations under the fraud triangle analysis. In essence, ethical breakdowns resulted from the loss of a public interest emphasis, which in turn led to the explicit pursuit of commercial gain at the expense of the public interest. That the frauds were perpetrated within the context of a profession founded on a public interest notion is particularly concerning. In response to the problems observed, we identify key cultural reforms needed within the accounting academy, the accounting profession, and the tax system in order to restore trust and the public interest character of the tax profession to center stage and so guard against further adverse outcomes.
The Relevance of Information Technology Expenditures
Authors: Henderson B. Charlene , Kobelsky Kevin , Richardson Vernon J. , Smith Rodney E.
Published: November 2010

ABSTRACT: Although information technology (hereafter, IT) expenditures represent an increasingly large investment for most corporations, firms are not required to disclose them separately in their financial statements. We hypothesize and find evidence that information about a firm’s IT expenditures helps explain its future performance as reflected in both accounting measures (residual income, earnings volatility) and market measures (stock price and long-run abnormal returns). In particular, we provide evidence of market mispricing and suggest the lack of firm-level annual IT expenditure disclosure as one potential reason for such mispricing. Altogether, the evidence presents a persuasive case that information about a firm’s IT expenditures is useful to stock market participants. The evidence we report is useful to managers and accounting policy makers contemplating the public disclosure of firm-level information about IT investments.
New primers for single‐copy nuclear‐encoded chloroplast‐expressed glutamine synthetase (ncpGS) in Oxalidaceae
Authors: Oberlander Kenneth C. , Dreyer Léanne L. , Roets Francois
Published: November 2010

• Premise of the study: New primers were developed for the nuclear marker glutamine synthetase (ncpGS) in Oxalidaceae.

• Methods and Results: New forward and reverse primers were designed and tested across a wide range of Oxalidaceae. Selected taxa were sequenced to confirm homology. Potential for phylogenetic study was assessed by comparing sequenced taxa with commonly used nuclear and plastid markers.

• Conclusions: Four out of five Oxalidaceae genera and all tested Oxalis spp. amplified successfully. Sequencing confirmed homology of the amplicon. Parsimony analysis of ncpGS showed that it is a promising candidate for future phylogenetic work in Oxalidaceae.
Peroxisome Proliferator-Activated Receptor α and γ Agonists Together with TGF-β Convert Human CD4+CD25− T Cells into Functional Foxp3+ Regulatory T Cells
Authors: Lei Jin , Hasegawa Hitoshi , Matsumoto Takuya , Yasukawa Masaki
Published: November 2010

Human peripheral CD4+CD25− T cells can be induced to express Foxp3 when activated in vitro by TCR stimulation with TGF-β and IL-2. However, these TGF-β–induced Foxp3+ regulatory T cells (iTregs) lack a regulatory phenotype. From libraries of nuclear receptor ligands and bioactive lipids, we screened three peroxisome proliferator-activated receptor (PPAR)α (bezafibrate, GW7647, and 5,8,11,14-eicosatetraynoic acid) and two PPARγ agonists (ciglitazone and 15-deoxy-Δ-12,14-PG J2) as molecules that increased Foxp3 expression in human iTregs significantly compared with that in DMSO-treated iTregs (control). These PPARα and PPARγ agonist-treated iTregs maintained a high level of Foxp3 expression and had suppressive properties. There were no significant differences in the suppressive properties of iTregs treated with the three PPARα and two PPARγ agonists, and all of the treated iTregs increased demethylation levels of the Foxp3 promoter and intronic conserved noncoding sequence 3 regions. Furthermore, PPARα and PPARγ agonists, together with TGF-β, more strongly inhibited the expression of all three DNA methyltransferases (DNMTs) (DNMT1, DNMT3a, and DNMT3b) in activated CD4+ T cells. These results demonstrate that PPARα and PPARγ agonists together with TGF-β elicit Foxp3 DNA demethylation through potent downregulation of DNMTs and induce potent and stable Foxp3 expression, resulting in the generation of functional iTregs. Moreover, trichostatin A and retinoic acid enhanced the generation of iTregs synergistically with PPARα and PPARγ agonists.
Pseudolocality for the Ricci Flow and Applications
Authors: Chau Albert , Tam Luen-Fai , Yu Chengjie
Published: November 2010

Perelman established a differential Li-Yau-Hamilton (LYH) type inequality for fundamental solutions of the conjugate heat equation corresponding to the Ricci flow on compact manifolds. As an application of the LYH inequality, Perelman proved a pseudolocality result for the Ricci flow on compact manifolds. In this article we provide the details for the proofs of these results in the case of a complete noncompact Riemannian manifold. Using these results we prove that under certain conditions, a finite time singularity of the Ricci flow must form within a compact set. The conditions are satisfied by asymptotically flatmanifolds. We also prove a long time existence result for the Kähler-Ricci flow on complete nonnegatively curved Kähler manifolds.
Analyzing behavioral properties of semantic business processes with parametric data
Authors: Ibáñez María José , Álvarez Pedro , Ezpeleta Joaquín
Published: November 2010

One of the basic problems in (semantic) business process management concerns the behavioral analysis at design time so that only correct processes are exposed. Although this analysis requires the semantic propagation of data and system preconditions through processes and between processes to be considered, some concrete data are usually obtained at runtime and cannot be used in early process development phases. This paper proposes Parametric Unary RDF Annotated Petri Net Systems (P‐U‐RDF‐PN Systems) as a formalism to alleviate this problem. The formalism allows analyzing behavioral properties of semantic business processes at design time. Parametric values are used to represent the data that will be obtained at runtime, allowing to also consider them in the analysis phase. The paper formally defines the semantics of the formalism in terms of enabling and firing of transitions as well as the concept of reachability graph. It also presents how to compute and analyze this parametric reachability graph. The analysis is based on an adaption of model checking techniques, being temporal logic the formalism used to specify the system properties to be analyzed. Finally, an implementation prototype using RDF and SPARQL tools and a Satisfiability Modulo Theories solver is presented, with some experiments evaluating how scalable the prototype is. Copyright © 2010 John Wiley & Sons, Ltd.
Definitive treatment of metastatic nasopharyngeal carcinoma: Report of 5 cases with review of literature
Authors: Setton Jeremy , Wolden Suzanne , Caria Nicola , Lee Nancy
Published: November 2010

Background

To review the treatment outcomes of patients presenting to Memorial Sloan‐Kettering Cancer Center with metastatic nasopharyngeal carcinoma.

Methods

From April 1999 to April 2008, 5 patients with histologically confirmed nasopharyngeal carcinoma initially presenting with distant metastasis underwent chemotherapy and definitive radiation therapy at our institution. Each patient received platinum‐based chemotherapy concurrently with definitive radiotherapy to the primary region and subsequent consolidation radiotherapy to distant metastases. In addition, 2 patients received induction chemotherapy (cisplatin, fluorouracil), and 3 others received adjuvant chemotherapy (cisplatin or carboplatin, fluorouracil).

Results

Of 5 patients initially presenting to our institution with M1 disease, 2 have no evidence of disease as of their last follow‐up (29 and 91 months). The remaining 3 patients had progression of disease within 12 months of the start of treatment.

Conclusions

Long‐term disease‐free survival is possible in a select group of patients with M1 disease at presentation treated with platinum‐based chemotherapy and definitive radiotherapy © 2010 Wiley Periodicals, Inc. Head Neck, 2012
A coding RNA segment that enhances the ribosomal recruitment of chicken ccn1 mRNA
Authors: Mukudai Yoshiki , Kubota Satoshi , Eguchi Takanori , Sumiyoshi Kumi , Janune Danilo , Kondo Seiji , Shintani Satoru , Takigawa Masaharu
Published: November 2010

CCN1, a member of the CCN family of proteins, plays important physiological or pathological roles in a variety of tissues. In the present study, we initially found a highly guanine–cytosine (GC)‐rich region of approximately 200 bp near the 5′‐end of the open reading frame, which was always truncated by amplification of the corresponding cDNA region through the conventional polymerase chain reaction. An RNA in vitro folding assay and selective ribonuclease digestion of the corresponding segment of the ccn1 mRNA confirmed the involvement of a stable secondary structure. Subsequent RNA electromobility‐shift assays demonstrated the specific binding of some cytoplasmic factor(s) in chicken embryo fibroblasts to the RNA segment. Moreover, the corresponding cDNA fragment strongly enhanced the expression of the reporter gene in cis at the 5′‐end, but did not do so at the 3′‐end. According to the results of a ribosomal assembly test, the effect of the mRNA segment can predominantly be ascribed to the enhancement of transport and/or entry of the mRNA into the ribosome. Finally, the minimal GC‐rich mRNA segment that was predicted and demonstrated to form a secondary structure was confirmed to be a functional regulatory element. Thus, we here uncover a novel dual‐functionality of the mRNA segment in the ccn1 open reading frame, which segment acts as a cis‐element that mediates posttranscriptional gene regulation, while retaining the information for the amino acid sequence of the resultant protein. J. Cell. Biochem. 111: 1607–1618, 2010. © 2010 Wiley‐Liss, Inc.
Exposure of biological preparations to radiofrequency electromagnetic fields under low gravity
Authors: Jacquot Jean Francois , le Bail Jean-Luc , Bardet Michel , Tabony James
Published: November 2010

There is interest as to whether the electromagnetic fields used in mobile radiotelephony might affect biological processes. Other weak fields such as gravity intervene in a number of physical and biological processes. Under appropriate in vitro conditions, the macroscopic self-organization of microtubules, a major cellular component, is triggered by gravity. We wished to investigate whether self-organization might also be affected by radiotelephone electromagnetic fields. Detecting a possible effect requires removing the obscuring effects triggered by gravity. A simple manner of doing this is by rotating the sample about the horizontal. However, if the external field does not also rotate with the sample, its possible effect might also be averaged down by rotation. Here, we describe an apparatus in which both the sample and an applied radiofrequency electromagnetic field (1.8 GHz) are stationary with respect to one another while undergoing horizontal rotation. The electromagnetic field profile within the apparatus has been measured and the apparatus tested by reproducing the in vitro behavior of microtubule preparations under conditions of weightlessness. Specific adsorption rates of electromagnetic energy within a sample are measured from the initial temperature rise the incident field causes. The apparatus can be readily adapted to expose samples to various other external fields and factors under conditions of weightlessness.
The adiabatic approximation in time-dependent density matrix functional theory: Response properties from dynamics of phase-including natural orbitals
Authors: Giesbertz K. J. H. , Gritsenko O. V. , Baerends E. J.
Published: November 2010

The adiabatic approximation is problematic in time-dependent density matrix functional theory. With pure density matrix functionals (invariant under phase change of the natural orbitals) it leads to lack of response in the occupation numbers, hence wrong frequency dependent responses, in particular α(ω→0)≠α0 (the static polarizability). We propose to relinquish the requirement that the functional must be a pure one-body reduced density matrix (1RDM) functional, and to introduce additional variables which can be interpreted as phases of the one-particle states of the independent particle reference system formed with the natural orbitals, thus obtaining so-called phase-including natural orbital (PINO) functionals. We also stress the importance of the correct choice of the complex conjugation in the two-electron integrals in the commonly used functionals (they should not be of exchange type). We demonstrate with the Löwdin–Shull energy expression for two-electron systems, which is an example of a PINO functional, that for two-electron systems exact responses (polarizabilities, excitation energies) are obtained, while writing this energy expression in the usual way as a 1RDM functional yields erroneous responses.
Analysis of particle penetration length into the wall crevices
Authors: Krasheninnikova Natalia S.
Published: November 2010

The present work investigates the effects of the surface roughness on the plasma-wall interactions via kinetic simulations of an initial value problem using the particle-in-cell code VPIC [K. J. Bowers et al., Phys. Plasmas 15, 055703 (2008)]. Collisionless plasma immersed in parallel to the wall magnetic field is self-consistently interacting with a nonflat surface, whose roughness is varied relative to the thermal ion gyroradius. The analysis of the numerical results and analytical estimates yields a scaling of the penetration length that can be described by an analytical formula.
Current-induced resonant depinning of a transverse magnetic domain wall in a spin valve nanostrip
Authors: Metaxas P. J. , Anane A. , Cros V. , Grollier J. , Deranlot C. , Lemaître Y. , Xavier S. , Ulysse C. , Faini G. , Petroff F. , Fert A.
Published: November 2010

We study the impact of rf and dc currents on domain wall depinning in the soft layer of a 120 nm wide Co/Cu/NiFe spin valve nanostrip. A strong resonant reduction in the depinning field (from ∼75 to 25 Oe) is observed for rf currents near 3.5 GHz. Notably, the features of the resonant depinning depend not only on the rf current but also on the simultaneously applied dc current. Consequently, we discuss both the role of the adiabatic spin torque at resonance and that of the current generated Oersted fields.
Savings and investment in South Asia
Authors: Wahid Abu N.M. , Salahuddin Mohammad , Noman Abdullah M.
Published: November 2010

Purpose

This paper seeks to contribute to the study of the relationship between savings and investment in a panel of five South Asian countries.

Design/methodology/approach

A number of unit root tests such as Levin, Lin, and Chu or LLC, Breitung, Im, Pesaran, and Shin or IPS, Fisher‐type tests using ADF and Fisher‐type tests using PP tests are conducted that confirm the non‐stationarity of data. Then the paper applies maximum likelihood‐based panel cointegration method to examine the relationship between savings and investment using data on investment and savings for five South Asian developing countries, namely, Bangladesh, Pakistan, India, Nepal, and Sri Lanka over the period 1973‐2007 compiled from the World Development Indicator (WDI) Database 2008 CD‐ROM.

Findings

The results obtained suggest that savings and investment are cointegrated, which implies that the Feldstein‐Horioka (F‐H) puzzle does not hold in this region. It is also found that most of these countries have maintained an international solvency condition.

Originality/value

This is another contribution that would enrich the existing literature on the F‐H puzzle. The paper includes data that involve the longest sample period. No other study, as of now, has employed the panel cointegration method to study the savings investment relationship in this region.
E‐books at BookExpo 2010
Authors: Cassell Kay Ann , Mercado Marina I.
Published: November 2010

Purpose

The purpose of this paper is to report on a visit to Book Expo 2010 which displayed a range of new and more seasoned vendors of e‐book technology and content.

Design/methodology/approach

Report based on visit to Book Expo.

Findings

E‐books are quickly changing. New technology makes it possible to have content in color with a variety of formats as well as audio.

Practical implications

Librarians must keep up with the many changes in the e‐book market.

Originality/value

This report identifies new e‐book vendors and new technology.
Delay‐discounting rewards from consumer sales promotions
Authors: Coker Kesha K. , Pillai Deepa , Balasubramanian Siva K.
Published: November 2010

Purpose

Rewards from sales promotions may be either immediate (e.g. instant savings, coupons, instant rebates) or delayed (e.g. rebates, refunds). The latter type is of interest in this study. The purpose of this paper is to present the hyperbolic discounting framework as an explanation for how consumers delay‐discount rewards, and test whether this holds for both high‐price and low‐price product categories.

Design/methodology/approach

Data were collected by administering two online surveys to respondents. One survey presented choice scenarios between sales promotion formats for a high‐priced product (a laptop, n=154) and the other for a low‐priced product (a cell phone, n=98). Hyperbolic and exponential functions were then fitted to the data.

Findings

The hyperbolic function had a better fit than the exponential function for the low‐priced product. However, this effect was not evident in the case of the high‐priced product; no significant difference was found between the functions. The rate of discounting was greater for the high‐priced product than for the low‐priced product. Thus, for low‐priced products, rather than discount a reward rationally, consumers tend to discount the value of the reward at a decreasing rate.

Originality/value

This study addresses delay discounting in the context of a typical consumer buying situation. It also addresses the possibility of consumers applying different forms of discounting to products at different price levels and tests for the same. The results are of considerable significance for marketers wishing to offer price discounts to consumers. For low‐priced products, marketers seem to have more flexibility in delaying the reward, since the rate of discounting decreases for longer delay periods. At the same time, the discount rate for high‐priced products is higher than that for low‐priced products, hence delay periods may have a more critical role as discounted values fall steeply with an increase in delay to reward.
Invested resource, competitive intellectual capital, and corporate performance
Authors: Cheng Meng‐Yuh , Lin Jer‐Yan , Hsiao Tzy‐Yih , Lin Thomas W.
Published: November 2010

Purpose

On the health care industry, the paper aims to study the effects of intellectual capital, identify using an input‐process‐output concept of human, customer, innovative and process capitals, on company performances.

Design/methodology/approach

From a resource‐based and intellectual capital perspective, the structural path model is applied to financial data to analyze the six‐value creation relationships among the four components of intellectual capital, as well as the causal effects of intellectual capital on company performance.

Findings

Empirical findings suggest a significant relationship between intellectual capital and company performance. These results also suggest that innovative capacity and process reformation shall be considered first, and through the human value‐added of human capital, firms can improve their company's performance.

Originality/value

There have been many arguments as to whether intellectual capital is quantitatively measurable. This paper provides a tangible means of quantifying intellectual capital.
Prediction of recurrence using exfoliative cytology and melanoma‐associated antigen‐A mRNA analysis following wide excision of oral squamous cell carcinoma: short report
Authors: Mollaoglu N. , Metzler P. , Zenk J. , Nkenke E. , Neukam F. W. , Ries J.
Published: November 2010

N. Mollaoglu, P. Metzler, J. Zenk, E. Nkenke, F. W. Neukam and J. Ries  Prediction of recurrence using exfoliative cytology and melanoma‐associated antigen‐A mRNA analysis following wide excision of oral squamous cell carcinoma: short report

Background:  Oral squamous cell carcinoma (OSCC) is the sixth most common cancer. The local recurrence of OSSC might result from the existence of occult cancer cells around tumour margins. Exfoliative cytology has lately gained great importance as a method for obtaining RNA samples from suspicious oral mucosal lesions in order to carry out molecular diagnosis. In addition, melanoma associated‐A antigens (MAGE‐A) are expressed in various tumours and their detection is a highly accurate sign that cancer cells are present.

Objective:  The prediction of a recurrence using MAGE‐A mRNA expression analysis to follow‐up OSCC cases using a newly established molecular diagnostic technique applied to cytological materials.

Methods:  RNA was extracted from three recurrent OSCC cases and from 20 healthy volunteers as a control group using a cytobrush. The expression of MAGE‐A3, A4, A6, A10 and A12 was investigated in these specimens using quantitative real‐time (RT‐PCR).

Results:  There was no expression of MAGE‐A in the specimens of normal oral mucosa. However, the expression analysis of five different MAGE‐A genes indicated a high potential for malignant change in biopsy‐proven recurrent OSCC cases. Except for MAGE‐A10, the rest of the genes were expressed in different ratios by the three recurrent cases, which had been determined on histopathology to be OSCC or carcinoma in situ.

Conclusion:  It is suggested that analysis of MAGE‐A expression may be used as a risk prediction method in the diagnosis of recurrence after wide excision of OSCC to enhance the accuracy of exfoliative cytology, which has limitations due to false negative and false positive results.
Obesity, weight loss and conditional cardiovascular risk factors
Authors: Tzotzas T. , Evangelou P. , Kiortsis D. N.
Published: November 2010

Obesity is a pathological condition aggregating a substantial number of proatherogenic factors, such as insulin resistance, type 2 diabetes mellitus, dyslipidaemia and hypertension. In addition to these classic cardiometabolic risk factors, atherosclerosis may be aggravated by other non‐classic factors, which are characterized as conditional, including homocysteine, fibrinogen, lipoprotein(a), LDL particle size and high‐sensitivity CRP. Some of these biomarkers are disturbed in obesity because of a combination of dietary factors, hypertrophic adipose tissue, low‐grade inflammation, insulin resistance and other parameters under investigation. For the reduction of these risk factors, weight loss exceeding 10–20% of the initial body weight is probably necessary, achieved through either conventional lifestyle measures or more drastic interventions such as bariatric surgery. It has been shown that certain well‐balanced diets, such as the Mediterranean diet, constitute a means of improving in a concerted manner the levels of CRP, fibrinogen, homocysteine and small dense LDL particles, regardless of weight loss. The significance of considering these factors in weight management intervention is an issue that needs further investigation.
The Causal Power of Discourse
Authors: ELDER‐VASS DAVE
Published: November 2010

This paper outlines a realist approach to the social ontology of discourse. It seeks to synthesise some elements of the approach to discourse found in the early work of Michel Foucault with a critical realist understanding of the causal power of social structures. It will argue that discursive structures can be causally significant when they are normatively endorsed and enforced by specific groups of people; that it is not discourse as such but these groups—discursive circles—that are causally effective; and that such an account allows us to reconcile the role of discourse with that of the subject.
Urine concentrating mechanism in the inner medulla of the mammalian kidney: role of three‐dimensional architecture
Authors: Dantzler W. H. , Pannabecker T. L. , Layton A. T. , Layton H. E.
Published: November 2010

The urine concentrating mechanism in the mammalian renal inner medulla (IM) is not understood, although it is generally considered to involve countercurrent flows in tubules and blood vessels. A possible role for the three‐dimensional relationships of these tubules and vessels in the concentrating process is suggested by recent reconstructions from serial sections labelled with antibodies to tubular and vascular proteins and mathematical models based on these studies. The reconstructions revealed that the lower 60% of each descending thin limb (DTL) of Henle’s loops lacks water channels (aquaporin‐1) and osmotic water permeability and ascending thin limbs (ATLs) begin with a prebend segment of constant length. In the outer zone of the IM (i) clusters of coalescing collecting ducts (CDs) form organizing motif for loops of Henle and vasa recta; (ii) DTLs and descending vasa recta (DVR) are arrayed outside CD clusters, whereas ATLs and ascending vasa recta (AVR) are uniformly distributed inside and outside clusters; (iii) within CD clusters, interstitial nodal spaces are formed by a CD on one side, AVR on two sides, and an ATL on the fourth side. These spaces may function as mixing chambers for urea from CDs and NaCl from ATLs. In the inner zone of the IM, cluster organization disappears and half of Henle’s loops have broad lateral bends wrapped around terminal CDs. Mathematical models based on these findings and involving solute mixing in the interstitial spaces can produce urine slightly more concentrated than that of a moderately antidiuretic rat but no higher.
Spt10 and Spt21 Are Required for Transcriptional Silencing in Saccharomyces cerevisiae
Authors: Chang Jennifer S. , Winston Fred
Published: November 2010

In
Saccharomyces cerevisiae
, transcriptional silencing occurs at three classes of genomic regions: near the telomeres, at the silent mating type loci, and within the ribosomal DNA (rDNA) repeats. In all three cases, silencing depends upon several factors, including specific types of histone modifications. In this work we have investigated the roles in silencing for Spt10 and Spt21, two proteins previously shown to control transcription of particular histone genes. Building on a recent study showing that Spt10 is required for telomeric silencing, our results show that in both
spt10
and
spt21
mutants, silencing is reduced near telomeres and at
HML
α, while it is increased at the rDNA. Both
spt10
and
spt21
mutations cause modest effects on Sir protein recruitment and histone modifications at telomeric regions, and they cause significant changes in chromatin structure, as judged by its accessibility to dam methylase. These silencing and chromatin changes are not seen upon deletion of
HTA2-HTB2
, the primary histone locus regulated by Spt10 and Spt21. These results suggest that Spt10 and Spt21 control silencing in
S. cerevisiae
by altering chromatin structure through roles beyond the control of histone gene expression.
Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues
Authors: Zhou Chao , Cohen David W. , Wang Yihong , Lee Hsiang-Chieh , Mondelblatt Amy E. , Tsai Tsung-Han , Aguirre Aaron D. , Fujimoto James G. , Connolly James L.
Published: November 2010

Three-dimensional (3D) tissue imaging methods are expected to improve surgical management of cancer. In this study, we examined the feasibility of two 3D imaging technologies, optical coherence tomography (OCT) and optical coherence microscopy (OCM), to view human breast specimens based on intrinsic optical contrast. Specifically, we imaged 44 ex vivo breast specimens including 34 benign and 10 malignant lesions with an integrated OCT and OCM system developed in our laboratory. The system enabled 4-μm axial resolution (OCT and OCM) with 14-μm (OCT) and 2-μm (OCM) transverse resolutions, respectively. OCT and OCM images were compared with corresponding histologic sections to identify characteristic features from benign and malignant breast lesions at multiple resolution scales. OCT and OCM provide complimentary information about tissue microstructure, thus showing distinctive patterns for adipose tissue, fibrous stroma, breast lobules and ducts, cysts and microcysts, as well as in situ and invasive carcinomas. The 3D imaging capability of OCT and OCM provided complementary information to individual 2D images, thereby allowing tracking features from different levels to identify low-contrast structures that were difficult to appreciate from single images alone. Our results lay the foundation for future in vivo optical evaluation of breast tissues, using OCT and OCM, which has the potential to guide core needle biopsies, assess surgical margins, and evaluate nodal involvement in breast cancer. Cancer Res; 70(24); 10071–9. ©2010 AACR.
Federal Trade Commission Actions on Prescription Drugs, 2000-2022
Authors: Daval C. Joseph Ross , Egilman Alexander C. , Sarpatwari Ameet , Kesselheim Aaron S.
Published: May 2024

Importance

The Federal Trade Commission’s (FTC) oversight role in the pharmaceutical market is critical to the health of patients and the health care system. This study characterized the FTC’s policy on the pharmaceutical market in recent decades, identifying the types of actions it has favored, barriers it has faced, and authorities that remain untested.

Objective

To review FTC legal actions in the pharmaceutical market from 2000-2022.

Evidence Review

Legal actions were determined through manual review of search results from the FTC’s online Legal Library as well as a 2023 FTC report on pharmaceutical actions. The alleged misconduct, type of legal action taken, timing, and outcome were collected from press releases, complaints, orders, and other legal documents.

Findings

From 2000-2022, the FTC challenged 62 mergers, brought 22 enforcement actions against allegedly unlawful business practices, and made 1 rule related to pharmaceuticals. Alleged misconduct in enforcement actions involved anticompetitive settlements in patent litigation (n = 11), unilateral actions by brand manufacturers to delay generic competition (n = 6), noncompete agreements (n = 4), and monopolization (n = 3), with 10 outcomes involving monetary payment, totaling $1.6 billion. Of the 62 mergers the FTC challenged, 61 were allowed to continue, 58 after divesting certain drugs to third-party competitors. The FTC’s reliance on drug divestitures decreased from 18 drugs per year from 2000-2017 to 4.3 per year from 2017-2023.

Conclusions and Relevance

The FTC brought about 1 enforcement action and 3 merger actions per year against pharmaceutical manufacturers from 2000-2022, pursuing a small fraction of the estimated misconduct and consolidation in the pharmaceutical marketplace. Although the FTC faces substantial legal and practical limitations, important tools remain untested, including a rule defining “unfair methods of competition,” that may allow it to more effectively prevent repetitive patterns of anticompetitive behavior.
Time- vs Step-Based Physical Activity Metrics for Health
Authors: Hamaya Rikuta , Shiroma Eric J. , Moore Christopher C. , Buring Julie E. , Evenson Kelly R. , Lee I-Min
Published: May 2024

Importance

Current US physical activity (PA) guidelines prescribe moderate to vigorous PA (MVPA) time of at least 150 minutes per week for health. An analogous step-based recommendation has not been issued due to insufficient evidence.

Objective

To examine the associations of MVPA time and step counts with all-cause mortality and cardiovascular disease (CVD).

Design, Setting, and Participants

This cohort study analyzed data from an ongoing follow-up study of surviving participants of the Women’s Health Study, a randomized clinical trial conducted from 1992 to 2004 in the US to evaluate use of low-dose aspirin and vitamin E for preventing cancer and CVD. Participants were 62 years or older who were free from CVD and cancer, completed annual questionnaires, and agreed to measure their PA with an accelerometer as part of a 2011-2015 ancillary study. Participants were followed up through December 31, 2022.

Exposures

Time spent in MVPA and step counts, measured with an accelerometer for 7 consecutive days.

Main Outcomes and Measures

The associations of MVPA time and step counts with all-cause mortality and CVD (composite of myocardial infarction, stroke, and CVD mortality) adjusted for confounders. Cox proportional hazards regression models, restricted mean survival time differences, and area under the receiver operating characteristic curve (AUC) were used to evaluate the associations.

Results

A total of 14 399 women (mean [SD] age, 71.8 [5.6] years) were included. The median (IQR) MVPA time and step counts were 62 (20-149) minutes per week and 5183 (3691-7001) steps per day, respectively. During a median (IQR) follow-up of 9.0 (8.0-9.9) years, the hazard ratios (HR) per SD for all-cause mortality were 0.82 (95% CI, 0.75-0.90) for MVPA time and 0.74 (95% CI, 0.69-0.80) for step counts. Greater MVPA time and step counts (top 3 quartiles vs bottom quartile) were associated with a longer period free from death: 2.22 (95% CI, 1.58-2.85) months and 2.36 (95% CI, 1.73-2.99) months at 9 years follow-up, respectively. The AUCs for all-cause mortality from MVPA time and step counts were similar: 0.55 (95% CI, 0.52-0.57) for both metrics. Similar associations of these 2 metrics with CVD were observed.

Conclusion and Relevance

Results of this study suggest that among females 62 years or older, MVPA time and step counts were qualitatively similar in their associations with all-cause mortality and CVD. Step count–based goals should be considered for future guidelines along with time-based goals, allowing for the accommodation of personal preferences.
Risk Factors and Mortality Among Women With Interval Breast Cancer vs Screen-Detected Breast Cancer
Authors: Song Huiyeon , Tran Thi Xuan Mai , Kim Soyeoun , Park Boyoung
Published: May 2024

Importance

The risk factors for interval breast cancer (IBC) compared with those for screen-detected breast cancer (SBC) and their association with mortality outcomes have not yet been evaluated among Korean women.

Objective

To evaluate risk factors associated with IBC and survival among Korean women with IBC compared with those with SBC.

Design, Setting, and Participants

This retrospective cohort study used data from the Korean National Health Insurance Service Database. Women who participated in a national mammographic breast cancer screening program between January 1, 2009, and December 31, 2012, were included. Mortality outcomes were calculated from the date of breast cancer diagnosis to the date of death or December 31, 2020. Data were analyzed from March 1 to June 30, 2023.

Exposure

Breast cancer diagnosed within 6 to 24 months after a negative screening result (ie, IBC) or within 6 months after a positive screening result (ie, SBC).

Main Outcomes and Measures

Risk factors and survival rates for IBC and SBC.

Results

This study included 8702 women with IBC (mean [SD] age, 53.3 [8.6] years) and 9492 women with SBC (mean [SD] age, 54.1 [9.0] years). Compared with SBC, the probability of IBC decreased as mammographic density increased. Lower body mass index, menopausal status, hormone replacement therapy (HRT) use, and lack of family history of breast cancer were associated with a higher likelihood of IBC. When stratified by detection time, younger age at breast cancer diagnosis and family history of breast cancer were associated with an increased likelihood of IBC diagnosed at 6 to 12 months but a decreased likelihood of IBC diagnosed at 12 to 24 months. Overall mortality of IBC was comparable with SBC, but total mortality and cancer-related mortality of IBC diagnosed between 6 and 12 months was higher than that of SBC.

Conclusions and Relevance

The findings of this cohort study suggest that breast density, obesity, and HRT use were associated with IBC compared with SBC. These findings also suggest that higher supplemental breast ultrasound use among Korean women, especially those with dense breasts, could be attributed to a lower incidence of IBC among women with dense breasts compared with women with SBC, due to greater detection. Finally, overall mortality of IBC was comparable with that of SBC.
Evolution of Gene Therapy for Inborn Errors of Immunity
Authors: Somekh Ido , Hendel Ayal , Somech Raz
Published: May 2024

This Viewpoint reviews the history and current state of gene therapy for inborn errors of immunity.
Phosphatidylserine‐Incorporated Exosome Mimetics Encapsulating CXCR3 Antagonist Alleviate Osteoporosis
Authors: Kang Minjee , Li Zhi , Chang Insoon , Xu Changlu , Chiang Michelle , Kim Lauren , Wu Yutong , Fan Jiabing , Aghaloo Tara , Lee Min
Published: May 2024

Exosomes derived from mesenchymal stem cells are an active area of research due to their therapeutic potential in treating osteoporosis. To further harness their therapeutic performance in modulating bone resorption, equipped exosomes with osteoclast‐targeting moieties on their surface as well as chemokine receptor antagonists blocking osteoclast recruitment. Phosphatidylserine (PS), a membrane lipid exerting immunosuppressive and phagocytic signals, is incorporated in the membrane of exosome mimetics (EMs) to achieve a marked affinity for osteoclast precursors and potential anti‐resorptive effects. This is also aimed to tackle a CXCL9‐CXCR3 ligand‐receptor axis, a critical signaling axis in regulating osteoclast precursor recruitment and differentiation at bone resorption sites, by encapsulating a chemical antagonist of CXCR3, AMG487, in the PS‐incorporated EMs (PS‐EMs). The osteoclast‐targeting PS‐EMs loaded with AMG487 effectively protected against bone loss in an ovariectomized mouse model. These findings demonstrate the great promise of PS‐EMs as anti‐resorptive nanotherapies for alleviating osteoporosis.