bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Parents Control Who Teaches Their Children?
Authors: Hewson Kurtis
Published: February 2006

This case examines a number of key issues pertaining to teacher quality and parental involvement in schools, particularly schools that serve culturally distinct areas. It explores the support given to beginning teachers by administrators, colleagues and community, and the role of teacher evaluation. It also considers the perception of teacher demeanor within a community, the public ideal of what a teacher should represent and embody. This case can be used to examine positive and negative aspects of parental involvement in schools, the correlation between teacher quality and student learning and beginning teacher support.
The Case of Secretary versus Principal Or The Recalcitrant Secretary
Authors: MacNeil Angus , Fossey Richard
Published: February 2006

In this case, a principal arrives at a troubled school in mid-year to discover that the school secretary is exerting managerial powers usually reserved for the principal. When the principal tries to implement changes, the secretary is combative and resistant.

This case provides students an opportunity to explore the dynamics between a school principal and the school's support staff and to discuss the important role that a school secretary plays in a school's operation and culture. The case is accompanied by a brief review of literature on the secretary's role in a school and can be used in courses on human resources management, the principalship, or educational administration.
Conflict at Pierce College
Authors: Bergerson Amy A.
Published: February 2006

This case was written for use in courses in higher education leadership. It is particularly useful for examining the environment in which decisions are made in higher education institutions. In the case, a young administrator is confronted with an ethical dilemma. She initially receives the support of her superiors in handling the situation, but after she acts she discovers that this support has eroded. The case illustrates the importance of coalition-building as well as the necessity of understanding institutional politics. The case also provides an opportunity to examine and discuss ethics in higher education administration.
A Matter of Principle
Authors: Brinson Kenneth H. , Lovett Helen T. , Price R. Wayne
Published: February 2006

School principals are often faced with difficult decisions that challenge both their moral beliefs and ethical behaviors. Personal relationships and political associations can create an even greater challenge and level of frustration for building level administrators when attempting to carry out duties as moral agents and acting in loco parentis. As the new principal of Davidson High School, Jeffrey Jones encounters a series of events that become further complicated in light of his personal and professional relationships.
A Community Divided
Authors: Bueschel Ellen
Published: February 2006

This case is based in a small Midwestern school district. It was developed for use in a doctoral level course in Public Engagement and has been revised as a result of student feedback. As developed for this course, the concept of public engagement is not about convincing the public to do what the experts believe should be done. A desired consequence of said engagement is the restoration of the historical compact between the community and its public schools as one foundation for effecting school reform. The case deals with the impact of consolidation on the will of the community to support its schools.
Steele High School’s Legacy
Authors: Klinker JoAnn Franklin
Published: February 2006

This case involves overturning a 35-year-old program of weighted grading that defined a school’s identity. Examination of the practice revealed a curriculum that was discriminatory toward students and teachers with deep-seated values and beliefs among an elite group of core teachers perpetuating that discrimination. Further examination revealed unspecified differences in grading practices among staff. This case can be used in classes that consider instructional leadership, school board/superintendent relationships, superintendent/principal relationships, curriculum, school culture, and ethical decision-making.
Lester B. Pearson Elementary School: First Year on a Journey with the Change Process
Authors: Normore Anthony H.
Published: February 2006

The case is intended for use as a culminating experience in courses, seminars or workshops that deal with organizational behaviour and the change process. It expounds on the key steps in any systemic change process involving one school’s journey with change as it sets priorities and strategies, the problems encountered, where the support and assistance came from, as well as the differences that were made to improving learning opportunities for everyone. A brief synopsis of change studies, theories and practices informing change are presented to assist professors and graduate students in leadership preparation programs. This case study encourages a great deal of small and large group work participation and discussion. Professors and students of educational administration/leadership can use this case to supplement analysis and discussion related to organizational culture, educational change and change theory, school improvement, effective communication, motivation, morale, and leadership. Graduate students and professors who are interested in understanding change theory and how it looks in practice would benefit from an analysis of this case study.
The Case of the Field Trip Disaster
Authors: Collins Loucrecia , Redcross Joseph
Published: February 2006

For decades, the instructional field trip has been viewed as a strategy to enhance students’ learning experiences. Yet what happens when an award-winning teacher is accused of choking a student while on a field trip? Tempers flare among community members, parents contact the police, and the principal is assigned the daunting task of investigating a staff member for assault and battery. This case study provides an opportunity for aspiring principals to analyze legal challenges posed by the supervision of students during instructional field trips. In addition, students will explore school board and site-based school policies regarding field trips and examine guidelines regarding due process for teachers. Finally, an analysis of the principal’s relationship with the teacher’s union representative will help prepare future administrators in working with negotiated contracts.
Contested Territory
Authors: Mayrowetz David , Price John
Published: February 2006

This case exemplifies the frequent need for principals to negotiate the conflicting demands of parents and teachers. Parents are advocating increased participation in school decision making while teachers are demanding a more secure and isolated environment. Issues of class and race complicate this challenge for many urban administrators. Discussions spurred by this story should inform educators who work both inside and outside of cities about school community relations—especially parental input in schools—micropolitics, difference, and school safety. There are multiple opportunities for role playing, giving students the opportunity to examine this complex case from many angles.
The Liberty Elementary Story
Authors: Williams Ellen J. , Matthews Joe
Published: February 2006

Principals play a major role in uniting faculties into collective action to improve teaching and learning. Researchers have found that schools that function as teaching and learning communities are successful in raising student academic achievement. To create a learning community, principals must transform their school cultures from places of isolation to sites for collaboration so that teachers work interdependently to learn with and from each other to help all children succeed in schools. In this case, principal preparation students are challenged to devise a 5-year leadership strategy and a 5-year school improvement plan that a new principal might use to improve student learning.
Neglect of people with intellectual disabilities
Authors: Jenkins Robert , Davies Rachel
Published: February 2006

Evidence from numerous studies strongly suggests that many people with intellectual disabilities have greater health needs and also have restricted access to health care compared to the general population. Given this evidence and that this has existed for some time, when does failure to act on this knowledge constitute a form of abuse? The motivation for this article emerged from both observations made during a wider study on abuse policies and practice and a growing awareness that abuse literature is not fully engaged with a broader definition of neglect. This article considers these issues with reference to the wider context of duties of care, freedom of choice and the attitudes of staff that shape responses to abuse. Practitioners are challenged to consider what can be done to overcome neglect with specific reference to the neglect of health needs.
Paying the piper and calling the tune?
Authors: Hussein Shereen , Rapaport Joan , Manthorpe Jill , Moriarty Jo , Collins Jean
Published: February 2006

Increases in funding of advocacy schemes are leading to their general expansion in the UK. Little is known of how their activities are evaluated by funders. This article examines how local authorities evaluate the outcomes of advocacy schemes. It reports on and discusses the findings of a survey of local authorities. Respondents identified the types of support they provided to advocacy schemes and their requirements for service reports. Data are presented on the length of time that schemes have been funded, geographical variations and whether schemes are generalist or specialist. This analysis is set in the context of discussion with stakeholders. The authors conclude that monitoring and review systems are not well known or extensively used, that while user involvement in evaluation is seen as appropriate this is not well developed, but that advocacy services themselves are interested in contributing to processes of improvement and accountability.
Measurement of weldpiece distortion during pulsed laser welding using rapid laser profilometry
Authors: Gorkič A. , Jezeršek M. , Možina J. , Diaci J.
Published: February 2006

The present paper reports a new setup for acquisition of shape data for weldpieces during pulsed laser welding. The setup is based on illumination of the weldpiece surface by laser light, which is structured as multiple light planes, and acquisition of the image of the illuminated surface by a digital camera. The position of the optical system is fixed relative to the measured weldpiece. The acquired image is fed into a personal computer where it is processed to obtain the three-dimensional shape of the part of the weldpiece surface that was imaged by the camera. A setup that allows up to 20 shape measurements per second was developed based on this principle. The setup was applied to examine distortion of weldpieces during laser welding of low carbon thin steel sheets. According to the results the setup allows a rapid and accurate temporally and spatially resolved evaluation of weldpiece distortion.
Influence of carbon, manganese and nickel on microstructure and properties of strong steel weld metals: Part 2 – Impact toughness gain resulting from manganese reductions
Authors: Keehan E. , Karlsson L. , Andrén H.-O. , Bhadeshia H. K. D. H.
Published: February 2006

Two experimental high strength steel weld metals were produced with 7 wt-% nickel and either 2 or 0·5 wt-% manganese. Neural network predictions that it is advantageous to reduce the manganese concentration in high nickel alloys have been confirmed, with impact energy increasing from 32 to 113 J at −40°C. High resolution microstructural investigations showed that both weld metals contained mainly martensite at interdendritic regions and predominantly bainite at dendrite core regions, as a consequence of manganese and nickel segregation. In the high manganese weld metal significant amounts of coarse grained coalesced bainite formed whereas mainly upper bainite was seen with 0·5 wt-% manganese. Reducing manganese content increased the transformation temperature, promoting fine upper bainite at the expense of coarse coalesced bainite. Increased toughness was attributed to the finer grain size of bainite constituents and a more effectively tempered microstructure.
Influence of carbon, manganese and nickel on microstructure and properties of strong steel weld metals: Part 3 – Increased strength resulting from carbon additions
Authors: Keehan E. , Karlsson L. , Andrén H.-O. , Bhadeshia H. K. D. H.
Published: February 2006

Neural network predictions suggested that the strength of a high strength steel weld metal with 7 wt-% nickel and 0·5 wt-% manganese could be increased significantly at moderate expense to impact toughness by additions of carbon. Based on this, three experimental weld metals were produced with carbon contents between 0·03 and 0·11 wt-%. Mechanical test results were in agreement with predictions. At low carbon content the microstructure was largely bainitic in dendrite core regions whereas martensite was found at interdendritic regions. From microstructural studies and dilatometry experiments it was found that carbon stabilised austenite to lower transformation temperatures and that the microstructure became more martensitic in nature. Effects on strength and impact toughness were explainable in terms of a refinement of the microstructure and tempering behaviour.
Arc sensor sensitivity in short circuiting metal active gas welding with high speed torch oscillation
Authors: Kodama S. , Ichiyama Y. , Ikuno Y. , Baba N.
Published: February 2006

The present paper describes the characteristics of the arc sensor, focusing on the sensitivity of the change in welding voltage and current to the torch oscillation frequency, in the low current and high speed torch oscillation metal active gas (MAG) process. First, a mathematical model of the short circuiting transfer welding is proposed, based on a previously reported model of spray transfer welding. Then, the relationship between the oscillation frequency and the rate of short circuiting was investigated using the proposed model. Numerical calculation results revealed that short circuiting regularly occurs at both oscillating edges at oscillation frequencies close to half the rate of short circuiting obtained under non-oscillating conditions. This finding agrees satisfactorily with the experimental results. Fast Fourier transformation analyses of the signals of welding voltage and current showed that the sensitivity of the change in the voltage and current is maximised at a frequency equal to about half the short circuiting rate obtained under non-oscillating conditions. It is considered that accurate seam tracking by arc sensors in short circuiting MAG welding can be achieved by setting the torch oscillation frequency to the above value.
Wear mechanism in contact tube
Authors: Shimizu H. , Yokota Y. , Mizuno M. , Kurokawa T.
Published: February 2006

Stable sliding contact is the most important factor in the stable arc discharge of solid wire. If the contact tube wears seriously, arc discharge will become unstable and the wire position will be shifted. Ordinary non-Cu-coated solid wire causes much wear of the contact tube, about 10 times that caused by Cu-coated solid wire. The mechanism of contact tube wear is not only friction at high temperature, but also a molten bridge formed between the contact tube and wire surface. A complex of superfine particles decreases the amount of contact tube wear. For example, the mixture of graphite and magnetite reduces the amount of contact tube wear by 80%. These particles form an interface layer on the inner surface of the contact tube, and the layer prevents the transfer of molten Cu to the wire surface. The interface layer mainly consists of FeO and complex oxides.
Effect of dynamic loading on ductile crack initiation behaviour of notched specimen with strength mismatch
Authors: An G.-B. , Ohata M. , Park J.-U. , Toyoda M.
Published: February 2006

The present study focuses on the effects of a geometrical discontinuity, strength mismatching, which can increase plastic constraint due to heterogeneous plastic straining, and the loading rate on the critical condition for ductile fracture initiation using a two-parameter criterion based on equivalent plastic strain and stress triaxiality. Fracture initiation testing was conducted under dynamic loading using circumferentially notched bend specimens. In order to evaluate the condition for the ductile crack initiation state in the specimens, a thermal elastic/plastic dynamic finite element analysis considering the temperature increase due to plastic deformation was performed. The two-parameter criterion was shown to be applicable to ductile cracking from the surface of the prenotched root in the strength mismatched specimen under dynamic bend loading.
Optimisation of the GTA welding process using the Taguchi method and a neural network
Authors: Lin H. L. , Chou C. P.
Published: February 2006

There are many parameters that affect gas tungsten arc (GTA) welding process quality. Conventionally, the Taguchi method has been widely used in engineering; however, with this method the desired results can only be obtained with the use of very discrete control factors, thus leading to uncertainty about the real optimum. In this study, the Taguchi method was used for the initial optimisation of the GTA welding process parameters. A neural network was then used to construct the relationships between the welding process parameters and weld pool geometry of each weldment. The optimal parameters of the GTA welding process were determined by simulating significant process parameters obtained by the Taguchi method. Experimental results are provided to illustrate the proposed approach.
Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ
Authors: Chan Jennifer L. , Tang Katherine C. , Patel Anoop P. , Bonilla Larissa M. , Pierobon Nicola , Ponzio Nicholas M. , Rameshwar Pranela
Published: February 2006

Mesenchymal stem cells (MSCs) are mostly found around the vasculature system of the adult bone marrow (BM). They function as immune suppressors, express MHC-II, are phagocytic, and support T-cell cytotoxicity. We hypothesize that these contradictory properties of MSCs are important for BM homeostasis and occur partly through antigen presentation (antigen-presenting cells [APCs]) within a narrow window. Indeed, we have verified APC functions of MSCs to recall antigens, Candida albicans and Tetanus toxoid. The target cells have been identified to be CD4+ T cells. APC assays with IFNγ-knockdown MSCs and with anti–IFNγ receptor confirmed that MHC-II expression requires autocrine stimulation by IFNγ. During APC functions, as IFNγ levels become elevated, there was a concomitant decrease in MHC-II on MSCs. This observation was correlated with flow cytometry studies showing a gradual decrease in MHC-II expression as IFNγ levels were increased. The reduced levels of MHC-II correlated with losses in their allogeneic potential, as indicated in mixed lymphocyte reaction. In summary, endogenous and low levels of IFNγ are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFNγ levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.
Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer
Authors: Huber R. M. , Reck M. , Gosse H. , von Pawel J. , Mezger J. , Saal J. G. , Kleinschmidt R. , Steppert C. , Steppling H.
Published: February 2006

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg·m-2with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy.

Patients received topotecan intravenously on days 1–5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg·m-2and reduced to 1.0 mg·m-2in case of severe haematotoxicities.

Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg·m-2; in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg·m-2.

In conclusion, topotecan at a dose of 1.25 mg·m-2appears to be as effective as the dose of 1.5 mg·m-2, but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.
The effects of farming and birth order on asthma and allergies
Authors: Zekveld C. , Bibakis I. , Bibaki-Liakou V. , Pedioti A. , Dimitroulis I. , Harris J. , Newman Taylor A. J. , Cullinan P.
Published: February 2006

A farm childhood is apparently protective in allergic disease, but studies of this issue in Europe have been confined to particular types of farming practice. This study addressed whether or not this effect was generalisable.

A cross-sectional survey of 800 schoolchildren living in rural Crete was undertaken. Standard questions relating to allergic disease were included and atopy was measured through skin-prick tests involving 10 local aeroallergens.

The prevalence of atopy was 24%, but associated symptoms were far less common. At all ages, children from farming families had more frequent contact with farm animals (mainly goats), but were no less likely to be atopic. Atopy and seasonal rhinitis were significantly and independently more common among first-born children.

This community has an intermediate prevalence of atopy but a very low frequency of allergic disease; farming does not seem to be an important determinant, possibly because it is of the wrong sort. Thus farming effects may be specific to local practices. First-born children in this community also appear to be at increased risk of allergic disease.
Evaluation of the user-friendliness of 11 home mechanical ventilators
Authors: Gonzalez-Bermejo J. , Laplanche V. , Husseini F. E. , Duguet A. , Derenne J-P. , Similowski T.
Published: February 2006

The home ventilator market has grown in size and complexity. The aim of this study was to determine if common home ventilators are user-friendly for trained intensive care unit (ICU) physicians.

Eleven ventilator models were tested by 13 ICU physicians without practical experience in home mechanical ventilation. Six tests were defined (start-up, unlocking, mode and setting recognition, mode change, pressure setting and alarm). For each test, the physicians were timed and their performance compared with a reference time established by a technician. The physicians also had to rate their global assessment of each machine on a visual analogue scale.

The start-up test was the only test for which there was no significant difference between the physicians and the technician, except for two ventilators. The physicians were slower than the technician to unlock the ventilator and change the ventilatory mode, with some complete failures during these tests and heterogeneous results between physicians and between ventilators. Mistakes occurred in close to 50% of cases during the ventilatory mode and settings recognition test. The mean time for the most rapid of the physicians for all the tests was 58±53 s, compared with 15±9 s for the technician.

In conclusion, trained intensive care unit physicians perform poorly when confronted with home mechanical ventilators without specific prior training. Therefore, it is hypothesised that the user-friendliness of home ventilators for other categories of users might be questionable.
Avoiding the effect of BCG vaccination in detectingMycobacterium tuberculosisinfection with a blood test
Authors: Diel R. , Ernst M. , Döscher G. , Visuri-Karbe L. , Greinert U. , Niemann S. , Nienhaus A. , Lange C.
Published: February 2006

Bacille Calmette–Guérin (BCG) vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection (LTBI).

The TST was compared with aMycobacterium tuberculosis(MTB)-specific enzyme-linked immunospot (ELISPOT) assay during an outbreak of MTB infection at a police academy in Germany.

Participants were grouped according to their risk of LTBI in close (n = 36) or occasional (n = 333) contacts to the index case. For the TST, the positive response rate was 53% (19 out of 36) among close and 16% (52 out of 333) among occasional contacts. In total, 56 TST-positive contacts (56 out of 71 = 78.9%) and 27 TST-negative controls (27 out of 298 = 9.1%) underwent ELISPOT testing. The odds ratio (OR) of a positive test result across the two groups was 29.2 (95% confidence interval (CI) 3.5–245.0) for the ELISPOT and 19.7 (95% CI 2.0–190.2) for the TST with a 5 mm cut-off. Of 369 contacts, 158 (42.8%) had previously received BCG vaccination. The overall agreement between the TST and the ELISPOT was low, and positive TST reactions were confounded by BCG vaccination (OR 4.8 (95% CI 1.3–18.0)). In contrast, use of a 10-mm induration cut-off for the TST among occasional contacts showed strong agreement between TST and ELISPOT in nonvaccinated persons.

In bacille Calmette–Guérin-vaccinated individuals, theMycobacterium tuberculosis-specific enzyme-linked immunospot assay is a better indicator for the risk of latent tuberculosis infection than the tuberculin skin test.
Incidence and prevalence of systemic lupus erythematosus in a district of North Italy
Authors: Govoni M , Castellino G , Bosi S , Napoli N , Trotta F
Published: February 2006

The objective of this study was to investigate the incidence and the prevalence of systemic lupus erythematosus (SLE) in an area of northeast Italy. We retrospectively examined all patients of 16 years and older of native Italian origin and resident in Ferrara district either admitted to hospital or referred to our outpatient clinic with a diagnosis of SLE determined between 1 January 1996 and 31 December 2002. SLE subjects were identified both by a search of hospital discharge code 710.0 according to the international classification of diseases-9 codes, and using a computerized search for this pathology code in the national health care system. Incidence and prevalence rates were calculated as number of cases per 100 000 inhabitants. Population data were based on the 2002 National Census. A total of 299 cases of SLE were identified. After a review of all cases by one experienced investigator, 98 were excluded because did not satisfied the 1982 revised criteria of the American College Rheumatology. Therefore, 201 patients had a definite diagnosis of SLE. The prevalence of SLE in the district was 57.9/100 000. The mean age at diagnosis was 41 years, the average duration of the disease from symptoms onset to diagnosis was 4.8 years and the female/male ratio 9: 1. Annual incidence in 2000 was 2.01/100 000, in 2001 1.15/100 000 and in 2002 2.6/100 000. This is the first study dealing with prevalence and incidence of SLE in an Italian district. Data obtained concerning prevalence, incidence, age at diagnoses and female predominance are in agreement with those published in literature.
Circulating levels of β2-glycoprotein I in thrombotic disorders and in inflammation
Authors: Lin F , Murphy R , White B , Kelly J , Feighery C , Doyle R , Pittock S , Moroney J , Smith O , Livingstone W , Keenan C , Jackson J
Published: February 2006

β22-glycoprotein I (β2GPI) is a plasma protein suspected to have a role in inhibition of thrombosis. This suspicion is reinforced by the observation that β2GPI is the major target for autoantibodies in the antiphospholipid syndrome. However, little is known about its circulating levels in common thrombotic diseases or inflammation. We measured β2GPI levels in 344 healthy controls, 58 normal pregnancies, 102 patients with non-haemorrhagic stroke, 121 patients with acute coronary syndrome and 200 patients with elevated C-reactive protein (CRP). In healthy individuals, we found a strong positive correlation between age and β2GPI concentration ( r = 0.274, P < 0.001) and that β2GPI levels fall significantly after the eighth week of pregnancy ( P = 0.002). We also found significantly reduced levels of β2GPI in patients with stroke and in elderly patients with myocardial syndrome ( P = 0.013 and 0.043). However, in neither group did β2GPI levels change in the following six months, suggesting that the reduced levels were not a transient post-event phenomenon. In patients with inflammation, β2GPI levels showed a significant negative correlation with CRP ( r =-0.284, P < 0.001) and positively correlated with albumin and transferrin ( r = 0.372 and 0.453, respectively with P < 0.001 for both). Furthermore, the largest reduction in β2GPI levels occurred in patients with the highest CRP values ( P < 0.001).
Sustained remission of lupus nephritis
Authors: Barber C EH , Geldenhuys L , Hanly J G
Published: February 2006

The aim of this study was to describe the clinical course of patients with lupus nephritis (LN) who attain a sustained remission (SR) and identify predictors of SR. A retrospective study of patients with biopsy-proven LN were followed for up to 10 years. SR was defined as normal renal function, urine protein <0.5 g/day, and an inactive urine sediment without significant immunosuppressive maintenance therapy for no less than three years. Control patients had LN but did not fulfill the criteria for SR. Data was collected at diagnosis of LN (T0), at onset of remission (T1), and at final follow-up (T2). A total of 35 patients were identified, 16 with a SR of LN and 19 controls, with a mean ± SD follow-up of 126.4 ± 8.5 months. Remission of LN was achieved following 37.7 ± 6.8 months of therapy. At diagnosis (T0) the WHO classification of nephritis, activity and chronicity scores of renal biopsies were comparable in the two groups. At final follow-up (T2), the mean estimated creatinine clearance for the SR group was significantly higher than in controls ( P = 0.009) and disease activity (SLEDAI scores) was lower ( P = 0.002). Cumulative damage (SDI scores) in the SR group did not increase after patients entered remission ( P = 0.250), whereas the mean SDI score in the control group increased significantly ( P = 0.014) even when renal variables were excluded ( P = 0.016). Multivariate analysis revealed that female gender ( P = 0.023), older age ( P = 0.034), higher non-renal SLEDAI scores ( P = 0.016) at the time of diagnosis of LN and absence of azathioprine ( P = 0.010) were predictive of SR. It was concluded that remission of LN occurs in a substantial proportion of systemic lupus erythematosus (SLE) patients and may be sustained without maintenance immunosuppressive therapy. It is associated with a significantly slower accrual of both renal and non-renal damage over the ensuing seven years.
‘Give Them Hell’: The US Navy’s Night Combat Doctrine and the Campaign for Guadalcanal
Authors: Hone Trent
Published: February 2006

Examinations of the US Navy’s tactical performance during the nocturnal engagements of the Guadalcanal campaign have largely ignored pre-war tactical developments, focusing instead on the details of the actions and extrapolating from their results to draw conclusions about the navy’s preparedness for war. This article adopts a different methodology, concentrating first on the pre-war preparations and then examining the night battles in light of the tactical doctrine the navy developed before the Second World War. The result is a comprehensive view of the navy’s night tactical doctrine, which provides the reasons for its successes and failures off Guadalcanal.
Quality of Life in the Intergroup Exemestane Study: A Randomized Trial of Exemestane Versus Continued Tamoxifen After 2 to 3 Years of Tamoxifen in Postmenopausal Women With Primary Breast Cancer
Authors: Fallowfield Lesley J. , Bliss Judith M. , Porter Lucy S. , Price Miranda H. , Snowdon Claire F. , Jones Stephen E. , Coombes R. Charles , Hall Emma
Published: February 2006

Purpose

To compare and describe the quality of life (QOL) of women allocated to tamoxifen or exemestane within the Intergroup Exemestane Study (IES).

Patients and Methods

Postmenopausal women with primary breast cancer who were disease free after 2 to 3 years were randomly assigned to switch from tamoxifen to exemestane or continue with tamoxifen until 5 years of treatment were completed. A subset of IES centers participated in a QOL substudy. The Functional Assessment of Cancer Therapy–Breast (FACT-B) and endocrine subscale (ES) were administered before random assignment and at predefined follow-up times. The primary end point was the FACT-B composite Trial Outcome Index (TOI). Secondary end points included total FACT-B+ES score, total ES score, and severity of individual endocrine symptoms. This analysis reports QOL up to 24 months.

Results

Five hundred eighty-two patients from eight countries were enrolled onto the substudy. Completion and return of questionnaires was excellent, with 85% available for analysis. QOL was generally good and stable over 2 years, with no clinically meaningful differences found between groups in TOI or ES. Prevalence of severe endocrine symptoms at trial entry was high for vasomotor complaints and sexual problems, which persisted for both groups during the study. No significant differences between groups were seen for any endocrine symptoms apart from vaginal discharge, which was more pronounced with tamoxifen (P < .001).

Conclusion

The switch from tamoxifen to exemestane neither increased nor decreased endocrine symptoms present after 2 to 3 years of tamoxifen; the switch also did not initiate significant reports of new symptoms. Results indicate that the clinical benefits of exemestane over tamoxifen are achieved without significant detrimental effect on QOL.
Osteonecrosis of the Jaw in Multiple Myeloma Patients: Clinical Features and Risk Factors
Authors: Badros Ashraf , Weikel Dianna , Salama Andrew , Goloubeva Olga , Schneider Abraham , Rapoport Aaron , Fenton Robert , Gahres Natalie , Sausville Edward , Ord Robert , Meiller Timothy
Published: February 2006

Purpose

To describe the clinical, radiologic, and pathologic features and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients.

Patients and Methods

A retrospective review of 90 MM patients who had dental assessments, including 22 patients with ONJ. There were 62 men; the median age was 61 years in ONJ patients and 58 years among the rest. Prior MM therapy included thalidomide (n = 67) and stem-cell transplantation (n = 72). Bisphosphonate therapy included zoledronate (n = 34) or pamidronate (n = 17) and pamidronate followed by zoledronate (n = 33). Twenty-seven patients had recent dental extraction, including 12 patients in the ONJ group. Median time from MM diagnosis to ONJ was 8.4 years for the whole group.

Results

Patients usually presented with pain. ONJ occurred posterior to the cuspids (n = 20) mostly in the mandible. Debridement and sequestrectomy with primary closure were performed in 14 patients; of these, four patients had major infections and four patients had recurrent ONJ. Bone histology revealed necrosis and osteomyelitis. Microbiology showed actinomycetes (n = 7) and mixed bacteria (n = 9). More than a third of ONJ patients also suffered from long bone fractures (n = 4) and/or avascular necrosis of the hip (n = 4). The variables predictive of developing ONJ were dental extraction (P = .009), treatment with pamidronate/zoledronate (P = .009), longer follow-up time (P = .03), and older age at diagnosis of MM (P = .006).

Conclusion

ONJ appears to be time-dependent with higher risk after long-term use of bisphosphonates in older MM patients often after dental extractions. No satisfactory therapy is currently available. Trials addressing the benefits/risks of continuing bisphosphonate therapy are needed.
Providing Health Insurance in Rural China: From Research to Policy
Authors: Liu Yuanli , Rao Keqin
Published: February 2006

The focus of this case study is utilizing research to influence policy in a large developing country. Our experiences involve the lack of health insurance for China's rural populations and how our research helped shape China's recent policy attention and efforts on this issue. More than 80 percent of China's 700 million rural residents have no health insurance. This has been the case for the past thirty years, since the collapse of the once-successful Rural Cooperative Medical System after the economic reforms of the early 1980s. In 2002, the Chinese government announced a new rural health financing policy to provide health insurance for its rural populations, financed by a matching fund with contributions from central and local governments, as well as from individual households. This article documents the authors' experiences in addressing several critical questions for converting research results into policy actions, including the following: How are researchers to address policy relevant questions? How are they to acquire the attention of top policy makers to a specific problem? When is the issue at hand serious but not yet critical? And lastly, how are researchers to develop policy recommendations that stand a good chance of being accepted and enacted? Major lessons learned include the need to better understand the mandates and institutional constraints of the policy makers, the appropriateness of timing of both research result and policy efforts, how to use a country's cultural context to garner support of the government, how to enhance the policy's impact by combining formal and informal channels of communication for research dissemination, and the importance of following the policy process through the implementation phase to ensure the original objectives are achieved.
Notch1b and neuregulin are required for specification of central cardiac conduction tissue
Authors: Milan David J. , Giokas Andrea C. , Serluca Fabrizio C. , Peterson Randall T. , MacRae Calum A.
Published: February 2006

Normal heart function is critically dependent on the timing and coordination provided by a complex network of specialized cells: the cardiac conduction system. We have employed functional assays in zebrafish to explore early steps in the patterning of the conduction system that previously have been inaccessible. We demonstrate that a ring of atrioventricular conduction tissue develops at 40 hours post-fertilization in the zebrafish heart. Analysis of the mutant cloche reveals a requirement for endocardial signals in the formation of this tissue. The differentiation of these specialized cells, unlike that of adjacent endocardial cushions and valves, is not dependent on blood flow or cardiac contraction. Finally, both neuregulin and notch1b are necessary for the development of atrioventricular conduction tissue. These results are the first demonstration of the endocardial signals required for patterning central `slow' conduction tissue, and they reveal the operation of distinct local endocardial-myocardial interactions within the developing heart tube.
BRICK1/HSPC300 functions with SCAR and the ARP2/3 complex to regulate epidermal cell shape in Arabidopsis
Authors: Djakovic Stevan , Dyachok Julia , Burke Michael , Frank Mary J. , Smith Laurie G.
Published: February 2006

The Arp2/3 complex, a highly conserved nucleator of F-actin polymerization,is essential for a variety of eukaryotic cellular processes, including epidermal cell morphogenesis in Arabidopsis thaliana. Efficient nucleation of actin filaments by the Arp2/3 complex requires the presence of an activator such as a member of the Scar/WAVE family. In mammalian cells, a multiprotein complex consisting of WAVE, PIR121/Sra-1, Nap1, Abi-2 and HSPC300 mediates responsiveness of WAVE to upstream regulators such as Rac. Essential roles in WAVE complex assembly or function have been demonstrated for PIR121/Sra-1, Nap1 and Abi-2, but the significance of HSPC300 in this complex is unclear. Plant homologs of all mammalian WAVE complex components have been identified, including HSPC300, the mammalian homolog of maize BRICK1 (BRK1). We show that, like mutations disrupting the Arabidopsis homologs of PIR121/Sra-1, Nap1 and Scar/WAVE, mutations in the Arabidopsis BRK1gene result in trichome and pavement cell morphology defects (and associated alterations in the F-actin cytoskeleton of expanding cells) similar to those caused by mutations disrupting the ARP2/3 complex itself. Analysis of double mutants provides genetic evidence that BRK1 functions in a pathway with the ARP2/3 complex. BRK1 is required for accumulation of SCAR1 protein in vivo,potentially explaining the apparently essential role of BRK1 in ARP2/3 complex function.
Differential effects of N-cadherin-mediated adhesion on the development of myotomal waves
Authors: Cinnamon Yuval , Ben-Yair Raz , Kalcheim Chaya
Published: February 2006

Myotomal fibers form by a first wave of pioneer myoblasts from the medial epithelial somite, and by a second wave from all four lips of the dermomyotome. Then, a third wave of mitotic progenitors colonizes the myotome,initially stemming from the extreme lips and, later, from the central dermomyotome sheet. In vitro studies have suggested that N-cadherin plays a role in myogenesis, but its role in vivo remains poorly understood. We find that during the growth phase of the dermomyotome sheet, when the orientation of mitotic spindles is parallel to the mediolateral extent of the epithelium,N-cadherin protein is inherited by both daughter cells. Prior to dermomyotome dissociation into dermis and muscle progenitors, when mitoses become perpendicularly oriented, N-cadherin remains associated only with the apical cell located in apposition to the myotome, generating molecular asymmetry between basal and apical progeny. Local gene missexpression confirms that N-cadherin-mediated adhesion is sufficient to promote myotome colonization,whereas its absence drives cells towards the subectodermal domain, hence coupling the asymmetric distribution of N-cadherin to a shift in mitotic orientation and to fate segregation. Site-directed electroporation to additional, discrete somite regions, further reveals that N-cadherin-mediated adhesion is necessary for maintaining the epithelial configuration of all dermomyotome domains while promoting the onset of Myod transcription and the translocation into the myotome of myofibers and/or of Pax-positive progenitors. By contrast, N-cadherin has no effect on migration or differentiation of the first wave of myotomal pioneers. Altogether, we show for the first time that the asymmetric localization of N-cadherin during mitosis indirectly influences fate segregation by differentially driving the allocation of progenitors to muscle versus dermal primordia, that the adhesive domain of N-cadherin maintains the integrity of the dermomyotome epithelium,which is necessary for myogenic specification, and that different molecular mechanisms underlie the establishment of pioneer and later myotomal waves.
Identification of α-tubulin as a granzyme B substrate during CTL-mediated apoptosis
Authors: Goping Ing Swie , Sawchuk Tracy , Underhill D. Alan , Bleackley R. Chris
Published: February 2006

Cytotoxic lymphocytes induce target cell apoptosis via two major pathways: Fas/FasL and granule exocytosis. The latter pathway has largely been defined by the roles of the pore-forming protein perforin and by the serine proteinases granzymes A and B. Upon entry into target cells, the granzymes cleave substrates that ultimately result in cell death. To gain further insight into granzyme B function, we have identified novel substrates. SDS-PAGE analysis of S100 cell lysates identified a 51 kDa protein that was cleaved by granzyme B. Mass spectrometry analysis revealed that this fragment was the microtubule protein, α-tubulin, which was confirmed by western blotting. In addition, two-dimensional gel analysis showed that the truncated form of α-tubulin had a more basic isoelectric point than the full-length molecule, suggesting that granzyme B removed the acidic C-terminus. Site-directed mutagenesis within this region of α-tubulin revealed the granzyme B recognition site, which is conserved in a subset of α-tubulin isoforms. Significantly, we showed that α-tubulin was cleaved in target cells undergoing apoptosis as induced by cytotoxic T lymphocytes. Therefore, in addition to its role in the activation of mitochondria during apoptosis, these results suggest a role for granzyme B in the dismantling of the cytoskeleton.
Elmo1 inhibits ubiquitylation of Dock180
Authors: Makino Yoshinori , Tsuda Masumi , Ichihara Shin , Watanabe Takuya , Sakai Mieko , Sawa Hirofumi , Nagashima Kazuo , Hatakeyama Shigetsugu , Tanaka Shinya
Published: February 2006

Dock180, a member of the CDM family of proteins, plays roles in biological processes such as phagocytosis and motility through its association with the signalling adaptor protein Crk. Recently, the complex formation between Dock180 and Elmo1 was reported to function as a bipartite guanine nucleotide exchange factor for Rac. In this study, we demonstrated that the amount of Dock180 increased when Elmo1 was co-expressed. Dock180 was found to be ubiquitylated and Dock180 protein levels could be augmented by treatment with proteasome inhibitor. The ubiquitylation of Dock180 was enhanced by epidermal growth factor (EGF), Crk and adhesion-dependent signals. Furthermore, Elmo1 inhibited ubiquitylation of Dock180, resulting in the increase in Dock180 levels. The Elmo1 mutant Δ531, which encompasses amino acids required for Dock180 binding, preserved the inhibitory effects on ubiquitylation of Dock180. Upon EGF stimulation, both Dock180 and ubiquitin were demonstrated to translocate to the cell periphery by immunofluorescence, and we found ubiquitylation of Dock180 and its inhibition by Elmo1 to occur in cellular membrane fractions by in vivo ubiquitylation assay. These data suggest that Dock180 is ubiquitylated on the plasma membrane, and also that Elmo1 functions as an inhibitor of ubiquitylation of Dock180. Therefore, an ubiquitin-proteasome-dependent protein degradation mechanism might contribute to the local activation of Rac on the plasma membrane.
PTEN couples Sema3A signalling to growth cone collapse
Authors: Chadborn Neil H. , Ahmed Aminul I. , Holt Mark R. , Prinjha Rabinder , Dunn Graham A. , Jones Gareth E. , Eickholt Britta J.
Published: February 2006

Distinct changes in glycogen synthase kinase-3 (GSK-3) signalling can regulate neuronal morphogenesis including the determination and maintenance of axonal identity, and are required for neurotrophin-mediated axon elongation. In addition, we have previously shown a dependency on GSK-3 activation in the semaphorin 3A (Sema3A)-mediated growth-cone-collapse response of sensory neurons. Regulation of GSK-3 activity involves the intermediate signalling lipid phosphatidylinositol 3,4,5-trisphosphate, which can be modulated by phosphatidylinositol 3-kinase (PI3K) and the tumour suppressor PTEN. We report here the involvement of PTEN in the Sema3A-mediated growth cone collapse. Sema3A suppresses PI3K signalling concomitant with the activation of GSK-3, which depends on the phosphatase activity of PTEN. PTEN is highly enriched in the axonal compartment and the central domain of sensory growth cones during axonal extension, where it colocalises with microtubules. Following exposure to Sema3A, PTEN accumulates rapidly at the growth cone membrane suggesting a mechanism by which PTEN couples Sema3A signalling to growth cone collapse. These findings demonstrate a dependency on PTEN to regulate GSK-3 signalling in response to Sema3A and highlight the importance of subcellular distributions of PTEN to control growth cone behaviour.