bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of patient and professional diagnostic delays on the risk of recurrence in laryngeal carcinoma
Authors: Teppo H. , Hyrynkangas K. , Koivunen P. , Jokinen K. , Alho O.‐P.
Published: April 2005

Objectives:  To evaluate the impact of patient and professional diagnostic delays on the risk of recurrence in laryngeal squamocellular carcinoma (LSCC).

Design:  Retrospective study using primary health care records completed before the diagnosis of malignancy.

Setting:  One primary health care district (onset of symptoms), one tertiary centre (final diagnosis).

Participants:  A population‐based sample of 99 patients, of which 66 fulfilled the entry criteria, with LSCC diagnosed in northern Finland in 1990–1995.

Main outcome measures:  Impact of patient delay (interval between the onset of symptoms and the first visit to a physician) and professional delay (interval between the first medical visit and histologically verified diagnosis) on the risk of local, neck and distant recurrence in LSCC.

Results:  Professional delay of 1 year or longer was an independent predictor of both local [adjusted relative hazard (HR) 4.62, P = 0.02] and neck (HR 9.5, P = 0.015) recurrence. Longer professional delay was associated with the risk of recurrence particularly among patients with early stage (stages I–II) disease. Professional delay was almost exclusively because of a delay in referring patients from primary care to an ENT centre.

Conclusions:  Lengthened professional diagnostic delay is an independent predictor of an increased risk of local and neck recurrence in early stage LSCC. These patients could benefit from more aggressive primary treatment or more meticulous follow‐up.
How we do it: ENT prescribing to competitive athletes – a review of current regulations
Authors: Mace A. , Smith R. , Sandhu G.
Published: April 2005

Keypoints

• Otolaryngologists may be called upon to treat and advise amateur or professional athletes.

• The effect of a positive anti‐doping test on an athlete's career is devastating.

• It is, therefore, important to ensure that any substance prescribed should be approved for use and should not adversely affect the athlete's performance.

• This article explains the testing system and provides an overview of the current status of medications commonly prescribed in routine ENT practice.
Recruitment of E‐cadherin associated with α‐ and β‐catenins and p120ctn to the nectin‐based cell‐cell adhesion sites by the action of 12‐O‐tetradecanoylphorbol‐13‐acetate in MDCK cells
Authors: Okamoto Ryoko , Irie Kenji , Yamada Akio , Katata Tatsuo , Fukuhara Atsunori , Takai Yoshimi
Published: April 2005

The formation of tight junctions (TJs) is dependent on the formation of adherens junctions (AJs) in MDCK cells. E‐Cadherin and nectin are major cell‐cell adhesion molecules (CAMs) at AJs, whereas claudin, occludin and junctional adhesion molecule (JAM) are major CAMs at TJs. When MDCK cells precultured at 2 µm Ca2+ are cultured at 2 mm Ca2+, nectin first forms cell‐cell adhesion and recruits E‐cadherin to the nectin‐based cell‐cell adhesion sites to form AJs. Thereafter, nectin recruits first JAM‐A and then claudin‐1 and occludin to the apical side of AJs to form TJs. In contrast, when MDCK cells precultured at 2 µm Ca2+ are cultured at 2 µm Ca2+ in the presence of a phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a TJ‐like structure is formed without the formation of the E‐cadherin‐based AJs. We showed here that GFP‐E‐cadherin, which did not trans‐interact due to 2 µm Ca2+ but associated with α‐ and β‐catenins and p120ctn, was recruited to the nectin‐based cell‐cell adhesion sites by the action of TPA. The nectin inhibitors, which inhibited the trans‐interaction of nectin, inhibited the recruitment of GFP‐E‐cadherin and their associating catenins by the action of TPA. Microbeads coated with the extracellular fragment of nectin recruited not only cellular nectin but also GFP‐E‐cadherin and their associating catenins by the action of TPA. These results indicate that when the TJ‐like structure is formed by the action of TPA, non‐trans‐interacting E‐cadherin and its associating catenins are recruited to the nectin‐based cell‐cell adhesion sites and that the trans‐interaction of E‐cadherin is not essential for the formation of TJs.
Participation of Rho‐dependent transcription termination in oxidative stress sensitivity caused by an rpoB mutation
Authors: Kawamura Nobuyuki , Kurokawa Kenji , Ito Takahiro , Hamamoto Hiroshi , Koyama Hiroshi , Kaito Chikara , Sekimizu Kazuhisa
Published: April 2005

The role of transcription termination process for gene expression regulation is poorly understood. Either a multicopy supply of the rof gene or bicyclomycin, both of which inhibit the transcription termination Rho factor, suppressed the increased sensitivity to oxidative stress of the rifampicin‐resistant rpoB mutation in Escherichia coli. Multi‐copy supply of the rnk gene also suppressed oxidative stress sensitivity, coincident with the recovery of the reduced concentration of nucleoside triphosphates in the mutant cells, which is one of the factors that affects transcription termination efficiency in vitro. Thus, an appropriate, nonexcessive termination frequency at Rho‐dependent transcription terminators might contribute to oxidative stress survival. Clinical application of oxidative stress against drug resistant bacteria is also discussed.
Enhancing methodological clarity: principle‐based concept analysis
Authors: Penrod Janice , Hupcey Judith E.
Published: April 2005

Aims. The aim of this paper is to operationalize the principle‐based method of concept analysis.

Background. While nursing has embraced the use of concept analysis as a valid and significant entrée into an area of research, methodological development has created strategies of inquiry that vary in purpose and in the nature of their findings.

Discussion. We propose that, as the primary utility of concept analysis is to determine the existing state of the science so that further work may be strategically and appropriately planned, the method described as principle‐based concept analysis is superior in providing evidence to support subsequent inquiry into the concept of interest.

Three problematic issues are discussed in an effort to clarify and procedurally explicate the strategies employed in this approach: selecting disciplinary literatures for inclusion in the analysis; conceptually‐driven sampling issues; and within‐ and across‐discipline analytic techniques.

Conclusion. In this form of concept analysis, each principle contributes to an understanding of the strengths and limitations of the present state of the concept in the scientific literature. We believe that this perspective will enable nursing to begin to harness the power of concept analysis foradvancingscience rather than simply imagining what a conceptcould beor constructing what we believe itshould be.
Developing assessment of Emergency Nurse Practitioner competence – a pilot study
Authors: Mason Suzanne , Fletcher Alan , McCormick Simon , Perrin Julie , Rigby Alan
Published: April 2005

Aim.  This paper reports a study evaluating baseline competence levels among Emergency Nurse Practitioners using an Objective Structured Clinical Examination. The study also aimed to document change in competence over time and following an educational intervention.

Background.  Emergency Nurse Practitioners form an increasingly established part of the minor injury service workforce in the United Kingdom (UK). At present, there is no national requirement for them to undergo formal preparation, gain a formal qualification, have continuing professional development or revalidate. Given that it is certain that the use of these professionals to deliver unplanned emergency care will increase in the UK, skill maintenance and extension of skills need to be considered in order to ensure the continued delivery of a quality service. Objective Structured Clinical Examinations aim to test a wide range of knowledge and skills in an objective fashion and can be developed to serve a number of educational requirements.

Methods.  A competence assessment was planned using an Objective Structured Clinical Examination. It was developed following questionnaire consultation with Emergency Nurse Practitioners and also in conjunction with Emergency Department specialists and experts in medical education. The Objective Structured Clinical Examination was piloted with Emergency Department junior doctors. Baseline Objective Structured Clinical Examination assessment was conducted in 2001. An educational intervention followed and then a further Objective Structured Clinical Examination assessment took place in 2002.

Results.  A total of 17 of 20 Emergency Nurse Practitioners consented to involvement in the study. Comparison of their performance showed a statistically significant overall improvement in performance between the two assessment periods (P < 0·05). Participant feedback on the experience of undertaking an Objective Structured Clinical Examination assessment was very positive.

Conclusions.  The assessment process worked well, and provides a framework for competence assessment that can be compared over time, between practitioners and between departments.
Professional doctorates for nurses: mapping provision and perceptions
Authors: Ellis Lorraine B.
Published: April 2005

Aim. This paper reports a study to map the range of developments of professional doctorates in the United Kingdom (UK) and report the views of key stakeholders as to the value of the professional doctorate relative to the more traditional PhD.

Background. As the highest university degree that can be awarded, the traditional Doctor of Philosophy (PhD) represents the pinnacle of advanced learning and scholarly enquiry, demonstrated by subject expertise and the creation of new knowledge. The last decade the UK has witnessed the introduction of an alternative form of doctoral preparation for nurses and other health care professions known as the taught or professional doctorate, a form of doctoral provision not unlike the United States of America (USA) model of PhD in Nursing.

Methods. An illuminative evaluation was carried out in date in the UK in 2003. Data were collected using content analysis of curricula and related documentation, and telephone interviews with 55 academics at 41 institutions of higher education.

Results. Mapping of the professional doctorate revealed a continuum of provision from highly prescriptive to minimally prescriptive programmes and a wide range of attitudes towards the professional doctorate, varying from enthusiasm through ambivalence to scepticism.

Conclusion. Educators face an uphill battle in convincing practitioners of the efficacy and value of continuing professional education at doctoral level, a challenge that is likely to be increased by the general lack of clarity and consensus amongst academics reported in this study. Shared understanding of the concept of a professional doctorate is needed if the benefits of these programmes are to be realised.
Expression of Three Gene Families Encoding Cell–Cell Communication Molecules in the Prepubertal Nonhuman Primate Hypothalamus
Authors: Mungenast A. E. , Ojeda S. R.
Published: April 2005

Transsynaptic and glial–neuronal communication are important components of the mechanism underlying the pubertal activation of luteinizing hormone‐releasing hormone (LHRH) secretion. The molecules required for the architectural organization of these cell–cell interactions have not been identified. We now show that the hypothalamus of the prepubertal female rhesus monkey expresses a multiplicity of genes encoding three families of adhesion/signalling proteins involved in the structural definition of both neurone‐to‐neurone and bi‐directional neurone–glia communication. These include the neurexin/neuroligin (NRX/NRL) and protocadherin‐α (PCDHα) families of synaptic specifiers/adhesion molecules, and key components of the contactin‐dependent neuronal–glial adhesiveness complex, including contactin/F3 itself, the contactin‐associated protein‐1 (CASPR1), and the glial receptor protein tyrosine phosphatase β. Prominently expressed among members of the NRX family is the neurexin isoform involved in the specification of glutamatergic synapses. Although NRXs, PCDHαs and CASPR1 transcripts are mostly detected in neurones, the topography of expression appears different. NRX1 mRNA‐containing neurones are scattered throughout the hypothalamus, PCDHα mRNA transcripts appear more abundant in neurones of the arcuate nucleus and periventricular region, and neurones positive for CASPR1 mRNA exhibit a particularly striking distribution pattern that delineates the hypothalamus. Examination of LHRH neurones, using the LHRH‐secreting cell line GT1‐7, showed that these cells contain transcripts encoding NRXs and one of their ligands (NRL1), at least one PCDHα (CNR‐8/PCDHα10), and the CASPR1/contactin complex. The results indicate that the prepubertal female monkey hypothalamus contains a plethora of adhesion/signalling molecules with different but complementary functions, and that an LHRH neuronal cell line expresses key components of this structural complex. The presence of such cell–cell communication machinery in the neuroendocrine brain suggests an integrated participation of their individual components in the central control of female sexual development.
Central Regulation of the Hypothalamic‐Pituitary‐Adrenal Axis During Fetal Development in the Guinea‐Pig
Authors: Owen D. , Banjanin S. , Gidrewicz D. , McCabe L. , Matthews S. G.
Published: April 2005

We have previously shown that the foetal guinea‐pig hypothalamic‐pituitary‐adrenal (HPA) axis is activated near the time of parturition and that this is associated with changes in limbic glucocorticoid receptors (GR) and mineralocorticoid receptors. In the present study, we hypothesized that the foetal hypothalamic paraventricular nucleus (PVN) and pituitary contribute significantly to foetal HPA drive but that these areas remain sensitive to negative feedback by circulating glucocorticoids in late gestation. However, we observed decreased corticotrophin‐releasing hormone mRNA expression in the PVN and decreased pro‐opiomelanocortin (POMC) mRNA levels in the anterior pituitary with advanced gestational age. The reduction in POMC mRNA expression was likely the result of negative feedback via circulating glucocorticoids because GR mRNA was unchanged during development in the foetal pituitary. Furthermore, we found that maternally administered glucocorticoids significantly decreased foetal pituitary POMC mRNA expression in a dose‐dependent manner at gestational day (gd) 62 with male foetuses being more sensitive to these effects. These findings show that the foetal HPA axis remains highly sensitive to glucocorticoid feedback even as plasma adrenocorticotropic hormone and cortisol levels are elevated at the end of gestation.
Expression of Immediate Early Genes and Vasopressin Heteronuclear RNA in the Paraventricular and Supraoptic Nuclei of Rats After Acute Osmotic Stimulus
Authors: Kawasaki M. , Yamaguchi K. , Saito J. , Ozaki Y. , Mera T. , Hashimoto H. , Fujihara H. , Okimoto N. , Ohnishi H. , Nakamura T. , Ueta Y.
Published: April 2005

Monitoring the expression of immediate early genes (IEGs) is useful for following stress‐induced cellular responses in the neuroendocrine system. We have examined the transcriptional activities of four IEGs (c‐fos, junB, NGFI‐A and NGFI‐B) and of the arginine vasopressin (AVP) gene in the hypothalamic paraventicular (PVN) and supraoptic nuclei (SON) of rats after acute osmotic stimuli, using in situ hybridization histochemistry. After intraperitoneal (i.p.) administration of hypertonic saline (2% body weight, 900 mOsm/kg), the expression levels of all IEG mRNAs were increased significantly both in the PVN and SON at as early as 10 min, peaked at 30 min and remained elevated until 60 min. The expression of AVP heteronuclear (hn)RNA also peaked at 30 min, and remained elevated until 180 min. Thirty min after i.p. administration of hypertonic saline (600 mOsm/kg), the expression levels of all IEG mRNAs in the PVN and SON were significantly increased in comparison with those after i.p. administration of isotonic saline (290 mOsm/kg). Regression analysis revealed that expression levels of the IEG mRNAs and AVP hnRNA were positively correlated with the plasma concentration of sodium, and the rates of increase of the expression levels of all IEG mRNAs were similar. The expression levels of all IEG mRNAs examined are useful markers for following the changes of the AVP gene transcription in the PVN and SON after acute osmotic stimuli in rats.
Antibacterial activity of glass–ionomer cements, compomers and resin composites: relationship between acidity and material setting phase
Authors: VERMEERSCH G. , LELOUP G. , DELMÉE M. , VREVEN J.
Published: April 2005

summary  Agar diffusion testing was used with four different media to evaluate the antibacterial activity of six products (one conventional glass–ionomer cement (GIC), two light‐activated glass–ionomers, two polyacid‐modified resin composites and one resin composite) on Streptoccoccus mutans. Their respective antibacterial activities were also compared during and after setting. The relationship between product acidity and antibacterial activity was evaluated.

All the GICs demonstrated antibacterial properties in contrast to the polyacid‐modified resin composites and resin composite which did not shown any antibacterial effects. Vitrebond GIC exhibited higher antibacterial action, probably because of a cytotoxic photo‐initiator diphenyliodoniumchloride. A direct relationship between material acidity and growth inhibition of S. mutans was observed.
Condylar resorption during active orthodontic treatment and subsequent therapy: report of a special case dealing with iatrogenic TMD possibly related to orthodontic treatment
Authors: SHEN Y. H. , CHEN Y. K. , CHUANG S. Y.
Published: April 2005

summary  A 28‐year‐old female underwent orthodontic treatment for approximately 22 months. During the later stages of this treatment, the patient reported right shoulder and neck‐muscle pain. In addition, temporomandibular joint disorder (TMD) with a ‘clicking’ sound during mastication commenced 5 months prior to treatment completion. Specific medication to deal with these symptoms was suggested by medical specialists, as were some stress‐relief methods, although the pain still progressed, and subsequent clinical and radiographical examinations were undertaken by another orthodontist. Right mandibular condylar resorption was observed from both the panorex and temporomandibular joint (TMJ) radiographs. No clinical signs of rheumatic disease were observed, although bruxism was noted. Following the termination of the orthodontic treatment by the second practitioner, the patient was treated with splint therapy 1 month subsequent to which, the previous symptoms of pain in the shoulder and neck, and the clicking sound during mastication had subsided. During the 14‐month period of splint therapy and follow‐up, new bone growth in the right condyle was observed from radiographs.
Allergy and infection: understanding their relationship
Authors: Custovic A. , Murray C. , Simpson A.
Published: April 2005

Sensitization to indoor allergens has long been recognized as a risk factor for asthma and its associated phenotypes. Immunoglobulin E antibody quantification may be used to confirm that a particular sensitization has a role in the development of respiratory symptoms. However, in order to use quantitative information effectively, it is essential to understand the factors that contribute to the deterioration of symptoms and cause exacerbations. One such risk factor is high allergen exposure. Worsening asthma control is also associated with virus infections, in particular rhinovirus infection. Each of these factors in isolation is unlikely to have a major effect on symptoms. However, the combination of respiratory virus infection, allergen sensitization and concurrent high exposure to allergens markedly increases the risk for hospitalization. Further investigation of this synergism could help to understand the mechanisms of asthma exacerbations and lead to the development of strategies for prevention.
When allergies complicate allergies
Authors: Wickman M.
Published: April 2005

The ‘allergic march’ is a term used to describe an individual's progress from one clinical manifestation of allergy to another, with age. Not all sensitized children will join the allergic march, but it appears that individuals who do not join the allergic march have a greater risk of displaying symptoms of allergic disease in adulthood. Consequently, there is a need for early diagnosis of allergy in children. Immunoglobulin E (IgE) antibody quantification is increasingly used for this purpose. However, rather than making a diagnosis based on single positive IgE antibody results only, it may be more efficient to test a profile of airborne and food allergens and use the sum of IgE antibody concentrations ≥3.5 kUA/l in combination with the number of allergens that elicit positive results tests. Allergic diseases often co‐exist in patients, and the combination of several exposures at a given time (the allergen load) is related to disease severity. Therefore, a reduction of the allergen load is a key to successful treatment.
Food allergy – accurately identifying clinical reactivity
Authors: Sampson H. A.
Published: April 2005

Up to 25% of adults believe that they or their children are afflicted with a food allergy. However, the actual prevalence of food allergy is much lower: approximately 6–8% of children suffer from food allergy during their first 3 years of life, and many children then develop clinical tolerance. Food allergy encompasses a whole spectrum of disorders, with symptoms that may be cutaneous, gastrointestinal or respiratory in nature. Food disorders also differ according to the extent that they are immunoglobulin E (IgE)‐mediated. Skin‐prick testing is often used to identify food sensitization, although double‐blind, placebo‐controlled food challenge (DBPCFC) tests remain the gold standard for diagnosis. Recent evidence suggests that quantitative IgE measurements can predict the outcome of DBPCFC tests and can replace about half of all oral food challenges. When an extensive medical history is obtained in combination with IgE quantification, even fewer patients may require formal food challenges. It has also become possible to map the IgE‐binding regions of many major food allergens. This may help to identify children with persistent food allergy, as opposed to those who may develop clinical tolerance. In future, microarray technology may enable physicians to screen patients for a large number of food proteins and epitopes, using just a few drops of blood.
Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma?
Authors: Platts‐Mills T. A. E. , Erwin E. , Heymann P. , Woodfolk J.
Published: April 2005

The hygiene hypothesis states that a reduced exposure to allergens in early life is solely implicated in the growing propensity for allergy sensitization. Important elements of the hypothesis include helminth infection, exposure to endotoxins, exposure to pets and growing up on a farm. However, the hygiene hypothesis alone does not provide an adequate explanation for the observed increase in allergic disease. For example, in North American inner cities, asthma is increasing among children who live in very poor housing, which might be assumed to be somewhat dirty. In order to explain the increase in asthma, we need to take a broader view and also consider alterations related to the adoption of a western lifestyle. It has been suggested that lifestyle changes related to obesity (e.g. a change in diet) are associated with asthma. Other changes include a progressive decrease in physical activity. This lifestyle factor seems to correlate best with the recent increase in asthma. Clearly, the link between physical activity and asthma needs to be investigated in more detail.
Family Altruism and Incentives
Authors: Gatti Roberta
Published: April 2005

This paper characterizes the pattern of intergenerational transfers that emerges in an altruistic model of the family when children's effort is explicitly made endogenous and parents have imperfect information on the stochastic income realizations of their children. It is shown that, if parents can credibly commit to a pattern of transfers, they will choose not to compensate children in bad outcomes as much as predicted by the standard (no uncertainty, no asymmetric information) dynastic model of the family. In this context, Ricardian equivalence holds whenever non‐negativity constraints are not binding.
International Environmental Agreements and Strategic Voting*
Authors: Buchholz Wolfgang , Haupt Alexander , Peters Wolfgang
Published: April 2005

This paper explores the outcome of an international environmental agreement when the governments are elected by their citizens. It also considers a voter's incentives for supporting candidates who are less green than she is. In the extreme case of “global” pollution, the elected politicians pay no attention to the environment, and the resulting international agreement is totally ineffective. Moreover, if governments cannot negotiate and have to decide non‐cooperatively (and voters are aware of this), the elected politicians can be greener, ecological damage can be lower and the median voter's payoff can be higher than in the case with bargaining.
Financial Markets and Economic Growth
Authors: Miller Merton H.
Published: April 2005

The current economic problems in Southeast Asia can be attributed not to too much reliance on financial markets, but to too little. Like the U.S. economy a century ago, the emerging Asian economies do not have welldeveloped capital markets and so remain heavily dependent on their banking systems to finance growth.

For all its benefits, banking is “not only basically 19th‐century technology, but disaster‐prone technology.” The extreme maturity (and, in some cases, currency) mismatch on banks' balance sheets plus the first‐come, first‐served nature of the deposit obligations mean that banks are inherently vulnerable to massive runs by depositors—and that their economies are subjected to periodic credit crunches. And, as the author says, “in the summer of 1997 a banking‐driven disaster struck in East Asia, just as it had struck so many times before in U.S. history.”

In this century, In this century, the U.S. economy has steadily reduced its dependence on banks by developing “dispersed and decentralized” financial markets. In so doing, it has increased the efficiency of the U.S. capital allocation process and reduced its susceptibility to the credit crunches that have occurred throughout U.S. history. By contrast, Japan has not reduced its economy's dependence on banks, and its efforts to deal with its banking problems have served only to destabilize itself as well as its neighbors. Developing countries in Southeast Asia and elsewhere are urged not to follow the Japanese example, but to take measures aimed at developing financial markets and institutions that will either substitute for or complement bank products and services.
R&D AND CAPITAL MARKETS
Authors: Lev Baruch
Published: April 2005

The substantial growth of R&D expenditures over the last two decades, together with the continuous substitution of knowledge (intangible) capital for physical (tangible) capital in corporate production functions, has elevated the importance of R&D in the performance of business enterprises. At the same time, however, the evaluation of corporate R&D activities by investors is seriously hampered by antiquated accounting rules and insufficient disclosure by corporations. Despite the fact that the expected benefits of R&D stretch over extended periods of time, corporate investments in R&D are immediately written off in financial reports, leaving no trace of R&D capital on balance sheets and causing material distortions of reported profitability.

After a brief review of statistics documenting the growth and economic importance of corporate R&D in the U.S., the article presents a comparison of R&D disclosure regulations among industrialized nations that shows U.S. rules to be the least flexible in allowing management discretion in how they measure and report R&D. Next the author surveys the large and growing body of empirical research on R&D, which provides strong testimony to the substantial contribution of R&D to corporate productivity and shareholder value. Moreover, despite widespread allegations of stock market “short termism” throughout the 1980s and early '90s, the research indicates “unequivocally” that capital markets consider investments in R&D as a significant value‐increasing activity.

But if investors clearly demonstrate a willingness to take the long view of R&D, there is also evidence of undervaluation of some R&D‐intensive companies—particularly those with low profitability—as well as other potential costs to corporations and investors stemming from inadequate public information about R&D. To help correct the reporting biases and distortions of R&D, the author offers some suggestions for investors and analysts that follow R&D‐intensive companies. In particular, he proposes (1) adjustment of reported data to reflect the capitalization and amortization of (instead of expensing) corporate R&D and (2) the use of various quantitative measures for gauging research capabilities and output, including citations of the firm's patents and measures indicating the share of current revenues coming from products developed within recent years.
WHEN DO STRATEGIC ALLIANCES CREATE SHAREHOLDER VALUE?
Authors: Chan Su Han , Kensinger John W. , Keown Arthur J. , Martin John D.
Published: April 2005

This article reports the findings of the authors' study of the stock market reaction to 345 strategic alliances announced during the period 1983‐1992. The study reports statistically significant gains that, when translated into dollars, are divided roughly evenly between the larger and smaller partners (though the smaller partners experience larger percentage gains). Moreover, the value gains are largest in those cases in which two high‐tech firms ally to develop or apply new technology, while the market shows less enthusiasm for non‐technical or marketing alliances.

The underlying rationale for strategic alliances is that each partner contributes its expertise to the relationship and gains access to some special resource or competence that it lacks—but without incurring the costs associated with creating a larger organization through a merger or joint venture. Consistent with this argument, the authors report that alliances are relatively long‐lasting, and are not preludes to merger or formal creation of joint venture entities.
CREATING VALUE IN PENSION PLANS (OR, GENTLEMEN PREFER BONDS)
Authors: Gold Jeremy , Hudson Nick
Published: April 2005

Pension funds are typically one‐half to two‐thirds invested in equities because equities are expected to outperform other financial assets over the long term, and the long‐term nature of pension fund liabilities seems well suited to absorbing any short‐term return volatility. What's more, U.S. GAAP currently makes it possible to take credit in advance for the higher anticipated earnings on equity investments without acknowledging their inherent risk. But by allowing the higher expected returns from stocks to reduce a company's current pension expenses, the accounting treatment conflicts with some very basic principles of finance (in particular, the idea that investors must earn higher returns on riskier investments just to “break even”), conceals systematic biases in the actuarial analysis, and gives managers considerable latitude to manipulate the bottom line.

The authors suggest a startlingly different approach. They argue that pension assets should be invested entirely in duration‐matched debt instruments for two reasons: (1) to capture the full tax benefits of pre‐funding their pension obligations and (2) to improve overall corporate risk profiles by converting general stock market risk into firm‐specific operating risk, where corporate managers should have a comparative advantage and can generate real value. Investing exclusively in bonds would take better advantage of the tax‐exempt status of pension plans and greatly reduce fund management costs, while at the same time helping o shore up fund quality and sharpening corporate executives' focus on their real operating assets.
VOLUNTARY DISCLOSURE PRACTICES: THE USE OF PRO FORMA REPORTING
Authors: Entwistle Gary , Feltham Glenn , Mbagwu Chima
Published: April 2005

This article looks at how U.S. managers supplement GAAP earnings with pro forma reporting. Pro forma measures, which are not audited, are typically determined through an adjustment to GAAP‐based earnings. For example, a manager may choose to present an alternative to GAAP earnings that excludes period write‐offs and one‐time restructuring charges in order to present a more value‐relevant picture of the company's performance.

The authors find that 77% of S&P 500 companies report pro forma results, and that pro forma measures are generally given greater prominence than GAAP earnings in corporate press releases. Based on the evidence, U.S. managers are using pro forma reporting strategically to affect investor perception of corporate performance. The SEC has recently issued rules to ensure that pro forma disclosure is not misleading. The authors present some guidelines on voluntary disclosure that might help forestall further regulation and preserve the ability to pursue this potentially informative practice.
CREATING VALUE WITH MERGERS AND ACQUISITIONS
Authors: Hazelkorn Todd , Zenner Marc , Shivdasani Anil
Published: April 2005

This report addresses two key questions for today's top executives: Do acquisitions create value for acquirers? And under what circumstances have acquisitions created the most value for acquiring shareholders?

The authors' analysis of over 1,500 completed deals by non‐financial companies in the United States over the past 12 years shows that, at announcement, acquirers' shareholders suffer small losses, on average, in the short term around the initial deal announcement. Over longer intervals, such as one or two years following the announcement of the transaction, acquirers tend to slightly outperform industry peers.

The average or median market response hides tremendous variability in how the market has reacted to individual deals, however. This article provides evidence that the “right” M&A transaction can create substantial value for acquirers. One‐quarter of the transactions lead to market‐adjusted gains in excess of 5% for the acquirer and oneeighth of the transactions lead to gains in excess of 10% in the short term. However, some deals have also destroyed substantial shareholder value.

Financing structure is a key driver of the stock market reaction. Stock‐financed transactions, on average, have a negative stock market reaction, while cash‐financed transactions have benefited acquirers in both the short term as well as the long term.

Acquisitions of private companies or assets and units of public companies have consistently generated higher returns for acquirers than purchases of public companies.

Moreover, EPS dilution is not a major driver of how the stock market reacts to a deal. Although “accretive” deals perform slightly better than “dilutive” ones in the short and long run, the difference is small and not statistically significant. Over the long run, acquiring shareholders have benefited the most from deals within the same industry and that avoid targets with relatively optimistic earnings growth projections.
CORPORATE GOVERNANCE, EVA, AND SHAREHOLDER VALUE
Authors: Stern Joel
Published: April 2005

Together with corporate governance expert Stuart Gillan, the managing partner of Stern Stewart discusses important issues of corporate financial management, including the fundamental objective of the public corporation and how boards of directors can achieve it. Whereas financial economists have long argued that the corporate goal is the maximization of firm value, Stern advocates a variation of the concept known as “Market Value Added”–one that is designed to discourage corporate growth and capital raising that does not end up adding value for shareholders. To accomplish this goal, he emphasizes the importance of incentive compensation systems tied not to accounting earnings, but to a measure of economic profit like EVA. And, as Stern argues in closing, EVA‐based incentive systems are likely to be effective not only in the private sector, but in increasing the efficiency and value of state‐owned enterprises. Indeed, such systems could bring about a new kind of employee capitalism that ESOPs promised, but have largely failed, to deliver.
Unique Long Terminal Repeat and Surface Glycoprotein Gene Sequences of Feline Leukemia Virus as Determinants of Disease Outcome
Authors: Chandhasin Chandtip , Coan Patricia N. , Pandrea Ivona , Grant Chris K. , Lobelle-Rich Patricia A. , Puetter Adriane , Levy Laura S.
Published: April 2005

The outcome of feline leukemia virus (FeLV) infection in nature is variable, including malignant, proliferative, and degenerative disorders. The determinants of disease outcome are not well understood but are thought to include viral, host, and environmental factors. In particular, genetic variations in the FeLV long terminal repeat (LTR) and SU gene have been linked to disease outcome. FeLV-945 was previously identified as a natural isolate predominant in non-T-cell neoplastic and nonneoplastic diseases in a geographic cohort. The FeLV-945 LTR was shown to contain unique repeat elements, including a 21-bp triplication downstream of the enhancer. The FeLV-945 SU gene was shown to encode mutational changes in functional domains of the protein. The present study details the outcomes of infection with recombinant FeLVs in which the LTR and envelope (env) gene of FeLV-945, or the LTR only, was substituted for homologous sequences in a horizontally transmissible prototype isolate, FeLV-A/61E. The results showed that the FeLV-945 LTR determined the kinetics of disease. Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in a significantly more rapid disease onset but did not alter the tumorigenic spectrum. In contrast, substitution of both the FeLV-945 LTR andenvgene changed the disease outcome entirely. Further, the impact of FeLV-945envon the disease outcome was dependent on the route of inoculation. Since the TM genes of FeLV-945 and FeLV-A/61E are nearly identical but the SU genes differ significantly, FeLV-945 SU is implicated in the outcome. These findings identify the FeLV-945 LTR and SU gene as determinants of disease.
Gamma Interferon-Dependent, Noncytolytic Clearance of Sindbis Virus Infection from Neurons In Vitro
Authors: Burdeinick-Kerr Rebeca , Griffin Diane E.
Published: April 2005

Due to the nonrenewable nature of neurons, recovery from viral infection of the central nervous system requires noncytopathic mechanisms for control of virus replication. Recovery from alphavirus encephalitis can occur without apparent neurological damage through the effects of antibody and gamma interferon (IFN-γ). To establish an in vitro cell culture system that will allow the study of mechanisms of IFN-γ-mediated control of Sindbis virus (SINV) replication in neurons, we have characterized the susceptibility to SINV infection and IFN-γ responsiveness of two neuronal cell lines that can be differentiated in vitro: CSM14.1, a rat nigral cell line, and NSC34, a mouse motor neuron cell line. Undifferentiated CSM14.1 and NSC34 cells were permissive for SINV and susceptible to virus-induced cell death. With differentiation, CSM14.1 cells reduced virus replication and became progressively resistant to virus-induced cell death, resulting in prolonged virus replication. NSC34 cells did not differentiate completely and became only partially resistant to SINV infection. Both CSM14.1 and NSC34 cells responded to pretreatment with IFN-γ by decreasing SINV replication. Differentiated CSM14.1 cells treated 24 h after infection with IFN-γ responded with increased cell viability and clearance of infectious virus. IFN-γ treatment sequentially altered the ratio of genomic to subgenomic viral RNA synthesis, promoted recovery of cellular protein synthesis, reduced viral protein synthesis, and inhibited viral RNA transcription within 24 h after treatment. We conclude that CSM14.1 cells provide an excellent model for the study of IFN-γ-mediated noncytolytic clearance of SINV from mature neurons.
Covert Human Immunodeficiency Virus Replication in Dendritic Cells and in DC-SIGN-Expressing Cells Promotes Long-Term Transmission to Lymphocytes
Authors: Nobile Cinzia , Petit Caroline , Moris Arnaud , Skrabal Katharina , Abastado Jean-Pierre , Mammano Fabrizio , Schwartz Olivier
Published: April 2005

HIV-1 virions are efficiently captured by monocyte-derived immature dendritic cells (iDCs), as well as by cell lines expressing the lectin DC-SIGN. Viral infectivity can be retained for several days, and even enhanced, before transmission to CD4+lymphocytes. The role of DC-SIGN in viral retention and enhancement of infection is not fully understood and varies according to the cell line expressing the lectin. We studied here the mechanisms underlying this process. We focused our study on X4-tropic human immunodeficiency virus (HIV) strains, since they were widely believed not to replicate in iDCs. However, we first show that X4 HIV replicates covertly and slowly in iDCs. This is also the case in Raji-DC-SIGN cells, which are classically used to study HIV transmission. We used either single-cycle or replicative HIV and measured viral RT and replication to further demonstrate that transfer of incoming virions from iDCs or DC-SIGN+cells occurs only on the short-term (i.e., a few hours after viral exposure). There is no long-term storage of original HIV particles in these cells. A few days after viral exposure, replicative viruses, and not single-cycle virions, are transmitted to CD4+cells. The cell-type-dependent activity of DC-SIGN reflects the ability of HIV to replicate covertly in some cells, and not in others.
Dengue Virus Inhibits Alpha Interferon Signaling by Reducing STAT2 Expression
Authors: Jones Meleri , Davidson Andrew , Hibbert Linda , Gruenwald Petra , Schlaak Joerg , Ball Simon , Foster Graham R. , Jacobs Michael
Published: April 2005

Alpha/beta interferon (IFN-α/β) is a key mediator of innate antiviral responses but has little effect on the established replication of dengue viruses, which are mosquito-borne flaviviruses of immense global health importance. Understanding how the IFN system is inhibited in dengue virus-infected cells would provide critical insights into disease pathogenesis. In a recent study analyzing the ability of individual dengue virus-encoded proteins to antagonize the IFN response, nonstructural (NS) protein 4B and possibly NS2A and NS4A were identified as candidate IFN antagonists. In monkey cells, NS4B appeared to inhibit both the IFN-α/β and IFN-γ signal transduction pathways, which are distinct but overlapping (J. L. Munoz-Jordan, G. G. Sanchez-Burgos, M. Laurent-Rolle, and A. Garcia-Sastre, Proc. Natl. Acad. Sci. USA
100:
14333-14338, 2003). For this study, we examined the effects of dengue virus on the human IFN system, using cell lines that were stably transfected with self-replicating subgenomic dengue virus RNA (replicons) and that expressed all of the dengue virus nonstructural proteins together. We show here that in replicon-containing cells dengue virus RNA replication and the replication of encephalomyocarditis virus, an IFN-sensitive virus, are resistant to the antiviral effects of IFN-α. The presence of dengue virus replicons reduces global IFN-α-stimulated gene expression and specifically inhibits IFN-α but not IFN-γ signal transduction. In cells containing replicons or infected with dengue virus, we found reduced levels of signal transducer and activator of transcription 2 (STAT2), which is a key component of IFN-α but not IFN-γ signaling. Collectively, these data show that dengue virus is capable of subverting the human IFN response by down-regulating STAT2 expression.
Few Mutations in the 5′ Leader Region Mediate Fitness Recovery of Debilitated Human Immunodeficiency Type 1 Viruses
Authors: Yuste Eloísa , Bordería Antonio V. , Domingo Esteban , López-Galíndez Cecilio
Published: April 2005

Repeated bottleneck passages of RNA viruses result in fitness losses due to the accumulation of deleterious mutations. In contrast, repeated transfers of large virus populations result in exponential fitness increases. Human immunodeficiency virus type 1 (HIV-1) manifested a drastic fitness loss after a limited number of plaque-to-plaque transfers in MT-4 cells. An analysis of the mutations associated with fitness loss in four debilitated clones revealed mutation frequencies in
gag
that were threefold higher than those in
env
. We now show an increase in the fitness of the debilitated HIV-1 clones by repeated passages of large populations. An analysis of the entire genomic nucleotide sequences of these populations showed that few mutations, from two to seven per clone, mediated fitness recovery. Eight of the 20 mutations affected coding regions, mainly by the introduction of nonsynonymous mutations (75%). However, most of the mutations accumulated during fitness recovery (12 of 20) were located in the 5′ untranslated leader region of the genome, and more specifically, in the primer binding site (PBS) loop. Two of the viruses incorporated the same mutation in the primer activation signal in the PBS loop, which is critical for the tRNA
3
Lys
-mediated initiation of reverse transcription. Moreover, 25% of the mutations observed were reversions. This fact, together with the presence of a large proportion of nonsynonymous replacements, may disclose the operation, during large population passages, of strong positive selection for optimal HIV-1 replication, which seems to be primarily affected by binding of the tRNA to the PBS and the initiation of reverse transcription.