bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Toll-like receptor 2 impairs hypoxic pulmonary vasoconstriction in mice
Authors: Petersen Bodil , Bloch Kenneth D. , Ichinose Fumito , Shin Hae-Sook , Shigematsu Misako , Bagchi Aranya , Zapol Warren M. , Hellman Judith
Published: December 2007

Toll-like receptors (TLRs) mediate inflammation in sepsis, but their role in sepsis-induced respiratory failure is unknown. Hypoxic pulmonary vasoconstriction (HPV) is a unique vasoconstrictor response that diverts blood flow away from poorly ventilated lung regions. HPV is impaired in sepsis and after challenge with the TLR4 agonist lipopolysaccharide (LPS). Unlike TLR4 agonists, which are present only in Gram-negative bacteria, TLR2 agonists are ubiquitously expressed in all of the major classes of microorganisms that cause sepsis, including both Gram-positive and Gram-negative bacteria and fungi. We tested the hypothesis that (S)-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys4-OH, trihydrochloride (Pam3Cys), a TLR2 agonist, impairs HPV and compared selected pulmonary and systemic effects of Pam3Cys vs. LPS. HPV was assessed 22 h after challenge with saline, Pam3Cys, or LPS by measuring the increase in the pulmonary vascular resistance of the left lung before and during left lung alveolar hypoxia produced by left mainstem bronchus occlusion (LMBO). Additional endpoints included arterial blood gases during LMBO, hemodynamic parameters, weight loss, temperature, physical appearance, and several markers of lung inflammation. Compared with saline, challenge with Pam3Cys caused profound impairment of HPV, reduced systemic arterial oxygenation during LMBO, weight loss, leukopenia, and lung inflammation. In addition to these effects, LPS-challenged mice had lower rectal temperatures, metabolic acidosis, and were more ill appearing than Pam3Cys-challenged mice. These data indicate that TLR2 activation impairs HPV and induces deleterious systemic effects in mice and suggest that TLR2 pathways may be important in sepsis-induced respiratory failure.
Role of CD38 in TNF-α-induced airway hyperresponsiveness
Authors: Guedes Alonso G. P. , Jude Joseph A. , Paulin Jaime , Kita Hirohito , Lund Frances E. , Kannan Mathur S.
Published: December 2007

CD38 is involved in normal airway function, IL-13-induced airway hyperresponsiveness (AHR), and is also regulated by tumor necrosis factor (TNF)-α in airway smooth muscle (ASM) cells. This study aimed to determine whether TNF-α-induced CD38 upregulation in ASM cells contributes to AHR, a hallmark of asthma. We hypothesized that AHR would be attenuated in TNF-α-exposed CD38-deficient (CD38KO) mice compared with wild-type (WT) controls. Mice ( n = 6–8/group) were intranasally challenged with vehicle control or TNF-α (50 ng) once and every other day during 1 or 4 wk. Lung inflammation and AHR, measured by changes in lung resistance after inhaled methacholine, were assessed 24 h following the last challenge. Tracheal rings were incubated with TNF-α (50 ng/ml) to assess contractile changes in the ASM. While a single TNF-α challenge caused no airway inflammation, both multiple-challenge protocols induced equally significant inflammation in CD38KO and WT mice. A single intranasal TNF-α challenge induced AHR in the WT but not in the CD38KO mice, whereas both mice developed AHR after 1 wk of challenges. The AHR was suppressed by extending the challenges for 4 wk in both mice, although to a larger magnitude in the WT than in the CD38KO mice. TNF-α increased ASM contractile properties in tracheal rings from WT but not from CD38KO mice. In conclusion, CD38 contributes to TNF-α-induced AHR after a brief airway exposure to the cytokine, likely by mediating changes in ASM contractile responses, and is associated with greater AHR remission following chronic airway exposure to TNF-α. The mechanisms involved in this remission remain to be determined.
Minority Rights, Multiculturalism and the Roma of Europe
Authors: Barth William
Published: December 2007

In this article, I review legal initiativaes to improve conditions for the Roma peoples who live in the states of Europe. The question is timely given the accession of Romania and Bulgaria to the European Union on 1 January 2007. Romania contains the largest concentration of the Roma population in Europe. My article uncovers a schism between political theory and international law on the question of minority rights. I distinguish how the conclusions of Will Kymlicka, one of the most prolific writers on the subject of multiculturalism in political theory, differ from the international jurisprudence that protects minority groups. In this essay, I analyse Kymlicka's claim that multicultural policies are contextually dependent, and an inappropriate subject for a common legal regime of international human rights treaties. To determine the implications of human rights jurisprudence for this normative claim, I also research court cases filed by the Roma under the European Framework Convention for the Protection of Minorities and the European Convention for the Protection of Human Rights and Fundamental Freedoms. I contrast the international treaties that protect minority groups from political theorist accounts of multiculturalism in three areas. First, my article discusses jurisdictional issues concerning whether the particular groups defined by minority rights, irrespective of their geographical location or contextual experience, are proper subjects for protection by a common rights regime. Next, I illustrate how cultural rights are distinguishable from traditional civil rights laws. Finally, I examine how the historic persecution of the Roma violates human rights standards that protect minorities. The Roma have a long and unique relationship with the European states, which serves to demonstrate whether or not a common regime of minority rights safeguards the cultural development of the Roma.
Constraining Chaos
Authors:   Fraser
Published: December 2007

With the help of the integrated study of time, the paper traces the evolution of causation and time. Then, based on what has been learned and assisted by a critique of the idea that our experience of passage is rooted in cosmic entropy increase, it suggests that the human experience of time derives from the constitutive conflicts of matter, life, and personal and collective human identities. It shows that all of these conflicts derive from the evolutionary constraints upon the primeval chaos.
In Search of Dead Time: Faulkner's "A Rose for Emily"
Authors:   Harris
Published: December 2007

Gilles Deleuze discovers in Marcel Proust a mode of thinking about time specific to literature. Deleuze's analysis may be used as a framework for showing how William Faulkner's fiction induces readers to undertake a similar thinking process. Faulkner's story "A Rose for Emily" provides a fruitful example, because its enigmatic qualities in relation to chronology engender a deeper inquiry into the nature of time in the story. While Proust undertakes a search for lost time, Faulkner sends his reader in search of a dead time encrypted in the heart of his tale.
Mythen, die unter die Haut gehen—zur literarischen Form der Tätowierelegie (PBrux. inv. e 8934 und PSorb. inv. 2254)
Authors:   Bernsdorff
Published: December 2007

In the tattoo elegy, written on a papyrus from the second century BC, a speaker threatens to tattoo pictures of mythical sinners and their punishment on someone's skin. I try to show that this alludes to the ancient practice of tattooing a text which describes the offences of a criminal on his body. At the same time, the possible erotic context of the poem suggests that it modifies the mainly elegiac topos of leaving marks (notae in Latin) on the skin of the beloved (part 1). In the following parts I concentrate on the two most important literary forms the tattoo elegy combines, namely ecphrasis and catalogue. The poet stresses the catalogue form on different levels of content as well as of form (part 2). The combination of both forms is already prepared for in archaic poetry (part 3). The speaker exploits the uncertainty whether the description only tells what is represented in the pictures or whether it becomes a narrative expansion without a visible equivalent. This uncertainty is inherent in every ecphrasis, but in this special case, where the production of the picture is connected with the pain of the tattooing, it reaches a new degree of intensity.
When Success Becomes a Liability: Challenges of State Building in Eritrea (1991-2005)
Authors: Bereketeab Redie
Published: December 2007

The article aims to discuss and analyze the post-liberation state building challenges in Eritrea. It interrogates how and why the promising start was transformed into a nightmare. It traces two sets of explanatory factors. The first is the political culture that was developed during the liberation struggle. A political culture characterized by centralization, hierarchy, collectivism, strong loyalty and discipline became an obstacle to state building and transition from a guerrilla to civilian governance. The second set of factors pertains to the second war with Ethiopia. The second war not only erased all the post-liberation achievements, but also plunged the nation into social, economic, and political structural and systemic crisis. To exist from this predicament would require emancipation from the political culture of the liberation struggle and smooth transition to a civilian democratic and constitutional governance system.
The Effects of Polygyny and Domicility on Offspring Sex Ratio in Ghana
Authors: Amankwaa Adansi
Published: December 2007

This article explores how family structure and domicility influences offspring sex ratio bias, specifically living arrangements of husband in polygynous unions. Data from three Ghana Demographic and Health Surveys were used to examine the relationship between family structure and offspring sex ratio at birth, something that previous studies have not been able to do. This study estimate models of sex ratio offspring if the wives live together with husband present and wives live in separate dwellings and are visited by husband in turn. The results suggest that within polygynous marriages there are more male births, especially when husbands reside in the same dwelling as wives, than when husbands reside in separate dwellings from their wives. The analyses show that offspring sex ratio is related to the structure of living arrangement of husbands in polygynous unions. Indeed, the findings suggest that living arrangements and family structure among humans are important factors in predicting offspring sex ratio bias.
Hermeneutic Reflections from Visiting a Project in Dumaria, India
Authors: Smythe Liz , Robinson Bob , Scrimgeour Frank
Published: December 2007

When people from one culture visit the transformational development work in another country the question of 'understanding' is raised. This paper draws on the philosophical writings of Heidegger and Gadamer to show how interpretations are made in an experience of 'being there'. We argue that understanding is always on-the-way, influenced by past experience, interest, and mood. 'Being-there' affords an opportunity to move beyond taken-for-granted assumptions, to become more attuned to the hermeneutic 'as' that reveals the complex nature of 'meaning'. At the same time, we recognise that understanding always comes with the possibility of misunderstanding. Dialogue, where partners seeks to understand the experience of 'other, opens the way forward.
Toward a Theological 'Theory of Everything'
Authors: Barrett Peter
Published: December 2007

The emergence of a new scientific world-picture during the course of the 20thcentury has created the challenge to theology, as in the time of Aquinas, to act as the great integrating discipline, drawing upon the full range of knowledge to formulate a grand narrative of the evolving cosmos. First, key questions of the science-theology debate of the past three decades are outlined, with emphasis on the epistemic aspects. George Ellis's theistic cosmology is then presented briefly, as an example of a limited integration that brings together the realms of the physical and the moral. Using the same hypothetico-deductive approach, an axiomatic framework is proposed as a way of extending his model into a more comprehensive scheme - one that is based on a fundamental idea of trinitarian theology, the kenosis of God. This is then linked to the traditional triad of transcendental values - truth, goodness and beauty - with reference on the one hand to the neglect of beauty in modern culture, and on the other hand to the role of the Holy Spirit as the One who affirms particularity and inspires beauty.
The Poor in the Old Testament: Some Observations1
Authors: Levin Christoph
Published: December 2007

The positive religious attitude to poverty distinguishes the Old Testament from its environment in the Ancient Near East. According to the worldview held in antiquity, poverty was simply a given fact. In the ancient ideology of kingship, for example, concern for the poor counted as one of the king's special duties; but this concern was designed to preserve the world order, not to change it. The Old Testament view is very different. Prophecy condemns the oppression of the poor in the strongest terms and proclaims Yahweh's comprehensive judgment on their oppressors. Everything thrusts towards change and fundamental remedy. At the same time, the poor (Anawim) count as Yahweh's people in a special sense. It emerges from literary analysis that this special character did not as yet exist in the pre-exilic period. The relevant texts are evidently brief and late ad hoc additions. This is true both of the Torah (Exod 22; Deut 15; 22) and of the prophets (Isa 1-3; Jer; Ezek; Amos; Zeph; Hab; Zech), as well as of the Psalms (passim). There are historical reasons for this. We know from Nehemiah 5 that the impoverishment of wide sections of the population was a problem in the post-exilic community. One possible cause was the economic 'modernisation' which took place in the Persian and Hellenistic period. The poor, who interpreted their fate as the fruit of obedience to the Torah, expected Yahweh to bring about the reversal of that fate, either through the intervention of the Last Judgment or through the coming of the Messiah. As well as Moses (Num 12:3), the Messiah himself (Zech 9:9), was in the end also viewed as being one of the poor.
John Hick's Theology of Religions and Inter-Religious Dialogue: a Critique
Authors: Meyer John R.
Published: December 2007

While denying that belief in Jesus Christ is an essential element for personal salvation, John Hick presupposes Christian concepts of salvation. Even though he denies the universality of Christ vis-à-vis other world religions, the Christian doctrine of salvation is at the very heart of his project, albeit in a controversial form (as universal salvation or apocatastasis). I explore the influence of Immanuel Kant and Friedrich Schleiermacher in Hick's thought and discuss how his theology of religions and his concept of inter-religious dialogue are related to Christianity and yet are divorced from some of its central tenets.
The Restrainer Removed: A Truly Alarming Thought (2 Thess 2:1-12)
Authors: Tonstad Sigve
Published: December 2007

While many of the apocalyptic images in 2 Thessalonians have puzzled readers, it is question of the identities of "the lawless one" in 2:8 and "the retrainer" in 2:6 that has occasioned the most debate. The author of the letter is apparently building upon and assuming earlier discussions that the modern reader cannot re-create. However, this article argues that by placing these terms in the context of biblical prophecy, esp. Isa. 14:12-20 and Hab. 2:3, it becomes likely that "the lawless one" is Satan or a representative thereof and that "the restrainer" is God. This reading further suggests that a complex apocalyptic narrative underlies these texts.
The Matrix of Oppression and Privilege
Authors: Ferber Abby L. , Herrera Andrea O'Reilly , Samuels Dena R.
Published: December 2007

This article discusses a creative, collaborative model the authors have developed between the Ethnic Studies and Women's Studies programs on their campus that provides a paradigm that other universities around the country might learn from. After situating the program within a historical and national context, this article examines the specific challenges faced within the university setting and offers a range of institutional strategies that have proven successful. The authors examine their collaboration, which consciously mirrors and attempts to implement the growing movement in teaching and research toward an intersectional approach to teaching about privilege and oppression. Within the university context, this framework has been institutionalized within the curriculum as well as the structure of the program. In the new millennium, this framework can serve as a model for other campuses.
“Assume the Position . . . You Fit the Description”
Authors: Smith William A. , Allen Walter R. , Danley Lynette L.
Published: December 2007

The present study examines the experiences of 36 Black male students, in focus group interviews, enrolled at Harvard University; Michigan State University; University of California, Berkeley; University of Illinois; and the University of Michigan. Two themes emerged: (a) anti-Black male stereotyping and marginality (or Black misandry), which caused (b) extreme hypersurveillance and control. Respondents experienced racial microaggressions in three domains: (a) campus—academic, (b) campus—social, and (c) campus—public spaces. Black males are stereotyped and placed under increased surveillance by community and local policing tactics on and off campus. Across these domains, Black males were defined as being “out of place” and “fitting the description” of illegitimate nonmembers of the campus community. Students reported psychological stress responses symptomatic of racial battle fatigue (e.g., frustration, shock, anger, disappointment, resentment, anxiety, helplessness, hopelessness, and fear). There was unanimous agreement in the subjective reports that the college environment was more hostile toward African American males than other groups.
Ten- to 14-Year Follow-up of the Nirschl Surgical Technique for Lateral Epicondylitis
Authors: Dunn Jonathan H. , Kim John J. , Davis Lonnie , Nirschl Robert P.
Published: December 2007

Background

Good to excellent short-term results have been reported for the surgical treatment of lateral epicondylitis using various surgical techniques.

Hypothesis

Surgical treatment for lateral epicondylitis using the mini-open Nirschl surgical technique will lead to durable results at long-term follow-up.

Study Design

Case series; Level of evidence, 4.

Methods

Records from 139 consecutive surgical procedures (130 patients) for lateral epicondylitis performed by 1 surgeon between 1991 and 1994 were retrospectively reviewed. Eighty-three patients (92 elbows) were available by telephone for a mean follow-up of 12.6 years (range, 10–14 years). Outcome measures included the Numeric Pain Intensity Scale, Nirschl and Verhaar tennis elbow–specific scoring systems, and American Shoulder and Elbow Surgeons elbow form. Preoperative data were collected retrospectively.

Results

The mean age of the study group was 46 years (range, 23–70 years) with 45 men and 38 women. Eighty-seven of the procedures were primary, and 5 were revision tennis elbow surgeries. Concomitant procedures were performed in 30 patients including ulnar nerve release in 24 patients, medial tennis elbow procedures in 23 patients, shoulder arthroscopy in 2 patients, carpal tunnel release in 1 patient, and triceps debridement and osteophyte excision in 1 patient. The mean duration of preoperative symptoms was 2.2 years (range, 2 months to 10 years). The mean Nirschl tennis elbow score improved from 23.0 to 71.0, and the mean American Shoulder and Elbow Surgeons score improved from 34.3 to 87.7 at a minimum of 10-year follow-up ( P < .05). The Numeric Pain Intensity Scale pain score improved from 8.4 preoperatively to 2.1 ( P < .05). Results were rated as excellent in 71 elbows, good in 6 elbows, fair in 9 elbows, and poor in 6 elbows by the Nirschl tennis elbow score. By the criteria of Verhaar et al, the results were excellent in 45 elbows, good in 32 elbows, fair in 8 elbows, and poor in 7 elbows. Eighty-four percent good to excellent results were achieved using both scoring systems. Ninety-two percent of the patients reported normal elbow range of motion. The overall improvement rate was 97%. Patient satisfaction averaged 8.9 of 10. Ninety-three percent of those available at a minimum of 10-year follow-up reported returning to their sports.

Conclusion

The mini-open Nirschl surgical technique with accurate resection of the tendinosis tissue remains highly successful in the long term.
The Effects of Sequential Sectioning of Defined Posterior Cruciate Ligament Fiber Regions on Translational Knee Motion
Authors: Covey D. C. , Sapega Alexander A. , Riffenburgh R. H.
Published: December 2007

Background

Recent studies have shown that the posterior cruciate ligament (PCL) is composed of a continuum of fiber regions that display characteristic mechanical behavior under different motion and loading conditions.

Hypothesis

The anterior, central, and posterior fiber regions of the PCL differentially contribute to control of posterior translation of the tibia.

Study Design

Controlled laboratory study.

Methods

Nine intact, fresh-frozen cadaveric knees were instrumented with excursion wires implanted within the anterior, central, and posterior fiber regions of the PCL. In groups of 3, patterns of incremental posterior tibial translation using a 74-N posterior force were analyzed as a function of the variable linear separation distance between tibial and femoral fiber region attachment sites during posterior drawer testing at knee flexion angles of 20° and 90° before and after sequential fiber region abs.

Results

At 20° of knee flexion, there was no statistical difference in the relatively small amount of posterior tibial translation, regardless of whether the anterior, central, or posterior fibers were alone transected ( P = .350). At 90° of knee flexion, whether the posterior fibers were cut first, second, or third (order of section), the incremental difference in posterior tibial translation this produced was significantly different ( P = .039). For the fiber regions combined, the third fiber region section resulted in a significantly larger incremental translation than did either the first or second section with the knee flexed 90° ( P < .001). After transection of all fiber regions, significantly more total posterior tibial translation occurred at 90° versus 20° of flexion ( P = .002).

Conclusions

This study shows that fiber regions within the PCL have unique characteristics and behave differently in response to posterior drawer forces.

Clinical Relevance

This study provides additional information on the complex mechanical behavior of the PCL and suggests that some partial tears (ie, those involving 1 or 2 fiber regions) may only result in minimal posterior translation during drawer testing at 90°.
Individuals, Families, and Achievement
Authors: Ellefsen Giselle , Beran Tanya N.
Published: December 2007

The authors investigated the relationship between student academic achievement and individual child and family factors. The sample consisted of 10- to 11-year-olds ( N = 2,081) from the Canadian National Longitudinal Survey of Children and Youth, which is a stratified random sample of 22,831 households in Canada. From scale and factor analyses, several factors were created and included in a latent variable path model. The model fit the data well (Comparative Fit Index = .97), with a standardized residual mean error of .03, χ 2(28) = 79.63, p < .000. Student learning and behaviour problems are directly related to achievement, whereas family factors are distal correlates of achievement. Results suggest that school psychologists need to consider several factors that relate to achievement.
School Psychologists' Views and Management of Obsessive-Compulsive Disorder in Children and Adolescents
Authors: Gallant Jason , Storch Eric A. , Valderhaug Robert , Geffken Gary R.
Published: December 2007

Over the past decade, an increasing body of research has been conducted on evidence-based psychological and psychiatric treatment for pediatric obsessive-compulsive disorder (OCD). Despite this improved understanding, however, these treatments are not being performed. This study descriptively examined the practices and views of school psychologists on the management of pediatric OCD. Two hundred twenty-seven clinicians responded to a survey adapted from previous work by Valderhaug, Gotestam, and Larsson. Results suggested that school psychologists preferred cognitive-behavioral, medical, and family/systemic orientations relative to psychodynamic and humanistic approaches. Although respondents reported an adherence to evidence-based treatment, only 7% reported using behavioral exposure. Many respondents reported only moderate treatment success and expressed an overwhelming need for further training in both the assessment and treatment of pediatric OCD. Our results suggest that school psychologists are not adequately trained to assess and provide evidence-based treatment of pediatric OCD.
Polyrotaxanes composed of β-cyclodextrin and polydimethylsiloxanes: synthesis, morphology and thermal behavior
Authors: Marangoci Narcisa , Farcas Aurica , Pinteala Mariana , Harabagiu Valeria , Simionescu Bogdan C. , Sukhanova Tatiana , Bronnikov Sergei , Grigoryev Anatolii , Gubanova Galina , Perminova Maria , Perichaud Alain
Published: December 2007

Epoxy-terminated polydimethylsiloxanes (E-PDMSs) of different molecular weight Mn were proved to undergo inclusion complexation into the inner cavity of β-cyclodextrin (β-CD), resulting in polyrotaxanes (PRots). The dethreading of the macrocycle was prevented by blocking the siloxane chain with a bulky substituent derived from 4-aminophenyltriphenyl methane (APhTPhM). As revealed by thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), wide-angle X-ray diffraction and statistical analysis of SEM images, the thermal properties and the morphology of polyrotoxanes are dependent upon Mn, β-CD/E-PDMS molar ratio and the presence of free β-CD in the complexes.
Polyketimines with Pendent Azo Groups: Synthesis, Characterization and Optical Properties
Authors: Iwan Agnieszka , Jarzabek Bozena , Mazurak Zbigniew , Sek Danuta
Published: December 2007

The synthesis and characterization of polymers containing ketimine linkages in the main chain (P1—P6) are reported. Two ketimine polymers additionally containing a nitrogen-nitrogen double bond in the side chain were synthesized by melt polycondensation of so-called `Solvent Brown 1' with p-dibenzoylbenzene and trans-1,2-dibenzoylethylene (P3, P6), respectively. The properties of these polymers were compared with four ketimine polymers without pendent N=N bonds. Polymers were characterized by elemental analysis, FT-IR, NMR, UV-vis and photoluminescence (PL) spectroscopy. Calculated energy gaps for blends of these polymers with poly(methyl methacrylate) PMMA was 2.0 eV. Photoluminescence emission spectra of polyketimines in solution are characterized by one band in the 450—560 nm range. Polymers with N=N bond in the side chain (P3, P6) in DMA solution exhibit bathochromic shift of the emission band of about 60 nm. Additionally, the photoluminescence spectra of the polyketimines blended with PMMA were also determined. Polymers P3 and P6 blended with PMMA are about 120 nm hypsochromically shifted with respect to the PL spectra of P3 and P6 measured in DMA solution.
A Confirmatory Factor Analysis of an Abbreviated Social Support Instrument: The MOS-SSS
Authors: Gjesfjeld Christopher D. , Greeno Catherine G. , Kim Kevin H.
Published: December 2007

Objective: Confirm the factor structure of the original 18-item Medical Outcome Study Social Support Survey (MOS-SSS) as well as two abbreviated versions in a sample of mothers with a child in mental health treatment. Method: The factor structure, internal consistency, and concurrent validity of the MOS-SSS were assessed using a convenience sample of 330 mothers. Results: A 12-item version that included subscales and a 4-item version maintained a good fit. Conclusion: 12- and 4-item versions of the MOS-SSS are psychometrically sound social support instruments and are appropriate for clinical and research uses. Given the diverse populations that social work serves, confirming instruments in various samples is important to legitimize an instrument's use and advance the evidence base for support interventions.
Finding Our Roots
Authors: Beatty Joy E. , Leigh Jennifer S. A. , Lund Dean Kathy
Published: December 2007

Teaching philosophy statements clarify why we do what we do in the classroom, and the process of drafting a philosophy offers an opportunity for developmental reflection. Personal teaching philosophies can be grounded in the shared foundation of historical educational philosophies. The authors offer here for facilitators a reflective card-sort exercise that helps surface the philosophical roots of personal teaching philosophies and helps teachers create or renew a teaching philosophy statement. They explain the exercise activities and typical outcomes based on their experiences facilitating the exercise. The authors conclude with insights and considerations for facilitators.
The Emergence of Implicit Criteria Actually Used by Reviewers of Qualitative Research Articles
Authors: Savall Henri , Zardet Veronique , Bonnet Marc , Peron Michel
Published: December 2007

This article brings to light the actual evaluation practices of reviewers when assessing qualitative manuscripts. The authors conducted the first empirical research entirely based on reviewer reports for a journal on management sciences over a 28-year period. Content analysis of 474 reviewer reports written by 56 reviewers identified 19 critical points and 10 criteria, making up a synthetic table of 190 possible cells, 51 of which proved to be actually used by reviewers. These findings are then compared with the quality criteria identified in the extant U.S. literature. Comparison reveals some shared quality criteria but also throws new light on a number of discrepancies. Analysis over time shows marked evolution from emphasis on internal validity criteria over the first 10 years toward emphasis on external validity criteria in the past 10 years. Factors ensuring reliability and replicability of the results of this research are discussed at length.
Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat
Authors: Cao Y. , Shumsky J.S. , Sabol M.A. , Kushner R.A. , Strittmatter S. , Hamers F.P.T. , Lee D.H.S. , Rabacchi S.A. , Murray M.
Published: December 2007

Objective. The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). Methods. Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. Results. Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. Conclusions. NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.
Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria
Authors: Brodsky Robert A. , Young Neal S. , Antonioli Elisabetta , Risitano Antonio M. , Schrezenmeier Hubert , Schubert Jörg , Gaya Anna , Coyle Luke , de Castro Carlos , Fu Chieh-Lin , Maciejewski Jaroslaw P. , Bessler Monica , Kroon Henk-André , Rother Russell P. , Hillmen Peter
Published: December 2007

The terminal complement inhibitor eculizumab was recently shown to be effective and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non–placebo-controlled, 52-week, phase 3 clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 ± 2 days for 4 weeks; 900 mg 7 ± 2 days later; followed by 900 mg every 14 ± 2 days for a total treatment period of 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P < .001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 ± 1.1 points (P < .001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin level occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient before treatment to 0.0 units per patient during the study (P < .001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire 52-week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at http://clinicaltrials.gov as NCT00130000.
Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia
Authors: Oki Yasuhiro , Jelinek Jaroslav , Shen Lanlan , Kantarjian Hagop M. , Issa Jean-Pierre J.
Published: December 2007

Decitabine's mechanism of action in chronic myelomonocytic leukemia remains incompletely understood. We studied the dynamics of neoplastic cell clearance during decitabine treatment (100 mg/m2 per course every 4 weeks) using quantitative monitoring of mutant alleles by pyrosequencing. Patients with chronic myelomonocytic leukemia were first screened for JAK2 and NPM1 mutations, and 3 patients with mutations were identified. Mutant allele percentages in mononuclear cell DNA were followed after treatment, along with methylation of LINE1 and 10 other genes. The clearance of mutant alleles was modest after the first cycle, despite induction of hypomethylation. Delayed substantial clearance was observed after 2 to 4 cycles that correlated with clinical response. Two patients had complete disappearance of mutant alleles and sustained clinical remissions. In another patient, mutant allele was detectable at clinical remission, which lasted for 8 months. Our data suggest a predominantly noncytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic clone and/or normal cells. This trial was registered at www.ClinicalTrials.gov as #NCT00067808.
Epigenetic regulation of dendritic cell–derived interleukin-12 facilitates immunosuppression after a severe innate immune response
Authors: Wen Haitao , Dou Yali , Hogaboam Cory M. , Kunkel Steven L.
Published: December 2007

Patients who survive sepsis have significant deficiencies in their immune responses caused by poorly understood mechanisms. We have explored this phenomenon by studying dendritic cells (DCs) recovered from animals surviving severe peritonitis-induced sepsis, using the well-established cecal ligation and puncture (CLP) model. Immediately after the initiation of sepsis there is a depletion in DCs from the lung and spleen, which is followed by repopulation of these cells back to the respective organs. DCs recovered from surviving animals exhibited a significant and chronic suppression of interleukin-12 (IL-12), a key host defense cytokine. The suppression of DC-derived IL-12 persisted for at least 6 weeks after CLP and was not due to immunoregulatory cytokines, such as IL-10. Using chromatin immunoprecipitation (ChIP) techniques, we have shown that the deficiency in DC-derived IL-12 was due to epigenetic alterations. Specifically, IL-12 expression was regulated by stable reciprocal changes in histone H3 lysine-4 trimethylation (H3K4me3) and histone H3 lysine-27 dimethylation (H3K27me2), as well as changes in cognate histone methyltransferase (HMT) complexes on the Il12p35 and Il12p40 promoters. These data implicate histone modification enzymes in suppressing DC-derived IL-12, which may provide one of the mechanisms of long-term immunosuppression subsequent to the septic response.
Discovery of novel alternatively spliced C. elegans transcripts by computational analysis of SAGE data
Authors: Ruzanov Peter , Jones Steven J , Riddle Donald L
Published: December 2007

Background

Alternative RNA splicing allows cells to produce multiple protein isoforms from one gene. These isoforms may have specialized functions, and may be tissue- or stage-specific. Our aim was to use computational analysis of SAGE and genomic data to predict alternatively spliced transcripts expressed in C. elegans.

Results

We predicted novel alternatively spliced variants and confirmed five of eighteen candidates selected for experimental validation by RT-PCR tests and DNA sequencing.

Conclusion

We show that SAGE data can be efficiently used to discover alternative mRNA isoforms, including those with skipped exons or retained introns. Our results also imply that C. elegans may produce a larger number of alternatively spliced transcripts than initially estimated.
Stromal cell-derived factor 1-α (SDF)-induced human T cell chemotaxis becomes phosphoinositide 3-kinase (PI3K)-independent: role of PKC-θ
Authors: Shahabi Nahid A , McAllen K , Sharp Burt M
Published: December 2007

Stromal cell-derived factor 1α (SDF-1α) is the exclusive ligand for the chemokine receptor CXCR4. This receptor plays a pivotal role in immune responses, the pathogenesis of infection such as HIV, and cellular trafficking. However, the signaling mechanisms regulating SDF-driven T cell migration are not well defined. In this study, we determined the role of PI3K and protein kinase C- θ (PKC-θ) in SDF-induced human T cell migration in fresh versus cultured T cells. Purified human T cells (fresh vs. 48 h in media, unstimulated or activated by anti-CD3+anti-CD28) were used. Western blots showed that SDF induced phospho-(p)-Akt [threonine (Thr)308 and serine 473], a proxy for PI3K activity, in fresh cells and p-PKC-θ in 48 h unstimulated cells. LY294002 (PI3K inhibitor) reduced SDF-induced chemotaxis in fresh cells by 51%, whereas it minimally affected chemotaxis in 48 h unstimulated or activated cells. However, a specific PKC-θ inhibitor, pseudosubstrate for PKC-θ, reduced chemotaxis in 48 h unstimulated and stimulated T cells by 72% and 87%, respectively. Thus, chemotaxis becomes independent of PI3K signaling in human T cells cultured for 48 h. Under these conditions, PKC-θ is phosphorylated (Thr538) by SDF, and chemotaxis becomes largely PKC-θ-dependent.
Impairment of human NK cell cytotoxic activity and cytokine release by cigarette smoke
Authors: Mian M Firoz , Lauzon Nicole M , Stämpfli Martin R , Mossman Karen L , Ashkar Ali A
Published: December 2007

NK cells play essential roles in innate host defense against microbial infections and tumor surveillance. Although evidence suggests that smoking has adverse effects on the immune system, little is known about whether smoking compromises NK cell effector functions. In this study, we show that cigarette smoke-conditioned medium (SCM) dose-dependently inhibits in vitro IFN-γ production by polyinosinic:polycytidylic acid (poly I:C)-activated PBMC and NK cells isolated from nonsmoking individuals. Similarly, SCM attenuated poly I:C-induced TNF-α production by PBMC and NK cells. The inhibitory effect of cigarette smoke on TNF-α production was reversible. PBMC and NK cells isolated from smokers displayed significant reduction of IFN-γ and TNF-α secretions compared with nonsmokers in response to poly I:C activation. We further observed that SCM attenuated NK cell cytotoxic activity, which was associated with decreased up-regulation of perforin expression. Attenuated cytotoxic activity was also observed in PBMCs isolated from smokers. Finally, anti-IL-12 mAb-blocking data revealed that an attenuation of IFN-γ production by PBMC was indirect, likely via attenuation of IL-12 production, and the effect on NK cells was IL-12-independent. Our data indicate that cigarette smoke compromises function of human NK cells. This may contribute to a higher incidence of viral infections and cancer among smokers.
Cost of scaling up mental healthcare in low-and middle-income countries
Authors: Chisholm Dan , Lund Crick , Saxena Shekhar
Published: December 2007

Background

No systematic attempt has been made to calculate the costs of scaling up mental health services in low-and middle-income countries.

Aims

To estimate the expenditures needed to scale up the delivery of an essential mental healthcare package over a 10-year period (2006–2015).

Method

A core package was defined, comprising pharmacological and/or psychosocial treatment of schizophrenia, bipolar disorder, depression and hazardous alcohol use. Current service levels in 12 selected low-and middle-income countries were established using the WHO–AIMS assessment tool. Target-level resource needs were derived from published need assessments and economic evaluations.

Results

The cost per capita of providing the core package attarget coverage levels (in US dollars) ranged from $1.85 to $2.60 per year in low-income countries and $3.20 to $6.25 per year in lower-middle-income countries, an additional annual investment of $0.18–0.55 per capita.

Conclusions

Although significant new resources need to be invested, the absolute amount is not large when considered at the population level and against other health investment strategies.
Mental health and quality of residential environment
Authors: Thomas Hollie , Weaver Nikki , Patterson Joanne , Jones Phil , Bell Truda , Playle Rebecca , Dunstan Frank , Palmer Stephen , Lewis Glyn , Araya Ricardo
Published: December 2007

Background

There is increasing interest in the proposition that residential environment can affect mental health.

Aims

To study the degree to which common mental disorder clusters according to postcode units and households. To investigate whether contextual measures of residential environment quality and geographical accessibility are associated with symptoms of common mental disorder.

Method

A total of 1058 individuals aged 16–75 years (response rate 66%) participated in a cross-sectional survey The 12-item General Health Questionnaire measured symptoms of common mental disorder.

Results

Only 2% (95% CI 0–6) of the unexplained variation in symptoms existed at postcode unit level, whereas 37% (95% CI 27–49) existed at household-level, but the postcode unit variation was reduced to zero after adjustments. There was little evidence to suggest that residential quality or accessibility were associated with symptoms.

Conclusions

There was substantial unexplained variation at the household level but we could find no evidence of postcode unit variation and no association with residential environmental quality or geographical accessibility. It is likely that the psychosocial environment is more important than the physical environment in relation to common mental disorder.
Computer-aided psychotherapy: revolution or bubble?
Authors: Marks I. M. , Cavanagh K. , Gega L.
Published: December 2007

Research into computer-aided psychotherapy is thriving around the world. Most of it concerns computer-aided cognitive–behavioural therapy (CCBT). A recent narrative review found 97 computer-aided psychotherapy systems from nine countries reported in 175 studies, of which 103 were randomised controlled trials. The rapid spread of the mass delivery of psychotherapy through CCBT, catalysed in the UK by the National Institute for Health and Clinical Excellence's recommendation of two CCBT programmes and the Department of Health's CCBT implementation guidance, seems unprecedented. This editorial is a synopsis of the current status of CCBT and its future directions.
IL‐7 Modulates Osteoclastogenesis in Patients Affected by Solid Tumors
Authors: ROATO ILARIA , GORASSINI EVA , BRUNETTI GIACOMINA , GRANO MARIA , CIUFFREDA LIBERO , MUSSA ANTONIO , FERRACINI RICCARDO
Published: December 2007

Abstract:  High levels of interleukin‐7 (IL‐7) have been associated with bone loss due to its stimulatory osteoclastogenic activity. Osteolytic patients' peripheral blood mononuclear cells (PBMCs) differentiate into osteoclasts without adding stimulating factors. Now, we investigated the potential role of IL‐7 in the spontaneous osteoclastogenesis occurring in these patients. We identified significant differences in serum IL‐7 levels between patients with/without bone metastases, suggesting that IL‐7 might be effective as a clinical marker of disease progression. In patients' PBMC cultures we demonstrated that IL‐7 stimulates osteoclastogenesis by inducing TNF‐α release by T and B cells. These findings add further details to the disclosure of the mechanisms controlling bone metastases in solid tumors.
Studies of Osteotropism on Both Sides of the Breast Cancer–Bone Interaction
Authors: MOREAU JODIE , ANDERSON KRISTEN M. , MAUNEY JOSHUA R. , KAPLAN DAVID , ROSENBLATT MICHAEL
Published: December 2007

Abstract:  While important advances have been made in the treatment of breast cancer (BrCa), little progress has been made in developing therapies for metastasis to bone, a complication that signals entry of the disease into an incurable phase. The process of identifying genes and gene signatures of BrCa associated with metastasis has begun. In contrast, knowledge of the contributions of bone to tumor–stroma interaction is still rudimentary. We are performing research designed to elucidate the mechanisms by which human BrCa metastasizes to bone (osteotropism). With evidence mounting that there is mutual recognition of BrCa and bone, we are investigating osteotropism from both sides of the tumor–stroma interface. We created a novel “all human” model in which human bone is transplanted into immunodeficient (NOD/SCID) mice. Human BrCa cells are injected into the mammary fat pad. Metastases later appear as metastases in the human bone, but not mouse skeleton. The model recapitulates the metastatic sequence occurring in patients. Using DNA microarrays, we plan to identify putative osteotropic genes expressed by metastatic BrCa cells. We will test the hypothesis that distinct “tool kits” are used by BrCa metastasizing to human bone. In addition, using human tissue‐engineered bone, we are identifying components within bone stroma essential for metastasis, and osteotropism genes expressed by bone in response to the presence of BrCa. We recently demonstrated that tissue‐engineered bone based on a silk sponge platform is a target for human BrCa metastasis, even in preference to the mouse skeleton.