bluuebunny/crossref_metadata_2025 huggingface dataset:
Catch Me If You Can
Authors: Levenson Jill S. , Ackerman Alissa R. , Harris Andrew J.
Published: April 2013

The presumed dangers presented by sex offenders who have absconded from authorities have played a prominent role in public discourse surrounding state and federal sex offender management policy. The current study is the first to empirically investigate the characteristics of absconded sex offenders and explore how this group compares to other groups of sex offenders. Utilizing data from the Florida sex offender registry ( N = 23,557), this exploratory study compares the characteristics and risk factors of absconders with those of compliant and noncompliant (nonabsconding) registrants as well as with those with convictions for failure to register (FTR). Absconders, as a group, were less likely than compliant registrants to be listed as predators, and less likely than both compliants and noncompliants to have a minor victim or to be a repeat sex offender. Absconders were also least likely to have a prior FTR conviction, but those with a previous FTR conviction were more likely to abscond from registration than probation. The findings fail to support the hypothesis that fugitive sex offenders are more sexually dangerous (especially to children), and suggest a multitude of explanations for absconding.
Visuospatial Working Memory in ADHD Patients, Unaffected Siblings, and Healthy Controls
Authors: van Ewijk Hanneke , Heslenfeld Dirk J. , Luman Marjolein , Rommelse Nanda N. , Hartman Catharina A. , Hoekstra Pieter , Franke Barbara , Buitelaar Jan K. , Oosterlaan Jaap
Published: April 2013

Objective: The aim of this study was to (a) test the usefulness of visuospatial working memory (VSWM) as an endophenotype for ADHD and (b) study the developmental trajectory of VSWM in ADHD. Method: A total of 110 ADHD patients, 60 unaffected siblings, and 109 controls, aged 8 to 29 years, were assessed on VSWM functioning. Multilevel analyses were carried out to account for the correlation between measurements within families. Results: ADHD patients showed impaired VSWM performance compared with unaffected siblings and controls, with comparable performance between unaffected siblings and controls. Impaired VSWM in ADHD patients was not more pronounced on higher memory loads, signifying executive rather than storage deficits as an underlying mechanism. ADHD patients, unaffected siblings, and controls showed parallel developmental trajectories of VSWM. Conclusion: Current findings question the usefulness of VSWM as a neurocognitive endophenotype for ADHD and provide unique insights into the developmental trajectory of VSWM in ADHD.
Rudolf Laban and Topological Movement
Authors: Sutil Nicolas Salazar
Published: April 2013

This article explores the somewhat neglected theory of topological movement developed by the Hungarian artist and researcher Rudolf Laban. The piece begins with an examination of Laban’s understanding of space in relation of the notion of the kinesphere. I argue that Laban’s idea of space is essentially derived from a rationalization of outer movement (geometry), which enables him to break movement down into analytical units, and rearrange these into a meaningful syntax, a language (dance, mime, or theatre). I then go on to explain Laban’s idea of a synthesis between outer movement, and another sphere of movement known as dynamospheric (which refers to more fundamental inner forces that involve psychological and emotional dynamics). Crucially, these dynamic forms are modelled by Laban through the use of topological surfaces. I further support my analysis by an investigation of Laban’s unpublished book Effort and Recovery, and also by taking a videographic approach to a number of important filmic studies of topological movement observation. The article concludes with the idea that Laban’s graphic approach to movement analysis can be further enhanced, particularly within the study of topological dynamics, with the help of vision technologies such as film, video, and computer animation. I briefly discuss William Forsythe’s reinterpretation of Laban’s analysis via moving-image technologies, before concluding with a short description of a video study entitled Labanimations, which I carried out recently with video artist Sebastian Melo, and in which I reexamine Laban’s artwork through video techniques such as long exposure photography and slit scan.
Large differences between patients with acute myocardial infarction included in two Swedish health registers
Authors: Aspberg Sara , Stenestrand Ulf , Köster Max , Kahan Thomas
Published: April 2013

Background: Acute myocardial infarction (MI) is a leading cause for morbidity and mortality in Sweden. We aimed to compare patients with an acute MI included in the Register of information and knowledge about Swedish heart intensive care admissions (RIKS-HIA, now included in the register Swedeheart) and in the Swedish statistics of acute myocardial infarctions (S-AMI). Methods: Population based register study including RIKS-HIA, S-AMI, the National patient register and the Cause of death register. Odds ratios were determined by logistic regression analysis. Results: From 2001 to 2007, 114,311 cases in RIKS-HIA and 198,693 cases in S-AMI were included with a discharge diagnosis of an acute MI. Linkage was possible for 110,958 cases. These cases were younger, more often males, had fewer concomitant diseases and were more often treated with invasive coronary artery procedures than patients included in S-AMI only. There were substantial regional differences in proportions of patients reported to RIKS-HIA. Conclusions: Approximately half of all patients with an acute MI were included in RIKS-HIA. They represented a relatively more healthy population than patients included in S-AMI only. S-AMI covered almost all patients with an acute MI but had limited information about the patients. Used in combination, these two registers can give better prerequisites for improved quality of care of all patients with acute coronary syndromes.
Bilateral Pulmonary Emboli Secondary to Indwelling Hemodialysis Reliable Outflow Catheter
Authors: Coan Kathryn E. , O’Donnell Mark E. , Fankhauser Grant T. , Bodnar Zachary , Chandrasekaran Krishnaswamy , Stone William M.
Published: April 2013

We present a 33-year-old dialysis-dependent female who presented with new onset split second heart sound. Following a failed left upper extremity dialysis fistula, a right upper extremity hemodialysis reliable outflow (HeRO) graft was performed in 2011. Her subsequent cadaveric renal transplant had delayed function necessitating concurrent use of hemodialysis. However, as renal function improved, hemodialysis was discontinued. Two weeks following transplantation, the HeRO graft occluded. Subsequent clinical and radiological assessment confirmed widespread pulmonary emboli. Following cessation of hemodialysis and subsequent HeRO graft occlusion, removal was deemed appropriate to reduce further thromboembolic phenomenon. Right atrial thrombi are complications associated with central venous catheters. However, their actual incidence varies significantly. Right heart thromboemboli are associated with a 4% to 6% pulmonary embolism rate. Katzman et al assessed 38 patients who underwent HeRO graft and reported 1 (2.6%) patient with right atrial emboli and likely pulmonary embolism. Although thrombotic complications remain rare, consideration of graft removal should always be evaluated particularly in the absence of an alternative thrombotic source.
Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella Pneumoniae in mice
Authors: Patterson Craig M , Morrison Richard L , D’Souza Alain , Teng Xu S , Happel Kyle I
Published: April 2013

Background

Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia.

Methods

C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured.

Results

Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model.

Conclusions

Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses.
Identification of drought-responsive and novel Populus trichocarpamicroRNAs by high-throughput sequencing and their targets using degradome analysis
Authors: Shuai Peng , Liang Dan , Zhang Zhoujia , Yin Weilun , Xia Xinli
Published: April 2013

Background

MicroRNAs (miRNAs) are endogenous small RNAs (sRNAs) with a wide range of regulatory functions in plant development and stress responses. Although miRNAs associated with plant drought stress tolerance have been studied, the use of high-throughput sequencing can provide a much deeper understanding of miRNAs. Drought is a common stress that limits the growth of plants. To obtain more insight into the role of miRNAs in drought stress, Illumina sequencing of Populus trichocarpa sRNAs was implemented.

Results

Two sRNA libraries were constructed by sequencing data of control and drought stress treatments of poplar leaves. In total, 207 P. trichocarpa conserved miRNAs were detected from the two sRNA libraries. In addition, 274 potential candidate miRNAs were found; among them, 65 candidates with star sequences were chosen as novel miRNAs. The expression of nine conserved miRNA and three novel miRNAs showed notable changes in response to drought stress. This was also confirmed by quantitative real time polymerase chain reaction experiments. To confirm the targets of miRNAs experimentally, two degradome libraries from the two treatments were constructed. According to degradome sequencing results, 53 and 19 genes were identified as targets of conserved and new miRNAs, respectively. Functional analysis of these miRNA targets indicated that they are involved in important activities such as the regulation of transcription factors, the stress response, and lipid metabolism.

Conclusions

We discovered five upregulated miRNAs and seven downregulated miRNAs in response to drought stress. A total of 72 related target genes were detected by degradome sequencing. These findings reveal important information about the regulation mechanism of miRNAs in P. trichocarpa and promote the understanding of miRNA functions during the drought response.
The relationship between obesity and neurocognitive function in Chinese patients with schizophrenia
Authors: Guo Xiaofeng , Zhang Zhanchou , Wei Qinling , Lv Hailong , Wu Renrong , Zhao Jingping
Published: April 2013

Background

Studies have reported that up to 60% of individuals with schizophrenia are overweight or obese. This study explored the relationship between obesity and cognitive performance in Chinese patients with schizophrenia.

Methods

Outpatients with schizophrenia aged 18–50 years were recruited from 10 study sites across China. Demographic and clinical information was collected. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was used to assess cognitive function, and these 4 individual domains were transformed into a neurocognitive composite z score. In addition, height and weight were measured to calculate body mass index (BMI). Patients were categorized into 4 groups (underweight, normal weight, overweight and obese) based on BMI cutoff values for Asian populations recommended by the World Health Organization.

Results

A total number of 896 patients were enrolled into the study. Fifty-four percent of participants were overweight or obese. A higher BMI was significantly associated with lower scores on the Wechsler Memory Scale-Revised (WMS-R) Visual Reproduction subscale, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol subscale, and the composite z score (p’s ≤ 0.024). Obese patients with schizophrenia had significantly lower scores than normal weight patients on the Trail Making Test B, the WMS-R Visual Reproduction subscale, the WAIS Digit Symbol subscale, and the composite z score (p’s ≤ 0.004).

Conclusions

Our study suggests that, in addition to its well established risk for various cardiometabolic conditions, obesity is also associated with decreased cognitive function in Chinese patients with schizophrenia. Future studies should explore if weight loss and management can improve cognitive function in obese patients who suffer from schizophrenia.
Stages of change, treatment outcome and therapeutic alliance in adult inpatients with chronic anorexia nervosa
Authors: Mander Johannes , Teufel Martin , Keifenheim Katharina , Zipfel Stephan , Giel Katrin Elisabeth
Published: April 2013

Background

Anorexia nervosa (AN) is associated with high rates of chronicity and relapse risk is a considerable therapeutic challenge in the disorder. The aim of the present study was to investigate the association of stages of change and outcome with a focus on the relapse struggle in the maintenance stage in patients with predominantly chronic AN. Further, therapeutic alliance and stages of change associations were explored.

Methods

As an instrument measuring relapse struggle in the maintenance stage, we applied the short form of the University of Rhode Island Change Assessment-Short (URICA-S). We assessed stages of change in 39 patients with a predominantly chronic course of AN in early, middle, and late stages of inpatient psychotherapy. General symptom severity as assessed by the SCL-90-R and weight change were investigated as outcome measures.

Results

In-line with earlier evidence, contemplation significantly predicted therapeutic alliance. Further, we demonstrated that relapse risk as operationalized by URICA-S maintenance is an important predictor of general psychopathology. BMI change was not predicted by stages of change.

Conclusions

The URICA-S maintenance scale might be applied to help identify patients at relapse risk. High URICA-S maintenance scores could be considered as one critical aspect of AN patients who might especially benefit from relapse-preventing aftercare programs.
Activation of renin-angiotensin system is involved in dyslipidemia-mediated renal injuries in apolipoprotein E knockout mice and HK-2 cells
Authors: Ni Jie , Ma Kun-Ling , Wang Chang-Xian , Liu Jing , Zhang Yang , Lv Lin-Li , Ni Hai-Feng , Chen Ya-Xi , Ruan Xiong-Zhong , Liu Bi-Cheng
Published: April 2013

Background

Dyslipidemia and activation of renin-angiotensin system (RAS) contribute to the progression of chronic kidney disease (CKD). This study investigated possible synergistic effects of intrarenal RAS activation with hyperlipidemia in renal injuries.

Methods

Apolipoprotein knockout mice were fed with normal chow diet (control) or high fat diet (HF group) for eight weeks. Human proximal tubular epithelial cell line (HK-2) was treated without (control) or with cholesterol (30 μg/ml) plus 25-hydroxycholesterol (1 μg/ml) (lipid group) for 24 hours. The plasma lipid profile and RAS components were determined by clinical biochemistry assay and radiommunoassay, respectively. Collagen deposition in kidneys was evaluated by Masson-staining. The gene and protein expressions of molecules involved in RAS components and biomarkers of epithelial mesenchymal transition (EMT) were examined by real-time PCR, immunochemical staining, and Western blot.

Results

The mice fed with high-fat diet showed significant hyperlipidemia with collagen deposition in renal tubular interstitium compared to controls. The plasma levels of renin, angiotensin I, and angiotensin II were no difference in two groups. However, the kidneys of HF group showed up-regulated RAS components, which were positively associated with increased plasma levels of triglyceride, total cholesterol, and LDL. These effects were further confirmed by in vitro studies. Lipid loading induced HK-2 cells underwent EMT, which was closely associated with the increased expressions of intracellular RAS components.

Conclusions

Local RAS activation was involved in hyperlipidemia-mediated renal injuries, suggesting that there are synergistic effects resulting from RAS activation with hyperlipidemia that accelerates the progression of CKD.
Surface modification of TPGS-b-(PCL-ran-PGA) nanoparticles with polyethyleneimine as a co-delivery system of TRAIL and endostatin for cervical cancer gene therapy
Authors: Zheng Yi , Chen Hongbo , Zeng Xiaowei , Liu Zhigang , Xiao Xiaojun , Zhu Yongqiang , Gu Dayong , Mei Lin
Published: April 2013

The efficient delivery of therapeutic genes into cells of interest is a critical challenge to broad application of non-viral vector systems. In this research, a novel TPGS-b-(PCL-ran-PGA) nanoparticle modified with polyethyleneimine was applied to be a vector of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin for cervical cancer gene therapy. Firstly, a novel biodegradable copolymer, TPGS-b-(PCL-ran-PGA), was synthesized and characterized. The nanoparticles were fabricated by an emulsion/solvent evaporation method and then further modified with polyethyleneimine (PEI) carrying TRAIL and/or endostatin genes. The uptake of pIRES2-EGFP and/or pDsRED nanoparticles by HeLa cells were observed by fluorescence microscopy and confocal laser scanning microscopy. The cell viability of TRAIL/endostatin-loaded nanoparticles in HeLa cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Severe combined immunodeficient mice carrying HeLa tumor xenografts were treated in groups of six including phosphate-buffered saline control, blank TPGS-b-(PCL-ran-PGA) nanoparticles, blank TPGS-b-(PCL-ran-PGA)/PEI nanoparticles, and three types of gene nanoparticles. The activity was assessed using average increase in survival time, body weight, and solid tumor volume. All the specimens were then prepared as formalin-fixed and paraffin-embedded tissue sections for hematoxylin-eosin staining. The data showed that the nanoparticles could efficiently deliver plasmids into HeLa cells. The cytotoxicity of the HeLa cells was significantly increased by TRAIL/endostatin-loaded nanoparticles when compared with control groups. The use of TPGS in combination with TRAIL and endostatin had synergistic antitumor effects. In conclusion, the TRAIL/endostatin-loaded nanoparticles offer considerable potential as an ideal candidate for in vivo cancer gene delivery.
Gender, Variation in Opioid Receptor Genes and Sensitivity to Experimental Pain
Authors: Sato Hiroe , Droney Joanne , Ross Joy , Olesen Anne Estrup , Staahl Camilla , Andresen Trine , Branford Ruth , Riley Julia , Arendt-Nielsen Lars , Drewes Asbjørn Mohr
Published: April 2013

Background

Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes ( OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included.

Results

Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain.

Conclusion

This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.
Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness
Authors: Candiello Joseph , Singh Satish S , Task Keith , Kumta Prashant N , Banerjee Ipsita
Published: April 2013

Background

Embryonic stem cells (ESCs) have been implicated to have tremendous impact in regenerative therapeutics of various diseases, including Type 1 Diabetes. Upon generation of functionally mature ESC derived islet-like cells, they need to be implanted into diabetic patients to restore the loss of islet activity. Encapsulation in alginate microcapsules is a promising route of implantation, which can protect the cells from the recipient’s immune system. While there has been a significant investigation into islet encapsulation over the past decade, the feasibility of encapsulation and differentiation of ESCs has been less explored. Research over the past few years has identified the cellular mechanical microenvironment to play a central role in phenotype commitment of stem cells. Therefore it will be important to design the encapsulation material to be supportive to cellular functionality and maturation.

Results

This work investigated the effect of stiffness of alginate substrate on initial differentiation and phenotype commitment of murine ESCs. ESCs grown on alginate substrates tuned to similar biomechanical properties of native pancreatic tissue elicited both an enhanced and incrementally responsive differentiation towards endodermal lineage traits.

Conclusions

The insight into these biophysical phenomena found in this study can be used along with other cues to enhance the differentiation of embryonic stem cells toward a specific lineage fate.
Development of an electrotransformation protocol for genetic manipulation of Clostridium pasteurianum
Authors: Pyne Michael E , Moo-Young Murray , Chung Duane A , Chou C Perry
Published: April 2013

Background

Reducing the production cost of, and increasing revenues from, industrial biofuels will greatly facilitate their proliferation and co-integration with fossil fuels. The cost of feedstock is the largest cost in most fermentation bioprocesses and therefore represents an important target for cost reduction. Meanwhile, the biorefinery concept advocates revenue growth through complete utilization of by-products generated during biofuel production. Taken together, the production of biofuels from low-cost crude glycerol, available in oversupply as a by-product of bioethanol production, in the form of thin stillage, and biodiesel production, embodies a remarkable opportunity to advance affordable biofuel development. However, few bacterial species possess the natural capacity to convert glycerol as a sole source of carbon and energy into value-added bioproducts. Of particular interest is the anaerobe Clostridium pasteurianum, the only microorganism known to convert glycerol alone directly into butanol, which currently holds immense promise as a high-energy biofuel and bulk chemical. Unfortunately, genetic and metabolic engineering of C. pasteurianum has been fundamentally impeded due to lack of an efficient method for deoxyribonucleic acid (DNA) transfer.

Results

This work reports the development of an electrotransformation protocol permitting high-level DNA transfer to C. pasteurianum ATCC 6013 together with accompanying selection markers and vector components. The CpaAI restriction-modification system was found to be a major barrier to DNA delivery into C. pasteurianum which we overcame by in vivo methylation of the recognition site (5’-CGCG-3’) using the M.FnuDII methyltransferase. With proper selection of the replication origin and antibiotic-resistance marker, we initially electroporated methylated DNA into C. pasteurianum at a low efficiency of 2.4 × 101 transformants μg-1 DNA by utilizing conditions common to other clostridial electroporations. Systematic investigation of various parameters involved in the cell growth, washing and pulse delivery, and outgrowth phases of the electrotransformation procedure significantly elevated the electrotransformation efficiency, up to 7.5 × 104 transformants μg-1 DNA, an increase of approximately three order of magnitude. Key factors affecting the electrotransformation efficiency include cell-wall-weakening using glycine, ethanol-mediated membrane solubilization, field strength of the electric pulse, and sucrose osmoprotection.

Conclusions

C. pasteurianum ATCC 6013 can be electrotransformed at a high efficiency using appropriately methylated plasmid DNA. The electrotransformation method and tools reported here should promote extensive genetic manipulation and metabolic engineering of this biotechnologically important bacterium.
Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing – a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites
Authors: Guerid Samia , Darwiche Salim E , Berger Mette M , Applegate Lee Ann , Benathan Messod , Raffoul Wassim
Published: April 2013

Background

Wound healing involves complex mechanisms, which, if properly chaperoned, can enhance patient recovery. The abilities of platelets and keratinocytes may be harnessed in order to stimulate wound healing through the formation of platelet clots, the release of several growth factors and cytokines, and cell proliferation. The aim of the study was to test whether autologous keratinocyte suspensions in platelet concentrate would improve wound healing. The study was conducted at the Lausanne University Hospital, Switzerland in 45 patients, randomized to three different topical treatment groups: standard treatment serving as control, autologous platelet concentrate (PC) and keratinocytes suspended in autologous platelet concentrate (PC + K). Split thickness skin graft donor sites were chosen on the anterolateral thighs of patients undergoing plastic surgery for a variety of defects. Wound healing was assessed by the duration and quality of the healing process. Pain intensity was evaluated at day five.

Results

Healing time was reduced from 13.9 ± 0.5 days (mean ± SEM) in the control group to 7.2 ± 0.2 days in the PC group (P < 0.01). An addition of keratinocytes in suspension further reduced the healing time to 5.7 ± 0.2 days. Pain was reduced in both the PC and PC + K groups. Data showed a statistically detectable advantage of using PC + K over PC alone (P < 0.01).

Conclusion

The results demonstrate the positive contribution of autologous platelets combined with keratinocytes in stimulating wound healing and reducing pain. This strikingly simple approach could have a significant impact on patient care, especially critically burned victims for whom time is of the essence.

Clinical trial registry information

Protocol Record Identification Number: 132/03

Registry URL: http://www.clinicaltrials.gov
Randomized Controlled Trial of Cetuximab Plus Chemotherapy for Patients With KRAS Wild-Type Unresectable Colorectal Liver-Limited Metastases
Authors: Ye Le-Chi , Liu Tian-Shu , Ren Li , Wei Ye , Zhu De-Xiang , Zai Sheng-Yong , Ye Qing-Hai , Yu Yiyi , Xu Bo , Qin Xin-Yu , Xu Jianmin
Published: April 2013

Purpose

To assess the effects of cetuximab plus chemotherapy as first-line treatment for unresectable colorectal liver metastases (CLMs).

Patients and Methods

After resection of their primary tumors, patients with KRAS wild-type synchronous nonresectable liver-limited metastases from colorectal cancer were randomly assigned to receive chemotherapy (FOLFIRI [fluorouracil, leucovorin, and irinotecan] or mFOLFOX6 [modified fluorouracil, leucovorin, and oxaliplatin]) plus cetuximab (arm A) or chemotherapy alone (arm B). The primary end point was the rate of patients converted to resection for liver metastases. Secondary end points included tumor response and survival.

Results

The intent-to-treat population comprised 138 patients; 70 patients were randomly assigned to arm A and 68 to arm B. After a median of 25.0 months of follow-up, the 3-year overall survival (OS) rate and median survival time (MST) for all patients were 30% and 24.4 months, respectively. The R0 resection rates for liver metastases were 25.7% (18 of 70 patients) in arm A and 7.4% (five of 68 patients) in arm B, which were significantly different (P < .01). Patients in arm A had improved objective response rates (57.1% v 29.4%; P < .01), increased 3-year OS rate (41% v 18%; P = .013) and prolonged MST (30.9 v 21.0 months; P = .013) compared with those in arm B. In addition, in arm A, patients who had resection of liver metastases had a significantly improved MST (46.4 v 25.7 months; P < .01) compared with those who did not undergo surgery.

Conclusion

For patients with initially unresectable KRAS wild-type CLMs, cetuximab combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone.
Adherence to the World Cancer Research Fund/American Institute for Cancer Research Recommendations for Cancer Prevention Is Associated With Better Health-Related Quality of Life Among Elderly Female Cancer Survivors
Authors: Inoue-Choi Maki , Lazovich DeAnn , Prizment Anna E. , Robien Kim
Published: April 2013

Purpose

The 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet and physical activity guidelines encourage cancer survivors to follow its cancer prevention recommendations. We evaluated whether adherence to the WCRF/AICR recommendations was associated with health-related quality of life (HRQOL) among elderly female cancer survivors.

Patients and Methods

A total of 2,193 women with a confirmed cancer diagnosis (1986 through 2002) in the Iowa Women's Health Study were identified. We calculated a WCRF/AICR recommendation adherence score (range, 0 to 7), assigning one point each for seven recommendations. Physical and mental component summary scores (PCS, MCS) from the Medical Outcomes Study Short Form–36 Health Survey were compared by recommendation adherence scores.

Results

Mean adherence score was 4.0 ± 1.2. Overall, higher adherence to the WCRF/AICR guidelines was significantly associated with better PCS and MCS after adjustment for age, education, marital status, number of comorbidities, smoking, cancer stage, and current cancer treatment (Ptrend< .001 for both). PCS was 43.5 versus 37.0 and MCS was 54.2 versus 52.0 among women with adherence scores ≥ 5 compared with women scoring ≤ 3. Adherence to the physical activity recommendation was associated with higher PCS and MCS after adjusting for demographic and medical confounders, body mass index, and dietary recommendation adherence. For the body weight recommendation, adherence was associated with higher PCS but lower MCS, whereas adherence to the dietary recommendations was associated with higher MCS only.

Conclusion

Following the lifestyle guidelines for cancer prevention may improve HRQOL among elderly female cancer survivors. Physical activity may be a key lifestyle factor to improve HRQOL.
cAMP-Responsive Element Binding Protein: A Vital Link in Embryonic Hormonal Adaptation
Authors: Schindler Maria , Fischer Sünje , Thieme René , Fischer Bernd , Santos Anne Navarrete
Published: April 2013

The transcription factor cAMP responsive element-binding protein (CREB) and activating transcription factors (ATFs) are downstream components of the insulin/IGF cascade, playing crucial roles in maintaining cell viability and embryo survival. One of the CREB target genes is adiponectin, which acts synergistically with insulin. We have studied the CREB-ATF-adiponectin network in rabbit preimplantation development in vivo and in vitro. From the blastocyst stage onwards, CREB and ATF1, ATF3, and ATF4 are present with increasing expression for CREB, ATF1, and ATF3 during gastrulation and with a dominant expression in the embryoblast (EB). In vitro stimulation with insulin and IGF-I reduced CREB and ATF1 transcripts by approximately 50%, whereas CREB phosphorylation was increased. Activation of CREB was accompanied by subsequent reduction in adiponectin and adiponectin receptor (adipoR)1 expression. Under in vivo conditions of diabetes type 1, maternal adiponectin levels were up-regulated in serum and endometrium. Embryonic CREB expression was altered in a cell lineage-specific pattern. Although in EB cells CREB localization did not change, it was translocated from the nucleus into the cytosol in trophoblast (TB) cells. In TB, adiponectin expression was increased (diabetic 427.8 ± 59.3 pg/mL vs normoinsulinaemic 143.9 ± 26.5 pg/mL), whereas it was no longer measureable in the EB. Analysis of embryonic adipoRs showed an increased expression of adipoR1 and no changes in adipoR2 transcription. We conclude that the transcription factors CREB and ATFs vitally participate in embryo-maternal cross talk before implantation in a cell lineage-specific manner. Embryonic CREB/ATFs act as insulin/IGF sensors. Lack of insulin is compensated by a CREB-mediated adiponectin expression, which may maintain glucose uptake in blastocysts grown in diabetic mothers.
What’s Up, Doc?
Authors: Soloski Alexis
Published: April 2013

In this forum, critic Alexis Soloski gathers a range of contemporary theater artists, with an array of approaches to fact-based performance, to discuss the potential, integrity, and complications of documentary theater.
Dynamics of thymus organogenesis and colonization in early human development
Authors: Farley Alison M. , Morris Lucy X. , Vroegindeweij Eric , Depreter Marianne L. G. , Vaidya Harsh , Stenhouse Frances H. , Tomlinson Simon R. , Anderson Richard A. , Cupedo Tom , Cornelissen Jan J. , Blackburn C. Clare
Published: April 2013

The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45+CD34int/-. Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients.
Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina
Authors: Gnanaguru Gopalan , Bachay Galina , Biswas Saptarshi , Pinzón-Duarte Germán , Hunter Dale D. , Brunken William J.
Published: April 2013

Pathologies of retinal blood vessels are among the major causes of blindness worldwide. A key cell type that regulates retinal vascular development is the astrocyte. Generated extrinsically to the retina, astrocytes migrate into the retina through the optic nerve head. Even though there is a strong correlation between astrocyte distribution and retinal vascular development, the factors that guide astrocytes into the retina remain unclear. In this study, we show that astrocytes migrate within a laminin-containing basement membrane - the inner limiting membrane. Genetic deletion of the laminin β2 and γ3 chains affects astrocyte migration and spatial distribution. We show that laminins act as haptotactic factors in vitro in an isoform-specific manner, inducing astrocyte migration and promoting astrocyte differentiation. The addition of exogenous laminins to laminin-null retinal explants rescues astrocyte migration and spatial patterning. Furthermore, we show that the loss of laminins reduces β1 integrin expression in astrocytes. Culturing laminin-null retinal astrocytes on laminin substrates restores focal localization of β1 integrin. Finally, we show that laminins containing β2 and γ3 chains regulate subsequent retinal blood vessel growth and maintain vascular integrity. These in vivo and in vitro studies demonstrate clearly that laminins containing β2 and γ3 chains are indispensable for migration and spatial organization of astrocytes and that they play a crucial role during retinal angiogenesis in vivo.
Incorporating Direct Marketing Activity into Latent Attrition Models
Authors: Schweidel David A. , Knox George
Published: April 2013

When defection is unobserved, latent attrition models provide useful insights about customer behavior and accurate forecasts of customer value. Yet extant models ignore direct marketing efforts. Response models incorporate the effects of direct marketing, but because they ignore latent attrition, they may lead firms to waste resources on inactive customers.

We propose a parsimonious model that allows direct marketing to impact three relevant behaviors in latent attrition models—the frequency with which customers conduct transactions, the size of the transactions, and the duration for which customers remain active. Our model also accounts for how the organization targets its direct marketing across individuals and over time.

Using donation data from a nonprofit organization, we find that direct marketing increases donation incidence for active donors. However, our analysis also shows that direct marketing has the potential to shorten the length of a donor's relationship. We find that our proposed model offers superior predictive performance compared with models that ignore the impact of direct marketing activity or latent attrition. We demonstrate the managerial applicability of our modeling approach by estimating the impact of direct marketing on donation behavior and identifying those donors most likely to conduct transactions in the future.
A Direct Utility Model for Asymmetric Complements
Authors: Lee Sanghak , Kim Jaehwan , Allenby Greg M.
Published: April 2013

A symmetric complements refer to goods where one good is more dependent on the other, yet consumers receive enhanced utility from consuming both. Examples include garden hoses and sprinklers, chips and dip, and routine versus personalized services where the former has a broader base for utility generation and the latter is more dependent on the other's presence. Measuring asymmetric effects is difficult when all that is observed are the purchase quantities present in a consumer's market basket. We propose a direct utility model with a latent decision sequence for measuring asymmetric effects that allows us to capture differential responses to cross-category purchases and inventories. Scanner panel data of milk and cereal purchases are used to investigate the presence of asymmetric complementarity, and implications are explored through counterfactual analyses involving cross-price elasticities and spillover effects of merchandising variables.
Characteristics of Screen Media Use Associated With Higher BMI in Young Adolescents
Authors: Bickham David S. , Blood Emily A. , Walls Courtney E. , Shrier Lydia A. , Rich Michael
Published: April 2013

OBJECTIVES:

This study investigates how characteristics of young adolescents’ screen media use are associated with their BMI. By examining relationships between BMI and both time spent using each of 3 screen media and level of attention allocated to use, we sought to contribute to the understanding of mechanisms linking media use and obesity.

METHODS:

We measured heights and weights of 91 13- to 15-year-olds and calculated their BMIs. Over 1 week, participants completed a weekday and a Saturday 24-hour time-use diary in which they reported the amount of time they spent using TV, computers, and video games. Participants carried handheld computers and responded to 4 to 7 random signals per day by completing onscreen questionnaires reporting activities to which they were paying primary, secondary, and tertiary attention.

RESULTS:

Higher proportions of primary attention to TV were positively associated with higher BMI. The difference between 25th and 75th percentiles of attention to TV corresponded to an estimated +2.4 BMI points. Time spent watching television was unrelated to BMI. Neither duration of use nor extent of attention paid to video games or computers was associated with BMI.

CONCLUSIONS:

These findings support the notion that attention to TV is a key element of the increased obesity risk associated with TV viewing. Mechanisms may include the influence of TV commercials on preferences for energy-dense, nutritionally questionable foods and/or eating while distracted by TV. Interventions that interrupt these processes may be effective in decreasing obesity among screen media users.
Patterns of Inpatient Care for Newly Diagnosed Immune Thrombocytopenia in US Children’s Hospitals
Authors: Kime Courtney , Klima Jennifer , Rose Melissa J. , O’Brien Sarah H.
Published: April 2013

OBJECTIVE:

Although recent evidence-based guidelines for the management of immune thrombocytopenia (ITP) recommend a conservative, observation-based approach for the majority of patients with newly diagnosed pediatric ITP, current practice patterns are unknown. This study used the Pediatric Health Information System database to examine patterns of inpatient care in newly diagnosed ITP in freestanding US children’s hospitals and to examine geographic differences in care.

METHODS:

Data were extracted from Pediatric Health Information System for all newly diagnosed ITP admissions aged 1 to 18 years discharged between January 2008 and December 2010. Clinical data obtained included age, gender, length of stay, diagnoses, medications, and discharge status.

RESULTS:

We identified 2314 unique patients meeting the study diagnosis of newly diagnosed ITP. Noncutaneous bleeding occurred in 12% of patients (intracranial hemorrhage 0.6%), with epistaxis the most commonly reported symptom. Ninety percent of hospitalized patients received ITP-directed therapy, with intravenous immunoglobulin G the most commonly used therapy (78% of patients). We identified significant variation by geographic region in treatment strategies, length of stay, hospital charges, and likelihood of readmission.

CONCLUSIONS:

A substantial number of children with newly diagnosed ITP continue to be hospitalized and receive intravenous medications, although the majority of these patients do not have clinical bleeding events during the admission. By using these results as a backdrop, future studies will be able to identify if the number of ITP admissions, costs of care, and geographic variability in care decrease with the dissemination and implementation of recently published guidelines.
Adaptive 3D Image-Guided Brachytherapy: A Strong Argument in the Debate on Systematic Radical Hysterectomy for Locally Advanced Cervical Cancer
Authors: Mazeron Renaud , Gilmore Jennifer , Dumas Isabelle , Champoudry Jérôme , Goulart Jennifer , Vanneste Ben , Tailleur Anne , Morice Philippe , Haie-Meder Christine
Published: April 2013

Learning Objectives

Evaluate control rates of IGABT combined with CCRT for the treatment of locally advanced cervical cancer. Describe survival outcomes in patients treated with IGABT combined with CCRT for locally advanced cervical cancer. Describe toxicities in patients treated with IGABT combined with CCRT for locally advanced cervical cancer.

Purpose.

To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT).

Materials and Methods.

Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment.

Results.

Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5–79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005).

Conclusion.

IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.