bluuebunny/crossref_metadata_2025 huggingface dataset:
The Contribution of US Taxes and Social Transfers to Income Redistribution
Authors: Hierro Luis A. , Gómez-Alvarez Rosario , Atienza Pedro
Published: March 2012

The aim of this work is to solve the problem of nonadditivity revealed by work that calculates the redistributive effects of the budget or public policies made up of different instruments of income or public spending. To do this, the authors use the Shapley value. This technique allows us to consistently, symmetrically, and directly decompose the redistributive effect and the vertical and horizontal effects. This method is consistent because the total effects can be explained by the sum of the individual contributions; it is symmetrical because it does not depend on the aggregation ranking of the instruments; and it is direct because each index can be calculated without the need to calculate the rest. The main result obtained for the case of taxes and social transfers in the United States is that previous calculations undervalued the redistributive effects and their vertical and horizontal components for taxes and transfers. Undervaluation is more important for taxes.
Non-verbal communication between Registered Nurses Intellectual Disability and people with an intellectual disability: An exploratory study of the nurse’s experiences. Part 1
Authors: Martin Anne-Marie , Connor-Fenelon Maureen O’ , Lyons Rosemary
Published: March 2012

This is the first of two articles presenting the findings of a qualitative study which explored the experiences of Registered Nurses Intellectual Disability (RNIDs) of communicating with people with an intellectual disability who communicate non-verbally. The article reports and critically discusses the findings in the context of the policy and service delivery discourses of person-centredness, inclusion, choice and independence. Arguably, RNIDs are the profession who most frequently encounter people with an intellectual disability and communication impairment. The results suggest that the communication studied is both complicated and multifaceted. An overarching category of ‘familiarity/knowing the person’ encompasses discrete but related themes and subthemes that explain the process: the RNID knowing the service-user; the RNID/service-user relationship; and the value of experience. People with an intellectual disability, their families and disability services are facing a time of great change, and RNIDs will have a crucial role in supporting this transition.
Femorotibial Cartilage Thickness Change Distributions for Subjects without Signs, Symptoms, or Risk Factors of Knee Osteoarthritis
Authors: Buck Robert J. , Dreher Don , Eckstein Felix
Published: March 2012

Objective

To describe the distribution of longitudinal femorotibial cartilage thickness annualized rate of change (ΔThCtAB) from quasi–population-based studies, and to construct a reference distribution for men and women without signs, symptoms, or risk factors of knee osteoarthritis (OA).

Methods:

Segmented baseline and 1-year follow-up MRI from 43 men and 69 women of the Osteoarthritis Initiative (OAI) asymptomatic control cohort without risk factors and also baseline and 2-year follow-up data from 77 asymptomatic women of the Pfizer A9001140 study were included. The mean, standard deviation (SD), and correlation of ΔThCtAB in medial and lateral femorotibial subregions were estimated; distributions were tested for normality and for differences between cohorts and gender.

Results:

Distributions of femorotibial ΔThCtAB rates were consistent between cohorts and were normally distributed, with rates <0.7%/y. Subregion ΔThCtAB SDs were correlated with mean baseline cartilage thickness (ratio = 3%-5%). However, ΔThCtAB SD did not increase with baseline thickness when estimated for different tertiles of any given subregion, indicating the relationship may rather be due to spatial location than to baseline thickness.

Conclusions

Distributions of (subregional) longitudinal cartilage thickness rates of change appear to be normally distributed, not significantly different from zero, and similar for different cohorts of asymptomatic subjects. Given the spatial heterogeneity of subregional cartilage change observed in OA knees, the proposed reference distribution of subregional, ΔThCtAB may be used to describe and identify structural progression (i.e., cartilage loss) in individual OA knees with greater accuracy and sensitivity than conventional approaches, such as minimal detectable difference.
SRC is a signaling mediator in FLT3-ITD– but not in FLT3-TKD–positive AML
Authors: Leischner Hannes , Albers Corinna , Grundler Rebekka , Razumovskaya Elena , Spiekermann Karsten , Bohlander Stefan , Rönnstrand Lars , Götze Katharina , Peschel Christian , Duyster Justus
Published: March 2012

Mutations of Fms-like tyrosine kinase 3 (FLT3) are among the most frequently detected molecular abnormalities in AML patients. Internal tandem duplications (ITDs) are found in approximately 25% and point mutations within the second tyrosine kinase domain (TKD) in approximately 7% of AML patients. Patients carrying the FLT3-ITD but not the FLT3-TKD mutation have a significantly worse prognosis. Therefore, both FLT3 mutations seem to exert different biologic functions. FLT3-ITD but not FLT3-TKD has been shown to induce robust activation of the STAT5 signaling pathway. In the present study, we investigated the mechanisms leading to differential STAT5 activation and show that FLT3-ITD but not FLT3-TKD uses SRC to activate STAT5. Coimmunoprecipitation and pull-down experiments revealed an exclusive interaction between SRC but not other Src family kinases and FLT3-ITD, which is mediated by the SRC SH2 domain. We identified tyrosines 589 and 591 of FLT3-ITD to be essential for SRC binding and subsequent STAT5 activation. Using site-specific Abs, we found that both residues were significantly more strongly phosphorylated in FLT3-ITD compared with FLT3-TKD. SRC inhibition and knock-down blocked STAT5 activation and proliferation induced by FLT3-ITD but not by FLT3-TKD. We conclude that SRC might be a therapeutic target in FLT3-ITD+ AML.
Polycomb group ring finger 1 cooperates with Runx1 in regulating differentiation and self-renewal of hematopoietic cells
Authors: Ross Katharina , Sedello Anna K. , Todd Gabriele Putz , Paszkowski-Rogacz Maciej , Bird Alexander W. , Ding Li , Grinenko Tatyana , Behrens Kira , Hubner Nina , Mann Matthias , Waskow Claudia , Stocking Carol , Buchholz Frank
Published: March 2012

The transcription factor runt-related transcription factor 1 (Runx1) is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cells. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. In the present study, we describe a genome-scale RNA interference screen to detect genes that cooperate with Runx1 in regulating hematopoietic stem and progenitor cells. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation and show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of lineage marker–negative cells in vitro. We found an up-regulation of HoxA cluster genes on Pcgf1 knock-down that possibly accounts for the increase in self-renewal. Moreover, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1, together with the epigenetic repressor Pcgf1, is necessary for terminal differentiation. The results of the present study uncover a link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation.
Rac2-MRC-cIII–generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors
Authors: Nieborowska-Skorska Margaret , Kopinski Piotr K. , Ray Regina , Hoser Grazyna , Ngaba Danielle , Flis Sylwia , Cramer Kimberly , Reddy Mamatha M. , Koptyra Mateusz , Penserga Tyrone , Glodkowska-Mrowka Eliza , Bolton Elisabeth , Holyoake Tessa L. , Eaves Connie J. , Cerny-Reiterer Sabine , Valent Peter , Hochhaus Andreas , Hughes Timothy P. , van der Kuip Heiko , Sattler Martin , Wiktor-Jedrzejczak Wieslaw , Richardson Christine , Dorrance Adrienne , Stoklosa Tomasz , Williams David A. , Skorski Tomasz
Published: March 2012

Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC-cIII–generated ROS promote oxidative DNA damage to trigger genomic instability, resulting in an accumulation of chromosomal aberrations and tyrosine kinase inhibitor–resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)–positive polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC-cIII. In the present study, inhibition of Rac2 by genetic deletion or a small-molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC-cIII, expression of mitochondria-targeted catalase, or addition of ROS-scavenging mitochondria-targeted peptide aptamer reduced genomic instability. We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML.
An institutional perspective on the impact of recent antibiotic exposure on length of stay and hospital costs for patients with gram-negative sepsis
Authors: Micek Scott , Johnson Michael T , Reichley Richard , Kollef Marin H
Published: March 2012

Background

Prior antibiotic exposure has been associated with the emergence of antibiotic resistance in subsequent bacterial infections, whose outcomes are typically worse than similar infections with more antibiotic susceptible infections. The influence of prior antibiotic exposure on hospital length of stay (LOS) and costs in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia has not been previously examined.

Methods

A retrospective cohort study of hospitalized patients (January 2002-December 2007) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients with Gram-negative bacteremia complicated by severe sepsis or septic shock had data abstraction from computerized medical records. We examined a consecutive cohort of 754 subjects (mean age 59.3 ± 16.3 yrs, mean APACHE II 23.7 ± 6.7).

Results

Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common organisms isolated from blood cultures. 310 patients (41.1%) had exposure to antimicrobial agents in the previous 90 days. Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% v. 21.2%; p < 0.001) and hospital mortality (51.3% v. 34.0%; p < 0.001) compared to patients without recent antibiotic exposure. The unadjusted median LOS (25th percentile, 75th percentile) following sepsis onset in patients with prior antimicrobial exposure was 13.0 days (5.0 days, 24.0 days) compared to 8.0 days (5.0 days, 14.0 days) in those without prior antimicrobial exposure (p < 0.001). In a Cox model controlling for multiple confounders, prior antibiotic exposure independently correlated with remaining hospitalized (Adjusted hazard ratio: 1.473, 95% CI: 1.297-1.672, p < 0.001). Adjusting for potential confounders indicated that prior antibiotic exposure independently increased median attributable LOS by 5.0 days. Similarly, total hospital costs following sepsis onset was significantly greater among patients with prior antimicrobial exposure (median values: $94,737 v. $21,329; p < 0.001).

Conclusions

Recent antibiotic exposure is associated with increased LOS and hospital costs in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians and hospital administrators should consider the potential impact of recent antibiotic exposure when formulating empiric treatment decisions for patients with serious infections attributed to Gram-negative bacteria.
Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups
Authors: Macedo Ligia Traldi , da Costa Lima Andre Bacellar , Sasse Andre Deeke
Published: March 2012

Background

Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens.

Methods

A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen.

Results

Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS) and progression-free survival (PFS) (HR = 0.84; CI: 0.77-0.91; P < 0.00001 and HR = 0.72; CI: 0.66-0.78; P < 0.00001, respectively). However, heterogeneity of results was very high for both outcomes, and subgroup analyses supported the OS advantage with bevacizumab restricted to irinotecan-based regimens. Infusional fluorouracil subsets involved a minor proportion, and did not demonstrate statistical benefit in PFS or OS. Regarding toxicity, higher rates of grades 3-4 hypertension, bleeding, thromboembolic events and proteinuria were uniformly observed with bevacizumab, leading to increased treatment interruptions (HR = 1.47; P = 0.0004).

Conclusions

Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.
Patient-reported physical activity questionnaires: A systematic review of content and format
Authors: Williams Kate , Frei Anja , Vetsch Anders , Dobbels Fabienne , Puhan Milo A , Rüdell Katja
Published: March 2012

Background

Many patients with chronic illness are limited in their physical activities. This systematic review evaluates the content and format of patient-reported outcome (PRO) questionnaires that measure physical activity in elderly and chronically ill populations.

Methods

Questionnaires were identified by a systematic literature search of electronic databases (Medline, Embase, PsychINFO & CINAHL), hand searches (reference sections and PROQOLID database) and expert input. A qualitative analysis was conducted to assess the content and format of the questionnaires and a Venn diagram was produced to illustrate this. Each stage of the review process was conducted by at least two independent reviewers.

Results

104 questionnaires fulfilled our criteria. From these, 182 physical activity domains and 1965 items were extracted. Initial qualitative analysis of the domains found 11 categories. Further synthesis of the domains found 4 broad categories: 'physical activity related to general activities and mobility', 'physical activity related to activities of daily living', 'physical activity related to work, social or leisure time activities', and '(disease-specific) symptoms related to physical activity'. The Venn diagram showed that no questionnaires covered all 4 categories and that the '(disease-specific) symptoms related to physical activity' category was often not combined with the other categories.

Conclusions

A large number of questionnaires with a broad range of physical activity content were identified. Although the content could be broadly organised, there was no consensus on the content and format of physical activity PRO questionnaires in elderly and chronically ill populations. Nevertheless, this systematic review will help investigators to select a physical activity PRO questionnaire that best serves their research question and context.
From "best practice" to "next practice": the effectiveness of school-based health promotion in improving healthy eating and physical activity and preventing childhood obesity
Authors: Fung Christina , Kuhle Stefan , Lu Connie , Purcell Megan , Schwartz Marg , Storey Kate , Veugelers Paul J
Published: March 2012

Background

In 2005, we reported on the success of Comprehensive School Health (CSH) in improving diets, activity levels, and body weights. The successful program was recognized as a "best practice" and has inspired the development of the Alberta Project Promoting active Living and healthy Eating (APPLE) Schools. The project includes 10 schools, most of which are located in socioeconomically disadvantaged areas. The present study examines the effectiveness of a CSH program adopted from a "best practice" example in another setting by evaluating temporal changes in diets, activity levels and body weight.

Methods

In 2008 and 2010, we surveyed grade 5 students from approximately 150 randomly selected schools from the Canadian province of Alberta and students from 10 APPLE Schools. Students completed the Harvard Youth/Adolescent Food Frequency Questionnaire, questions on physical activity, and had their height and weight measured. Multilevel regression methods were used to analyze changes in diets, activity levels, and body weight between 2008 and 2010.

Results

In 2010 relative to 2008, students attending APPLE Schools were eating more fruits and vegetables, consuming fewer calories, were more physically active and were less likely obese. These changes contrasted changes observed among students elsewhere in the province.

Conclusions

These findings provide evidence on the effectiveness of CSH in improving health behaviors. They show that an example of "best practice" may lead to success in another setting. Herewith the study provides the evidence that investments for broader program implementation based on "best practice" are justified.
Comparison of worm development and host immune responses in natural hosts of schistosoma japonicum, yellow cattle and water buffalo
Authors: Yang Jianmei , Fu Zhiqiang , Feng Xingang , Shi Yaojun , Yuan Chunxiu , Liu Jinming , Hong Yang , Li Hao , Lu Ke , Lin Jiaojiao
Published: March 2012

Background

Yellow cattle and water buffalo are two of the most important natural hosts forSchistosoma japonicumin China. Previous observation has revealed that yellow cattle are more suited to the development ofS. japonicumthan water buffalo. Understanding more about the molecular mechanisms involved in worm development, as well as the pathological and immunological differences between yellow cattle and water buffalo post infection withS japonicumwill provide useful information for the vaccine design and its delivery procedure.

Results

The worm length (p< 0.01), worm recovery rate (p< 0.01) and the percentage of paired worms (p< 0.01) were significantly greater in yellow cattle than those in water buffalo. There were many white egg granulomas in the livers of yellow cattle, but fewer were observed in water buffalo at 7 weeks post infection. The livers of infected yellow cattle contained significantly increased accumulation of inflammatory cells, and the schistosome eggs were surrounded with large amounts of eosinophil infiltration. In contrast, no hepatocyte swelling or lymphocyte infiltration, and fewer white blood cells, was observed in water buffalo. The percentage of CD4+T cells was higher in yellow cattle, while the percentage of CD8+T cells was higher in water buffalo from pre-infection to 7 w post infection. The CD4/CD8 ratios were decreased in both species after challenge with schistosomes. Comparing with water buffalo, the IFN-γ level was higher and decreased significantly, while the IL-4 level was lower and increased gradually in yellow cattle from pre-infection to 7 w post infection.

Conclusions

In this study, we confirmed that yellow cattle were more suited to the development ofS. japonicumthan water buffalo, and more serious pathological damage was observed in infected yellow cattle. Immunological analysis suggested that CD4+T cells might be an integral component of the immune response and might associate with worm development in yellow cattle. A shift from Th1 to Th2 type polarized immunity was only shown clearly in schistosome-infected yellow cattle, but no shift in water buffalo. The results provide valuable information for increased understanding of host-schistosome interactions, and for control of schistosomiasis.
Automatic single-trial discrimination of mental arithmetic, mental singing and the no-control state from prefrontal activity: toward a three-state NIRS-BCI
Authors: Power Sarah D , Kushki Azadeh , Chau Tom
Published: March 2012

Background

Near-infrared spectroscopy (NIRS) is an optical imaging technology that has recently been investigated for use in a safe, non-invasive brain-computer interface (BCI) for individuals with severe motor impairments. To date, most NIRS-BCI studies have attempted to discriminate two mental states (e.g., a mental task and rest), which could potentially lead to a two-choice BCI system. In this study, we attempted to automatically differentiate three mental states - specifically, intentional activity due to 1) a mental arithmetic (MA) task and 2) a mental singing (MS) task, and 3) an unconstrained, "no-control (NC)" state - to investigate the feasibility of a three-choice system-paced NIRS-BCI.

Results

Deploying a dual-wavelength frequency domain near-infrared spectrometer, we interrogated nine sites around the frontopolar locations while 7 able-bodied adults performed mental arithmetic and mental singing to answer multiple-choice questions within a system-paced paradigm. With a linear classifier trained on a ten-dimensional feature set, an overall classification accuracy of 56.2% was achieved for the MA vs. MS vs. NC classification problem and all individual participant accuracies significantly exceeded chance (i.e., 33%). However, as anticipated based on results of previous work, the three-class discrimination was unsuccessful for three participants due to the ineffectiveness of the mental singing task. Excluding these three participants increases the accuracy rate to 62.5%. Even without training, three of the remaining four participants achieved accuracies approaching 70%, the value often cited as being necessary for effective BCI communication.

Conclusions

These results are encouraging and demonstrate the potential of a three-state system-paced NIRS-BCI with two intentional control states corresponding to mental arithmetic and mental singing.
Web-Based Tailored Education Program for Disease-Free Cancer Survivors With Cancer-Related Fatigue: A Randomized Controlled Trial
Authors: Yun Young Ho , Lee Keun Seok , Kim Young-Woo , Park Sang Yoon , Lee Eun Sook , Noh Dong-Young , Kim Sung , Oh Jae Hwan , Jung So Youn , Chung Ki-Wook , Lee You Jin , Jeong Seung-Yong , Park Kyu Joo , Shim Young Mog , Zo Jae Ill , Park Ji Won , Kim Young Ae , Shon En Jung , Park Sohee
Published: March 2012

Purpose

To determine whether an Internet-based tailored education program is effective for disease-free cancer survivors with cancer-related fatigue (CRF).

Patients and Methods

We randomly assigned patients who had completed primary cancer treatment within the past 24 months in any of four Korean hospitals and had reported moderate to severe fatigue for at least 1 week to participate in a 12-week, Internet-based, individually tailored CRF education program or to receive routine care. We based the program on the CRF guidelines of the National Comprehensive Cancer Network (NCCN) and incorporated the transtheoretic model (TTM). At baseline and 12 weeks, we used the Brief Fatigue Inventory (BFI) and Fatigue Severity Scale (FSS) as primary outcomes and the Hospital Anxiety and Depression Scale (HADS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) for secondary outcomes.

Results

We recruited 273 participants and randomly assigned 136 to the intervention group. Compared with the control group, the intervention group had an improvement in fatigue as shown by a significantly greater decrease in BFI global score (−0.66 points; 95% CI −1.04 to −0.27) and FSS total score (−0.49; 95% CI, −0.78 to −0.21). In secondary outcomes, the intervention group experienced a significantly greater decrease in HADS anxiety score (−0.90; 95% CI, −1.51 to −0.29) as well as global quality of life (5.22; 95% CI, 0.93 to 9.50) and several functioning scores of the EORTC QLQ-C30.

Conclusion

An Internet-based education program based on NCCN guidelines and TTM may help patients manage CRF.
Palliative Sedation in End-of-Life Care and Survival: A Systematic Review
Authors: Maltoni Marco , Scarpi Emanuela , Rosati Marta , Derni Stefania , Fabbri Laura , Martini Francesca , Amadori Dino , Nanni Oriana
Published: March 2012

Purpose

Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival.

Methods

A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed.

Results

Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival.

Conclusion

Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting, palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.
Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children's Oncology Group
Authors: Hunger Stephen P. , Lu Xiaomin , Devidas Meenakshi , Camitta Bruce M. , Gaynon Paul S. , Winick Naomi J. , Reaman Gregory H. , Carroll William L.
Published: March 2012

Purpose

To examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG) clinical trials between 1990 and 2005.

Patients and Methods

In total, 21,626 persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to 2005, representing 55.8% of ALL cases estimated to occur among US persons younger than age 20 years during this period. This period was divided into three eras (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to examine changes in 5- and 10-year survival over time and the relationship of those changes in survival to clinical covariates, with additional analyses of cause of death.

Results

Five-year survival rates increased from 83.7% in 1990-1994 to 90.4% in 2000-2005 (P < .001). Survival improved significantly in all subgroups (except for infants age ≤ 1 year), including males and females; those age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell or T-cell immunophenotype; and in those with National Cancer Institute (NCI) standard- or high-risk clinical features. Survival rates for infants changed little, but death following relapse/disease progression decreased and death related to toxicity increased.

Conclusion

This study documents ongoing survival improvements for children and adolescents with ALL. Thirty-six percent of deaths occurred among children with NCI standard-risk features emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure.
Preoperative Identification of a Low-Risk Group for Lymph Node Metastasis in Endometrial Cancer: A Korean Gynecologic Oncology Group Study
Authors: Kang Sokbom , Kang Woo Dae , Chung Hyun Hoon , Jeong Dae Hoon , Seo Sang-Soo , Lee Jong-Min , Lee Jae-Kwan , Kim Jae Weon , Kim Seok-Mo , Park Sang-Yoon , Kim Ki Tae
Published: March 2012

Purpose

The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery.

Patients and Methods

The medical records of 360 patients with endometrial cancer who underwent surgical staging were collected from four institutions and were retrospectively reviewed. By using serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging (MRI) data, a multivariate logistic model was created. Patients whose predicted probability was less than 4% were defined as low risk. The developed model was externally validated in 180 patients from two independent institutions.

Results

Serum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph node enlargement, and extension beyond uterine corpus) were found to be independent risk factors for nodal metastasis. The model classified 53% of patients as part of a low-risk group, and the false negative rate was 1.7%. In the validation cohort, the model classified 43% of patients as low-risk, and the false negative rate was 1.4%. The model showed good discrimination (area under the receiver operator characteristic curve = 0.85) and was calibrated well. The negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to 0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to 3.3%) at the assumed prevalence of nodal metastasis of 10%.

Conclusion

Using serum CA-125 and MRI as criteria resulted in the accurate identification of a low-risk group for lymph node metastasis among patients with endometrial cancer.
Dual Targeting of the Epidermal Growth Factor Receptor Using the Combination of Cetuximab and Erlotinib: Preclinical Evaluation and Results of the Phase II DUX Study in Chemotherapy-Refractory, Advanced Colorectal Cancer
Authors: Weickhardt Andrew J. , Price Tim J. , Chong Geoff , Gebski Val , Pavlakis Nick , Johns Terrance G. , Azad Arun , Skrinos Effie , Fluck Kate , Dobrovic Alexander , Salemi Renato , Scott Andrew M. , Mariadason John M. , Tebbutt Niall C.
Published: March 2012

Purpose

This preclinical and phase II study evaluated the efficacy and safety of the combination of cetuximab and erlotinib in metastatic colorectal cancer (mCRC).

Patients and Methods

The activity and mechanism of action of the combination of cetuximab plus erlotinib were investigated in vitro in colorectal cancer cell lines. In the clinical study, patients with chemotherapy-refractory mCRC were treated with cetuximab 400 mg/m2 as a loading dose and then weekly cetuximab 250 mg/m2 with erlotinib 100 mg orally daily. The primary end point was response rate (RR), which was evaluated separately in KRAS wild-type (WT) versus KRAS mutant tumors. Secondary end points included toxicity, progression-free survival (PFS), and overall survival. Target accrual was 50 patients, with a one-stage design.

Results

Preclinical studies demonstrated synergistic activity of cetuximab and erlotinib cotreatment on growth inhibition of colon cancer cell lines both as a result of enhanced inhibition of the epidermal growth factor receptor pathway and differential effects on STAT3. In the clinical study, 50 patients were enrolled, with 48 patients evaluable for response. The overall RR was 31% (95% CI, 26% to 57%), with a median PFS of 4.6 months (95% CI, 2.8 to 5.6 months). RR was 41% (95% CI, 26% to 57%) in KRAS WT tumors, with a median PFS of 5.6 months (95% CI, 2.9 to 5.6 months). There was no response in 11 patients with KRAS mutations. Frequent grade 3 and 4 toxicities were rash (48%), hypomagnesaemia (18%), and fatigue (10%).

Conclusion

The combination of cetuximab and erlotinib synergistically inhibits growth of colon cancer cell lines, achieves promising efficacy in patients with KRAS WT mCRC, and merits evaluation in further randomized studies.
Psychosocial Care of Adolescent and Young Adult Patients With Cancer and Survivors
Authors: Zebrack Brad , Isaacson Sinéad
Published: March 2012

The delivery of quality care for adolescent and young adult (AYA) patients with cancer and survivors requires an understanding of the unique qualities of this group—the shared norms, attitudes, and beliefs that determine their behavior as well as the unique stresses they face on a day-to-day basis. All AYAs have typical concerns about being comfortable with who they are and who they want to become (identity development, including sexual identity), their bodies (body image), initiating intimate and emotional relationships, separating from parents, and making independent decisions about future goals such as career, higher education, and/or family (autonomy). Yet efforts of AYA patients with cancer and survivors to mature are often confounded by restrictions and limitations placed on them by their disease and treatment. This article promotes understanding of psychosocial challenges faced by AYAs when diagnosed with and treated for cancer. It reviews evidence-based psychosocial support interventions for AYAs with cancer and other life-threatening or chronic diseases, particularly the positive effects of peer support, technology-based interventions, and skill-based interventions. The article concludes with recommendations for clinical care that are intended to promote the ability of AYAs to cope with cancer.
Psychosocial Care for Family Caregivers of Patients With Cancer
Authors: Northouse Laurel , Williams Anna-leila , Given Barbara , McCorkle Ruth
Published: March 2012

Purpose

To understand family caregivers' needs for better preparation and care, this state-of-the-science review examines the effect of caregiving on the health and well-being of caregivers, the efficacy of research-tested interventions on patient and caregiver outcomes, implications of the research on policy and practice, and recommendations for practice and future research.

Methods

We reviewed research that described the multiple effects of cancer on caregivers' well-being. Five meta-analyses were analyzed to determine the effect of interventions with caregivers on patient and caregiver outcomes. In addition, we reviewed legislation such as the Affordable Care Act and the Family Leave Act along with current primary care practice to determine whether family caregivers' needs have been addressed.

Results

Research findings indicate that caregiver stress can lead to psychological and sleep disturbances and changes in caregivers' physical health, immune function, and financial well-being. Research-tested interventions delivered to caregivers of patients with cancer or other chronic illnesses can reduce many of these negative effects and improve caregivers' coping skills, knowledge, and quality of life. Although these interventions also decrease patients' symptoms, reduce mortality (non-dementia patients), and improve patients' physical and mental health, they are seldom implemented in practice.

Conclusion

Recommendations for practice include development of standardized guidelines that address caregiver assessment, education, and resources; identification of “caregiver champions” in practice settings; provision of referrals to established support organizations for caregivers (eg, Cancer Support Community, Cancer Care); and collaboration among caregiving, professional, and cancer-related organizations to advocate policy and practice changes for family caregivers.
Communication Skills Training for Oncology Professionals
Authors: Kissane David W. , Bylund Carma L. , Banerjee Smita C. , Bialer Philip A. , Levin Tomer T. , Maloney Erin K. , D'Agostino Thomas A.
Published: March 2012

Purpose

To provide a state-of-the-art review of communication skills training (CST) that will guide the establishment of a universal curriculum for fellows of all cancer specialties undertaking training as oncology professionals today.

Methods

Extensive literature review including meta-analyses of trials, conceptual models, techniques, and potential curricula provides evidence for the development of an appropriate curriculum and CST approach. Examples from the Memorial Sloan-Kettering Cancer Center CST program are incorporated.

Results

A core curriculum embraces CST modules in breaking bad news and discussing unanticipated adverse events, discussing prognosis, reaching a shared treatment decision, responding to difficult emotions, coping with survivorship, running a family meeting, and transitioning to palliative care and end of life. Achievable outcomes are growth in clinician's self-efficacy, uptake of new communication strategies and skills, and transfer of these strategies and skills into the clinic. Outcomes impacting patient satisfaction, improved adaptation, and enhanced quality of life are still lacking.

Conclusion

Future communication challenges include genetic risk communication, concepts like watchful waiting, cumulative radiation risk, late effects of treatment, discussing Internet information and unproven therapies, phase I trial enrollment, and working as a multidisciplinary team. Patient benefits, such as increased treatment adherence and enhanced adaptation, need to be demonstrated from CST.
Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis
Authors: Hollevoet Kevin , Reitsma Johannes B. , Creaney Jenette , Grigoriu Bogdan D. , Robinson Bruce W. , Scherpereel Arnaud , Cristaudo Alfonso , Pass Harvey I. , Nackaerts Kristiaan , Rodríguez Portal José A. , Schneider Joachim , Muley Thomas , Di Serio Francesca , Baas Paul , Tomasetti Marco , Rai Alex J. , van Meerbeeck Jan P.
Published: March 2012

Purpose

Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis.

Methods

The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis.

Results

At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%).

Conclusion

In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research.
Oncologist Burnout: Causes, Consequences, and Responses
Authors: Shanafelt Tait , Dyrbye Lotte
Published: March 2012

Although the practice of oncology can be extremely rewarding, it is also one of the most demanding and stressful areas of medicine. Oncologists are faced with life and death decisions on a daily basis, administer incredibly toxic therapies with narrow therapeutic windows, must keep up with the rapid pace of scientific and treatment advances, and continually walk a fine line between providing palliation and administering treatments that lead to excess toxicity. Personal distress precipitated by such work-related stress may manifest in a variety of ways including depression, anxiety, fatigue, and low mental quality of life. Burnout also seems to be one of the most common manifestations of distress among physicians, with studies suggesting a prevalence of 35% among medical oncologists, 38% among radiation oncologists, and 28% to 36% among surgical oncologists. Substantial evidence suggests that burnout can impact quality of care in a variety of ways and has potentially profound personal implications for physicians including suicidal ideation. In this review, we examine the causes, consequences, and personal ramifications of oncologist burnout and explore the steps oncologists can take to promote personal well-being and professional satisfaction.
Evidence-Based Treatment of Delirium in Patients With Cancer
Authors: Breitbart William , Alici Yesne
Published: March 2012

Delirium is the most common neuropsychiatric complication seen in patients with cancer, and it is associated with significant morbidity and mortality. Increased health care costs, prolonged hospital stays, and long-term cognitive decline are other well-recognized adverse outcomes of delirium. Improved recognition of delirium and early treatment are important in diminishing such morbidity. There has been an increasing number of studies published in the literature over the last 10 years regarding delirium treatment as well as prevention. Antipsychotics, cholinesterase inhibitors, and alpha-2 agonists are the three groups of medications that have been studied in randomized controlled trials in different patient populations. In patients with cancer, the evidence is most clearly supportive of short-term, low-dose use of antipsychotics for controlling the symptoms of delirium, with close monitoring for possible adverse effects, especially in older patients with multiple medical comorbidities. Nonpharmacologic interventions also appear to have a beneficial role in the treatment of patients with cancer who have or are at risk for delirium. This article presents evidence-based recommendations based on the results of pharmacologic and nonpharmacologic studies of the treatment and prevention of delirium.
Information, Technology, and Information Worker Productivity
Authors: Aral Sinan , Brynjolfsson Erik , Van Alstyne Marshall
Published: March 2012

We econometrically evaluate information worker productivity at a midsize executive recruiting firm and assess whether the knowledge that workers accessed through their electronic communication networks enabled them to multitask more productively. We estimate dynamic panel data models of multitasking, knowledge networks, and productivity using several types of micro-level data: (a) direct observation of more than 125,000 email messages over a period of 10 months; (b) detailed accounting data on individuals' project output and team membership for more than 1,300 projects spanning five years; and (c) survey and interview data about the same workers' IT skills, IT use, and information sharing. We find that (1) more multitasking is associated with more project output, but diminishing marginal returns, and (2) recruiters whose network contacts have heterogeneous knowledge—an even distribution of expertise over many project types—are less productive on average but more productive when juggling diverse multitasking portfolios. These results show how multitasking affects productivity and how knowledge networks, enabled by IT, can improve worker performance. The methods developed can be replicated in other settings, opening new frontiers for research on social networks and IT value.
Local Sustainable Development: Lessons Learned from the New Deal for Communities
Authors: Stanton John
Published: March 2012

Sustainable development has, in recent times, come to feature prominently on the government agenda, particularly in respect of local communities. In line with this, the New Deal for Communities programme was established to work towards the regeneration of some of the most deprived neighbourhoods in England. Now that the scheme has reached its conclusion, this article evaluates the extent to which it met with the government's policies for ‘building sustainable communities' as set out in the Strategies on Sustainable Development 1999 and 2005.
Designer chiral phase-transfer catalysts for green sustainable chemistry
Authors: Maruoka Keiji
Published: March 2012

A series of chiral quaternary ammonium salts derived from commercially available (R)- or (S)-binaphthol have been designed as new C
2-symmetric chiral phase-transfer catalysts. In order to realize the flexible design of these phase-transfer catalysts, the combinatorial design approach has been developed. Chiral high-performance organocatalysts, thus obtained, have been successfully applied to the highly practical asymmetric synthesis of various amino acid derivatives, including α-alkyl and α,α-dialkyl-α-amino acids in addition to alkaloids. Furthermore, several chiral bifunctional phase-transfer catalysts have been designed and synthesized for effecting base-free phase-transfer reactions under essentially neutral conditions in order to realize green sustainable chemistry.
Toward controlled synthesis of carbon nanotubes and graphenes
Authors: Itami Kenichiro
Published: March 2012

A bottom-up synthesis of structurally uniform carbon nanotubes (CNTs) and graphenes is recognized as one of the greatest challenges of primary importance in nanocarbon science. This paper highlights our efforts to address these challenges since 2005. These endeavors have led to (i) modular, size-selective, and scalable synthesis of [n]cycloparapheneylenes (CPPs), the shortest segment of armchair CNTs, (ii) design and synthesis of the shortest segment of chiral CNTs, and (iii) efficient synthesis of carbon nanosheets through catalytic C–H bond arylation of polycyclic aromatic hydrocarbons (PAHs). We consider these works as a possible first step toward a controlled synthesis of structurally uniform CNTs and nanographenes.