bluuebunny/crossref_metadata_2025 huggingface dataset:
Meningitis in Korean patients with systemic lupus erythematosus: analysis of demographics, clinical features and outcomes; experience from affiliated hospitals of the Catholic University of Korea
Authors: Kim J-M , Kim K-J , Yoon H-S , Kwok S-K , Ju J-H , Park K-S , Cho C-S , Kim H-Y , Park S-H
Published: February 2011

Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified (‘septic meningitis’), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis ( p = 0.025) and displayed mental changes more often ( p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher ( p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group ( p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis ( p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.
Being a good nurse and doing the right thing: A replication study
Authors: Catlett Shelia , Lovan Sherry R
Published: February 2011

This qualitative research study, a replication of a study published in 2002, investigated the qualities of a good nurse and the role ethics plays in decision making. After reviewing the limitations of the published work, the current study implemented modifications related to the research questions, sample selection, data collection, and use of software for data analysis. The original study identified seven categories that related to being a good nurse and doing the right thing. In the present study, the use of relational analysis led to the recognition of four categories: (1) personal traits and attributes; (2) technical skills and management of care; (3) work environment and co-workers; and (4) caring and caring behaviors. To understand what it means to be a good nurse and do the right thing is a complex task; however, this research adds to the small amount of empirical data that exists to describe those characteristics.
Moral imagination in simulation-based communication skills training
Authors: Chen Ruth P
Published: February 2011

Clinical simulation is used in nursing education and in other health professional programs to prepare students for future clinical practice. Simulation can be used to teach students communication skills and how to deliver bad news to patients and families. However, skilled communication in clinical practice requires students to move beyond simply learning superficial communication techniques and behaviors. This article presents an unexplored concept in the simulation literature: the exercise of moral imagination by the health professional student. Drawing from the works of Hume, Aristotle and Gadamer, a conceptualization of moral imagination is first provided. Next, this article argues that students must exercise moral imagination on two levels: towards the direct communication exchange before them; and to the representative nature of simulation encounters. Last, the limits of moral imagination in simulation-based education are discussed.
Theory of protective empowering for balancing patient safety and choices
Authors: Chiovitti Rosalina F
Published: February 2011

Registered nurses in psychiatric-mental health nursing continuously balance the ethical principles of duty to do good (beneficence) and no harm (non-maleficence) with the duty to respect patient choices (autonomy). However, the problem of nurses’ level of control versus patients’ choices remains a challenge. The aim of this article is to discuss how nurses accomplish their simultaneous responsibility for balancing patient safety (beneficence and non-maleficence) with patient choices (autonomy) through the theory of protective empowering. This is done by reflecting on interview excerpts about caring from 17 registered nurses taking part in a grounded theory study conducted in three acute urban psychiatric hospital settings in Canada. The interplay between the protective and empowering dimensions of the theory of protective empowering was found to correspond with international, national, and local nursing codes of ethics and standards. The overall core process of protective empowering, and its associated reflective questions, is offered as a new lens for balancing patient safety with choices.
Stability of radially symmetric deformations of spheres of compressible non-linearly elastic materials
Authors: Murphy Jeremiah G , Rooney Francis J
Published: February 2011

The stability of homogeneous, isotropic, compressible pressurized non-linearly elastic spheres is considered. A simplified form of the classical method of adjacent equilibria is employed, where the assumed perturbed solution depends only on the radial co-ordinate of the undeformed configuration. The differential equation describing such perturbations and the associated boundary conditions are obtained for all compressible materials and an explicit instability criterion is then obtained. This criterion is studied for three general isotropic materials. The most general form of the strain-energy function for each of the corresponding three radially symmetric deformations is obtained. It is shown that the instability criterion also corresponds to the turning points of the corresponding pressure-inflation relation.
On azimuthal shear waves in a transversely isotropic viscoelastic mixture: Application to diffuse axonal injury
Authors: O'Callaghan Liam , O'Reilly Oliver M , Zhornitskaya Liya
Published: February 2011

Motivated by studies on a type of brain injury known as diffuse axonal injury, the dynamic azimuthal shearing of a mixture of a transversely isotropic viscoelastic material which is surrounded by a softer isotropic viscoelastic material is considered. It is demonstrated how the states of maximum strain and strain rate occur near the interface between the two materials. The dependency of these states of maximum strain and strain rate on the boundary conditions on the outer surface of the isotropic material is also discussed.
Scattering of ultrasonic-guided waves for health monitoring of fuel weep holes
Authors: Doherty C , Chiu WK
Published: February 2011

A novel and effective approach for nondestructive in situ structural health monitoring of a hard-to-inspect location is presented in this article. Laser vibrometry is used to confirm that Lamb waves, generated by low-profile surface bonded piezoceramic transducers, are able to create circumferential creeping waves on the free surface of cylindrical cavities. The behavior of the propagating ultrasonic stress waves around the cavity and their interaction with simulated fatigue damage emanating from the top of the cavity is visualized. The transformation to a cylindrical co-ordinate system is found to be useful in visualizing wave scattering due to the presence of an open notch. Nondestructive evaluation of the structure is shown to be viable with the strength of the scattered spiralling creeping wave field maintaining its form and growing in amplitude as the notch length in increased. An informed selection of the excitation frequency is recommended as the A0 Lamb mode is found to be more efficient than the S0 Lamb mode in generating creeping waves around the cavity. Results from a receiving low-profile piezoceramic transducer are used to substantiate the laser vibrometry measurements and further establish the potential of the technique.
Dose–Response Study of Mobilisation and Tactile Stimulation Therapy for the Upper Extremity Early After Stroke
Authors: Hunter Susan M. , Hammett Linda , Ball Sue , Smith Nina , Anderson Cheryl , Clark Allan , Tallis Raymond , Rudd Anthony , Pomeroy Valerie M.
Published: February 2011

Background. Physical therapy doses may need to be higher than provided in current clinical practice, especially for patients with severe paresis. The authors aimed to find the most effective and feasible dose of Mobilisation and Tactile Stimulation (MTS), which includes joint and soft-tissue mobilization and passive or active-assisted movement to enhance voluntary muscle contraction. Methods. This 2-center, randomized, controlled, observer-blinded feasibility trial compared conventional rehabilitation but no extra therapy (group 1) with conventional therapy plus 1 of 3 daily doses of MTS, up to 30 (group 2), 60 (group 3), or 120 (group 4) minutes for 14 days. The 76 participants had substantial paresis (Motricity Index [MI] < 61) a mean of 30 days (standard deviation [SD] = 20 days) after anterior circulation stroke. MTS was delivered using a standardized schedule of techniques (eg, sensory input, active-assisted movement). The primary outcome was the Motricity Index (MI) and secondary outcome was the Action Research Arm Test (ARAT) tested on day 16. Adverse events were monitored daily. Results. No difference was found in the change in control group MI compared with each of the 3 intervention groups ( P = .593) or in the ARAT. Mean actual daily treatment time for all MTS groups was less than expected. The attrition rate was 1.3%. No adverse events related to overuse occurred. Conclusion. The authors were not able to deliver a maximum dose of 120 minutes of daily therapy each day. The mean daily dose of MTS feasible for subsequent evaluation is between 37 and 66 minutes.
The Journey to Leadership for Academics in Higher Education
Authors: Inman Margaret
Published: February 2011

The literature on leadership in the compulsory education sector shows that there are multiple pathways through different stages and phases to becoming a headteacher. However although research exists on leadership in higher education, little has been written about those in ‘middle leadership’ positions such as heads of faculties and departments. This article explores the journey to leadership undertaken by 18 leader academics within six chartered and statutory universities in the south of Wales and the west of England. It is based on the longitudinal framework of stages and phases as proposed by Day and Bakioglu (1996), Gronn (1999) and modified by Ribbins (2003). The research reveals that although the journeys have similarities to those of leaders in schools, contextual factors that shape a leader’s agency appear to be different in the middle and latter stages. A recontextualized model is proposed to illustrate these differences and is intended to contribute to increased understanding of how leader academics develop. This article argues the importance of reflection on their journey to leadership so not only can leaders understand themselves better but also they can reflect on how they interrelate with, and lead, other people. This has important implications when developing potential leaders.
Leadership Support through Public—Private ‘Partnerships’: Views of School Leaders
Authors: Mertkan Sefika
Published: February 2011

The English education system has been radically transformed over the last two decades. Throughout this period, the New Right and New Labour government policies have embraced the rhetoric of empowering schools to become self-managing institutions. In the course of this transformation, school leadership and management have become exceptionally complex and increasingly demanding with the leadership team being accountable for business management as well as pedagogical leadership. This article explores through loosely structured thematic interviews with headteachers and school business managers whether there is a demand for voluntary business management support from businesses. Schools demonstrate a willingness to receive strategic business management support from businesses, but present a multifaceted picture. Personalized school—business partnerships that are flexible and adaptable to the changing needs and capacities of both partners seem to be the way forward.
Community-based day-care services for people with intellectual disabilities in Georgia: a step towards their social integration
Authors: Makharadze Tamar , Kitiashvili Anastasia , Bricout John C.
Published: February 2011

This article discusses the role of community-based day-care services in the lives of adults with intellectual disabilities in the Republic of Georgia. The study explores the impact of this service on users’ social-adaptive skills, social life and sense of happiness, comparing service users and a matched comparison group. A mixed-methods approach was used to assess the influence of day-care-centre services on social adaptation and integration. Results indicated that the level of social-adaptive skills was higher for day-care-centre participants than for the comparison group along several key dimensions. Similarly, the level of social integration was higher for the day-care-centre group, although the two groups did not differ significantly on reported happiness. The findings from this study revealed that day-care-centre participants with intellectual disabilities enjoyed a greater degree of social interaction and socializing opportunities than their non-participant peers.
The impact of social policy on changes in professional practice within learning disability services: different standards for children and adults? A two-part examination
Authors: Malin Nigel A. , Race David G .
Published: February 2011

This is the first of two articles examining links between policy developments and changes in professional practice within learning disability services in England, focusing upon emergent differences between children’s and adult provision. The article focuses on the evolving tension around policy directions and managerialism/professionalism, with the latter as a set of practices driving services, particularly following the 1988 Griffiths Report but referring also to its antecedents. Implications of this development are examined to highlight a difference in emphasis between the credibility and professional status of the workforce in children’s, as opposed to adult, services for people with learning disabilities. A historical narrative demonstrates a continuum from the policies of Thatcherism to those of New Labour, underpinned by the assertion that normalization ideas have shaped both social policy and professional directions. The origins of current policy initiatives covering the last 20 years are explored, showing the consequences of a developing gap between professional inputs for children’s and adult services.
Effects of topical corticosteroids on the sciatic nerve: an experimental study to adduce the safety in treating carpal tunnel syndrome
Authors: Wang P.-H. , Tsai C.-L. , Lee J.-S. , Wu K.-C. , Cheng K.-I. , Jou I.-M.
Published: February 2011

Despite known detrimental effects on the blood flow and histology of nerves after intraneural corticosteroid injection, the neurotoxic effect of corticosteroids remains unclear. We investigated the effect of topical dexamethasone on nerve function. Two sponge strips soaked with dexamethasone at doses of 0.8, 1.6, and 3.2 mg were placed under and over the left sciatic nerve of adult Wistar rats for 30 minutes. Mixed-nerve-elicited somatosensory evoked potentials and dermatomal somatosensory evoked potentials were evaluated immediately and repeated together with functional tests and histology 2 weeks later. Evoked potential amplitude was dose-dependently lower and latency was prolonged in dexamethasone-treated sciatic nerves compared to controls. The suppression persisted with incomplete recovery for at least 4 hours, but differences between treated and control nerves were not significant after 2 weeks. Topical dexamethasone adversely affected neural conduction in a dose-dependent manner. Our results suggest that caution is required when using large doses of corticosteroid for injection of the carpal tunnel.
Screw prominences related to palmar locking plating of distal radius
Authors: Sügün T. S. , Karabay N. , Gürbüz Y. , Özaksar K. , Toros T. , Kayalar M.
Published: February 2011

Fixation of unstable distal radius fractures with palmar locking plates provides a stable reduction and early return of function, but complications arising from unrecognized dorsally prominent screws penetrating the extensor compartments are increasingly reported. Standard radiographs and fluoroscopy may not adequately visualize screw lengths, owing to the complex shape of the dorsum of the distal radius. We examined 46 distal radius fractures treated with palmar locking plates by ultrasound. Of the total 230 locking screws, 59 protruded from the dorsal cortical surface by 0.5 mm or more (range 0.5–6.1 mm). The first extensor compartment was violated by one screw, the second compartment by 22 screws, the third compartment by 15 screws, and the fourth compartment by 21 screws. Asymptomatic tenosynovitis was detected in four and symptomatic tenosynovitis in 14 of the 59 prominent screws. Ultrasound imaging may be useful in cases where intra-articular and/or comminuted fractures require distal plate placement and engagement of screws in the dorsal cortex.
Neuropathological correlates of late-life depression in older
people
Authors: Tsopelas Christos , Stewart Robert , Savva George M. , Brayne Carol , Ince Paul , Thomas Alan , Matthews Fiona E.
Published: February 2011

Background

Depression is common in old age and is associated with risk of dementia,
but its neuropathological correlates in the community are unknown.

Aims

To investigate for the first time in a population-representative sample
of people with no dementia the association between depression observed
during life and neurofibrillary tangles, diffuse and neuritic plaques,
Lewy bodies, brain atrophy and cerebrovascular disease found in the brain
at post-mortem.

Method

Out of 456 donations to a population-based study, 153 brains were
selected where donors had no dementia measured in life. Alzheimer and
vascular pathology measures, Lewy bodies and neuronal loss were compared
between those with (n = 36) and without
(n = 117) depression ascertained using a fully
structured diagnostic interview during life. Brain areas examined
included frontal, parietal, temporal and occipital cortical areas as well
as the entorhinal cortex, hippocampus and brain-stem monoaminergic
nuclei.

Results

Depression was significantly associated with the presence of subcortical
Lewy bodies. No association was found between depression and
cerebrovascular or Alzheimer pathology in cortical or subcortical areas,
although depression was associated with neuronal loss in the hippocampus
as well as in some of the subcortical structures investigated (nucleus
basalis, substantia nigra, raphe nucleus).

Conclusions

Late-life depression was associated with subcortical and hippocampal
neuronal loss but not with cerebrovascular or Alzheimer pathology.
Efficacy of mood stabilisers in the treatment of impulsive or
repetitive aggression: systematic review and meta-analysis
Authors: Jones Roland M. , Arlidge James , Gillham Rebecca , Reagu Shuja , van den Bree Marianne , Taylor Pamela J.
Published: February 2011

Background

Individuals with repetitive or impulsive aggression in the absence of
other disorders may be diagnosed with intermittent explosive disorder
according to DSM–IV, but no such diagnostic category exists in ICD–10.
Mood stabilisers are often used off-license for the treatment of
aggression associated with a variety of psychiatric conditions, but their
efficacy in these and in idiopathic aggression is not known.

Aims

To summarise and evaluate the evidence for the efficacy of mood
stabilisers (anticonvulsants/lithium) in the treatment of impulsive or
repetitive aggression in adults.

Method

A meta-analysis of randomised controlled trials that compared a mood
stabiliser with placebo in adults without intellectual disability,
organic brain disorder or psychotic illness, identified as exhibiting
repetitive or impulsive aggression.

Results

Ten eligible trials (489 participants) were identified A pooled analysis
showed an overall significant reduction in the frequency/severity of
aggressive behaviour (standardised mean difference (SMD) =–1.02, 95% CI
−1.54 to −0.50), although heterogeneity was high (I2 = 84.7%). When analysed by drug type, significant effects
were found in the pooled analysis of three phenytoin trials (SMD =–1.34,
95% CI −2.16 to −0.52), one lithium trial (SMD =–0.81, 95% CI −1.35 to
−0.28), and two oxcarbazepine/carbamazepine trials (SMD =–1.20, 95% CI
−1.83 to −0.56). However, when the results of only those studies that had
a low risk of bias were pooled (347 participants), there was no
significant reduction in aggression (SMD =–0.28, 95% CI −0.73 to 0.17,
I2 = 71.4%).

Conclusions

There is evidence that mood stabilisers as a group are significantly
better than placebo in reducing aggressive behaviour, but not all mood
stabilisers appear to share this effect. There is evidence of efficacy
for carbamazepine/oxcarbazepine, phenytoin and lithium. Many studies,
however, were at risk of bias and so further randomised controlled trials
are recommended.
Assisted suicide: why psychiatrists should engage in the
debate
Authors: Hotopf Matthew , Lee William , Price Annabel
Published: February 2011

There is an increasing appetite for a change in the law to allow assisted
suicide. This editorial suggests that psychiatrists should engage in the
debate because the issues at stake will affect us, and we are likely to have
a significant part to play were the law to be changed. We suggest that there
are three main areas where psychiatrists' expertise may be informative: (a)
the extent to which safeguards to limit the availability of assisted dying
to target groups can be applied safely and fairly, including to individuals
with psychiatric disorders; (b) the complexities inherent in assessing
mental capacity; and (c) the degree to which individuals adapt or change
their desires, particularly in relation to suicidal behaviours.
Questioning the ‘neuroprotective’ hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia?
Authors: Moncrieff Joanna
Published: February 2011

The idea that psychotic disorders are characterised by progressive neurodegeneration that can be reversed by drug treatment is used to justify early treatment of increasing numbers of mostly young people. I argue that there is little evidence to support the view that old- or new-generation antipsychotics are ‘neuroprotective’, and some evidence that the drugs themselves may be responsible for the decline in brain matter observed in some studies.
Contribution of psychiatric disorders to occupation of NHS beds: analysis of Hospital Episode Statistics
Authors: Pillay Parvathy , Moncrieff Joanna
Published: February 2011

Aims and method

We looked at the contribution of psychiatric disorders to occupancy of National Health Service (NHS) beds in England in the past 11 years, using publicly available data on Hospital Episode Statistics from the financial years 1998–1999 to 2008–2009.

Results

Patients with psychiatric disorders occupied between 14 and 16% of NHS beds in each year examined, and schizophrenia and mood disorders were among the top ten medical diagnoses of people occupying beds in every year. In terms of duration of admission, many individuals with psychiatric disorders, including schizophrenia and mood disorders, had a longer length of admission than those with other medical conditions. In 2008–2009 mean duration of admission for people with schizophrenia was 108 days and for people with mood disorders 42 days. In comparison, people with cerebrovascular disease stayed in hospital for 20 days on average.

Clinical implications

Despite modern treatments, people with psychiatric disorders occupy a large proportion of NHS beds and stay in hospital for considerably longer than those with other medical conditions. Since the independent sector is providing increasing amounts of long-term in-patient care, these figures are likely to underestimate the total burden and costs of treating psychiatric disorders. Community services designed to reduce admissions have yet to have any substantial impact on bed use.
Randomized Trial of Carboplatin Versus Radiotherapy for Stage I Seminoma: Mature Results on Relapse and Contralateral Testis Cancer Rates in MRC TE19/EORTC 30982 Study (ISRCTN27163214)
Authors: Oliver R. Timothy D. , Mead Graham M. , Rustin Gordon J.S. , Joffe Johnathan K. , Aass Nina , Coleman Robert , Gabe Rhian , Pollock Philip , Stenning Sally P.
Published: February 2011

Purpose

Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported.

Patients and Methods

Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0).

Results

Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 × AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38).

Conclusion

These updated results confirm the noninferiority of single dose carboplatin (at 7 × AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.
Differences in Sleep Disturbance Parameters Between Oncology Outpatients and Their Family Caregivers
Authors: Carney Sara , Koetters Theresa , Cho Maria , West Claudia , Paul Steven M. , Dunn Laura , Aouizerat Bradley E. , Dodd Marylin , Cooper Bruce , Lee Kathryn , Wara William , Swift Patrick , Miaskowski Christine
Published: February 2011

Purpose

This study compared the occurrence rates for and severity ratings of sleep disturbance in patient-family caregiver (FC) dyads.

Patients and Methods

In total, 102 dyads were recruited from two radiation therapy (RT) departments. Patients and their FCs completed the Pittsburgh Sleep Quality Index (PSQI) and the General Sleep Disturbance Scale (GSDS) and wore wrist actigraphs to obtain subjective and objective measures of the occurrence and severity of sleep disturbance at the initiation of RT. Match paired t tests were used to evaluate for dyadic differences.

Results

No differences were found in the occurrence of clinically significant levels of sleep disturbance between patients and their FCs that ranged between 40% and 50% using subjective and objective measures. Few differences were found in the severity of any of the sleep-wake parameters between patients and FCs using both the subjective and objective measures of sleep disturbance.

Conclusion

The findings from this study suggest that patients with cancer and their FCs experience similar levels of sleep disturbance and that both groups could benefit from interventions that aim to promote restful sleep. In addition to routine and systematic assessment of sleep disturbance by oncology clinicians, interventions are needed that take into account the specific needs of the patient and the FC as well as the potential for partners' sleep patterns to influence one another.
Impact of Pretransplantation Minimal Residual Disease, As Detected by Multiparametric Flow Cytometry, on Outcome of Myeloablative Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
Authors: Walter Roland B. , Gooley Ted A. , Wood Brent L. , Milano Filippo , Fang Min , Sorror Mohamed L. , Estey Elihu H. , Salter Alexander I. , Lansverk Emily , Chien Jason W. , Gopal Ajay K. , Appelbaum Frederick R. , Pagel John M.
Published: February 2011

Purpose

Allogeneic hematopoietic cell transplantation (HCT) benefits many patients with acute myeloid leukemia (AML) in first remission. Hitherto, little attention has been given to the prognostic impact of pretransplantation minimal residual disease (MRD).

Patients and Methods

We retrospectively studied 99 consecutive patients receiving myeloablative HCT for AML in first morphologic remission. Ten-color multiparametric flow cytometry (MFC) was performed on bone marrow aspirates before HCT. MRD was identified as a cell population showing deviation from normal antigen expression patterns compared with normal or regenerating marrow. Any level of residual disease was considered MRD positive.

Results

Before HCT, 88 patients met morphologic criteria for complete remission (CR), whereas 11 had CR with incomplete blood count recovery (CRi). Twenty-four had MRD before HCT as determined by MFC. Two-year estimates of overall survival were 30.2% (range, 13.1% to 49.3%) and 76.6% (range, 64.4% to 85.1%) for MRD-positive and MRD-negative patients; 2-year estimates of relapse were 64.9% (range, 42.0% to 80.6%) and 17.6% (range, 9.5% to 27.9%). After adjustment for all or a subset of cytogenetic risk, secondary disease, incomplete blood count recovery, and abnormal karyotype pre-HCT, MRD-positive HCT was associated with increased overall mortality (hazard ratio [HR], 4.05; 95% CI, 1.90 to 8.62; P < .001) and relapse (HR, 8.49; 95% CI, 3.67 to 19.65; P < .001) relative to MRD-negative HCT.

Conclusion

These data suggest that pre-HCT MRD is associated with increased risk of relapse and death after myeloablative HCT for AML in first morphologic CR, even after controlling for other risk factors.
Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
Authors: Robbins Paul F. , Morgan Richard A. , Feldman Steven A. , Yang James C. , Sherry Richard M. , Dudley Mark E. , Wunderlich John R. , Nahvi Azam V. , Helman Lee J. , Mackall Crystal L. , Kammula Udai S. , Hughes Marybeth S. , Restifo Nicholas P. , Raffeld Mark , Lee Chyi-Chia Richard , Levy Catherine L. , Li Yong F. , El-Gamil Mona , Schwarz Susan L. , Laurencot Carolyn , Rosenberg Steven A.
Published: February 2011

Purpose

Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma.

Patients and Methods

A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1–positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).

Results

Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma.

Conclusion

These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.
Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice
Authors: Sparks Erin E. , Perrien Daniel S. , Huppert Kari A. , Peterson Todd E. , Huppert Stacey S.
Published: February 2011

Abnormal Notch signaling in humans results in Alagille syndrome, a pleiotropic disease characterized by a paucity of intrahepatic bile ducts (IHBDs). It is not clear how IHBD paucity develops as a consequence of atypical Notch signaling, whether by a developmental lack of bile duct formation, a post-natal lack of branching and elongation or an inability to maintain formed ducts. Previous studies have focused on the role of Notch in IHBD development, and demonstrated a dosage requirement of Notch signaling for proper IHBD formation. In this study, we use resin casting and X-ray microtomography (microCT) analysis to address the role of Notch signaling in the maintenance of formed IHBDs upon chronic loss or gain of Notch function. Our data show that constitutive expression of the Notch1 intracellular domain in bi-potential hepatoblast progenitor cells (BHPCs) results in increased IHBD branches at post-natal day 60 (P60), which are maintained at P90 and P120. By contrast, loss of Notch signaling via BHPC-specific deletion of RBP-J (RBP KO), the DNA-binding partner for all Notch receptors, results in progressive loss of intact IHBD branches with age. Interestingly, in RBP KO mice, we observed a reduction in bile ducts per portal vein at P60; no further reduction had occurred at P120. Thus, bile duct structures are not lost with age; instead, we propose a model in which BHPC-specific loss of Notch signaling results in an initial developmental defect resulting in fewer bile ducts being formed, and in an acquired post-natal defect in the maintenance of intact IHBD architecture as a result of irresolvable cholestasis. Our studies reveal a previously unappreciated role for Notch signaling in the post-natal maintenance of an intact communicating IHBD structure, and suggest that liver defects observed in Alagille syndrome patients might be more complex than bile duct paucity.
Investigation of Matched and Mismatched Duplex DNA by Electrospray Ionization-Mass Spectrometry
Authors: Zheng Bo , Yuan Gu
Published: February 2011

In this research, the gas-phase stabilities of matched and mismatched duplex DNA were investigated by electrospray ionization-mass spectrometry (ESI-MS). The wild-type p53 duplex DNA [ds1, perfectly-matched (PM) DNA] was successfully distinguished from its three mutated DNAs [double-base mismatched DNA (DM)]. Moreover, the three DM DNAs were also well discriminated from each other using ESI-MS. Results show that the gas-phase thermodynamic stability of the DM DNAs decreased as the two mismatch spots moved closer. This implies that the dissociation of DM duplexes into two single strands prefers the mode “from middle to terminals”.
A management control approach to monitor large-scale change: an illustration in the context of reconfiguration
Authors: Spurgeon Peter , Mazelan Patti , Barwell Fred
Published: February 2011

The paper describes how Hospital Episode Statistics (HES) data can be retrospectively analysed over a number of years to evaluate and monitor organizational change in National Health Service (NHS) trusts. A methodology based on joinpoint regression analysis and management control theory has been developed which is able to represent in a framework (called an ‘activity map’) the complexity of HES data in a more user-friendly way than the unwieldy and often overwhelming tables or spreadsheets that are typically utilized. The ‘activity map’ has been designed to provide a common frame of reference for health professionals from different backgrounds to visualize and interpret the actual patterns of hospital activity changes that have occurred over the years. The aim is to facilitate a more effective, faster and more intuitive exploration of very large and unwieldy HES data-sets to assist health-care staff in monitoring planned and unplanned activity changes. It is hoped that making HES data more easily assimilated will encourage a greater sense of meaningful engagement in creatively contributing to service innovation.
A planning model for the short-term management of cash
Authors: Broyles Robert W , Mattachione Steven , Khaliq Amir
Published: February 2011

This paper develops a model that enables the health administrator to identify the balance that minimizes the projected cost of holding cash. Adopting the principles of mathematical expectation, the model estimates the expected total costs of adopting each of the several strategies concerning the cash balance that the organization might maintain. Expected total costs consist of anticipated short costs, resulting from a potential shortage of funds. Long costs are associated with a potential surplus of funds and an opportunity cost represented by foregone investment income. Of importance to the model is the potential for the health service organization to realize a surplus of funds during periods characterized by a net cash disbursement. The paper also develops an interactive spreadsheet that enables the administrator to perform sensitivity analysis and examine the response of the desired or target cash balance to changes in the parameters that define the expected long and short cost functions.
The interplay between policy guidelines and local dynamics in shaping the scope of networks: the experience of the Italian Departments of Mental Health
Authors: Compagni Amelia , Gerzeli Simone , Bergamaschi Mara
Published: February 2011

In the mental health field, the creation of networks that can guarantee the smooth coordination of services and organizations across sectors is a priority in the policy agenda of several countries. In Italy, Departments of Mental Health (DMHs) have been designated responsible for the system of specialist mental health services, and also mandated as the conveners and leaders of interorganizational and cross-sectoral networks, by a system-wide reform. This study aims to understand how mental health networks have been assembled in this context and the factors and motivations that have shaped their scope. By combining an analysis of policies with a survey of DMH directors, we have determined that DMHs have preferentially formed collaborative relationships with social service providers (local governments) and the voluntary sector. In contrast, relationships with substance abuse and addiction services and primary care providers were weak and stifled by a lack of trust and by conflict about respective contributions to mental care. We explore the reasons for this selectivity in interorganizational relationships and propose that a lack of targeted incentives in policy guidelines, on the one hand, and the existence of a mandated network leadership, on the other, have led to a rather narrow range of collaborations.
A systematic review of lung-sparing extirpative surgery for pleural mesothelioma
Authors: Teh Elaine , Fiorentino Francesca , Tan Carol , Treasure Tom
Published: February 2011

Summary

Objectives

There is a resurgence of interest in lung-sparing extirpative surgery for malignant pleural mesothelioma with recent reports of better survival and fewer adverse consequences than with extrapleural pneumonectomy. However, these operations are not well-characterized and to offer evidence-based clinical recommendations and to plan future trials a summary of what is already known is required.

Design

A formal literature search was performed and all recovered titles were sequentially sifted by title, abstract and full-text reading according to prespecified criteria. Papers were selected if they contained data relevant to the area of enquiry. Quantitative synthesis and textual analysis, appropriate to the material, were performed.

Setting

Follow-up studies of patients undergoing surgery for malignant pleural mesothelioma in specialist thoracic or cardiothoracic units.

Participants

Among the operated patients described in these papers, a total of 1270 patients had undergone lung-sparing surgery for mesothelioma.

Results

There were no randomized trials or other forms of controlled studies. From 464 titles, 26 papers contained sufficient data on 1270 patients to be included in the systematic review. Operative descriptions for all series were extracted and tabulated and variation was found in the nature of surgery within and between series, and the degree of detail with which it was described. There was more operative detail in recent papers. All available numerical data were extracted, tabulated and summarized using quantitative methods. The average survival at 1, 2, 3, 4 and 5 years was 51%, 26%, 16%, 11% and 9%, respectively. There were no data on patients’ performance status, symptomatic change, or other patient reported outcomes.

Conclusions

In the absence of any form of control data, no conclusions can be drawn concerning survival differences or symptomatic benefits attributable to surgery. As mesothelioma surgery is restricted to a selected minority of patients who often have multiple therapies, future research will require controlled studies with explicit definitions of the clinical and surgical intent.
A flexible linker region in Fip1 is needed for efficient mRNA polyadenylation
Authors: Ezeokonkwo Chukwudi , Zhelkovsky Alexander , Lee Rosanna , Bohm Andrew , Moore Claire L.
Published: February 2011

Synthesis of the poly(A) tail of mRNA in Saccharomyces cerevisiae requires recruitment of the polymerase Pap1 to the 3′ end of cleaved pre-mRNA. This is made possible by the tethering of Pap1 to the Cleavage/Polyadenylation Factor (CPF) by Fip1. We have recently reported that Fip1 is an unstructured protein in solution, and proposed that it might maintain this conformation as part of CPF, when bound to Pap1. However, the role that this feature of Fip1 plays in 3′ end processing has not been investigated. We show here that Fip1 has a flexible linker in the middle of the protein, and that removal or replacement of the linker affects the efficiency of polyadenylation. However, the point of tethering is not crucial, as a fusion protein of Pap1 and Fip1 is fully functional in cells lacking genes encoding the essential individual proteins, and directly tethering Pap1 to RNA increases the rate of poly(A) addition. We also find that the linker region of Fip1 provides a platform for critical interactions with other parts of the processing machinery. Our results indicate that the Fip1 linker, through its flexibility and protein/protein interactions, allows Pap1 to reach the 3′ end of the cleaved RNA and efficiently initiate poly(A) addition.
Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing
Authors: Miller Heather B. , Robinson Timothy J. , Gordân Raluca , Hartemink Alexander J. , Garcia-Blanco Mariano A.
Published: February 2011

Tat specific factor 1 (Tat-SF1) interacts with components of both the transcription and splicing machineries and has been classified as a transcription-splicing factor. Although its function as an HIV-1 dependency factor has been investigated, relatively little is known about the cellular functions of Tat-SF1. To identify target genes of Tat-SF1, we utilized a combination of RNAi and exon-specific microarrays. These arrays, which survey genome-wide changes in transcript and individual exon levels, revealed 450 genes with transcript level changes upon Tat-SF1 depletion. Strikingly, 98% of these target genes were down-regulated upon depletion, indicating that Tat-SF1 generally activates gene expression. We also identified 89 genes that showed differential exon level changes after Tat-SF1 depletion. The 89 genes showed evidence of many different types of alternative exon use consistent with the regulation of transcription initiation sites and RNA processing. Minimal overlap between genes with transcript-level and exon-level changes suggests that Tat-SF1 does not functionally couple transcription and splicing. Biological processes significantly enriched with transcript- and exon-level targets include the cell cycle and nucleic acid metabolism; the insulin signaling pathway was enriched with Tat-SF1 transcript-level targets but not exon-level targets. Additionally, a hexamer, ATGCCG, was over-represented in the promoter region of genes showing changes in transcription initiation upon Tat-SF1 depletion. This may represent a novel motif that Tat-SF1 recognizes during transcription. Together, these findings suggest that Tat-SF1 functions independently in transcription and splicing of cellular genes.
Late peri-prosthetic femoral fracture as a major mode of failure in uncemented primary hip replacement
Authors: Streit M. R. , Merle C. , Clarius M. , Aldinger P. R.
Published: February 2011

Peri-prosthetic femoral fracture after total hip replacement (THR) is associated with a poor outcome and high mortality. However, little is known about its long-term incidence after uncemented THR.

We retrospectively reviewed a consecutive series of 326 patients (354 hips) who had received a CLS Spotorno replacement with an uncemented, straight, collarless tapered titanium stem between January 1985 and December 1989. The mean follow-up was 17 years (15 to 20). The occurrence of peri-prosthetic femoral fracture during follow-up was noted. Kaplan-Meier survival analysis was used to estimate the cumulative incidence of fracture.

At the last follow-up, 86 patients (89 hips) had died and eight patients (eight hips) had been lost to follow-up. A total of 14 fractures in 14 patients had occurred. In ten hips, the femoral component had to be revised and in four the fracture was treated by open reduction and internal fixation. The cumulative incidence of peri-prosthetic femoral fracture was 1.6% (95% confidence interval 0.7 to 3.8) at ten years and 4.5% (95% confidence interval 2.6 to 8.0) at 17 years after the primary THR. There was no association between the occurrence of fracture and gender or age at the time of the primary replacement.

Our findings indicate that peri-prosthetic femoral fracture is a significant mode of failure in the long term after the insertion of an uncemented CLS Spotorno stem. Revision rates for this fracture rise in the second decade. Further research is required to investigate the risk factors involved in the occurrence of late peri-prosthetic femoral fracture after the implantation of any uncemented stem, and to assess possible methods of prevention.