bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in Transforming Growth Factor-β Receptor Type II Cause Familial Thoracic Aortic Aneurysms and Dissections
Authors: Pannu Hariyadarshi , Fadulu Van Tran , Chang Jessica , Lafont Andrea , Hasham Sumera N. , Sparks Elizabeth , Giampietro Philip F. , Zaleski Christina , Estrera Anthony L. , Safi Hazim J. , Shete Sanjay , Willing Marcia C. , Raman C.S. , Milewicz Dianna M.
Published: July 2005

Background—

A genetic predisposition for progressive enlargement of thoracic aortic aneurysms leading to type A dissection (TAAD) is inherited in an autosomal-dominant manner in up to 19% of patients, and a number of chromosomal loci have been identified for the condition. Having mapped a TAAD locus to 3p24–25, we sequenced the gene for transforming growth factor-β receptor type II (
TGFBR2
) to determine whether mutations in this gene resulted in familial TAAD.

Methods and Results—

We sequenced all 8 coding exons of
TGFBR2
by using genomic DNA from 80 unrelated familial TAAD cases. We found
TGFBR2
mutations in 4 unrelated families with familial TAAD who did not have Marfan syndrome. Affected family members also had descending aortic disease and aneurysms of other arteries. Strikingly, all 4 mutations affected an arginine residue at position 460 in the intracellular domain, suggesting a mutation “hot spot” for familial TAAD. Despite identical mutations in the families, assessment of linked polymorphisms suggested that these families were not distantly related. Structural analysis of the TGFBR2 serine/threonine kinase domain revealed that R460 is strategically located within a highly conserved region of this domain and that the amino acid substitutions resulting from these mutations will interfere with the receptor’s ability to transduce signals.

Conclusion—

Germline
TGFBR2
mutations are responsible for the inherited predisposition to familial TAAD in 5% of these cases. Our results have broad implications for understanding the role of TGF-β signaling in the pathophysiology of TAAD.
Effect of the Proton Pump Inhibitor Omeprazole on the Pharmacokinetics of Extended‐Release Formulations of Oxybutynin and Tolterodine
Authors: Dmochowski Roger , Chen Andrew , Sathyan Gayatri , MacDiarmid Scott , Gidwani Shalini , Gupta Suneel
Published: July 2005

This study assessed the effect of the proton pump inhibitor omeprazole on the bioavailability of the extended‐release formulations of oxybutynin and tolterodine. Forty‐four healthy volunteers received each of 4 treatments in a 4‐period crossover design. The treatments consisted of osmotically controlled extended‐release oxybutynin chloride tablets at 10 mg/d or extended‐release tolterodine tartrate capules at 4 mg/d, with and without preceding treatment with 20 mg omeprazole daily for 4 days. Blood samples collected predose and at scheduled time points for 36 hours postdose were analyzed for oxybutynin and its active metabolite, N‐desethyloxybutynin, or tolterodine and its active 5‐hydroxymethyl metabolite, as appropriate. The AUC∞ ratios for oxybutynin and its metabolite with and without prior omeprazole fell within the 80% to 125% range (accepted as the criterion for bioequivalence), as did those for tolterodine and its active moiety. The peak concentration ratios for oxybutynin and metabolite also conformed to this range; those for tolterodine did not. Increasing gastric pH with omeprazole does not substantially alter the pharmacokinetic properties of extended‐release oxybutynin but may alter those of extended‐release tolterodine.
Mycophenolate Mofetil in Islet Cell Transplant: Variable Pharmacokinetics but Good Correlation Between Total and Unbound Concentrations
Authors: Jacobson Pamala A. , Green Kathleen G. , Hering Bernhard J.
Published: July 2005

The authors investigated the pharmacokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC0‐12 mcg•h/mL before day 60 was 62.1–67.8, declining to 33.6–64.7 thereafter (P = .61). Median total trough concentrations were 1.16–2.90 mcg/mL. Unbound AUC0‐12 was 412–673 ng•h/mL and did not change over time (P = .30). Median percent unbound mycophenolic acid was 0.95% of total concentrations. Individual unbound and total mycophenolic acid concentrations were highly correlated (r2 = 0.94). Total mycophenolic acid trough concentration and total AUC0‐12 were modestly correlated (r2 = 0.65). Intra‐ and interpatient variability of systemic mycophenolic acid exposure was high. Six patients required dose reductions prior to day 60 due to adverse effects. All subjects achieved insulin independence; 3 later lost graft function. The trend toward higher exposure in the early periods followed by dose reductions suggests that lower initial doses and therapeutic drug monitoring may be necessary.
Transgenic Crops in Argentina: The Ecological and Social Debt
Authors: Pengue Walter A.
Published: July 2005

There is no doubt that soybean is the most important crop for Argentina, with a planted surface that rose 11,000,000 hectares and a production of around 35,000,000 metric tons. During the 1990s, there was a significant agriculture transformation in the country, motorize by the adoption of transgenic crops (soy-bean, maize, and cotton) under the no-tillage system. The expansion of this model has been spread not only in the Pampas but also in very rich areas with high biodiversity, opening a new agricultural border to important eco-regions like the Yungas, Great Chaco, and the Mesopotamian Forest. Transgenic cropping is a powerful technology. This produced relevant transformations over the environment and society where it is allowed. Migration, concentration of agribusiness, and loss of food sovereignty are some of the social results. Landscape transformation in the rural sector is evident, and the appearance of tolerance weeds to glyphosate is a reality. Nutrient depletion, soil-structure degradation, potential desertification, and loss of species are other consequences on the environmental level.
The Myth of Coexistence: Why Transgenic Crops Are Not Compatible With Agroecologically Based Systems of Production
Authors: Altieri Miguel A.
Published: July 2005

The coexistence of genetically modified (GM) crops and non-GM crops is a myth because the movement of transgenes beyond their intended destinations is a certainty, and this leads to genetic contamination of organic farms and other systems. It is unlikely that transgenes can be retracted once they have escaped, thus the damage to the purity of non-GM seeds is permanent. The dominant GM crops have the potential to reduce biodiversity further by increasing agricultural intensification. There are also potential risks to biodiversity arising from gene flow and toxicity to nontarget organisms from herbicide-resistant (HT) and insect-resistant (Bt) crops. Unless whole regions are declared GM agriculture free, the development of distinct systems of agriculture (GM and non-GM) will be impossible as GM agriculture emerges at the expense of all other forms of production.
Transgenic Crops and Sustainable Agriculture in the European Context
Authors: Ponti Luigi
Published: July 2005

The rapid adoption of transgenic crops in the United States, Argentina, and Canada stands in strong contrast to the situation in the European Union (EU), where a de facto moratorium has been in place since 1998. This article reviews recent scientific literature relevant to the problematic introduction of transgenic crops in the EU to assess if there are specific reasons why transgenic crops have a potentially greater adverse impact on sustainable agriculture in the EU context than elsewhere. Sustainable agriculture integrates three main goals: environmental health, economic profitability, and socioeconomic equity. Transgenic crops do not appear a suitable tool for sustainable agriculture in the EU due to specific environmental, economic, and socioeconomic reasons. Therefore, a moratorium on transgenic crops based on the precautionary principle should be officially adopted until proper risk assessment. In addition, agroecological alternatives to transgenic crops fit better the EU vision of agriculture.
Transgenic Crops: Implications for Biodiversity and Sustainable Agriculture
Authors: Garcia Maria Alice , Altieri Miguel A.
Published: July 2005

The potential for genetically modified (GM) crops to threaten biodiversity conservation and sustainable agriculture is substantial. Megadiverse countries and centers of origin and/or diversity of crop species are particularly vulnerable regions. The future of sustainable agriculture may be irreversibly jeopardized by contamination of in situ preserved genetic resources threatening a strategic resource for the world—s food security. Because GM crops are truly biological novelties, their release into the environment poses concerns about the unpredictable ecological and evolutionary responses that GM species themselves and the interacting biota may express in the medium and long term. One of the consequences of these processes may be a generalized contamination of natural flora by GM traits and a degradation and erosion of the commonly owned genetic resources available today for agricultural development. GM plants carrying pharmaceutical and industrial traits will pose even more dangerous risks if released in the environment.
Transgenic Crops to Address Third World Hunger? A Critical Analysis
Authors: Rosset Peter M.
Published: July 2005

Industry and mainstream research and policy institutions often suggest that transgenic crop varieties can raise the productivity of poor third world farmers, feed the hungry, and reduce poverty. These claims are critically evaluated by examining global-hunger data, the constraints that affect the productivity of small farmers in the third world, and the factors that explain their poverty. No significant role is found for crop genetics in determining hunger, productivity, or poverty, casting doubt on the ability of new transgenic crop varieties produced by genetic engineering to address these problems. An examination of the special risks these varieties pose for poor farmers in the complex, diverse, and risk-prone environments that characterize peasant agriculture on a global scale suggests that transgenic crop varieties are likely to be more of hindrance than a help to the advancement of poor farmers.
Scholar/’shippers and Spikeaholics
Authors: Burr Vivien
Published: July 2005

Matt Hills argues that cultural theorists have been unable or unwilling to transcend a dichotomy that places academic discourse and identities in the realm of the rational or passionless, and fan identities in the realm of the immersed or open. As a result, the scholar-fan and the fan-scholar have become liminal and transgressive persona. This article draws on the author’s own experience, and that of 13 other delegates who participated in the Slayage Conference on Buffy the Vampire Slayer held in Tennessee in May 2004, as a basis for exploring the way in which the issues of the fan-scholar identity are lived out. Questions addressed include the way in which tensions between fan and academic identities were manifested, and the ways in which individuals managed their fan and academic identities.
How Newly Acquainted Dyads Develop Shared Stereotypic Impressions through Conversation
Authors: Ruscher Janet B. , Cralley Elizabeth L. , O’Farrell Kimberly J.
Published: July 2005

This study investigated how feelings of closeness at initial acquaintance encourage the development of shared stereotypic impressions of others through conversation. At least early in a relationship, closer dyads may be especially inclined to get along with one another. In order to satisfy this goal, they should focus their conversations around easily agreed upon stereotypic attributes and spontaneously express agreement about those attributes. As a consequence, the shared impressions that they form should be relatively stereotypic. In this study, closeness was manipulated in previously unacquainted college-age dyads, who then discussed their impressions of an elderly woman. Closer dyads allocated more discussion time to stereotypic attributes, expressed agreement about those attributes, invoked stereotypic exemplars, and ultimately formed more stereotypic shared impressions. The discussion considers study limitations and possible boundary conditions of the effects, as well as implications for the transmission of outgroup stereotypes during socialization to a new ingroup.
The content of available practice literature in dementia and intellectual disability
Authors: Jokinen Nancy
Published: July 2005

Adults with intellectual disability are living to ages seen within the general population and they, too, are at risk of developing dementia. The purpose of this review was to identify the nature and content of the literature related to adults with intellectual disability and dementia and bring together guidelines for services and staff providing care. The preponderance of work between 1995 and 2004 focuses on the biomedical, diagnosis and assessment aspects of the disease. Although guidelines exist, there is a lack of published literature on the efficacy of practice strategies to guide the provision of daily care. Future research is discussed that could support continued community living and high quality of life during all stages of the disease.
Planning ahead
Authors: Hatzidimitriadou Eleni , Milne Alisoun
Published: July 2005

Despite the acknowledged increase in the number of older people with intellectual disabilities (ID) in the UK, the age-related health and social care needs of this population have yet to be fully understood and addressed. Although there is some evidence of positive development, the current picture of service provision is characterized by fragmentation and limited choice of resources and specialist care. Policy aims are variably met and inconsistently applied. Research suggests that service planning is often incoherent, that many older people with ID and their carers receive poor quality non-specialist care and that staff are inadequately trained to manage the often multiple and complex needs of this user group. There is a considerable co-joined service development and research challenge in this emerging field. If older people with ID and their carers are to receive quality provision, a coherent and well-funded service planning system is required which is underpinned by articulated agency partnerships, informed by good practice developments in the fields of ID, gerontology and dementia care, and linked to evidence about effective models of care and services. The incorporation of the perspectives of users and carers in the planning process is an essential pre-requisite as is a commitment to the development of effective support across the life course of all individuals with ID.
Group home care for adults with intellectual disabilities and Alzheimer’s disease
Authors: Janicki Matthew P. , Dalton Arthur J. , McCallion Philip , Baxley Diann Davies , Zendell Anna
Published: July 2005

The growing numbers of individuals with intellectual disabilities affected by Alzheimer’s disease and related dementias has raised new challenges for community care providers. This article examines means of providing community group home-based care in a sample of care providers in five different countries. The aim is to identify trends that have emerged. Two samples of group homes for adults with intellectual disabilities affected by dementia were studied to determine: (1) what are the physical characteristics of the homes; (2) what physical environmental adaptations have been made in response to behavioral deterioration expressed by residents with dementia; and (3) what are the demands on staff resulting from dementia care. The first sample of group homes in five countries provided comparative international data on home designs, staffing, costs, and residents. The second sample, drawn from homes in the USA and the UK, provided data on the impact of dementia. Findings revealed staffing and design of homes varied but generally abided by general practices of dementia care; homes relied on existing resources to manage changes posed by dementia care; programmatic and environmental adaptations were implemented to address progression of dementia; and residents with dementia presented more demands on staff time with respect to hygiene maintenance and behavior management when compared to other residents not affected by dementia.
Equipping staff to support people with an intellectual disability and dementia in care home settings
Authors: Wilkinson Heather , Kerr Diana , Cunningham Colm
Published: July 2005

The knowledge, experiences and skills of direct care staff working in care home settings are essential in ensuring a good quality of life and care for a person with an intellectual disability (ID) who develops dementia. Drawing on the findings of a wider study, the issues of training, support and the wider needs of staff when trying to support a resident who develops dementia are explored, specifically as relating to the role played by staff and the need to determine their experiences and related training needs. Following an introduction to the policy and practice context for working with people with an ID and dementia, and a brief description of the research method, the authors discuss the attitudes and practices of staff; supportive changes at an organizational level; and the knowledge and training needs of staff and specific gaps in knowledge. The authors argue that, within the policy and practice context of aiming to support residents to ‘age in place’, support for staff is a crucial aspect of ensuring that such an approach is effective and provides a coordinated approach to planning, resourcing and support.
A comparison of reports of caregiver burden between foster family care providers and staff caregivers in other settings
Authors: McCallion Philip , Nickle Tara , McCarron Mary
Published: July 2005

There has been increasing concern about the impact of dementia symptoms on the lives and on the care being provided for persons with intellectual disability (ID) in out-of-home settings. One such setting that has received little attention is foster family care homes. These settings in the USA replicate family living and while some supports and resources are provided, they are not designed to meet intensive care needs. As a preliminary step in understanding family experiences and to expand the range of interest in Alzheimer’s disease (AD) in persons with ID beyond traditional out-of-home settings, a pilot study was initiated that included aging persons with ID and symptoms of AD who were living in foster family care settings in two regions of New York State as well as more traditional out-of-home care subjects. Comparisons of matched samples on subjective and objective burden measures suggest that there are few differences in experiences. The limitations of these findings are considered and recommendations made for future, related research.
The experience of chronic pain in elderly nursing home residents
Authors: Higgins Isabel
Published: July 2005

The overall purpose of the study reported here was to explore the experience of being old and in chronic pain while living in a nursing home. The aims of the study were to discover what it was like for older people to live with chronic pain, and how and in what way chronic pain impacts on their lives. One major theme from the study is presented here, ‘Being constantly pained’, as it represents the essential feature of the lived experience of pain. In presenting the findings, seven sub-themes are discussed, including: ‘the painfulness of pain’, ‘the certainty/uncertainty of pain’, ‘overwhelming pain’, ‘unvoicing pain’, ‘being old and worn out’, ‘being forgotten’ and ‘taking punishment’. The findings of this study have the potential to increase understanding of the experience of chronic pain in elderly people by nurses and other healthcare professionals. In addition, the findings also have implications for the provision of healthcare in nursing homes and for conducting research with those who are very old. In a climate of limited government funding and support for services in nursing homes, the data highlight concerns about the role of unqualified staff in this setting.
Exploring the impact of Acute Pain Teams (APTs) on patient outcomes using routine data
Authors: McDonnell Ann , Nicholl Jon , Read Susan
Published: July 2005

Acute Pain Teams (APTs) in every hospital performing surgery have been advocated to improve the management of post-operative pain. Poor postoperative analgesia is a perennial problem that may result in complications such as chest infection and pulmonary embolus which may have an impact on outcomes such as mortality and length of stay.

This paper considers the feasibility of using routine data to explore the impact of APTs on patient outcomes, using as an illustrative example a study which investigated relationships between the introduction of APTs and post-operative length of stay and in-patient post-operative mortality.
A multinational study of pain management among Hispanics
Authors: Sherwood Gwen , McNeill Jeanette A. , Hernandez Lesbia , Penarrieta Isabel , Petersen Jeannie M.
Published: July 2005

A multinational project involving pain research teams from three countries examined pain management outcomes in Hispanics. The limited research on pain management outcomes in Hispanics are primarily from the USA, lacking the distinct multinational cultural influences. This article compares the descriptive analysis of the post-operative pain experience of Hispanics in the USA, Puerto Rico and Mexico and tests the reliability of a new Spanish language instrument, the Cuestionario de Houston Sobre el Dolor (Houston Pain Outcome Instrument, HPOI).

There were similarities in expectations related to pain relief, proportion of patients reporting worst pain, usual pain and pain-related interference with function. Significant differences were found on adequacy of pain management. Participants reported high use of non-pharmacologic approaches, particularly prayer and family support. The newly developed instrument indicated acceptable reliability in all settings, Chronbach’s Alpha > 0.75, with some variability by study site. Further cross-ethnic and multinational research are needed to provide culturally relevant evidence-based practice models to overcome barriers and reduce disparity.
The experiences of overseas black and minority ethnic registered nurses in an English hospital
Authors: Alexis Obrey , Vydelingum Vasso
Published: July 2005

Overseas black and minority ethnic nurses have contributed significantly to the National Health Service (NHS) in the UK. Yet despite this, there was little information on how they had fared. This study was conducted to explore, describe and develop a greater understanding of the experiences of overseas black and minority ethnic nurses who are working in the NHS in the south of England. A phenomenological method was used. A total of 12 overseas black and minority ethnic nurses were interviewed in their own homes. Semi-structured interviews were tape-recorded, transcribed verbatim and analysed. The findings revealed eight themes, namely not feeling appreciated, feeling inadequate, feeling unwelcome, lack of opportunities for skill development and training, unfairness in nursing practice, performance review, support from overseas black and minority ethnic colleagues and proving self. The paper concludes by arguing that overseas black and minority ethnic nurses should be treated with respect as they play a significant role in the delivery of services in the NHS.
Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study
Authors: Liu Glenn , Rugo Hope S. , Wilding George , McShane Teresa M. , Evelhoch Jeffrey L. , Ng Chaan , Jackson Edward , Kelcz Frederick , Yeh Benjamin M. , Lee Fred T. , Charnsangavej Chusilp , Park John W. , Ashton Edward A. , Steinfeldt Heidi M. , Pithavala Yazdi K. , Reich Steven D. , Herbst Roy S.
Published: July 2005

Purpose

Identifying suitable markers of biologic activity is important when assessing novel compounds such as angiogenesis inhibitors to optimize the dose and schedule of therapy. Here we present the pharmacodynamic response to acute dosing of AG-013736 measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Patients and Methods

Thirty-six patients with advanced solid tumors were treated with various doses of AG-013736. In addition to standard measures of objective disease response and pharmacokinetic analysis, DCE-MRI scans were acquired at baseline and repeated at cycle 1—day 2 after the scheduled morning dose of the AG-013736 in 26 patients. Indicators of a vascular response, such as the volume transfer constant (Ktrans) and initial area under the curve (IAUC), were calculated to assess the effect of treatment on tumor vascular function.

Results

Evaluable vascular response data were obtained in 17 (65%) of 26 patients. A linear correlation was found in which the percentage change from baseline to day 2 in Ktrans and IAUC was inversely proportional to AG-013736 exposure. Using a conservative a priori assumption that a ≥ 50% decrease in Ktrans was indicative of an objective vascular response, a 50% decrease in Ktrans was achieved and corresponded to a plasma AUC0-24 of > 200 ng · h/mL.

Conclusion

A sufficient decrease in tumor vascular parameters was observed at a dose chosen for additional phase II testing by conventional toxicity criteria. In addition, the day 2 vascular response measured using DCE-MRI seems to be a useful indicator of drug pharmacology, and additional research is needed to determine if it is a suitable marker for predicting clinical activity.
Randomized Trial of Antioxidant Vitamins to Prevent Acute Adverse Effects of Radiation Therapy in Head and Neck Cancer Patients
Authors: Bairati Isabelle , Meyer François , Gélinas Michel , Fortin André , Nabid Abdenour , Brochet François , Mercier Jean-Philippe , Têtu Bernard , Harel François , Abdous Belkacem , Vigneault Éric , Vass Sylvie , del Vecchio Pierre , Roy Jean
Published: July 2005

Purpose

Many cancer patients take antioxidant vitamin supplements with the hope of improving the outcome of conventional therapies and of reducing the adverse effects of these treatments. A randomized trial was conducted to determine whether supplementation with antioxidant vitamins could reduce the occurrence and severity of acute adverse effects of radiation therapy and improve quality of life without compromising treatment efficacy.

Patients and Methods

We conducted a randomized, double-blind, placebo-controlled trial among 540 head and neck cancer patients treated with radiation therapy. Patients were randomly assigned into two arms. The supplementation with α-tocopherol (400 IU/d) and β-carotene (30 mg/d) or placebos was administered during radiation therapy and for 3 years thereafter. During the course of the trial, supplementation with β-carotene was discontinued because of ethical concerns.

Results

Patients randomly assigned in the supplement arm tended to have less severe acute adverse effects during radiation therapy (odds ratio [OR], 0.72; 95% CI, 0.52 to 1.02). The reduction was statistically significant when the supplementation combined α-tocopherol and β-carotene for adverse effects to the larynx (OR, 0.38; 95% CI, 0.21 to 0.71) and overall at any site (OR, 0.38; 95% CI, 0.20 to 0.74). Quality of life was not improved by the supplementation. The rate of local recurrence of the head and neck tumor tended to be higher in the supplement arm of the trial (hazard ratio, 1.37; 95% CI, 0.93 to 2.02).

Conclusion

Supplementation with high doses of α-tocopherol and β-carotene during radiation therapy could reduce the severity of treatment adverse effects. However, this trial suggests that use of high doses of antioxidants as adjuvant therapy might compromise radiation treatment efficacy.
Knowledge Based Solution Strategies in Medical Reasoning
Authors: Patel Vimla L. , Groen Guy J.
Published: July 2005

The techniques of propositionol analysis are used to examine the protocols of seven cardiologists in a task involving the diagnosis of a case of acute bacterial endocarditis and an explanation of its underlying pathophysiology. It is shown that the explanations of physicians making an accurate diagnosis can be accounted for in terms of a model consisting of pure forward reasoning through a network of causal rules, actuated by relevant propositions embedded in the stimulus text. These rules appear to derive from the physician's underlying knowledge base rather than any information in the text itself. In contrast, subjects with inacurate diagnoses tend to make use of a mixture of forward and backward reasoning, beginning with a high level hypothesis and proceeding in a top‐down fashion to the propositions embedded in stimulus text, or to the generation of irrelevant rules.
The Scan‐Copier Mechanism and the Positional Level of Language Production: Evidence from Phonemic Paraphasia
Authors: Buckingham Hugh W.
Published: July 2005

In this paper I argue that phonemic paraphasia in the fluent aphasias is best characterized as a computational disruption in the processes that map the Functional Level onto the Positional Level of the model of sentence production developed by Merrill Garrett. I claim that a scan‐copying mechanism of the sort proposed by Shattuck‐Hufnagel operates among the computations leading to the Positional Level and that mechanism, when it derails, gives rise to the production of phonemic level errors in the language of fluent aphasies with posterior left cerebral lesions. I then argue that phonetic level errors in non‐fluent, verbal apraxia cannot be handled by the scan‐copier, nor can they be accounted for at the Positional Level.
Explaining the phase behaviour of the pharmaceutically relevant polymers poly(ethylene glycol) and poly(vinyl pyrrolidone) in semi-fluorinated liquids
Authors: Paul Alison , Griffiths Peter C , James Robert , Willock David J , Rogueda Philippe G
Published: July 2005

Phase behaviour studies of low molecular weight poly(ethylene glycol) (denoted PEG 600 and PEG 1000, corresponding to molecular weights of 600 and 1000 g mol−1, respectively) have been carried out in 2H, 3H-perfluoropentane (HPFP) with and without added poly(vinyl pyrrolidone). The concentration and temperature dependencies of their phase behaviour and the effect of moisture on these systems have been established. Furthermore, the solubility of PEG 600 in binary mixtures of HPFP and per-fluoropentane (PFP), as well as HPFP and perfluorodecalin (PFD) have been considered at high HPFP contents. A phase separation phenomenon in fluorinated non-aqueous media is reported for the first time: PEG 600 and PEG 1000 both show a lower critical solution temperature type phase separation boundary. The size of the PEGs was obtained from small-angle neutron scattering (radius of gyration) and pulsed-gradient spin-echo NMR (hydrodynamic radius) measurements. It is shown that polymer conformation follows a regular trend with solution concentration; the size increases from <10 Å at 3wt% in HPFP to 45 ± 2 Å at 20wt% PEG. On changing the solvent composition by substitution of HPFP by PFP or PFD, the size decreases, consistent with a decrease in the hydrogen-bonding capacity of the solvent mixture. Computer modelling indicates an interaction between the PEG oxygen and the hydrogen of HPFP, an interaction that is absent for the fully fluorinated solvents. This indicates that hydrogen bonding is the driving force for polymer solubility in these solvents.
Intranasal immunization using biphasic lipid vesicles as delivery systems for OmlA bacterial protein antigen and CpG oligonucleotides adjuvant in a mouse model
Authors: Alcón V L , Baca-Estrada M , Vega-López M A , Willson P , Babiuk L A , Kumar P , Foldvari M
Published: July 2005

The nasal mucosa is an important arm of the mucosal system since it is often the first point of contact for inhaled antigens. The ineffectiveness of the simple delivery of soluble antigens to mucosal membranes for immunization has stimulated extensive studies in appropriate delivery systems and adjuvants. We have evaluated biphasic lipid vesicles as a novel intranasal (i.n.) delivery system (designated as vaccine targeting adjuvant, VTA) containing bacterial antigens and CpG oligode-oxynucleotides (ODNs). Results show that administration of antigen and CpG ODNs in biphasic lipid vesicles resulted in greater induction of IgA levels in serum (P<0.05) and mucosal antibody responses such as IgA in nasal secretions and lung (P<0.01) after immunization with a combined subcutaneous (s.c.)/i.n. as compared to s.c./s.c. approach. Based on antibody responses, VTA formulations were found to be suitable as delivery systems for antigens and CpG ODNs by the intranasal route, resulting in a Th2-type of immune response, characterized by IgG1 and IL-4 production at the systemic level.
Order Quantity and Timing Flexibility in Supply Chains: The Role of Demand Characteristics
Authors: Milner Joseph M. , Kouvelis Panos
Published: July 2005

We study how differences in product demand characteristics affect the strategic value of different types of supply chain flexibility for accurate response. We propose a single-period inventory modelling framework with two ordering opportunities. The second order reflects updated demand information and potentially capitalizes on supply chain flexibility. We consider two complementary forms of flexibility: quantity flexibility in production and timing flexibility in scheduling. In this framework, we analyze the total inventory cost of a firm for alternate demand types. We model functional products through the standard assumption of independent demand over the period, fashion-driven innovative products through a Bayesian model, and innovative products with evolving demand through a Martingale process. The three demand processes exhibit very different behavior with respect to the value of the alternate forms of flexibility. We observe that quantity flexibility is of moderate value for functional goods and of high value for fashion-driven products for all lead times. Quantity flexibility is of low value for goods with evolving demand with long lead times but of high value for short lead times. Alternately, we observe timing flexibility is of highest value for functional goods, especially for cases of high holding cost, and is of lesser value for fashion-driven goods. It is of least value for goods with evolving demand. Both quantity and timing flexibility capabilities are required to significantly reduce the relevant supply chain costs for evolving-demand innovative goods when the lead times are long.
Individual Experience and Experience Working Together: Predicting Learning Rates from Knowing Who Knows What and Knowing How to Work Together
Authors: Reagans Ray , Argote Linda , Brooks Daria
Published: July 2005

Learning by doing represents an important mechanism through which organizations prosper. Some firms, however, learn from their experience at a dramatic rate, while other firms exhibit very little learning at all. Three factors have been identified that affect the rate at which firms learn: (a) the proficiency of individual workers, (b) the ability of firm members to leverage knowledge accumulated by others, and (c) the capacity for coordinated activity inside the organization. Each factor varies with a particular kind of experience. An increase in cumulative individual experience increases individual proficiency. An increase in cumulative organizational experience provides individuals with the opportunity to benefit from knowledge accumulated by others. An increase in cumulative experience working together promotes more effective coordination and teamwork. To gain insight into factors responsible for the learning curve, we examine the contribution of each kind of experience to performance, while controlling for the impact of the other two. The study context is a teaching hospital. The task is a total joint replacement procedure, and the performance metric is procedure completion time. We find that each kind of experience makes a distinct contribution to team performance. We discuss the implications of our findings for the learning-by-doing framework in general, and learning in the team context in particular.
Information Sharing in a Supply Chain Under ARMA Demand
Authors: Gaur Vishal , Giloni Avi , Seshadri Sridhar
Published: July 2005

In this paper we study how the time-series structure of the demand process affects the value of information sharing in a supply chain. We consider a two-stage supply chain model in which a retailer serves autoregressive moving-average (ARMA) demand and a manufacturer fills the retailer’s orders. We characterize three types of situations based on the parameters of the demand process: (i) the manufacturer benefits from inferring demand information from the retailer’s orders; (ii) the manufacturer cannot infer demand, but benefits from sharing demand information; and (iii) the manufacturer is better off neither inferring nor sharing, but instead uses only the most recent orders in its production planning. Using the example of ARMA(1,1) demand, we find that sharing or inferring retail demand leads to a 16.0% average reduction in the manufacturer’s safety-stock requirement in cases (i) and (ii), but leads to an increase in the manufacturer’s safety-stock requirement in (iii). Our results apply not only to two-stage but also to multistage supply chains.
Research Note: Customer Intimacy and Cross-Selling Strategy
Authors: Akçura M. Tolga , Srinivasan Kannan
Published: July 2005

Better targeting opportunities and the increasing role of information-intensive environments have created new challenges for firms in obtaining customer information. Such information can help firms increase their profits through cross-selling opportunities. However, revealing personal preferences and contact information can raise the risks for customers when dealing with a firm. Consequently, some customers trade off the benefit and risks of revealing information. As the opportunity to obtain a higher level of information increases, customers incur a higher level of risk when dealing with a firm. This increases the firm’s incentive to commit on a cross-selling level. By such a commitment, a firm can obtain customer intimacy and benefit from detailed customer information. As a result, profits increase while prices decrease. Thus, legal regulations that explicitly require firms to spell out the extent of cross-selling may actually improve the profits of the firm.
Optimization of Influenza Vaccine Selection
Authors: Wu Joseph T. , Wein Lawrence M. , Perelson Alan S.
Published: July 2005

The World Health Organization (WHO) recommends which strains of influenza to include in each year’s vaccine to countries around the globe. The current WHO strategy attempts to match the vaccine strains with the expected upcoming epidemic strains, a strategy we refer to as the follow policy. The recently proposed antigenic distance hypothesis suggests that vaccine efficacy can be enhanced by taking into account the antigenic histories of vaccinees. To assess the potential benefit of history-based vaccination, we formulate the annual vaccine-strains selection problem as a stochastic dynamic program using the theory of shape space, which maps each vaccine and epidemic strain into a point in multidimensional space. Computational results show that a near-optimal policy can be derived by approximating the entire antigenic history by a single reduced historical strain, and then solving the multiperiod problem myopically, as a series of single-period problems. The modest suboptimality of the follow policy, together with our current inability to quantitatively link the model’s objective function (a measure of cross-reactivity) with actual vaccine efficacy, leads us to recommend the continued use of the follow policy.
Clustering Sensors in Wireless Ad Hoc Networks Operating in a Threat Environment
Authors: Patel Dipesh J. , Batta Rajan , Nagi Rakesh
Published: July 2005

Sensors in a data fusion environment over hostile territory are geographically dispersed and change location with time. To collect and process data from these sensors, an equally flexible network of fusion beds (i.e., clusterheads) is required. To account for the hostile environment, we allow communication links between sensors and clusterheads to be unreliable. We develop a mixed-integer linear programming (MILP) model to determine the clusterhead location strategy that maximizes the expected data covered minus the clusterhead reassignments, over a time horizon. A column generation (CG) heuristic is developed for this problem. Computational results show that CG performs much faster than a standard commercial solver, and the typical optimality gap for large problems is less than 5%. Improvements to the basic model in the areas of modeling link failure, consideration of bandwidth capacity, and clusterhead changeover cost estimation are also discussed.
Evaluation of Channel Catfish Virus Latency on Fingerling Production Farms in Mississippi
Authors: Thompson David J. , Khoo Lester H. , Wise David J. , Hanson Larry A.
Published: July 2005

Channel catfish virus disease (CCVD) is an economically important disease to the channel catfish Ictalurus punctatus industry. Channel catfish virus develops a latent infection and is vertically transmitted from broodstock to offspring. In this study, the presence of latent channel catfish virus (CCV) in fry at 3–5 d of age was evaluated, via polymerase chain reaction, on five farms in the Delta region of Mississippi. We found over 10% of the fry sampled were positive for latent CCV on all five farms. Additionally, on one of those farms the presence of latent CCV was evaluated in three ponds through a typical CCVD season. Regression analysis of the CCV carrier level demonstrated an increase, but no overt CCVD outbreaks occurred and no CCV was cultured from the fish tissues in cell culture. Our results indicate that CCV is endemic in most channel catfish populations under commercial production in Mississippi and suggests that subclinical transmission of CCV does occur.
Impact of Invalid Biological Assumptions and Misapplication of Maturity Criteria on Size‐at‐Maturity Estimates for American Lobster
Authors: Waddy S. L. , Aiken D. E.
Published: July 2005

Size at maturity is an important tool for fishery management of the American lobster Homarus americanus, but many of the size‐at‐maturity assessments conducted to date have been confounded by errors of biological fact, misinterpretations of results, and misapplications of maturity assessment criteria. The result has been considerable uncertainty about the magnitude of egg production for various stocks of the American lobster, an undesirable situation for fishery managers. Size‐at‐maturity studies require an in‐depth understanding of the biology of molting and reproduction. The investigator must first determine the physiological state of the captured lobster and then estimate when molting or spawning will occur. Conclusions can then be drawn regarding the maturity of the animal. Three elements are important in the design of maturity studies: The criteria used to discriminate between immature and mature lobsters, the time of year the study is conducted, and the sizes and numbers of lobsters sampled. Maturity assessments should be conducted in the late spring, prior to the onset of the spawning and egg hatching seasons, when almost all mature lobsters are either ovigerous or preovigerous. Cement gland development should be used initially to separate preovigerous (mature) lobsters from those of uncertain reproductive status. Those of uncertain status can then be classified on the basis of ovary stage. If lobster ovaries are at stage 1 or 2, the lobsters are immature and will molt to a larger size before spawning. If lobster ovaries are at stage 3 or 4a, the lobsters are immature if their oviducts are clear and mature if the distal portion of their oviducts is yellow. Lobsters with ovaries at stages 4b to 6 are mature and should spawn within a few weeks. Once fishery biologists adopt a standard sampling protocol and begin applying validated maturity assessment criteria, size‐at‐maturity estimates will become comparable, reliable, and repeatable.
Manufacturing Uncertainty: Contested Science and the Protection of the Public’s Health and Environment
Authors: Michaels David , Monforton Celeste
Published: July 2005

Opponents of public health and environmental regulations often try to “manufacture uncertainty” by questioning the validity of scientific evidence on which the regulations are based. Though most identified with the tobacco industry, this strategy has also been used by producers of other hazardous products. Its proponents use the label “junk science” to ridicule research that threatens powerful interests.

This strategy of manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence available. The public health system must ensure that scientific evidence is evaluated in a manner that assures the public’s health and environment will be adequately protected.
Trial and Error: The Supreme Court’s Philosophy of Science
Authors: Haack Susan
Published: July 2005

Apparently equating the question of whether expert testimony is reliable with the question of whether it is genuinely scientific, in Daubert v Merrell Dow Pharmaceuticals, Inc (1993) the US Supreme Court ran together Karl Popper’s and Carl Hempel’s incompatible philosophies of science. But there can be no criterion discriminating scientific, and hence reliable, testimony from the unscientific and unreliable; for not all, and not only, scientific evidence is reliable.

In subsequent rulings (General Electric Co v Joiner, 1997; Kumho Tire Co v Carmichael, 1999) the Court has backed quietly away from Daubert’s confused philosophy of science, but not from federal judges’ responsibilities for screening expert testimony. Efforts to educate judges scientifically, and increased use of court-appointed experts are, at best, only partial solutions to the problems with scientific testimony.
A Cognitive Scientist Looks at Daubert
Authors: Lakoff George P.
Published: July 2005

Our system of justice requires that trials be maximally fair. It is part of what holds this society together. Indeed, it is part of the genius of the justice system to have a kind of balance between strict and nurturant morality within the judicial system, so that the system itself provides a kind of moral and political balance.

Daubert v Merrell Dow Pharmaceuticals, Inc (1993) has upset that balance and has made our judicial system significantly less fair and more politically conservative. Daubert is not just about the application of some procedural rule (Rule 702). Daubert functions in its application as a strategic initiative that significantly moves America in a conservative direction, in the moral and political spheres, as well as in the legal sphere.
The Weight of Scientific Evidence in Policy and Law
Authors: Krimsky Sheldon
Published: July 2005

The term “weight of evidence” (WOE) appears in regulatory rules and decisions. However, there has been little discussion about the meaning, variations of use, and epistemic significance of WOE for setting health and safety standards.

This article gives an overview of the role of WOE in regulatory science, discusses alternative views about the methodology underlying the concept, and places WOE in the context of the Supreme Court’s decision in Daubert v Merrell Dow Pharmaceuticals, Inc (1993). I argue that whereas the WOE approach to evaluating scientific evidence is gaining favor among regulators, its applications in judicial processes may be in conflict with some interpretations of how the Daubert criteria for judging reliable evidence should be applied.