bluuebunny/crossref_metadata_2025 huggingface dataset:
Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma
Authors: Yu Ji-wei , Wu Ju-gang , Zheng Lin-hai , Zhang Biao , Ni Xiao-chun , Li Xiao-qiang , Jiang Bo-jian
Published: April 2009

Background

To investigate influencing factors of the metastatic lymph nodes ratio (MLR) and whether it is related to survival in patients with gastric adenocarcinoma.

Methods

We retrospectively evaluated the clinical features of 121 patients with gastric adenocarcinoma enrolled in our hospital between 2000 and 2007. The receiver operating characteristic (ROC) curve was used to determine the cutoff of the MLR, and CK20 immunohistochemical staining was used to detect micrometastasis of the lymph nodes.

Results

The areas under the ROC curve of MLR used to predict the death of 3-year and 5-year postoperative patients were 0.826 ± 0.053 and 0.896 ± 0.046. Thus MLR = 30.95% and MLR = 3.15% were designated as cutoffs. The MLR was then classified into three groups: MLR1 (MLR<3.15%); MLR2(3.15% ≤ MLR ≤ 30.95%); and MLR3 (MLR>30.95%). We found that patients with a higher MLR demonstrated a much poorer survival period after radical operation than those patients with a lower MLR (P = 0.000). The COX model showed that MLR was an independent prognostic factor (P = 0.000). The MLR could also discriminate between subsets of patients with different 5-year survival periods within the same N stage (P < 0.05). The MLR has been shown to be 34.7% (242/697) by HE staining and 43.5% (303/697) by CK staining (P = 0.001). The clinicopathological characteristics of lymph vessel invasion and the depth of invasion could significantly affect the MLR.

Conclusion

MLR is an independent prognostic factor in gastric cancer. The combined ROC curve with MLR is an effective strategy to produce a curve to predict the 3-year and 5-year survival rates.
Flow cytometric analysis of CK19 expression in the peripheral blood of breast carcinoma patients: relevance for circulating tumor cell detection
Authors: Wang Lili , Wang Yanyan , Liu Yajing , Cheng Min , Wu Xu , Wei Haiming
Published: April 2009

Background

Immunocytochemistry and RT-PCR have been widely used for the detection of circulating tumor cells in patients with breast cancer but their specificity is limited. Our purpose is to utilize a convenient and specific technology to detect circulating tumor cells in breast cancer patients.

Methods

To determine the sensitivity and specificity of our method, A431 cells were serially diluted with human peripheral blood leukocytes and stained with CK19. A total of 73 blood specimens including 25 healthy volunteers and 48 patients with breast carcinoma and benign tumor were tested by flow cytometry to quantify the expression of CK19.

Results

The detectable upper limit of A431 cells was 1 cancer cell among 104 human white blood cells. CK19 was detected in 27% of breast cancer patients but none control gives positive result. The number of cancer cells increased gradually along with the disease stages for it was the least in stage I (0%) and the most in stage IV (1.29%). Fifteen patients were observed during three month chemotherapy after surgery, and most of their CK19 expression levels declined after treatment.

Conclusion

Our research convinces that the detection of CK19 in peripheral blood by flow cytometry is also a specific and feasible method to monitor circulating tumor cells in breast cancer.
Subtelomeric FISH analysis in 76 patients with syndromic developmental delay/intellectual disability
Authors: Belligni Elga F , Biamino Elisa , Molinatto Cristina , Messa Jole , Pierluigi Mauro , Faravelli Francesca , Zuffardi Orsetta , Ferrero Giovanni B , Silengo Margherita Cirillo
Published: April 2009

Background

Intellectual disability affects approximately 1 to 3% of the general population. The etiology is still poorly understood and it is estimated that one-half of the cases are due to genetic factors. Cryptic subtelomeric aberrations have been found in roughly 5 to 7% of all cases.

Methods

We performed a subtelomeric FISH analysis on 76 unrelated children with normal standard karyotype ascertained by developmental delay or intellectual disability, associated with congenital malformations, and/or facial dysmorphisms.

Results

Ten cryptic chromosomal anomalies have been identified in the whole cohort (13,16%), 8 in the group of patients characterized by developmental delay or intellectual disability associated with congenital malformations and facial dysmorphisms, 2 in patients with developmental delay or intellectual disability and facial dysmorphisms only.

Conclusion

We demonstrate that a careful clinical examination is a very useful tool for pre-selection of patients for genomic analysis, clearly enhancing the chromosomal anomaly detection rate. Clinical features of most of these patients are consistent with the corresponding emerging chromosome phenotypes, pointing out these new clinical syndromes associated with specific genomic imbalances.
Propofol: neuroprotection in an in vitro model of traumatic brain injury
Authors: Rossaint Jan , Rossaint Rolf , Weis Joachim , Fries Michael , Rex Steffen , Coburn Mark
Published: April 2009

Introduction

The anaesthetic agent propofol (2,6-diisopropylphenol) has been shown to be an effective neuroprotective agent in different in vitro models of brain injury induced by oxygen and glucose deprivation. We examined its neuroprotective properties in an in vitro model of traumatic brain injury.

Methods

In this controlled laboratory study organotypic hippocampal brain-slice cultures were gained from six- to eight-day-old mice pups. After 14 days in culture, hippocampal brain slices were subjected to a focal mechanical trauma and subsequently treated with different molar concentrations of propofol under both normo- and hypothermic conditions. After 72 hours of incubation, tissue injury assessment was performed using propidium iodide (PI), a staining agent that becomes fluorescent only when it enters damaged cells via perforated cell membranes. Inside the cell, PI forms a fluorescent complex with nuclear DNA.

Results

A dose-dependent reduction of both total and secondary tissue injury could be observed in the presence of propofol under both normo- and hypothermic conditions. This effect was further amplified when the slices were incubated at 32°C after trauma.

Conclusions

When used in combination, the dose-dependent neuroprotective effect of propofol is additive to the neuroprotective effect of hypothermia in an in vitro model of traumatic brain injury.
Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death
Authors: Benoist Hervé , Culerrier Raphaël , Poiroux Guillaume , Ségui Bruno , Jauneau Alain , Van Damme Els J M , Peumans Willy J , Barre Annick , Rougé Pierre
Published: April 2009

Subtle changes in cell surface N-glycan recognition can modulate the T lymphocyte fate.

Plant lectins displaying similar single sugar-binding specificity and identical molecular structure might present various biological effects. To explore this possibility, the effects on human lymphocytes of two mannose-specific and structurally closely related lectins, Morniga M from Morus nigra and artocarpin from Artocarpus integrifolia were investigated. In silico analysis revealed that Morniga M presents a more largely open carbohydrate-binding cavity than artocarpin, probably allowing interactions with a broader spectrum of carbohydrate moieties. In vitro, Morniga M interacted strongly with the lymphocyte surface and was uptaken quickly by cells. Morniga M and artocarpin triggered the proliferation and activation of human T and NK lymphocytes. A minority of B lymphocytes was activated in artocarpin-treated culture, whereas Morniga M favored the emergence of CD4+ CD8+ T lymphocytes. Moreover, cell death occurred in activated PBMC, activated T lymphocytes, and Jurkat T leukemia cells incubated with Morniga M only. The biological effects of both lectins were dependent on carbohydrate recognition. The Morniga M-induced cell death resulted, at least in part, from caspase-dependent apoptosis and FADD-dependent receptor-mediated cell death. Finally, Morniga M, but not artocarpin, triggered AICD of T lymphocytes. In conclusion, both lectins trigger lymphocyte activation, but only Morniga M induces cell death. In spite of similar in vitro mannose-binding specificities and virtually identical structure, only Morniga M probably interacts with carbohydrate moieties bound to molecules able to induce cell death. The present data suggest that subtle alterations in N-glycans can distinguish activation and cell death molecules at the lymphocyte surface.
Hypoxia increases macrophage motility, possibly by decreasing the heparan sulfate proteoglycan biosynthesis
Authors: Asplund Annika , Östergren-Lundén Gunnel , Camejo Germán , Stillemark-Billton Pia , Bondjers Göran
Published: April 2009

Hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression.

Macrophages are recruited and retained in hypoxic sites in atherosclerotic lesions and tumors. Furthermore, macrophages are suggested to be a major source of HSPG synthesis in atherosclerotic lesions. HSPG are, among other things, known to regulate cell motility, cell adhesion, and receptor interaction. The aim of this study was to investigate the effect of hypoxia on HSPG expression and macrophage motility. We also explored the potential regulation of HSPG by the transcription factor HIF-1α. The nondirected cell motility was increased in HMDM after 24 h exposure to hypoxia (0.5% O2) compared with normal cell culture condition (21% O2). Enzymatic degradation of HS GAG further increased the motility of the HMDM in hypoxia, indicating a role of reduced cell-associated HSPG in the increased HMDM motility. HMDM exposed to 24 h of hypoxia had lower mRNA expressions of syndecan-1 and −4 compared with cells exposed to normal cell culture conditions. Protein levels of syndecan-1 were also decreased significantly in response to hypoxia, and cells subjected to hypoxia had lower mRNA expression for key enzymes involved in HS biosynthesis. In addition, hypoxia was found to reduce the relative content of HS GAG. Transfecting THP-1 cells with siHIF-1α indicated that this transcription factor was not involved in the hypoxia-induced modifications of HSPG expression. Given the documented multiple functions of HSPG in macrophage behavior, the hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression.
TLR2 ligands augment cPLA2α activity and lead to enhanced leukotriene release in human monocytes
Authors: Lindner Sabine C , Köhl Ulrike , Maier Thorsten J , Steinhilber Dieter , Sorg Bernd L
Published: April 2009

Increased synthesis of inflammatory eicosanoids can be primed by innate immune receptor activation.

Toll-like receptors (TLRs) play an important role in innate immunity. They detect pathogen-associated receptor patterns (PAMPs) and initiate subsequent immune responses. Present studies investigate the influence of TLR2 ligands on leukotrienes (LT) formation in human monocytes. LTs are proinflammatory mediators derived from arachidonic acid (AA), which is released from membranes by phospholipase A2 (PLA2) enzymes. Pretreatment of MM6 cells with the TLR2 ligands LTA, FSL-1, or Pam3CSK4 resulted in an up to two- to threefold enhancement of ionophore-induced LT formation in a dose- and time-dependent manner and to an augmentation of ionophore-induced AA release with similar kinetics. Also in human peripheral blood mononuclear cells (hPBMC), TLR2 activators increased LT formation. Studies with PLA2 inhibitors indicated that the increase of AA release is a result of enhanced activity of group IV cPLA2 in MM6 cells. TLR2 ligands elicited the time-dependent activation of p38 MAPK and ERK1/2 pathways, which led to phosphorylation of cPLA2α at Ser505. Simultaneous inhibition of p38 MAPK and ERK1/2 pathways prevented the increase of cPLA2α phosphorylation and the augmentation of AA release. TLR2 ligand-induced increase of AA release was blocked by a neutralizing anti-hTLR2 antibody, indicating that TLR2 mediates augmented cPLA2 activation and subsequent LT biosynthesis.
PPARγ regulates retinoic acid-mediated DC induction of Tregs
Authors: Housley William J , O'Conor Catherine A , Nichols Frank , Puddington Lynn , Lingenheld Elizabeth G , Zhu Li , Clark Robert B
Published: April 2009

PPARγ plays a significant role in the induction of regulatory T cells (Tregs) by DC and can mediate enhanced conversion via secretion of retinoic acid.

CD4+ CD25+ Foxp3+ Tregs are critical regulators of immune responses and autoimmune diseases. nTregs are thymically derived; iTregs are converted in the periphery from CD4+ CD25– Foxp3– Teffs. Recent studies reported that GALT CD103+ DCs mediated enhanced iTreg conversion via the secretion of RA. However, the factors regulating RA secretion and hence, the induction of iTregs by DCs are not yet clear. Activation of the nuclear hormone receptor PPARγ has been shown to induce RA expression in human DCs, and thus, we postulated that PPARγ activation in DCs may be an important regulator of RA secretion and iTreg generation. Using in vitro and in vivo approaches, we now demonstrate that PPARγ activation enhances iTreg generation through increased RA synthesis from murine splenic DCs. In addition, we demonstrate that inhibition of DC PPARγ decreases iTreg generation, suggesting a role for endogenous PPARγ ligands in this process. Overall, our findings suggest that PPARγ may be important as a factor that stimulates DCs to produce RA and as a potential mechanism by which PPARγ ligands ameliorate autoimmunity.
Changes in dynamic shear moduli of carbonate rocks with fluid substitution
Authors: Baechle Gregor T. , Eberli Gregor P. , Weger Ralf J. , Massaferro Jose Luis
Published: April 2009

To assess saturation effects on acoustic properties in carbonates, we measure ultrasonic velocity on 38 limestone samples whose porosity ranges from 5% to 30% under dry and water-saturated conditions. Complete saturation of the pore space with water causes an increase and decrease in compressional- and shear-wave velocity as well as significant changes in the shear moduli. Compressional velocities of most water-saturated samples are up to [Formula: see text] higher than the velocities of the dry samples. Some show no change, and a few even show a decrease in velocity. Shear-wave velocity [Formula: see text] generally decreases, but nine samples show an increase of up to [Formula: see text]. Water saturation decreases the shear modulus by up to [Formula: see text] in some samples and increases it by up to [Formula: see text] in others. The average increase in the shear modulus with water saturation is [Formula: see text]; the average decrease is [Formula: see text]. The [Formula: see text] ratio shows an overall increase with water saturation. In particular, rocks displaying shear weakening have distinctly higher [Formula: see text] ratios. Grainstone samples with high amounts of microporosity and interparticle macro-pores preferentially show shear weakening, whereas recrystallized limestones are prone to increase shear strengths with water saturation. The observed shear weakening indicates that a rock-fluid interaction occurs with water saturation, which violates one of the assumptions in Gassmann’s theory. We find a positive correlation between changes in shear modulus and the inability of Gassmann’s theory to predict velocities of water-saturated samples at high frequencies. Velocities of water-saturated samples predicted by Gassmann’s equation often exceed measured values by as much as [Formula: see text] for samples exhibiting shear weakening. In samples showing shear strengthening, Gassmann-predicted velocity values are as much as [Formula: see text] lower than measured values. In 66% of samples, Gassmann-predicted velocities show a misfit to measured water-saturated P-wave velocities. This discrepancy between measured and Gassmann-predicted velocity is not caused solely by velocity dispersion but also by rock-fluid interaction related to the pore structure of carbonates. Thus, a pore analysis should be conducted to assess shear-moduli changes and the resultant uncertainty for amplitude variation with offset analyses and velocity prediction using Gassmann’s theory.
Thromboembolism in Patients With Advanced Gastroesophageal Cancer Treated With Anthracycline, Platinum, and Fluoropyrimidine Combination Chemotherapy: A Report From the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group
Authors: Starling Naureen , Rao Sheela , Cunningham David , Iveson Timothy , Nicolson Marianne , Coxon Fareeda , Middleton Gary , Daniel Francis , Oates Jacqueline , Norman Andrew Richard
Published: April 2009

Purpose

Data concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited.

Patients and Methods

This was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses.

Results

The incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043).

Conclusion

This analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment.
The Role of Genetic Variation in the Lamin A/C Gene in the Etiology of Polycystic Ovary Syndrome
Authors: Urbanek Margrit , Nampiaparampil Geetha , D'Souza Janine , Sefton Elizabeth , Ackerman Christine , Legro Richard S. , Dunaif Andrea
Published: April 2009

Objective: We performed this study to test the hypothesis that variation in the lamin a/c gene (LMNA) contributes to milder phenotypes of insulin resistance, hyperandrogenism, and/or metabolic syndrome associated with polycystic ovary syndrome (PCOS).

Research Design and Methods: We resequenced the coding region, flanking intronic, and proximal promoter regions of the lamin a/c gene in 43 women with PCOS with evidence of upper-body obesity (waist circumference >88 cm) and identified 56 variants, two of which were nonsynonymous substitutions (lmna11 exon1 E98D; lmna24 exon 7 R455C). We genotyped 53 single-nucleotide polymorphisms (44 identified through resequencing and nine included to maximize informativeness of the entire gene) in 624 index (PCOS) cases and 544 controls of European ancestry. We tested for association between these variants and PCOS. In a subset of individuals, we also tested for association with metabolic syndrome and quantitative traits (body mass index, waist circumference, total testosterone, dehydroepiandrosterone sulfate, fasting glucose and insulin, low-density lipoprotein, and total triglycerides).

Results: After correction for multiple testing, none of the variants showed significant evidence for association with PCOS, the metabolic syndrome, or any of the quantitative traits tested.

Conclusions: Whereas these studies cannot exclude the role of genetic variation in the lamin a/c gene in isolated cases of PCOS, we can conclude that common variation in the lamin a/c gene does not contribute to the etiology of PCOS in women of European ancestry.
Mechanosensing in actin stress fibers revealed by a close correlation between force and protein localization
Authors: Colombelli Julien , Besser Achim , Kress Holger , Reynaud Emmanuel G. , Girard Philippe , Caussinus Emmanuel , Haselmann Uta , Small John V. , Schwarz Ulrich S. , Stelzer Ernst H. K.
Published: April 2009

The mechanics of the actin cytoskeleton have a central role in the regulation of cells and tissues, but the details of how molecular sensors recognize deformations and forces are elusive. By performing cytoskeleton laser nanosurgery in cultured epithelial cells and fibroblasts, we show that the retraction of stress fibers (SFs) is restricted to the proximity of the cut and that new adhesions form at the retracting end. This suggests that SFs are attached to the substrate. A new computational model for SFs confirms this hypothesis and predicts the distribution and propagation of contractile forces along the SF. We then analyzed the dynamics of zyxin, a focal adhesion protein present in SFs. Fluorescent redistribution after laser nanosurgery and drug treatment shows a high correlation between the experimentally measured localization of zyxin and the computed localization of forces along SFs. Correlative electron microscopy reveals that zyxin is recruited very fast to intermediate substrate anchor points that are highly tensed upon SF release. A similar acute localization response is found if SFs are mechanically perturbed with the cantilever of an atomic force microscope. If actin bundles are cut by nanosurgery in living Drosophila egg chambers, we also find that zyxin redistribution dynamics correlate to force propagation and that zyxin relocates at tensed SF anchor points, demonstrating that these processes also occur in living organisms. In summary, our quantitative analysis shows that force and protein localization are closely correlated in stress fibers, suggesting a very direct force-sensing mechanism along actin bundles.
Look but do not fix: the pioneers of interventional cardiovascular radiology
Authors: Banerjee Ashis
Published: April 2009

The extension of endovascular radiological procedures to a one-stop combined investigation and treatment of cardiovascular disease has revolutionized clinical practice. The giants in this respect are Charles Dotter, working from Portland, OR; Mason Sones from the Cleveland Clinic; and Andreas Gruentzig from Zurich and latterly Atlanta, GA. Serendipity and lateral thinking were pivotal in developing procedures that are now routine.
Sir James Edward Smith (1759-1828) MD FRS, botanist, co-founder of the Linnean Society of London
Authors: Hawgood Barbara J
Published: April 2009

James Edward Smith's interest in botany led him to enter medicine at Edinburgh in 1781. Smith was continuing his medical studies in London when Sir Joseph Banks (1743-1820) suggested to him that he should purchase the collection of the famous Swedish naturalist Carl Linnaeus that had just been offered to Banks. Smith bought the Linnean Collection and Library in 1784. In 1786 he was awarded the degree of Doctor of Medicine from Leiden. In 1788 Smith, with two associates, founded the Linnean Society of London and became President for life. Smith turned from medicine to natural history as a lecturer and writer. During his lifetime he produced numerous botanical works of high value, including The English Flora (1824-28), and he did much to popularize botany.
Understanding Variation in Managers' Ambidexterity: Investigating Direct and Interaction Effects of Formal Structural and Personal Coordination Mechanisms
Authors: Mom Tom J. M. , van den Bosch Frans A. J. , Volberda Henk W.
Published: April 2009

Previous research focuses on firm and business unit level ambidexterity. Therefore, conceptual and empirically validated understanding about ambidexterity at the individual level of analysis is very scarce. This paper addresses this gap in the literature by investigating managers' ambidexterity, delivering three contributions to theory and empirical research on ambidexterity: first, by proposing three related characteristics of ambidextrous managers; second, by developing a model and associated hypotheses on both the direct and interaction effects of formal structural and personal coordination mechanisms on managers' ambidexterity; and third, by testing the hypotheses based on a sample of 716 business unit level and operational level managers.

Findings regarding the formal structural mechanisms indicate that a manager's decision-making authority positively relates to this manager's ambidexterity, whereas formalization of a manager's tasks has no significant relationship with this manager's ambidexterity. Regarding the personal coordination mechanisms, findings indicate that both the participation of a manager in cross-functional interfaces and the connectedness of a manager to other organization members positively relate to this manager's ambidexterity. Furthermore, results show positive interaction effects between the formal structural and personal coordination mechanisms on managers' ambidexterity. The paper's theoretical contributions and empirical results increase our understanding about managers' ambidexterity and about how different types and combinations of coordination mechanisms relate to variation in managers' ambidexterity.
Social exclusion and social justice: a rural perspective on resource allocation
Authors: Asthana Sheena , Halliday Joyce , Gibson Alex
Published: April 2009

The process by which the UK government allocates resources for public sector services has rarely been scrutinised from the perspective of social exclusion or social justice. Yet, not only is a significant proportion of public expenditure targeted at just these issues but also the resulting per capita and areal allocations vary significantly with important implications for distributional equity. One product is an apparent urban/rural divide. This article draws on examples of both discretionary and mainstream funding mechanisms to explore the consequences for social exclusion and social justice in rural areas, finding concern for both vulnerable groups and universal welfare.
From Forgotten Founder to Indispensable Icon: Crispus Attucks, Black Citizenship, and Collective Memory, 1770–1865
Authors: Kachun Mitch
Published: April 2009

This study illustrates and assesses the historical amnesia surrounding Crispus Attucks and his role in the American Revolution between his death at the 1770 Boston Massacre and the 1850s, when he first became widely used as a symbol of African American patriotism and citizenship. Studies of collective memory and the role it plays in shaping historical understanding, developing commemorative traditions, defining culture heroes, and constructing group or national identity, have been expanding in recent decades, including significant work related to the Revolutionary era and African American history. In particular, there are growing bodies of work on blacks’ uses of public commemoration and on the development of a pantheon of race heroes to advance both race pride and African Americans’ legitimate claims to American citizenship. Scholarship on figures such as Richard Allen, Sojourner Truth, Nat Turner, and others suggests the ways in which black Americans have constructed heroic traditions in ways that fostered both racial and American identities. After the 1850s, black activists presented Crispus Attucks as a “black Founding Father”—not merely an important race hero, but a legitimate national hero. But this seminal figure in African Americans’ quest to define their legitimate place in United States history and culture was virtually ignored by both blacks and whites in the early republic. Understanding the process of Attucks’s rediscovery after the 1830s contributes not only to our understanding of African American history, but also to our understanding of how collective memory is constructed and appropriated to serve particular political agendas.
The Christian Nation Debate and Witness Competency
Authors: Formisano Ronald P. , Pickering Stephen
Published: April 2009

Historians have examined closely the Founders’ intentions regarding the First Amendment’s religious establishment clause as well as the influence of Protestant Christianity in the public life of the early republic. The new national government, and particularly several states, often breached Jefferson’s “wall of separation” between church and state. While these complex and important subjects, hardly confined to academic circles, will continue to spur research and controversy, this article addresses one feature of the prominence of Christianity in civic life. In courtrooms across the country, well into the nineteenth century, judges allowed witnesses to be questioned regarding their religious beliefs, with some requiring belief in the “future state” doctrine of divine rewards and punishments before permitting them to testify. Some courts accepted witnesses who believed in divine punishment in this life, or in non-eternal retribution in the hereafter. This common law tradition affected primarily Universalists, various kinds of nonbelievers, and of course atheists. While the common law adapted to rapid change in the economic and technological realm, common law religious tests for witness competency proved remarkably durable.
Morrill and the Missing Industries: Strategic Lobbying Behavior and the Tariff, 1858–1861
Authors: Magness Phillip W.
Published: April 2009

A general consensus among political economists holds that tariffs are usually enacted under the influence of business lobbyists, who seek protection for their industries. Justin Morrill, author of the 1861 tariff that bears his name, explicitly denied this charge. Instead, Morrill claimed his bill was only “coldly welcomed” by manufacturers, and presented it as a “revenue” measure to restore the 1846 Walker Tariff’s rates. Though the 1861 Tariff enjoys a protectionist reputation today, historians have largely accepted Morrill’s word on lobbying, purporting the absence of industry pressure. The resulting literature is replete with contradiction regarding the tariff’s origins and purposes. Depictions of its protectionist characteristics range from “mild” to “extreme.” This article challenges the general acceptance of Morrill’s depiction by examining his correspondence with manufacturing interests. Far from being absent, manufacturers from dozens of industries collaborated with Morrill to draft the bill’s tariff schedule and obtain favorable levels of protection. The Morrill Tariff’s ad valorem equivalent rates are calculated from customs records, thereby facilitating a stronger assessment of its protective character. Though some tariff rate increases, particularly on luxury items, were clearly intended to augment federal revenue, the law imposed protective rates on many import-competing goods well beyond their 1846 levels. Protectionism was typically applied to products where documented lobbyist influence was strong, such as iron and its manufactures, glass, refined sugar, and certain woolens and cloth goods. Morrill’s depiction of his tariff should accordingly be interpreted as a political argument to advance the bill rather than an accurate recounting of its legislative origins.
Effects of Word Position and Stress on Onset Cluster Production: Evidence from Typical Development, Specific Language Impairment, and Dyslexia
Authors: Marshall Chloe R. , van der Lely Heather K. J.
Published: April 2009

Children with specific language impairment (SLI) and dyslexia have phonological deficits that are claimed to cause their language and literacy impairments and to be responsible for the overlap between the two disorders. Little is known, however, about the phonological grammar of children with SLI and dyslexia, and indeed whether they show differences in phonological development. We designed a nonword repetition task to investigate the impact of word position and stress on the production accuracy of onset clusters. We compared the performance of children with SLI and dyslexia, SLI only, and dyslexia only (mean age eleven), and three groups of typically developing children (aged five, seven, and nine). Analysis of cluster production accuracy revealed that all three clinical groups made significantly more errors on word-medial clusters compared to word-initial clusters. Unstressed clusters were more difficult than stressed clusters for the two dyslexic groups but not the SLI-only group. None of the groups of typically developing children showed an effect of word position or stress on cluster accuracy. All groups, however, created new clusters significantly more frequently in initial than medial positions. These results indicate a difference in phonological grammar in children with SLI and dyslexia that could potentially shed light on the relationship between the two disorders. Furthermore, they indicate that structural position and stress are developmentally independent elements in phonological representations.
Peaks Beyond Phonology: Adolescence, Incrementation, and Language Change
Authors: Tagliamonte Sali A. , D'Arcy Alexandra
Published: April 2009

What is the mechanism by which a linguistic change advances across successive generations of speakers? We explore this question by using the model of incrementation provided in Labov 2001 and analyzing six current changes in English. Extending Labov's focus on recent and vigorous phonological changes, we target ongoing morphosyntactic(-semantic) and discourse-pragmatic changes. Our results provide a striking validation of the incrementation model, confirming its value as a key to understanding the evolution of linguistic systems. However, although our findings reveal the predicted peak in the apparent-time progress of a change and corroborate the female tendency to lead innovation, there is no absolute contrast between men and women with respect to incrementation. Instead, quantitative differences in the social embedding of linguistic change correlate with the rate of the change in the speech community.
Suffix Ordering and Morphological Processing
Authors: Plag Ingo , Baayen Harald
Published: April 2009

There is a long-standing debate about the principles constraining the combinatorial properties of suffixes. Hay 2002 and Hay & Plag 2004 proposed a model in which suffixes can be ordered along a hierarchy of processing complexity. We show that this model generalizes to a larger set of suffixes, and we provide independent evidence supporting the claim that a higher rank in the ordering correlates with increased productivity. Behavioral data from lexical decision and word naming show, however, that this model has been one-sided in its exclusive focus on the importance of constituent-driven processing, and that it requires supplementation by a second and equally important focus on the role of memory. Finally, using concepts from graph theory, we show that the space of existing suffix combinations can be conceptualized as a directed graph, which, with surprisingly few exceptions, is acyclic. This acyclicity is hypothesized to be functional for lexical processing.
Semplates: A new concept in lexical semantics?
Authors: Levinson Stephen C. , Burenhult Niclas
Published: April 2009

This short report draws attention to an interesting kind of configuration in the lexicon that seems to have escaped theoretical or systematic descriptive attention. These configurations, which we dub SEMPLATES , consist of an abstract structure or template, which is recurrently instantiated in a number of lexical sets, typically of different form classes. A number of examples from different language families are adduced, and generalizations made about the nature of semplates, which are contrasted to other, perhaps similar, phenomena.
Learning Phonological Categories
Authors: Goldsmith John , Xanthos Aris
Published: April 2009

This article describes in detail several explicit computational methods for approaching such questions in phonology as the vowel/consonant distinction, the nature of vowel harmony systems, and syllable structure, appealing solely to distributional information. Beginning with the vowel/consonant distinction, we consider a method for its discovery by the Russian linguist Boris Sukhotin, and compare it to two newer methods of more general interest, both computational and theoretical, today. The first is based on spectral decomposition of matrices, allowing for dimensionality reduction in a finely controlled way, and the second is based on finding parameters for maximum likelihood in a hidden Markov model. While all three methods work for discovering the fairly robust vowel/consonant distinction, we extend the newer ones to the discovery of vowel harmony, and in the case of the probabilistic model, to the discovery of some aspects of syllable structure.
Some Observations on “Observational” Research
Authors: Bluhm Robyn
Published: April 2009

Evidence-based medicine (EBM) ranks different medical research methods on a hierarchy, at the top of which are randomized controlled trials (RCTs) and systematic reviews or meta-analyses of RCTs. Any study that does not randomly assign patients to a treatment or a control group is automatically placed at a lower level on the hierarchy. This article argues that what matters is whether the treatment and control groups are similar with respect to potential confounding factors, not whether they got that way through randomization. Moreover, nonrandomized studies tend to have other characteristics that make them useful sources of evidence, in that they tend to last longer and to enroll more patients than do randomized trials. Replacing the sharp dichotomy between randomized and nonrandomized studies with a continuum from “clean” studies (which have high internal validity but whose results do not readily generalize to clinical practice) to pragmatic studies (which are designed to more closely reflect clinical practice) would also make a place for outcomes research and research using clinical databases, which are not included in the current hierarchy of evidence but which can provide important information about the safety and efficacy of treatments.
Making the Grade: Assuring Trustworthiness in Evidence
Authors: Upshur Ross
Published: April 2009

Despite evidence-based medicine’s (EBM’s) significant evolution and maturation from its revolutionary origins to its current form as the preeminent means of practicing medicine, there are still good reasons to be unsatisfied with EBM. This essay explores two important new developments in EBM: recently articulated accounts of the scientific basis of EBM, and the related writings of the GRADE Working Group to create standards for interpretation of the medical literature and evaluation of recommendations. A review of Karanicolas, Kunz, and Guyatt’s (2008) three-step articulation of EBM’s scientific basis demonstrates that the supposed soundness of each principle is not attributable to its scientific status; instead, the normative language of each principle highlights EBM’s grounding in an only partially articulated philosophical framework. The GRADE Working Group’s effort similarly relies on credibility, consensus, and trust in its defense and justification of EBM. These recent developments in EBM reveal that if the clinical research literature is to be informative or foundational to the enterprise of health care, much work needs to be done to secure its trustworthiness and integrity. An agenda for examining trust and trustworthiness in the context of health research is proposed.
Iconoclast or Creed?: Objectivism, Pragmatism, and the Hierarchy of Evidence
Authors: Goldenberg Maya J.
Published: April 2009

Because “evidence” is at issue in evidence-based medicine (EBM), the critical responses to the movement have taken up themes from post-positivist philosophy of science to demonstrate the untenability of the objectivist account of evidence. While these post-positivist critiques seem largely correct, I propose that when they focus their analyses on what counts as evidence, the critics miss important and desirable pragmatic features of the evidence-based approach. This article redirects critical attention toward EBM’s rigid hierarchy of evidence as the culprit of its objectionable epistemic practices. It reframes the EBM discourse in light of a distinction between objectivist and pragmatic epistemology, which allows for a more nuanced analysis of EBM than previously offered: one that is not either/or in its evaluation of the decision-making technology as either iconoclastic or creedal.
Ethics and Evidence in Psychiatric Practice
Authors: Gupta Mona
Published: April 2009

Many psychiatrists have endorsed the idea of evidence-based psychiatry, the application of the principles of evidence-based medicine (EBM) to psychiatric practice. Proponents of an evidence-based approach to psychiatry hope that if practice is driven by “hard” scientific data, there will be greater potential to help patients. In other words, advocates of evidence-based psychiatry aim to bolster psychiatry’s ethical standing through scientific evidence. Can EBM provide this ethical substantiation to psychiatry? This article provides an overview of some of the main ethical issues within psychiatry and examines three interrelated questions: (1) to which ethical values is EBM committed? (2) which ethical theory is reflected in these values? and (3) can these values and theories resolve existing ethical issues in psychiatry? EBM strives for the “greatest good for the greatest number,” where good is defined as improved health. This utilitarian orientation cannot, however, address critical areas of moral importance for psychiatry, such as how its practitioners differentiate normal from abnormal, how they determine which forms of suffering should be alleviated through psychiatric means, and when involuntary intervention is ethically justified. The ethical principles implicit in EBM are too limited to serve as an ethical basis for psychiatry.
Justice in Health Research: What is the Role of Evidence-Based Medicine?
Authors: Rogers Wendy , Ballantyne Angela
Published: April 2009

Evidence-based medicine (EBM) aims to facilitate access to up-to-date, accurate information about the effectiveness of medical interventions, in order to improve human health. The quality of the research results available for EBM processes of synthesis and meta-analysis is critical to this process. If there are distortions or corruptions in the research process, EBM becomes a false prophet, collecting and propagating unreliable results. This article examines flaws in the current processes of research production and the implications of these for justice and for vulnerable patients, and explores possible solutions.
Complementary and Alternative Medicine: Between Evidence and Absurdity
Authors: Ernst Edzard
Published: April 2009

Complementary/alternative medicine (CAM) has become important, particularly because it is widely used. This article outlines CAM’s position between evidence and absurdity. It discusses misconceptions that often mislead the public and shows how CAM can and should be submitted to the principles of evidence- based medicine (EBM). Employing the example of acupuncture, the evidence as it currently stands is described. But there are numerous obstacles to applying EBM to CAM. EBM is defenseless against absurdity. We should, therefore, demarcate the absurd in order to avoid wasting time and resources. The new fad of “integrated” medicine has been proposed as a potential replacement for EBM.
Sequestered Evidence and the Distortion of Clinical Practice Guidelines
Authors: McGoey Linsey
Published: April 2009

As a result of the growth of evidence-based practices across the world, health-care providers and policymakers in the United States, United Kingdom, and Europe have established institutes such as the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) to produce clinical guidelines that physicians are asked to use in their daily practice. This article discusses how the withholding of clinical trial information by pharmaceutical companies and academic researchers affects the reliability of clinical guidelines. It first offers a case study analysis of the U.K. drug regulator’s failure to prosecute GlaxoSmithKline, manufacturer of the bestselling antidepressant Seroxat (manufactured as Paxil in North America), for withholding information on the safety of Seroxat from regulators. It next examines the idea of a “Sarbanes- Oxley for Science,” a recent proposal that seeks to introduce legislation forcing companies to disclose clinical trials that have indeterminate or negative results. Legislation such as Sarbanes-Oxley for Science would solve some problems with the withholding of data, but not all. Until practitioners and policymakers address the political and legal barriers preventing full access to clinical trial data for all medical treatments, the ideals of evidence-based practice will remain elusive.
Evidence-Based Policymaking: A Critique
Authors: Greenhalgh Trisha , Russell Jill
Published: April 2009

The idea that policy should be based on best research evidence might appear to be self-evident. But a closer analysis reveals a number of problems and paradoxes inherent in the concept of “evidence-based policymaking.” The current conflict over evidence-based policymaking parallels a long-standing “paradigm war” in social research between positivist, interpretivist, and critical approaches. This article draws from this debate in order to inform the discussions over the appropriateness of evidence- based policymaking and the related question of what is the nature of policymaking. The positivist, empiricist worldview that underpins the theory and practice of evidence-based medicine (EBM) fails to address key elements of the policymaking process. In particular, a narrowly “evidence-based” framing of policymaking is inherently unable to explore the complex, context-dependent, and value-laden way in which competing options are negotiated by individuals and interest groups. Sociolinguistic tools such as argumentation theory offer opportunities for developing richer theories about how policymaking happens. Such tools also have potential practical application in the policymaking process: by enhancing participants’ awareness of their own values and those of others, the quality of the collective deliberation that lies at the heart of policymaking may itself improve.
Valuing Evidence: Bias and the Evidence Hierarchy of Evidence-Based Medicine
Authors: Borgerson Kirstin
Published: April 2009

Proponents of evidence-based medicine (EBM) suggest that a hierarchy of evidence is needed to guide medical research and practice. Given a variety of possible evidence hierarchies, however, the particular version offered by EBM needs to be justified. This article argues that two familiar justifications offered for the EBM hierarchy of evidence—that the hierarchy provides special access to causes, and that evidence derived from research methods ranked higher on the hierarchy is less biased than evidence ranked lower—both fail, and that this indicates that we are not epistemically justified in using the EBM hierarchy of evidence as a guide to medical research and practice. Following this critique, the article considers the extent to which biases influence medical research and whether meta-analyses might rescue research from the influence of bias. The article concludes with a discussion of the nature and role of biases in medical research and suggests that medical researchers should pay closer attention to social mechanisms for managing pervasive biases.