bluuebunny/crossref_metadata_2025 huggingface dataset:
Binomial regression with a misclassified covariate and outcome
Authors: Luo Sheng , Chan Wenyaw , Detry Michelle A , Massman Paul J , Doody Rachelle S
Published: March 2012

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease–exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach is motivated and applied to a dataset from the Baylor Alzheimer's Disease and Memory Disorders Center.
‘Who’ll Pay Reparations on My Soul?’1 Compensation, Social Control and Social Suffering
Authors: Moon Claire
Published: March 2012

Contemporary debate about compensation for past wrongs turns on the assumption that state reparation benefits the victims of atrocity by acknowledging harm and ameliorating victim suffering. Indeed, much recent theoretical and practical work has concurred to establish reparation to victims of state crimes as a cornerstone of human rights. However, this article argues that reparation can also function to placate victim demands for criminal justice and to regulate the range of political and historical meanings with which the crimes of the past are endowed. This is most evident in transitional political contexts in which gestures of reparation are usually concomitant with the inauguration of new political orders, and formal investigations of past atrocity are conditioned by the balancing of the political demands of new and old regimes. This article argues that in such contexts, state reparation can work to control social suffering with the consequence that it sometimes intensifies rather than alleviates it. To evidence this claim, the article investigates the refusal of reparations by the victims towards whom it is addressed, with reference to Argentina’s Madres de Plaza de Mayo. This analysis of their refusal demonstrates how victim groups make important challenges to some of the core assumptions in the field, reveals internal inconsistencies within the analytical architecture of the scholarly and professional discourse, and indicates the ways in which reparations carry political, and not just palliative, significance.
Posttraumatic Growth, Coping Strategies, and Psychological Distress in Adolescent Survivors of Cancer
Authors: Turner-Sack Andrea M. , Menna Rosanne , Setchell Sarah R.
Published: March 2012

Only recently have researchers begun to empirically examine positive outcomes such as posttraumatic growth in adolescent cancer. This article examines associations between posttraumatic growth, coping strategies, and psychological distress in adolescent cancer survivors. Adolescents who finished cancer treatment 2 to 10 years prior (N = 31) completed self-report measures of posttraumatic growth, coping, symptomatology, and disease-related characteristics. Younger age at diagnosis and less use of avoidant coping strategies predicted lower levels of psychological distress. Adolescents’ beliefs that they were more likely to relapse and the use of more acceptance coping strategies predicted higher levels of posttraumatic growth. Adolescent cancer survivors may be capable of experiencing posttraumatic growth. Those who believe they are more prone to relapse and use more acceptance coping strategies are likely to have higher levels of posttraumatic growth. As health care professionals encourage adolescent cancer survivors to use fewer avoidant coping strategies, they can also encourage survivors to use more acceptance coping strategies.
Developing a hardware in-the-loop simulator for a backpack energy harvester
Authors: Papatheou Evangelos , Sims Neil D
Published: March 2012

Energy harvesting from ambient sources has been the subject of several studies. Some of the proposed approaches attempt to generate electrical energy from the human movement. However, many of them can be uncomfortable or they impose a significant burden on the person’s gait. In the current article, the design of a hardware in-the-loop simulator for an energy-harvesting backpack is presented. The idea is based on the energy produced by a suspended load that moves vertically on a backpack while a person walks. The energy created from such a linear system can be maximised when it resonates with the walking frequency of the person. However, such a configuration can also cause great forces to be applied on the back of the user. The system that is proposed here consists of a mass attached on a rucksack, which is controlled by a motor in order to simulate the suspended-load backpack. The advantage of this setup is the ability to test different settings, regarding the spring stiffness or the damping coefficient, of the backpack harvester, and study their effect on the energy-harvesting potential, as well as on the human gait. The present contribution describes the design, analysis and preliminary testing of the hardware in-the-loop backpack system.
A mathematical model for bacterial self-healing of cracks in concrete
Authors: Zemskov Serguey V , Jonkers Henk M , Vermolen Fred J
Published: March 2012

In the current research, a mathematical model for bacterial self-healing of a crack is considered. The study is embedded within the framework of investigating the potential of bacteria to act as a catalyst of the self-healing process in concrete, which is the ability of concrete to repair occurring cracks autonomously. Spherical clay capsules containing the healing agent (calcium lactate) and nutrients for bacteria are embedded in the concrete structure. Water entering a newly appearing crack initiates the release of the capsule content and activates the bacteria to convert calcium lactate to calcium carbonate (limestone). The crack is sealed through the metabolically mediated limestone precipitation. The model of the self-healing process is based on a moving boundary problem in which two fragments of the boundary move resulting from calcium carbonate precipitation and the dissolution of the capsule content, respectively. A Galerkin finite element method is used to solve the diffusion equations. The moving boundaries are tracked using a level set method.
Light White Oils Exhibit Low Tissue Accumulation Potential and Minimal Toxicity in F344 Rats
Authors: McKee Richard H. , Drummond John G. , Freeman James J. , Letinski Daniel J. , Miller Mary Jo
Published: March 2012

Female F344 rats were fed diets containing 0.02%, 0.2%, or 2.0% white mineral oil for 90 days. There were no gross or microscopic differences in target organs at the 0.02% level. In the higher-dose groups, relative liver and mesenteric lymph node (MLN) weights were increased, and MLN inflammation was observed. At the 2% level, there was very limited evidence of microgranuloma formation in the liver but at a lower incidence and at lesser severity than has been reported in studies of C22 -C25 oils. Analysis of liver extracts from treated rats revealed that C15 -C20 constituents were underrepresented by comparison to their corresponding concentrations in the test oil. These results provide evidence that although hydrocarbons with carbon numbers <C20 are absorbed, they are not preferentially retained and do not contribute to inflammatory processes in liver.
Mapping regional grey and white matter atrophy in relapsing–remitting multiple sclerosis
Authors: Riccitelli Gianna , Rocca Maria A , Pagani Elisabetta , Martinelli Vittorio , Radaelli Marta , Falini Andrea , Comi Giancarlo , Filippi Massimo
Published: March 2012

Objective:

We aimed to investigate the regional distribution of grey matter (GM) and white matter (WM) atrophy in patients with relapsing–remitting (RR) MS and their relationship with gender, clinical findings, and T2 lesions.

Methods:

Clinical and magnetic resonance imaging assessments were obtained from 78 patients with RRMS and 88 controls. GM and WM atrophy were estimated using voxel-based morphometry (SPM8).

Results:

Patients with RRMS experienced atrophy of the deep GM nuclei, and several cortical regions mainly located in the fronto-parietal lobes. WM atrophy involved posterior regions of the brain, including the cerebellum and brainstem. Compared with men, affected women showed atrophy of several WM tracts, while gender did not impact GM atrophy. Disease duration > 5 years was associated with atrophy of the thalami and inferior frontal gyrus, while WM atrophy was already prominent in patients with disease duration ≤ 5 years. Expanded Disability Status Scale score > 3.0 was associated with diffuse WM atrophy and basal ganglia and precentral gyrus atrophy. T2 lesions were marginally associated to focal atrophy.

Discussion:

In RRMS, GM and WM atrophy have distinct patterns of regional distribution, with a sparing of GM infratentorial regions. Gender, disease duration and disability affect differently the topography of GM/WM atrophy, while T2 lesions play a modest role.
The place of race and racism in cultural competence: What can we learn from the English experience about the narratives of evidence and argument?
Authors: Bhui Kamaldeep , Ascoli Micol , Nuamh Olivia
Published: March 2012

This paper outlines the history of workforce strategies for providing mental health care to “black and ethnic minorities” in England. Universal mental health policies failed to deliver equity in care, and thus specific policies were launched to address ethnic inequalities in care experiences and outcomes. The emphasis on race equality rather than cultural complexity led to widespread acceptance of the need for change. The policy implementation was delivered in accord with multiple regional and national narratives of how to reduce inequalities. As changes in clinical practice and services were encouraged, resistance emerged in various forms from clinicians and policy leaders. In the absence of commitment and then dispute about forms of evidence, divergent policy and clinical narratives fuelled a shift of attention away from services to silence issues of race equality. The process itself represents a defence against the pain of acknowledging systemic inequities whilst rebutting perceived criticism. We draw on historical, psychoanalytic, and learning theory in order to understand these processes and the multiple narratives that compete for dominance. The place of race, ethnicity, and culture in history and their representation in unconscious and conscious thought are investigated to reveal why cultural competence training is not simply an educational intervention. Tackling inequities requires personal development and the emergence and containment of primitive anxieties, hostilities, and fears. In this paper we describe the experience in England of moving from narratives of cultural sensitivity and cultural competence, to race equality and cultural capability, and ultimately to cultural consultation as a process. Given the need to apprehend narratives in care practice, especially at times of disputed evidence, cultural consultation processes may be an appropriate paradigm to address intersectional inequalities.
A Neurologist’s Guide to Acute Migraine Therapy in the Emergency Room
Authors: Gelfand Amy A. , Goadsby Peter J.
Published: March 2012

Migraine is a common reason for visits to the emergency room. Attacks that lead patients to come to the emergency room are often more severe, refractory to home rescue medication, and have been going on for longer. All of these features make these attacks more challenging to treat. The purpose of this article is to review available evidence pertinent to the treatment of acute migraine in adults in the emergency department setting in order to provide neurologists with a rational approach to management. Drug classes and agents reviewed include opioids, dopamine receptor antagonists, triptans, nonsteroidal anti-inflammatory drugs, corticosteroids, and sodium valproate.
The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis
Authors: Lai Janice Ching , Ponti Svetlana , Pan Dejing , Kohler Hubertus , Skoda Radek C. , Matthias Patrick , Nagamine Yoshikuni
Published: March 2012

The DEAH helicase RHAU (alias DHX36, G4R1) is the only helicase shown to have G-quadruplex (G4)–RNA resolvase activity and the major source of G4-DNA resolvase activity. Previous report showed RHAU mRNA expression to be elevated in human lymphoid and CD34+ BM cells, suggesting a potential role in hematopoiesis. Here, we generated a conditional knockout of the RHAU gene in mice. Germ line deletion of RHAU led to embryonic lethality. We then targeted the RHAU gene specifically in the hematopoiesis system, using a Cre-inducible system in which an optimized variant of Cre recombinase was expressed under the control of the Vav1 promoter. RHAU deletion in hematopoietic system caused hemolytic anemia and differentiation defect at the proerythroblast stage. The partial differentiation block of proerythroblasts was because of a proliferation defect. Transcriptome analysis of RHAU knockout proerythroblasts showed that a statistically significant portion of the deregulated genes contain G4 motifs in their promoters. This suggests that RHAU may play a role in the regulation of gene expression that relies on its G4 resolvase activity.
The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury
Authors: Tauchi Ryoji , Imagama Shiro , Natori Takamitsu , Ohgomori Tomohiro , Muramoto Akio , Shinjo Ryuichi , Matsuyama Yukihiro , Ishiguro Naoki , Kadomatsu Kenji
Published: March 2012

Background

Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.

Methods

The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite growth assay and an in vivo neuronal injury model, spinal cord contusion injury, were employed.

Results

ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury.

Conclusions

Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.
Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells
Authors: Bertin Jonathan , Barat Corinne , Bélanger Dave , Tremblay Michel J
Published: March 2012

Background

Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B4(LTB4) and cysteinyl-leukotrienes such as LTC4are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells.

Methods

To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).

Results

We report in this study that virus replication is reduced upon treatment of MDMis with LTB4and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.

Conclusions

These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.
Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids
Authors: Strazzullo Maria , Corteggio Annunziata , Altamura Gennaro , Francioso Romina , Roperto Franco , D'Esposito Maurizio , Borzacchiello Giuseppe
Published: March 2012

Background

Sarcoids are peculiar equine benign tumours. Their onset is associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2) infection. Little is known about the molecular interplay between viral infection and neoplastic transformation. The data regarding papillomavirus infections in human species show the inactivation of a number of tumour suppressor genes as basic mechanism of transformation. In this study the putative role of the tumour suppressor gene Fragile Histidine Triad (FHIT) in sarcoid tumour was investigated in different experimental models. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissue.

Results

Nine paraffin embedded sarcoids and sarcoid derived cell lines were analysed for the expression of FHIT protein by immunohistochemistry, immunofluorescence techniques and western blotting. These analyses revealed the absence of signal in seven out of nine sarcoids. The two sarcoid derived cell lines too showed a reduced signal of the protein. To investigate the causes of the altered protein expression, the samples were analysed for the DNA methylation profile of the CpG island associated with the FHIT promoter. The analysis of the 32 CpGs encompassing the region of interest showed no significative differential methylation profile between pathological tissues and cell lines and their normal counterparts.

Conclusion

This study represent a further evidence of the role of a tumour suppressor gene in equine sarcoids and approaches the epigenetic regulation in this well known equine neoplasm. The data obtained in sarcoid tissues and sarcoid derived cell lines suggest that also in horse, as in humans, there is a possible involvement of the tumour suppressor FHIT gene in BPV induced tumours. DNA methylation seems not to be involved in the gene expression alteration. Further studies are needed to understand the basic molecular mechanisms involved in reduced FHIT expression.
Soil-transmitted helminth infections and physical fitness in school-aged Bulang children in southwest China: results from a cross-sectional survey
Authors: Yap Peiling , Du Zun-Wei , Chen Ran , Zhang Li-Ping , Wu Fang-Wei , Wang Jian , Wang Xue-Zhong , Zhou Hui , Zhou Xiao-Nong , Utzinger Jürg , Steinmann Peter
Published: March 2012

Background

Chronic soil-transmitted helminth (STH) infections have been associated with reduced physical fitness, but available evidence is limited. The aim of this cross-sectional survey was to assess the feasibility of measuring children's physical fitness and to relate it to STH infections. Our study was carried out among school-aged children of the Bulang ethnic group in rural southwest People's Republic of China (P.R. China). Standardized, quality-controlled methods were employed to determine STH infections (Kato-Katz technique), haemoglobin levels, anthropometry (body weight and height) and physical fitness (20-m shuttle run test).

Results

A compliance of 87% suggested good acceptance of the methods used. Among 69 children with complete data records, infection prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm were 81%, 44% and 6%, respectively. The maximum volume of oxygen that can be utilized within 1 min during exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.94 ml kg-1 min-1 lower than that of their non-infected counterparts (P = 0.005). Until exhaustion, T. trichiura-infected children had completed 6.14 20-m laps less (P = 0.004). Additionally, the mean VO2 max estimate of stunted children was lowered by 1.63 ml kg-1 min-1 (P = 0.002) and they completed 5.32 20-m laps less (P = 0.001) compared to children of normal stature. No significant association between stunting and infection with any STH species could be established.

Conclusions

Implementation of physical fitness tests in rural, resource-constraint settings is feasible. The physical fitness of children who are stunted or infected with STHs, particularly T. trichiura, is significantly impaired. We have launched a larger study and will determine the dynamics of school-aged children's physical fitness over a 7-month period after administration of anthelminthic drugs.
Novel mutatıons and diverse clinical phenotypes in recombınase-activating gene 1 deficiency
Authors: Kutukculer Necil , Gulez Nesrin , Karaca Neslihan Edeer , Aksu Guzide , Berdeli Afig
Published: March 2012

Background

Severe combined immunodeficiency is within a heterogeneous group of inherited defects throughout the development of T- and/or B-lymphocytes. Mutations in recombinase-activating genes 1 or 2 (RAG1/2) represent approximately 10% of all SCID cases. RAG1/2 are essential for V(D)J rearrangement of the B- and T-cell receptors.

Objectives

The aim of this study was to review clinical, immunological and molecular findings of Turkish SCID patients with RAG1 defects and to draw attention to novel mutations, genotype-phenotype correlations and the high rate of BCG infections within this group.

Methods

Eleven patients (F/M: 6/5) were included. Molecular, immunological and clinical data were evaluated.

Results

Five patients were classified as T-B-NK + SCID, four patients as T + B-NK + SCID (two of these patients were diagnosed as classical Omenn syndrome) and two patients as T + B + NK + SCID with respect to clinical presentations and immunological data. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were: 33.0 ± 42.8, 3.1 ± 3.3 and 10.4 ± 13.5 months, respectively. Consanguinity rate was 54%. Some novel mutations were found in RAG1 gene in addition to previously reported mutations. Genotype-phenotype correlation was not significantly apparent in most of the cases. BCG infection was observed in 36.4% of patients (two BCG-osis and two BCG-itis).

Conclusion

Epigenetic factors such as compound genetic defects, enviromental factors, and exposure to recurrent infections may modify phenotypical characteristics of RAG deficiencies. Inoculation of live vaccines such as BCG should be postponed until primary immunodeficiency disease is excluded with appropriate screening tests in suspected cases.
Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation
Authors: Bělohlávek Jan , Mlček Mikuláš , Huptych Michal , Svoboda Tomáš , Havránek Štěpán , Ošt'ádal Petr , Bouček Tomáš , Kovárník Tomáš , Mlejnský František , Mrázek Vratislav , Bělohlávek Marek , Aschermann Michael , Linhart Aleš , Kittnar Otomar
Published: March 2012

Introduction

Extracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO.

Methods

In 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined.

Results

CaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%).

Conclusions

In a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.
Alveolar macrophages in diabetes: friends or foes?
Authors: Sunahara Karen K S , Martins Joilson O
Published: March 2012

AMs constitute an important bridge between innate and adaptive immunity. AMs patrol the lungs against pathogens, remove senescent cells, and help repair tissue. AM function is altered in many diseases, including DM, where AM abnormal immune responses may worsen infections or lead to exacerbation of inflammatory reactions. In vivo experimental models have greatly contributed to our knowledge of AM function. Studies have shown that during hyperglycemic states, the phagocytic function of AMs and the expression of adhesion molecules may be altered, interfering with the recruitment of immune cells to the inflammatory site. Insulin treatment seems to recover the normal function of impaired AMs. However, much research is still needed to characterize AMs and to better understand their role in inflammation and infection, particularly in diabetic patients. In this review, we attempt to explore recently accumulated knowledge about AM function and how this function is deficient in DM. Additionally, AM polarization is compared briefly with that of T cells, and this may interfere with how immune response is driven. This review discusses how impaired AMs lead to an aberrant immune response that contributes to worsening infection and autoimmunity, opening up discussion for future work in the field.
Surveillance of Patients With Breast Cancer After Curative-Intent Primary Treatment: Current Practice Patterns
Authors: Margenthaler Julie A. , Allam Emad , Chen Ling , Virgo Katherine S. , Kulkarni Udayan Mayur , Patel Anand P. , Johnson Frank E.
Published: March 2012

The intensity of post-treatment surveillance performed by ASCO members caring for patients with breast cancer varies markedly despite evidence from well-designed, adequately powered randomized controlled trials.
Optimizing the Design of Preprinted Orders for Ambulatory Chemotherapy: Combining Oncology, Human Factors, and Graphic Design
Authors: Jeon Jennifer , White Rachel E. , Hunt Richard G. , Cassano-Piché Andrea L. , Easty Anthony C.
Published: March 2012

This study illustrates how human factors professionals, clinicians, and designers can leverage each other's expertise to uncover commonly overlooked patient safety hazards and provide health care professionals with tools to minimize those hazards.
Endocrine Therapy Initiation From 2001 to 2008 Varies by Age at Breast Cancer Diagnosis and Tumor Size
Authors: Bowles Erin J. Aiello , Buist Diana S.M. , Chubak Jessica , Yu Onchee , Johnson Jeanene , Chestnut Janet , Boudreau Denise M.
Published: March 2012

Differential initiation over time, as well as by age and tumor size, suggests patient preferences and provider recommendations for endocrine therapy vary, despite guideline recommendations.
Extending Oncology Clinical Services to Rural Areas of Texas Via Teleoncology
Authors: Sharma Jivesh J. , Gross Gary , Sharma Poonam
Published: March 2012

Abstracts

Purpose:

For patients in rural Texas, accessing cancer specialists is quite challenging. Texas has many remote areas without community-based cancer care, requiring patients to travel long distances for specialized cancer professional consultations and services. An anticipated shortage of medical oncology expertise will exacerbate this situation. The advent of telemedicine tools has created an opportunity to easily extend specialized cancer services to underserved populations of patients with cancer in Texas. However, more research is needed to explore how well telemedicine tools will be accepted and used by both patients and oncologists alike. Data suggesting that teleoncology services are well accepted and liked by patients and health care professionals would provide a basis for expanding this method of delivering care. If effective, telemedicine tools could help patients with cancer in rural Texas, and throughout the United States, access the same quality of cancer care as their counterparts living in urban areas.

Methods:

This pilot study will compare the effectiveness and reliability of remote oncologic clinical evaluations conducted via a telemedicine application with the traditional method of onsite evaluations in a private practice setting in rural East Texas. Patient and physician satisfaction with the clinical consultations and their perceptions of the telemedicine application will be assessed using a questionnaire administered at the conclusion of the clinical meetings.

Results:

Initial results indicate high patient and physician satisfaction scores as well as high reliability and adequacy of the equipment and technology being used.

Conclusion:

Both patients and physicians are highly satisfied with the quality of teleoncology examinations and express openness to this method of delivering care.
Reduction in Chemotherapy Mixing Errors Using Six Sigma: Illinois CancerCare Experience
Authors: Heard Bridgette , Miller Laura , Kumar Pankaj
Published: March 2012

Purpose:

Chemotherapy mixing errors (CTMRs), although rare, have serious consequences. Illinois CancerCare is a large practice with multiple satellite offices. The goal of this study was to reduce the number of CTMRs using Six Sigma methods.

Patients and Methods:

A Six Sigma team consisting of five participants (registered nurses and pharmacy technicians [PTs]) was formed. The team had 10 hours of Six Sigma training in the DMAIC (ie, Define, Measure, Analyze, Improve, Control) process. Measurement of errors started from the time the CT order was verified by the PT to the time of CT administration by the nurse. Data collection included retrospective error tracking software, system audits, and staff surveys.

Results:

Root causes of CTMRs included inadequate knowledge of CT mixing protocol, inconsistencies in checking methods, and frequent changes in staffing of clinics. Initial CTMRs (n = 33,259) constituted 0.050%, with 77% of these errors affecting patients. The action plan included checklists, education, and competency testing. The postimplementation error rate (n = 33,376, annualized) over a 3-month period was reduced to 0.019%, with only 15% of errors affecting patients. Initial Sigma was calculated at 4.2; this process resulted in the improvement of Sigma to 5.2, representing a 100-fold reduction. Financial analysis demonstrated a reduction in annualized loss of revenue (administration charges and drug wastage) from $11,537.95 (Medicare Average Sales Price) before the start of the project to $1,262.40.

Conclusion:

The Six Sigma process is a powerful technique in the reduction of CTMRs.
Countering the Misincentivization of Cancer Medicine by Real-Time Personal Professional Education
Authors: Hrushesky William , Kumar Akhil , Davis Sharon , Fishman Marc
Published: March 2012

Purpose:

In the United States, public and private payer misincentivization of medical care and the invisibility of costs to the consumers of that care have conspired to create unsustainable growth in health care expenditure that undermines our economy, diminishes our productivity, and limits our international competitiveness. Cancer medicine provides a small yet salient example. On average, Medicare reimburses oncologists 6% above the average acquisition price for essential anticancer agents and supportive therapies. The costs of these agents vary across a stunning five orders of magnitude, from a few dollars to more than $400,000 per course of treatment. The profitability to providers varies across approximately four orders of magnitude, from cents to thousands of dollars per treatment. National guidelines (National Comprehensive Cancer Network [NCCN], American Society of Clinical Oncology [ASCO]) help providers select the most effective therapies without regard for cost.

Methods:

We created an oncologist-to-oncologist professional education program to help cancer physicians optimally use expensive long-acting white blood cell growth factors, in accordance with these national guidelines. We then compared their use across a population of approximately 97,000 Medicare members before and after our intervention. Baseline use was recorded over two consecutive quarters (2009 to 2010). In March 2010, our oncologists initiated real-time discussions with the oncologists of 22 separate groups if these agents were ordered for use with regimens that placed patients at less than 10% risk of febrile neutropenia, according to NCCN guidelines. Neither NCCN nor ASCO recommend the routine use of these agents in this low-risk group. The care of 82 such patients was thoroughly discussed in the following 6 months.

Results:

The monthly costs for these agents decreased by more than 50% by the final month of our intervention, although savings began immediately, reducing costs by more than $150,000 per quarter. No episode of febrile neutropenia was recorded in any patient in the intervention group. These savings generalize to the entire Medicare population at $30 million each month.

Conclusion:

We conclude that personal, oncologist-to-oncologist, real-time professional education will favorably modify oncologic prescribing behavior and can do so with significant immediate savings at no risk to patients with cancer.
Calvino, Llull, Lucretius: Two Models of Literary Combinatorics
Authors: Duncan Dennis
Published: March 2012

A recurring problem in much critical writing about the Oulipo is a tendency to homogenize the output of the group's writers in order to present a universal poetics of constrained writing. Oulipians rightly bristle at these attempts to oversimplify the group's history, and a useful distinction has been made by Jacques Roubaud, who notes the widening of the group's membership beginning in 1966, when he joined, and postulates that a second era — the “Perecquian era” — of the Oulipo began in 1969, when Georges Perec published La Disparition, his infamous novel without the letter e. This essay looks at the theoretical writing of Italo Calvino over the six-year period from 1967 to 1973 —the years between his translation of Raymond Queneau's novel Les Fleurs bleues and his full election to the Oulipo — arguing that during this time Calvino's own poetics underwent a significant change with regard to the perceived relationship between creativity and constraint. The essay makes its case by analogy with two authors often cited by the Oulipo — the medieval theologian Ramón Llull and the Atomist philosopher Lucretius — between whom Calvino draws a parallel in one of his final works, the undelivered lectures Six Memos for the Next Millennium. It argues, however, that Llull and Lucretius represent two opposing models of combinatorics and that the former encapsulates Calvino's views at the start of the period in question, while the latter neatly exemplifies his later position. The essay also suggests that the trend in Calvino's thought is germane to the distinction Roubaud makes — that Calvino's earlier position is characteristic of the “pre-Perecquian Oulipo,” while his later views are closer to those of his peers among the group's second wave.
Nurturing Hope, Deepening Democracy, and Combating Inequalities in Brazil: Lula, the Workers' Party, and Dilma Rousseff's 2010 Election as President
Authors: French John , Fortes Alexandre
Published: March 2012

In explaining the 2010 election of President Dilma Rousseff, John French and Alexandre Fortes explore the stunning success of the Brazilian Workers Party (PT) and its leader, Lula, former trade unionist, in winning a third consecutive presidential victory. In historical perspective, the authors examine the ways in which Lula's government (2002 – 10) represented a break with the past while summarizing its substantive achievements in redistributing wealth and opportunity. Focusing on the tension between a historic party-centric petismo (declared partisan party support) and the broader personal popularity of its leader (lulismo), they offer evidence that Lula and the PT have retained their foundational ethos of enhancing popular self-esteem while fostering citizen participation and civil society mobilization, albeit under new conditions. They conclude with a diagnosis of the new government's challenges in light of international financial markets, labor mobilization, and the constraints of the Brazilian political system.
The Irish Girls' Rising: Building the Women's Labor Movement in Progressive-Era Chicago
Authors: Hoy Suellen
Published: March 2012

The Chicago Women's Trade Union League (CWTUL), inaugurated at Hull House in 1904, had its roots in the 1900 stockyard strike of Irish women, the short-lived Maud Gonne Club, and Local 183 of the Amalgamated Meat Cutters, the first women's union in the stockyards. Mary E. McDowell, head resident of the University of Chicago Settlement and advisor to Local 183, served as CWTUL's first president from 1904 to 1907. The working-class leadership of the Chicago branch — unlike its better-known counterpart in New York — was “old immigrant” (primarily Irish Catholic but also including Germans and Scandinavians) with a distinct culture that derived from its ethnic makeup and its settlement-house attachments. In “The Irish Girls' Rising,” Suellen Hoy explores these developments and highlights CWTUL's significance in building the women's labor movement in Chicago at the turn of the twentieth century.
High-fat-diet-induced obesity causes an inflammatory and tumor-promoting microenvironment in the rat kidney
Authors: Stemmer Kerstin , Perez-Tilve Diego , Ananthakrishnan Gayathri , Bort Anja , Seeley Randy J. , Tschöp Matthias H. , Dietrich Daniel R. , Pfluger Paul T.
Published: March 2012

Obesity and concomitant comorbidities have emerged as public health problems of the first order. For instance, obese individuals have an increased risk for kidney cancer. However, direct mechanisms linking obesity with kidney cancer remain elusive. We hypothesized that diet-induced obesity (DIO) promotes renal carcinogenesis by inducing an inflammatory and tumor-promoting microenvironment. We compared chow-fed lean Wistar rats with those that were sensitive (DIOsens) or partially resistant (DIOres) to DIO to investigate the impact of body adiposity versus dietary nutrient overload in the development of renal preneoplasia and activation of tumor-promoting signaling pathways. Our data clearly show a correlation between body adiposity, the severity of nephropathy, and the total number and incidence of preneoplastic renal lesions. However, similar plasma triglyceride, plasma free fatty acid and renal triglyceride levels were found in chow-fed, DIOres and DIOsens rats, suggesting that lipotoxicity is not a critical contributor to the renal pathology. Obesity-related nephropathy was further associated with regenerative cell proliferation, monocyte infiltration and higher renal expression of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6, IL-6 receptor and leptin receptor. Accordingly, we observed increased signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) phosphorylation in tubules with preneoplastic phenotypes. In summary, our results demonstrate that high body adiposity induces an inflammatory and proliferative microenvironment in rat kidneys that promotes the development of preneoplastic lesions, potentially via activation of the STAT3 and mTOR signaling pathways.
Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction
Authors: Cooper Katrina F. , Scarnati Matthew S. , Krasley Elizabeth , Mallory Michael J. , Jin Chunyan , Law Michael J. , Strich Randy
Published: March 2012

The yeast cyclin-C–Cdk8p kinase complex represses the transcription of a subset of genes involved in the stress response. To relieve this repression, cyclin C is destroyed in cells exposed to H2O2 by the 26S proteasome. This report identifies Not4p as the ubiquitin ligase mediating H2O2-induced cyclin C destruction. Not4p is required for H2O2-induced cyclin C destruction in vivo and polyubiquitylates cyclin C in vitro by utilizing Lys48, a ubiquitin linkage associated with directing substrates to the 26S proteasome. Before its degradation, cyclin C, but not Cdk8p, translocates from the nucleus to the cytoplasm. This translocation requires both the cell-wall-integrity MAPK module and phospholipase C, and these signaling pathways are also required for cyclin C destruction. In addition, blocking cytoplasmic translocation slows the mRNA induction kinetics of two stress response genes repressed by cyclin C. Finally, a cyclin C derivative restricted to the cytoplasm is still subject to Not4p-dependent destruction, indicating that the degradation signal does not occur in the nucleus. These results identify a stress-induced proteolytic pathway regulating cyclin C that requires nuclear to cytoplasmic relocalization and Not4p-mediated ubiquitylation.
Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia
Authors: Li Jifen , Goossens Steven , van Hengel Jolanda , Gao Erhe , Cheng Lan , Tyberghein Koen , Shang Xiying , De Rycke Riet , van Roy Frans , Radice Glenn L.
Published: March 2012

It is generally accepted that the intercalated disc (ICD) required for mechano-electrical coupling in the heart consists of three distinct junctional complexes: adherens junctions, desmosomes and gap junctions. However, recent morphological and molecular data indicate a mixing of adherens junctional and desmosomal components, resulting in a ‘hybrid adhering junction’ or ‘area composita’. The α-catenin family member αT-catenin, part of the N-cadherin–catenin adhesion complex in the heart, is the only α-catenin that interacts with the desmosomal protein plakophilin-2 (PKP2). Thus, it has been postulated that αT-catenin might serve as a molecular integrator of the two adhesion complexes in the area composita. To investigate the role of αT-catenin in the heart, gene targeting technology was used to delete the Ctnna3 gene, encoding αT-catenin, in the mouse. The αT-catenin-null mice are viable and fertile; however, the animals exhibit progressive cardiomyopathy. Adherens junctional and desmosomal proteins were unaffected by loss of αT-catenin, with the exception of the desmosomal protein PKP2. Immunogold labeling at the ICD demonstrated in the αT-catenin-null heart a preferential reduction of PKP2 at the area composita compared with the desmosome. Furthermore, gap junction protein Cx43 was reduced at the ICD, including its colocalization with N-cadherin. Gap junction remodeling in αT-catenin-knockout hearts was associated with an increased incidence of ventricular arrhythmias after acute ischemia. This novel animal model demonstrates for the first time how perturbation in αT-catenin can affect both PKP2 and Cx43 and thereby highlights the importance of understanding the crosstalk between the junctional proteins of the ICD and its implications for arrhythmogenic cardiomyopathy.
Selecting clinical quality indicators for laboratory medicine
Authors: Barth Julian H
Published: March 2012

Background

Quality in laboratory medicine is often described as doing the right test at the right time for the right person. Laboratory processes currently operate under the oversight of an accreditation body which gives confidence that the process is good. However, there are aspects of quality that are not measured by these processes. These are largely focused on ensuring that the most clinically appropriate test is performed and interpreted correctly.

Methods

Clinical quality indicators were selected through a two-phase process. Firstly, a series of focus groups of clinical scientists were held with the aim of developing a list of quality indicators. These were subsequently ranked in order by an expert panel of primary and secondary care physicians.

Results

The 10 top indicators included the communication of critical results, comprehensive education to all users and adequate quality assurance for point-of-care testing. Laboratories should ensure their tests are used to national standards, that they have clinical utility, are calibrated to national standards and have long-term stability for chronic disease management. Laboratories should have error logs and demonstrate evidence of measures introduced to reduce chances of similar future errors. Laboratories should make a formal scientific evaluation of analytical quality.

Conclusions

This paper describes the process of selection of quality indicators for laboratory medicine that have been validated sequentially by deliverers and users of the service. They now need to be converted into measureable variables related to outcome and validated in practice.