bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying multiple perspectives to the design of a commercialization process
Authors: Prebble Dean Richard , De Waal Gerrit Anton , De Groot Cristiaan
Published: May 2008

Most commercialization models begin by taking an idea through some sort of stage‐gate product development process. There is much talk about building market thinking into this process, but this paper argues that much more is required. The research identified three perspectives required to be present at all stages of product development. The first is labelled ‘technical and operational’, the second ‘strategic’ and the third ‘commercial’. The paper argues that each perspective is required at every stage to drive the right activities that lead to successful commercialization. The science, idea and opportunity stage leads onto the technology and feasibility stage, which in turn leads onto the product and market readiness stage. The research applied the grounded theory methodology to categorize and represent data obtained from interviews and desk research. The resulting model was introduced to a New Zealand Crown Research Institute during a consulting assignment in 2004. Three external experts were selected based on their particular perspectives and experience in the area of product development. Each perspective was built into the commercialization process. Applying multiple perspectives has led to a more robust approach to product development and a greater awareness of how multiple tools work together to create a holistic product development process. Each perspective of the commercialization process can be broken down into detailed stages. The technical and operational perspective addresses areas such as opportunity creation, proof of concept and market readiness. The strategic perspective addresses areas such as strategic fit, strategic analysis/choice and pathways to market. Finally, the commercial perspective addresses areas such as opportunity assessment, feasibility study/business planning and launch.After being in place for 18 months, the challenges faced in implementation were discussed with the current commercialization manager and the model was adapted to another institute wishing to develop a design‐led commercialization process. A key finding of the research was the common understanding of language and meaning across three distinct disciplines and the involvement of each discipline in the decision‐making process. All parties accepted the value of each other's contribution once the different perspectives were understood and accepted. The paper provides useful insights for those involved in the design of commercialization processes and establishes a multi‐dimensional framework that assists in facilitating the different perspectives required for successful commercialization.
The Nature and Basis of Human Dignity
Authors: LEE PATRICK , GEORGE ROBERT P.
Published: May 2008

Abstract. We argue that all human beings have a special type ofdignitywhich is the basis for (1) the obligation all of us have not to kill them, (2) the obligation to take their well‐being into account when we act, and (3) even the obligation to treat them as we would have them treat us, and indeed, that all human beings areequalin fundamental dignity. We give reasons to oppose the position that only some human beings, because of their possession of certain characteristics in addition to their humanity (for example, an immediately exercisable capacity for self‐consciousness, or for rational deliberation), have full moral worth. What distinguishes human beings from other animals, what makes human beingspersonsrather thanthings, is their rational nature, and human beings are rational creatures by virtue of possessing natural capacities for conceptual thought, deliberation, and free choice, that is, the natural capacity to shape their own lives.
Contract Rights and Remedies, and the Divergence between Law and Morality*
Authors: BIX BRIAN H.
Published: May 2008

Abstract. There is an ongoing debate in the philosophical and jurisprudential literature regarding the nature and possibility of Contract theory. On one hand, are those who argue (or assume) that there is, or should be, a single, general, universal theory of Contract Law, one applicable to all jurisdictions and all times. On the other hand, are those who assert that Contract theory should be localized to particular times and places, perhaps even with different theories for different types of agreements. This article considers one facet of this debate: evaluating the relevance of the fact that the remedies available for breach of contract can vary significantly from one jurisdiction to another. This wide variation in remedies for breach of a (contractual) promise is one central difference between promises in morality and enforceable agreements in law. The article asserts that variation of remedies strongly supports the conclusion that there is (and can be) no general, universal theory of Contract Law.
On the Wrong Track: Andrei Marmor on Legal Positivism, Interpretation, and Easy Cases
Authors: CHIASSONI PIERLUIGI
Published: May 2008

Abstract.  The paper argues for the following points: (1) Marmor's own understanding of “legal positivism” is different from the understanding defended, e.g., by Herbert Hart and Norberto Bobbio, and apparently misleads him into the wrong track of a theoretical inversion; (2) Marmor's two‐stages model of (legal) interpretation—the understanding‐interpretion model—provides no support for Marmor's own positivistic theory of law; (3) Marmor's concept of interpretation is at odds both with the basic tenets of Hartian and Continental methodological legal positivism, on the one hand, and with the actual practice of legal interpretation in the Western world, on the other hand; (4) Marmor's concept of an easy case is likewise objectionable.
Comparison of patch test results among white Europeans and patients from the Indian subcontinent living within the same community
Authors: Fairhurst DA , Shah M
Published: May 2008

Background  There are few studies comparing the incidence of allergic contact dermatitis among different racial groups living within the same community.

Objectives  The objectives of this study were to compare white European patients with Fitzpatrick's skin phototypes (FSP) I to IV and patients from Indian, Pakistan and Bangladesh with FSP V living within the same community. Referral rates for patch testing, incidence of contact allergies and differences in contact allergens found were assessed.

Method  All patients referred to the Contact Dermatitis Unit at Dewsbury and District Hospital between 2004 and 2006, inclusive, were included in the study. All patients were patch tested to the British Contact Dermatitis Society standard series, plus other series according to their clinical history, occupational history and clinical findings.

Results  Four hundred and thirty‐five consecutive patients from the patch testing clinic were included in the study. Fewer patients from the Indian subcontinent underwent patch testing (11.5%) than would have been expected for the size of the local population (18%). Fewer patients from the Indian subcontinent (44%) had one or more positive reactions compared with the white European patients (56%). No significant differences in the contact allergens responsible were detected between the two racial groups.

Conclusion  There is a lower incidence of positive patch test results among patients with racial origins from the Indian subcontinent compared with white Europeans. This modest difference could be explained by a lower average age within the study population, and increased or differing exposure to contact allergens rather than demonstration of variability in the susceptibility to develop contact sensitivities following equal exposure.
Flooding tolerance in halophytes
Authors: Colmer Timothy D. , Flowers Timothy J.
Published: May 2008

Flooding is a common environmental variable with salinity. Submerged organs can suffer from O2deprivation and the resulting energy deficits can compromise ion transport processes essential for salinity tolerance. Tolerance of soil waterlogging in halophytes, as in glycophytes, is often associated with the production of adventitious roots containing aerenchyma, and the resultant internal O2supply. For some species, shallow rooting in aerobic upper soil layers appears to be the key to survival on frequently flooded soils, although little is known of the anoxia tolerance in halophytes. Halophytic species that inhabit waterlogged substrates are able to regulate their shoot ion concentrations in spite of the hypoxic (or anoxic) medium in which they are rooted, this being in stark contrast with most other plants which suffer when salinity and waterlogging occur in combination. Very few studies have addressed the consequences of submergence of the shoots by saline water; these have, however, demonstrated tolerance of temporary submergence in some halophytes.
Novel approaches in herbal cosmetics
Authors: Chanchal Deep , Swarnlata Saraf
Published: May 2008

Nutracosmetics are an emerging class of health and beauty aid products that combine the benefits of nutracosmetical ingredients with the elegance, skin feel, and delivery systems of cosmetics. Herbs and spices have been used in maintaining and enhancing human beauty because herbs have many beneficial properties, such as sunscreen, antiaging, moisturizing, antioxidant, anticellulite, and antimicrobial effects. As compared with synthetic cosmetic products, herbal products are mild, biodegradable, and have low toxicity profile. To enhance these properties, research is being done in the development of newer approaches, which could improve both the aesthetic appeal and performance of a cosmetic product. In this respect, the approaches studied and discussed include liposomes, phytosomes, transferosomes, nanoemulsions, nanoparticles, microemulsions, nanocrystals, and cubosomes.
Neuroimmunomodulatory compound for sensitive skin care: in vitro and clinical assessment
Authors: Dieamant Gustavo de Campos , Velazquez Pereda Maria Del Carmen , Eberlin Samara , Nogueira Cecília , Werka Rejane Maria , Queiroz Mary Luci de Souza
Published: May 2008

Background  The pathophysiology of sensitive skin consists of an inflammatory reaction resulting from the abnormal penetration in the skin of potentially irritating substances, which occurs due to skin barrier dysfunction and changes in the production of local neuromediators.

Aims  The therapeutic potential of l‐carnosine and Rhodiola rosea, as antioxidant and neuromodulatory, respectively, leads us to investigate the effects of the R. rosea extract/l‐carnosine–associated compound (RCAC) on sensitive skin alterations.

Methods  A double‐blind comparative study was conducted on 124 volunteers with sensitive skin, who were selected by their reactivity to stinging test. Two randomized groups of 62 each received either a formulation containing 1% of RCAC or placebo, which was applied twice a day for 28 consecutive days. One perceptibility questionnaire was applied at the onset and at the end of the treatment to evaluate the subjective response to test product. Additionally, in vitro studies were performed to investigate RCAC neuroimmunomodulatory mechanisms.

Results  RCAC treatment produced in vivo protective effects in skin barrier function and a positive subjective response of sensitive skin volunteers. In vitro treatment promoted the release of proopiomelanocortin peptides and restored to normal the increased levels of neuropeptides and cytokines produced by keratinocytes exposed to ultraviolet radiation. Clinical effectiveness was measured by reduction of transepidermal water loss, positive perceptions of improvements in skin dryness and skin comfort sensation, and reduction of discomfort sensation after stinging test.

Conclusions  The protective effect of RCAC in skin barrier function and the positive response produced in human subjects with sensitive skin could be partially explained by our in vitro results showing a significant increase in opioid peptides release, an inhibitory effect on neuropeptides production, and modulation of cytokines production by keratinocytes under ultraviolet stress.
Protective effect of conditioning agents on Afro‐ethnic hair chemically treated with thioglycolate‐based straightening emulsion
Authors: Dias Tania Cristina de Sá , Baby André Rolim , Kaneko Telma Mary , Velasco Maria Valéria Robles
Published: May 2008

Straightening is a chemical process by which excessively curly hair is straightened in an irreversible way. Generally, products are formulated as emulsions with high pH value (9.0–12.0), which, after applied on hair, cause considerable damage, making it dry and fragile. This research work evaluated the protective effect of lauryl PEG/PPG‐18/18 methicone, cyclopentasiloxane (and) PEG‐12 dimethicone cross‐polymer, jojoba oil, and aqua (and) cystine bis‐PG propyl silanetriol, as conditioning agents, on Afro‐ethnic hair locks treated with thioglycolate‐based straightening emulsions by protein loss, combability, and traction to rupture. Standard Afro‐ethnic hair locks were prepared following a protocol for straightening emulsion application. Considering the assays performed, the addition of conditioning agents to the straightening emulsion with ammonium thioglycolate benefited the hair fiber, thus diminishing protein loss, protecting the hair thread, and improving resistance to breakage. Jojoba oil and lauryl PEG/PPG‐18/18 methicone were the conditioning agents that presented the best results. Straightening emulsions with ammonium thioglycolate containing aqua (and) cystine bis‐PG propyl silanetriol and cyclopentasiloxane (and) PEG‐12 dimethicone cross‐polymer were the ones that provided higher breakage resistance of the thread.
Treatment of facial port‐wine stains with intense pulsed light: a prospective study
Authors: Özdemir Mustafa , Engin Burhan , Mevlitoǧlu İnci
Published: May 2008

Background  Intense pulsed light (IPL) has been used for the treatment of port‐wine stains for 10 years. There are many IPL systems that have different setting. Some of them have been reported in the treatment of fresh or laser‐resistant port‐wine stains localized in different body regions.

Objective  Our aim was to conduct a prospective trial to assess the effectiveness of Lynton (The Lumina Family of Medical Flashlamp Systems) of the IPL family in the treatment of fresh facial port‐wine stains.

Material and methods  Twelve patients with facial and/or neck port‐wine stains without previous treatment were enrolled in the trial. Patient demographics, treatment setting, outcome of clearing, and treatment complications were noted.

Results  The treatment intervals were 4 to 6 weeks for three to six treatment sessions. Moderate improvement (50–75%) was achieved in 47% of the patients. Complete clearing was seen in only one patient (8.3%) after four treatment sessions. Hypertrophic scar formation in two patients occurred after healing blister. Except for the side effects, long‐term complications were not seen.

Conclusion  Moderate effectiveness was achieved with IPL treatment in the facial port‐wine stains.
Angioedema after ovine hyaluronidase injection for treating hyaluronic acid overcorrection
Authors: Andre Pierre , Fléchet Marie Laure
Published: May 2008

Background  Hyaluronic acid injections are becoming popular in aesthetic dermatology, and, sometimes, misplacements and very rarely adverse events have been reported. Hyaluronidase, an enzyme that hydrolyzes hyaluronic acid, is used to treat overcorrection or granulomatous reactions. Allergic reactions are well known except for how frequent they occur.

Objective  This paper aims to confirm the efficacy of hyaluronidase injections to dissolve hyaluronic acid, but insists on the risk of hypersensitivity with animal‐derived products.

Methods  A case of angioedema due to ovine hyaluronidase is reported, and treatment is discussed.

Conclusion  Hyaluronidase is highly effective, but skin test must be done before injection to avoid risk of angioedema and/or Quincke's edema.
Treatment of a resistant port‐wine stain with a new variable pulse‐duration pulsed‐dye laser
Authors: Bernstein Eric F
Published: May 2008

Background and objectives  Because of the heterogeneity in port‐wine stains, a number of them prove resistant to treatment with the pulsed‐dye laser (PDL). A new variable pulse‐duration PDL improves a refractory port‐wine stain.

Study design/materials and methods  A 26‐year‐old man with a congenital port‐wine stain underwent eight treatments with the 1.5‐ms pulse‐duration PDL resulting in minimal improvement. A single treatment was then administered with the 3‐ms pulse‐duration PDL.

Results  Initial results of treatment with the 3‐ms pulse‐duration PDL on this patient's port‐wine stain show dramatic clearance in areas previously treated with significantly higher fluences, an identical spot size, but with a pulse duration half as long.

Conclusion  Vessel heterogeneity may require changing pulse durations once a port‐wine stain or a portion of a port‐wine stain becomes refractory to given pulse‐duration.
Mothers’ Recollections of Early Features of Autism Spectrum Disorders
Authors: McConkey Roy , Truesdale‐Kennedy Maria , Cassidy Arlene
Published: May 2008

Background:  Early intervention is recommended for autism spectrum disorders but often this is delayed because children have not received a formal diagnosis. Nonetheless parents are likely to identify features of ASD from an early age. The main aim of this study was to document through thematic analysis how parents described the features that alerted them to the child’s difficulties.

Method:  From a population of children diagnosed at a specialist, community‐based clinic, 72 parents agreed to be interviewed at home about their recollections of early difficulties which were analysed thematically.

Results:  Two‐thirds of parents reported the child’s problems were apparent by 18 months with speech and communication difficulties, along with behaviour problems, being the most commonly reported. Statistical analyses identified some relationships between certain features and the age of the child when they became apparent. Clusters of features were also identified.

Conclusions:  It is argued that health visitors and childcare personnel should be knowledgeable about the early signs of ASD and of the strategies required to promote the development of children whose parents report these early features of ASD. They should be proficient in sharing their knowledge with parents so that assessment and intervention can begin earlier.
Dockside Prostitution in South African Ports
Authors: Trotter Henry
Published: May 2008

Prostitution has been a staple of dockside social life for centuries. In South Africa, it dates from the Dutch East India Company's establishment of a refreshment station at the Cape of Good Hope. But unlike other prostitution sectors – streets, brothels, agencies – the women of the dockside sex trade in Cape Town and Durban participate in a global traffic of ideas, diseases, DNA, contraband and currency through their ceaseless interactions with foreign sailors. They exploit their knowledge of the seamen's languages and cultures so as to more effectively solicit their marks in a competitive and cosmopolitan environment. Social historians provide passing glimpses of dockside prostitution in their consideration of larger historical themes – Company rule, slavery, British colonial governance, the Mineral Revolution, the Anglo‐Boer War and apartheid – but they have yet to treat it as a distinct analytical category through which to view the past. However, popular intellectual trends suggest that research into the dockside sex trade would add new dimensions to the histories of cosmopolitanism, gender, globalization, maritime recreation and the Atlantic and Indian Oceans.
Voyages, Encounters, and Agency in Oceania: Captain Cook and Indigenous People
Authors: Douglas Bronwen
Published: May 2008

Beginning with a brief historiographic survey of the prolific literature on European voyages of exploration in Oceania, in particular those of James Cook, this article considers how embodied encounters helped shape the written and visual representations of indigenous Oceanian people by Cook and his naturalists and artists in New Holland (Australia), the New Hebrides (Vanuatu) and Van Diemen's Land (Tasmania). I treat encounters as situated and permeable: not as a generalised clash of incommensurate cultures but as ambiguous intersections of multiple personal agencies, both indigenous and foreign. This approach suggests an indirect liaison between particular local actors and the expanding stock of empirical information provided by travellers and drawn on by metropolitan natural historians to illustrate their deductions about mankind. I suggest that voyagers’ representations of Oceanian people should be read not merely as reflections of received knowledge derived from dominant metropolitan discourses or literary and artistic conventions but also as personal productions generated in the flux, stress, high emotion and uncertainty of meetings with actual people in the vulnerable settings of voyages under sail. Such representations were often significantly, if obliquely affected by local agency.
Comparing the efficacy and safety of apheresis and whole blood–derived platelet transfusions: a systematic review
Authors: Heddle Nancy M. , Arnold Donald M. , Boye Diana , Webert Kathryn E. , Resz Ilona , Dumont Larry J.
Published: May 2008

BACKGROUND: A systematic review and meta‐analysis was performed to determine if there were differences between apheresis platelet concentrates (APCs) or platelets (PLTs) derived from whole blood (WBD) for the outcomes acute reactions, alloimmunization, refractoriness, corrected count increment (CCI), radiolabeled recovery and survival, time to next transfusion, and bleeding.

STUDY DESIGN AND METHODS: We searched Medline, Embase, the Cochrane Registry of Controlled Trials, PapersFirst, ProceedingsFirst, and AABB and ASH abstracts for randomized controlled trials (RCTs) comparing APCs and WBD PLTs for clinical outcomes. Study selection, data extraction, and methodologic quality assessments were performed in duplicate. Results were pooled using meta‐analytic methods.

RESULTS: Ten RCTs met the inclusion criteria. Acute reactions per patient were lower for APCs (relative risk [RR], 0.65; 95% CI, 0.44‐0.98); however, when controlling for leukoreduction, there was no significant difference (leukoreduced [LR]‐APCs vs. LR‐WBDs; odds ratio, 1.78; 95% CI, 0.87‐3.62). There was no difference between products when reaction frequencies were assessed per transfusion (RR, 0.65; 95% CI, 0.33‐1.28). APCs were associated with significantly higher CCIs than WBD PLTs at both 1 hour (weighted mean difference [WMD], 2.49; 95% CI, 2.21‐2.77) and 18 to 24 hours (WMD, 1.64; 95% CI, 0.60‐2.67). No conclusions could be made for the outcomes of alloimmunization and refractoriness. No studies addressed outcomes of time to next transfusion or bleeding.

CONCLUSIONS: Owing to the small number of trials and lack of comparability of PLT products for leukoreduction, we were unable to draw definitive conclusions about the clinical benefits of APCs compared with WBD PLTs. Rigorous RCTs using clinically important end points are needed to settle this issue.
Flow cytometric measurement of CD62P (P‐selectin) expression on platelets: a multicenter optimization and standardization effort
Authors: Curvers Joyce , De Wildt‐Eggen Janny , Heeremans Judith , Scharenberg John , De Korte Dirk , Van Der Meer Pieter F.
Published: May 2008

BACKGROUND: One of the variables to determine the quality of platelets (PLTs) in vitro is measurement of CD62P expression. Different protocols are in use, however, making comparison of results virtually impossible. It was our aim to develop a uniform CD62P protocol that would yield comparable results in various laboratories.

STUDY DESIGN AND METHODS: The effects of fixation, source and dilution of CD62P antibody, source of immunoglobulin G (IgG) isotypic antibody, and analysis of results were investigated. Once the optimal variables were defined, comparative studies were performed at five participating centers. In the final comparative study, eight split PLT concentrates were shipped to the centers, where samples were stained and fixed according to the uniform protocol. Analyses were performed using commercially available flow cytometers (BD Biosciences and Beckman Coulter).

RESULTS: Uniformity between centers could be achieved by using a single clone for CD62P and IgG monoclonal antibody. A protocol was selected using fixation with 0.5 percent methanol‐free formaldehyde. To increase conformity between flow cytometers, in the analysis of electronic data the thresholds of the isotypic control were set at 0.5 percent for the BD Biosciences and 2 percent for the Beckman Coulter flow cytometers. In the final comparative study, the 95 percent confidence intervals (CIs) for CD62P ranged between 8 and 21 percent in fresh and 20 to 40 percent in 8‐day‐old PLT concentrates.

CONCLUSION: A uniform CD62P staining protocol and subsequent analysis can be used at multiple centers using different flow cytometers, yielding comparable results with acceptable 95 percent CIs.
Congressional Use of the Program Assessment Rating Tool
Authors: FRISCO VELDA , STALEBRINK ODD J.
Published: May 2008

This paper seeks to advance knowledge about congressional use of the program assessment rating tool (PART) in the 109th Congress. The research suggest that both congressional chambers use PART on a limited basis; affirms that congressional committees are exposed to PART scores through congressional budget justification score inclusion and in federal agency testimony; and that use was primarily driven by non‐congressional actors.
Taxes, Time, and Support for Security
Authors: DONAHUE AMY K. , ROBBINS MARK D. , SIMONSEN BILL
Published: May 2008

New technologies have been developed in response to terrorism. These present problems for local officials: implementing technologies will be expensive, and no technologies exist that can be used to gauge demand. We apply contingent valuation methodologies to determine support for additional taxes to pay for new terrorism‐related technologies and services. We present findings from a national survey about people's attitudes toward terrorism prevention and response. We find that respondents generally support new services and technologies and local tax increases to pay for them. We also find that respondents are willing to pay more if programs have everyday uses that would enhance public safety, but are less supportive as inconveniences increase.
Financing Homeland Security and Emergency Preparedness: Use of Interlocal Cost‐Sharing
Authors: MACMANUS SUSAN A. , CARUSON KIKI
Published: May 2008

Before this study, much of the research on interlocal collaboration has focused broadly on interlocal service agreements, of which interlocal cost‐sharing is but one dimension. This study is one of the first to examine the nature of interlocal cost‐sharing agreements for a specific (and critically important) functional area. A mail survey of Florida city and county finance officers finds that the most common interlocal cost‐sharing partnership is between local general purpose governments rather than with local special purpose governments. The strongest incentives for interlocal cost‐sharing are (1) inadequate funding for emergency management in a jurisdiction's capital budget, (2) the perceived inadequacy of federal and/or state homeland security funding, and (3) greater faith in horizontal (local‐to‐local) than vertical (federal‐state‐local) intergovernmental agreements. The research also highlights the importance of asking fiscal condition survey questions in a more functionally specific manner rather than as an “overall fiscal condition” question.
Property Tax Responses to State Aid Cuts in the Recent Fiscal Crisis
Authors: DYE RICHARD F. , RESCHOVSKY ANDREW
Published: May 2008

Many states experienced fiscal crises at the beginning of this decade. Some responded by cutting state aid to local governments. This paper explores the extent to which local governments responded to these aid cuts by raising property taxes. The authors hypothesize that changes in aid help explain the observed differences in per capita property tax revenue changes across states. They find that on average school districts increased property taxes by 23 cents for each dollar cut in state aid. These results highlight the important role that the property tax plays in maintaining the stability of the state and local sector.
The Cost‐Effectiveness of Welfare‐to‐Work Programs: A Meta‐Analysis
Authors: GREENBERG DAVID , CEBULLA ANDREAS
Published: May 2008

This article uses the tools of meta‐analysis to assess cost–benefit studies of 50 mandatory welfare‐to‐work programs that were targeted at Aid for Families with Dependent Children recipients and evaluated by random assignment. The findings suggest that the costs of a typical evaluated welfare‐to‐work program probably exceeded its benefits from the perspective of the government, but those assigned to the program, and possibly society as a whole, may reap small positive net benefits. However, there are individual programs that are very cost‐beneficial. Further analyses of the determinants of the cost‐benefits of welfare‐to‐work programs to government and society as a whole show that some services are cost‐neutral, but others entail net costs, which are sometimes substantial. The findings suggest that less successful programs might be made more cost‐beneficial by dropping vocational training and basic education as program components, leaving mainly lower cost components, such as mandated job search and sanctions, but also possibly the more costly financial incentives.
Spontaneous Closure of Ventricular Septal Defect Complicated with Acute Myocardial Infarction
Authors: Kim In‐Cheol , Kim Hyungseop , Jun Dong‐Hwan , Cho Yun‐Kyeong , Nam Chang‐Wook , Han Seong‐Wook , Hur Seung‐Ho , Kim Yoon‐Nyun , Kim Kwon‐Bae
Published: May 2008

A 79‐year‐old man was followed in our hospital for 4 years following primary percutaneous coronary intervention at another hospital to deploy two stents at the left anterior descending coronary artery for acute myocardial infarction (AMI). At the first visit in our hospital, echocardiography revealed a small ventricular septal defect (VSD, 0.8 to 1.0 cm) in the apicoseptal wall with an aneurysm that was probably the result of the AMI. There was no hemodynamic decompensation, and because the patient refused surgical correction we instead placed him under close follow‐up observation in the outpatient clinic. A second follow‐up echocardiography 6 months later still revealed a VSD. However, after 3 years the VSD murmur was no longer audible and follow‐up echocardiography showed the defect to be nearly closed.
Sensitivity Analysis: Distributional Assumptions and Confounding Assumptions
Authors: VanderWeele Tyler J.
Published: May 2008

SummaryIn a presentation of various methods for assessing the sensitivity of regression results to unmeasured confounding,Lin, Psaty, and Kronmal(1998,Biometrics54, 948–963) use a conditional independence assumption to derive algebraic relationships between the true exposure effect and the apparent exposure effect in a reduced model that does not control for the unmeasured confounding variable. However,Hernán and Robins(1999,Biometrics55, 1316–1317) have noted that if the measured covariates and the unmeasured confounder both affect the exposure of interest then the principal conditional independence assumption that is used to derive these algebraic relationships cannot hold. One particular result of Lin et al. does not rely on the conditional independence assumption but only on assumptions concerning additivity. It can be shown that this assumption is satisfied for an entire family of distributions even if both the measured covariates and the unmeasured confounder affect the exposure of interest. These considerations clarify the appropriate contexts in which relevant sensitivity analysis techniques can be applied.
Dose Finding for Continuous and Ordinal Outcomes with a Monotone Objective Function: A Unified Approach
Authors: Ivanova Anastasia , Kim Se Hee
Published: May 2008

SummaryIn many phase I trials, the design goal is to find the dose associated with a certain target toxicity rate. In some trials, the goal can be to find the dose with a certain weighted sum of rates of various toxicity grades. For others, the goal is to find the dose with a certain mean value of a continuous response. In this article, we describe a dose‐finding design that can be used in any of the dose‐finding trials described above, trials where the target dose is defined as the dose at which a certain monotone function of the dose is a prespecified value. At each step of the proposed design, the normalized difference between the current dose and the target is computed. If that difference is close to zero, the dose is repeated. Otherwise, the dose is increased or decreased, depending on the sign of the difference.
Area under the Free‐Response ROC Curve (FROC) and a Related Summary Index
Authors: Bandos Andriy I. , Rockette Howard E. , Song Tao , Gur David
Published: May 2008

Summary Free‐response assessment of diagnostic systems continues to gain acceptance in areas related to the detection, localization, and classification of one or more “abnormalities” within a subject. A free‐response receiver operating characteristic (FROC) curve is a tool for characterizing the performance of a free‐response system at all decision thresholds simultaneously. Although the importance of a single index summarizing the entire curve over all decision thresholds is well recognized in ROC analysis (e.g., area under the ROC curve), currently there is no widely accepted summary of a system being evaluated under the FROC paradigm. In this article, we propose a new index of the free‐response performance at all decision thresholds simultaneously, and develop a nonparametric method for its analysis. Algebraically, the proposed summary index is the area under the empirical FROC curve penalized for the number of erroneous marks, rewarded for the fraction of detected abnormalities, and adjusted for the effect of the target size (or “acceptance radius”). Geometrically, the proposed index can be interpreted as a measure of average performance superiority over an artificial “guessing” free‐response process and it represents an analogy to the area between the ROC curve and the “guessing” or diagonal line. We derive the ideal bootstrap estimator of the variance, which can be used for a resampling‐free construction of asymptotic bootstrap confidence intervals and for sample size estimation using standard expressions. The proposed procedure is free from any parametric assumptions and does not require an assumption of independence of observations within a subject. We provide an example with a dataset sampled from a diagnostic imaging study and conduct simulations that demonstrate the appropriateness of the developed procedure for the considered sample sizes and ranges of parameters.
Robustified Maximum Likelihood Estimation in Generalized Partial Linear Mixed Model for Longitudinal Data
Authors: You Qin Guo , Yi Zhu Zhong
Published: May 2008

SummaryIn this article, we study the robust estimation of both mean and variance components in generalized partial linear mixed models based on the construction of robustified likelihood function. Under some regularity conditions, the asymptotic properties of the proposed robust estimators are shown. Some simulations are carried out to investigate the performance of the proposed robust estimators. Just as expected, the proposed robust estimators perform better than those resulting from robust estimating equations involving conditional expectation likeSinha(2004,Journal of the American Statistical Association99, 451–460) andQin and Zhu(2007,Journal of Multivariate Analysis98, 1658–1683). In the end, the proposed robust method is illustrated by the analysis of a real data set.
Nonparametric Testing for DNA Copy Number Induced Differential mRNA Gene Expression
Authors: van Wieringen Wessel N. , van de Wiel Mark A.
Published: May 2008

Summary The central dogma of molecular biology relates DNA with mRNA. Array CGH measures DNA copy number and gene expression microarrays measure the amount of mRNA. Methods that integrate data from these two platforms may uncover meaningful biological relationships that further our understanding of cancer. We develop nonparametric tests for the detection of copy number induced differential gene expression. The tests incorporate the uncertainty of the calling of genomic aberrations. The test is preceded by a “tuning algorithm” that discards certain genes to improve the overall power of the false discovery rate selection procedure. Moreover, the test statistics are “shrunken” to borrow information across neighboring genes that share the same array CGH signature. For each gene we also estimate its effect, its amount of differential expression due to copy number changes, and calculate the coefficient of determination. The method is illustrated on breast cancer data, in which it confirms previously reported findings, now with a more profound statistical underpinning.
Asymmetry of larval diet breadth and oviposition preference inLeptinotarsa undecimlineata
Authors: Eben Astrid , López‐Carretero Antonio
Published: May 2008

The relationship between preference and performance was studied under laboratory conditions for larvae and adult females ofLeptinotarsa undecimlineata(Stål) (Coleoptera: Chrysomelidae).Leptinotarsa undecimlineatafeeds exclusively onSolanum lanceolatumL. (Solanaceae) in the centre of Veracruz, Mexico. A common sympatric species,Solanum myriacanthumDunal, is not used as host. We conducted a series of laboratory experiments to detect reasons for the exclusive use of one host plant.Leptinotarsa undecimlineatalarvae were reared under laboratory conditions on both plant species,Solanum lanceolatumandS. myriacanthum. Length of larval stages, pupal weight, and percent adult eclosion were compared, and larval preference for bothSolanumspecies was tested. Upon eclosion, adult females were exposed to each of the plants, and the effect of larval diet on adult preference was determined. Oviposition on bothSolanumspecies was observed in no‐choice tests. Larvae showed no significant preferences for either plant species. Pupal weight, however, was significantly higher onS. lanceolatum. Female beetles significantly preferredS. lanceolatumleaves, and no effect of preimaginal conditioning was found. Females reproduced in lower numbers after feeding onS. myriacanthum, oviposition initiated later, and females laid fewer eggs than females fed withS. lanceolatum. No female acceptedS. myriacanthumfor oviposition. Results obtained suggest that the potential host breadth ofL. undecimlineatais broader in larvae than in female beetles.
Evaluating the cytotoxic doses of narrowband and broadband UVB in human keratinocytes, melanocytes, and fibroblasts
Authors: Cho Tae‐Ho , Lee Jin‐Woo , Lee Mu‐Hyoung
Published: May 2008

Background: No comparative and simultaneous in vitro studies have been performed to determine the cytotoxic dose of narrowband UVB (NBUVB) and broadband UVB (BBUVB) for keratinocytes, melanocytes, and fibroblasts. Culture medium was often replaced with phosphate‐buffered saline (PBS) before UV irradiation; however, its amount differed across studies. We determined the cytotoxic doses of NBUVB and BBUVB and tested for changes in viability according to the amount of PBS.

Methods: We exposed cultured human keratinocytes, melanocytes, and fibroblasts to ultraviolet light in the range 12.5–1000 mJ/cm2 for NBUVB and 1.25–100 mJ/cm2 for BBUVB. The viability was assessed after 24 h. We also determined changes in viability at cytotoxic doses according to the amount of PBS (40, 80, and 120 μl/well in a 96‐well plate).

Results: Cytotoxicity was observed at doses of 100, 200, and 400 mJ/cm2 for NBUVB and 5, 10, and 25 mJ/cm2 for BBUVB in keratinocytes, melanocytes, and fibroblasts, respectively. At cytotoxic doses, there was no change in viability according to the amount of PBS.

Conclusions: Fibroblasts are more resistant to UVB irradiation, irrespective of the amount of NBUVB and BBUVB, than keratinocytes and melanocytes. The amount of PBS during irradiation had no effect on viability.
Discrepant levels of vascular endothelial growth factor in psoriasis patients treated with PUVA, Re‐PUVA and narrow‐band UVB
Authors: Akman Ayse , Dicle Ozlem , Yilmaz Fikriye , Coskun Mesut , Yilmaz Ertan
Published: May 2008

Background: Previous reports showed that serum levels of vascular endothelial growth factor (VEGF) are increased in patients with psoriasis. However, to our knowledge, no studies have evaluated the effects of PUVA, Re‐PUVA and narrow‐band UVB (NB‐UVB) treatments on serum levels of VEGF in patients with psoriasis.

Objective: The aim of the study was to evaluate the influence of PUVA, Re‐PUVA and NB‐UVB treatments on angiogenic activities in patients with psoriasis by comparing serum levels of VEGF.

Methods: Forty‐six patients with psoriasis and 20 healthy subjects were included in the study. Peripheral blood samples were collected before, during and after the therapies. The efficacy of PUVA, Re‐PUVA and NB‐UVB was delineated by the psoriasis area and severity index. A repeated measure of ANOVA, Mann–Whitney U‐test, χ2 and Pearson's correlation coefficient were used for statistical analysis.

Results: The VEGF levels were significantly decreased in the PUVA group at the end of the follow‐up period (P<0.001). However, the levels were significantly increased in the groups of NB‐UVB and Re‐PUVA (P<0.001).

Conclusions: We found that there was a discrepancy during the PUVA, Re‐PUVA and NB‐UVB treatments. We believe that VEGF plasma levels could not be a useful monitor of psoriasis activity and/or treatment response.
Narrowband UVB (311 nm, TL01) phototherapy for pityriasis lichenoides
Authors: Aydogan Kenan , Saricaoglu Hayriye , Turan Hakan
Published: May 2008

Background/purpose: Narrowband (NB) UVB (NB‐UVB) phototherapy has recently demonstrated high levels of efficacy and tolerability in a variety of skin diseases. The purpose of the present study was to assess the efficacy of NB‐UVB phototherapy in the management of pityriasis lichenoides (PL).

Methods: The therapeutic response in 31 PL patients (23 pityriasis lichenoides et varioliformis acuta; PLEVA, eight pityriasis lichenoides chronica; PLC) treated with NB‐UVB phototherapy between 2000 and 2007 was assessed.

Results: NB‐UVB treatment led to a complete response (CR) in 15 out of 23 PLEVA patients (65.2%) with a mean cumulative dose of 23 J/cm2 after a mean number of 43.4 exposures and a partial response (PR) in eight patients (34.8%) with a cumulative dose of 15.6 J/cm2 after a mean number of 32.3 exposures. NB‐UVB treatment led to CR in seven out of eight PLC patients (87.5%) with a mean cumulative dose of 18.4 J/cm2 after a mean number of 45.8 exposures and PR in one patient (12.5%) with a cumulative dose of 9.1 J/cm2 after a mean number of 19 exposures. Relapses occurred in four PL patients within a mean time period of 6 months.

Conclusion: NB‐UVB therapy is an effective, safe and practical alternative treatment modality for the management of PLEVA and PLC.
Polypodium leucotomos inhibits ultraviolet B radiation‐induced immunosuppression
Authors: Siscovick Jonathan R. , Zapolanski Tamar , Magro Cynthia , Carrington Kristel , Prograis Shannon , Nussbaum Marnie , Gonzalez Salvador , Ding Wanhong , Granstein Richard D.
Published: May 2008

Background: An extract of the tropical fern Polypodium leucotomos (PL) administered orally to mice inhibits ultraviolet B (UVB) radiation‐induced skin cancer formation. UVB‐induced murine skin cancers occur, in part, because of UVB‐induced immunosuppression. Thus, we examined whether PL inhibits UVB‐suppression of the induction of contact hypersensitivity (CHS) locally or systemically.

Methods: C57BL/6 mice received standard drinking water or water‐containing PL. In the local model, mice were shaved on the dorsum and exposed to 3500 J/m2 of UVB radiation daily for 4 days. Control mice were not irradiated. After the last irradiation they were sensitized to oxazolone topically at the irradiated site. To examine the ability of PL to inhibit systemic UVB‐induced immunosuppression, mice were given 10 000 J/m2 of UVB radiation once and immunized at a non‐exposed site 3 days later. Six days after immunization (in both models), mice were challenged on the ears with oxazolone and 24/48 h ear swelling assessed.

Results: PL in drinking water significantly reduced the inhibition of CHS observed with exposure to UVB radiation in both the local and systemic models.

Conclusions: The ability of PL to inhibit UVB radiation‐induced immune suppression may explain, in part, its ability to inhibit UVR‐induced skin cancer induction in mice.
Intraurban Population Estimation with Remotely Sensed Imagery: A Developing World Perspective
Authors: Hardin Perry J. , Shumway J. Matthew
Published: May 2008

According to the United Nations, this year (2008) over 50% of Earth's 6.6 billion human inhabitants will be living in urban areas. Given the increasing importance of cities as human habitat, there is a critical need for accurate population count data to support urban decision‐making. Models driven by remotely sensed imagery are one of the few economically viable alternatives available to countries with developing economies needing to measure intraurban population on a repeating basis. This article discusses the current methods to gather basic intraurban population counts from remotely sensed imagery and suggests avenues for future study. More methodological development and testing are necessary before any of the discussed methods can be operationalized for use in the developing world.
Interaction of Fish Myoglobin and Myofibrillar Proteins
Authors: Chaijan M. , Benjakul S. , Visessanguan W. , Lee S. , Faustman C.
Published: May 2008

ABSTRACT:  Interactions between fish myoglobin (Mb) and myofibrillar proteins were investigated in a Mb‐natural actomyosin (NAM) model at 4 °C. Increases in metmyoglobin (MetMb) formation and the relative content of bound Mb were observed, as were decreases in whiteness and Ca2+‐ATPase activity (P < 0.05). During the first 6 h of incubation, Mb bound preferably to myosin at domains other than the head portion, as evidenced by measurable ATPase activity. The potential binding of Mb to myosin heads occurred after 24‐h incubation as evidenced by the marked decrease in Ca2+‐ATPase activity of the NAM–Mb mixture when compared to that of NAM alone (P < 0.05). The interaction between fish Mb and myofibrillar proteins was more pronounced with increased storage time; formation of high‐molecular‐weight aggregates (> 206 kDa) also increased with time. Electrophoretic study revealed that disulfide bonds were not involved in Mb–NAM interactions.