bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial Pressure Waveform Analysis During Rest and Suctioning
Authors: Hickey Joanne V. , Olson DaiWai M. , Turner Dennis A.
Published: April 2009

Cerebral compliance is a measure of cerebral adaptability to increases in volume within the intracranial space and an indicator of risk for neurological deterioration. However, no direct measurement of compliance exists in clinical practice to guide nursing care or treatment decisions. Current use of mean intracranial pressure (MICP) and gross morphological intracranial pressure waveform (ICPW) analysis have great variability in predicting outcomes. The purpose of this review and pilot study was to evaluate the effects of suctioning on MICP and other measures estimating cerebral compliance derived from analysis of ICPW on patient outcome. We analyzed arterial blood pressure waveforms (ABPWs), ICPWs, and respiratory cycle variations using Fourier Transform analysis, to explore the potential benefits of studying ICPWs across single cardiac and respiratory cycles using linear modeling and calculation of correlation coefficients. ABPWs, ICPWs, and MICP were measured over individual cardiac cycles across multiple respiratory phases in five critically ill neurological patients. Both direct and derived ICP measures, including Fourier analysis of ABP and ICP and the cross-transform between ABP and ICP, were correlated with patient outcome. This more complex waveform analysis of individual ABPW and ICPW together, and derived measures during both single cardiac and respiratory cycles, may provide information relevant to cerebral compliance and patient outcomes. Pending confirmation with additional data sets, this technique may be a useful real-time clinical tool to provide a measure of compliance and risk of neurological deterioration for clinicians.
Gene Therapy and Informed Consent Decision Making: Nursing Research Directions
Authors: Kaspar Rita W. , Wills Celia E. , Kaspar Brian K.
Published: April 2009

Recent gene therapy clinical trials have demonstrated significant promise for treating a number of genetic neuromuscular disorders. Although nurses are experienced in educating patients and families about the benefits and risks of conventional therapeutics, there are significant challenges for guiding patients through the decision-making phase of gene therapy clinical trial participation. The first part of this review provides an overview and update on neuromuscular gene therapy, including viral delivery principles and historical progress. The second part discusses risk/benefit perception of gene therapy and factors affecting the decision making for patients interested in participating in a trial. Future challenges for gene therapy are targeted high-efficiency delivery, and additional research on developing patient-centered decision support interventions.
Networks of the dead or alive in cyberspace: public intellectuals in the mass and internet media
Authors: Danowski James A. , Park David W.
Published: April 2009

This article addresses whether dead public intellectuals differ from living public intellectuals in terms of their social network properties in the mass and internet media. Explicated at the theoretical level is the macro-level asynchrony of the web, moving beyond micro-level conceptualizations. Networks for 662 actors which Posner defined as public intellectuals are analyzed based on data from Nexis for magazines, newspapers and broadcast media, and on the web through Google and Google Groups. The differences between the media profiles of dead and living public intellectuals are assessed. As hypothesized, there are no significant differences between living and dead public intellectuals in hits for webpages and for Google Groups threadedness. Also, mass media hits show a significantly higher frequency for the living. Findings show that dead public intellectuals have a social `afterlife', a sociomorphic quality that continues in cyberspace and not in other media.
A theory of relational signals in online groups
Authors: Matzat Uwe
Published: April 2009

The outcomes of interaction in online communities depend to a large extent on finding solutions to typical problems of interaction, such as free-riding and lack of trust. This article presents a theory which argues that a member's online behaviour sends signals about how (s)he regards the relationship to other members and to the group. Under specific conditions, members take the signal sending into account when they decide whether to contribute to group discussions and to participate in trust-demanding online activities. Community administrators can use the insights to influence members' behaviour by using social control. Three forms of social control are distinguished. Group conditions influence which form is more adequate for diminishing free-riding and lack of trust. A theory-guided typology of online groups and communities clarifies what type of community is more likely to suffer from problems of interaction and the effects of each kind of social control.
A multinational study on online privacy: global concerns and local responses
Authors: Hichang Cho  , Rivera-Sánchez Milagros , Sun Sun Lim
Published: April 2009

This study surveyed 1261 internet users from five cities (Bangalore, Seoul, Singapore, Sydney and New York) to examine multinational internet users' perceptions and behavioural responses concerning online privacy. It identified a set of individual-level (demographics and internet-related experiences) and macro-level factors (nationality and national culture), and tested the extent to which they affected online privacy concerns and privacy protection behaviours. The results showed that individual differences (age, gender and internet experience), nationality and national culture significantly influenced internet users' privacy concerns to the extent that older, female internet users from an individualistic culture were more concerned about online privacy than their counterparts. The study also identified three underlying dimensions of privacy protection behaviour — avoidance, opt-out and proactive protection — and found that they distinctly related to the individual and macro-level factors. Overall, the findings highlight the conditional and multicultural nature of online privacy.
'Connected presence' in distributed family life
Authors: Christensen Toke Haunstrup
Published: April 2009

Concurrent with the explosive pervasion of information and communication technologies in recent years, mediated communication has gained a strong position in the daily interaction between family members. Based on the results of qualitative interviews with families in Denmark, this article shows how the mobile phone is used by parents and children to mediate a feeling of closeness while they are physically separated. This practice of `connected presence' is based on frequent calls and text messages between parents and children as well as between parents themselves. The article also analyses families' use of the mobile phone in the context of modern family life, emphasizing the importance of the temporal and spatial dispersion of family members in explaining the form and content of intra-familial mediated communication. Finally, the dual role of media technologies (including the mobile phone) in both integrating and dispersing families is discussed.
Educational Diagnosticians’ Understanding of Phonological Awareness, Phonemic Awareness, and Reading Fluency
Authors: Chappell Julia C. , Stephens Tammy L. , Kinnison Lloyd , Pettigrew Johnnie D.
Published: April 2009

This article summarizes the results of a study involving 42 educational diagnosticians from North Texas. The study was conducted to determine diagnosticians’ perceived understanding of early literacy development and their ability to effectively choose and interpret assessments of phonological awareness, phonemic awareness, and reading fluency. The results suggested that the educational diagnosticians who participated in the study were not sufficiently knowledgeable in identifying the numerous components of reading (e.g., phonological awareness, phonemic awareness, and fluency); nor were they prepared to choose appropriate assessment instruments to assess selected components of reading.
Management of Chronic Obstructive Pulmonary Disease
Authors: Mann Rebecca , Nichols Jake
Published: April 2009

Chronic obstructive pulmonary disease (COPD) is a complex disease currently affecting a large number of individuals across the world. Historically thought of as an older male disease, the prevalence in women is rising. Patients with COPD primarily suffer from dyspnea, decreased exercise capacity, and chronic cough, which are due to progressive airflow limitation. Although typically considered a respiratory disorder, COPD differs from asthma both in pathophysiology and treatment. The airway obstruction commonly encountered in COPD results from multiple pathophysiologic processes, some of which may be preventable and modifiable. The mainstays of treatment are bronchodilators, and as lung function declines, the importance of including lifestyle modifications becomes even more essential. National and international guidelines direct treatment and diagnosis and attempt to increase awareness and education on the proper care of patients with COPD.
Clinical supervision for nurses working in mental health settings in Queensland, Australia: a randomised controlled trial in progress and emergent challenges
Authors: White Edward , Winstanley Julie
Published: April 2009

Abstract

Several national and state-based inquiry documents have reported long-standing and major concerns about mental health service provision in Australia. In particular, accounts of the difficult circumstances that surround the recruitment and retention of high-quality mental health nurses have clearly emerged, independent of jurisdiction. However, the privately experienced cost of working and coping in contemporary mental health settings, especially when the resilience of nursing staff is tested remains poorly understood. Clinical supervision (CS), a structured staff support arrangement, has shown promise as a positive contribution to the clinical governance agenda and is now found reflected in central policy themes elsewhere in the world. However, the concept of CS remains underdeveloped in Australia. The background to a unique randomised controlled trial (RCT), currently in progress in Queensland, Australia, has been described in this study. The efficacy of the most widely adopted model of CS that may address the promotion of standards and clinical audit issues, the development of skills and knowledge and the personal well-being of the supervisee will be tested. This study, funded by the Queensland Treasury/Golden Casket Foundation, will focus not only on the outcomes for individual mental health nurses but also examine the quality of care they provide and the effects of both on patient outcomes. This study will seek to establish a sustainable, strategically significant contribution to the knowledge base both for the mental health nursing workforce in Queensland (and beyond) and the patients they seek to serve.
Acute pancreatitis secondary to hemobilia after percutaneous liver biopsy
Authors: Peña Luis R. , Horn Todd L. , Cross Christopher B.
Published: April 2009

Percutaneous liver biopsy (PLB) is a valuable diagnostic tool. Complication rates vary depending on the technique used, experience of the physician, number of passes, bleeding parameters and other factors. Hemorrhage is a common complication after PLB and can present as intraperitoneal bleeding, intrahepatic or subcapsular hematoma, or rarely as hemobilia. Acute pancreatitis is a rare complication of hemobilia. We describe a single case of acute pancreatitis caused by biliary obstruction due to hemobilia following PLB. The obstruction was successfully managed with biliary stent drainage.
Review: Therapeutic advances in functional gastrointestinal disease: irritable bowel syndrome
Authors: Gaman Alexandru , Bucur Maria Cristina , Kuo Braden
Published: April 2009

Reported prevalence rates of irritable bowel syndrome (IBS) are between 8% to 20% in the US general population with an average medical expenditure of US$1.35 billion direct and US$205 million indirect costs. Current pathophysiologic theories are based on abnormalities of both the brain and gut, thus setting a new stage for current and future therapeutic approaches. There are numerous treatment options in IBS acting centrally and peripherally by influencing motility and visceral sensitivity. Clinical evidence is variable; however, newer emerging treatments are being evaluated using better-designed clinical trials. Accurate assessment of IBS drug efficacy is still hampered by heterogeneity of the IBS population. Novel methods such as pharmacogenomics or brain imaging may be helpful in the future to better understand and characterize IBS patient subtypes, and this in turn will lead to more specific and efficient therapeutic options. Patient subpopulation measurement of side effects is also a clinical challenge and further understanding could improve treatment efficacy by enhancing the patient compliance.
The effect of metformin and standard therapy versus standard therapy alone in nondiabetic patients with insulin resistance and nonalcoholic steatohepatitis (NASH): a pilot trial
Authors: Shields William W. , Thompson K.E. , Grice G.A. , Harrison S.A. , Coyle W.J.
Published: April 2009

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n = 10) or group B (n = 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m2 in group A and 0.9 kg/m 2 in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.
Acrometastasis to the Foot
Authors: Ellington J. Kent , Kneisl Jeffrey S.
Published: April 2009

Acrometastasis (metastasis to the hand or foot) is a rare occurrence; however, bone is a common site of metastatic disease, which occurs in up to 30% of patients with malignancy. Although acrometastasis is rare, a high clinical suspicion must exist, especially in evaluating a patient with a known history of cancer. The diagnosis may be difficult and prolonged, which may ultimately affect the patient's outcome. Misdiagnosis of acrometastasis seems to be a common problem. Early diagnosis and treatment is important for improving quality of life in these patients. The authors report 3 cases of acrometastasis from a rare source, the colon.
Quantitative Ultrasonography of Calcaneal Bone Mass and Its Relationship to Calcium Consumption Among Impoverished Hispanic Women
Authors: Evans Kevin D. , Scott Jonathan M. , Taylor Christopher A. , Geraghty Maureen E. , Ashcraft Cregg D.
Published: April 2009

Perimenopausal Hispanic women need to be able to build and sustain peak bone mass, but this may be affected by their low socioeconomic status. This feasibility research study provided descriptive information on the relationship between calcium consumption and bone mass measured with sonography at the calcaneus. Little research exists to examine bone health with this specific age or ethnic group of women. This research found a strong positive correlation between the amount of self-reported calcium food consumed and the bone stiffness index recorded using quantitative sonography. The translational impact of this project will inform the development of culturally relevant patient education for Hispanic women of low socioeconomic status to encourage the development of peak bone mass.
Slip systems and critical resolved shear stress in pyrite: an electron backscatter diffraction (EBSD) investigation
Authors: Barrie C. D. , Boyle A. P. , Cox S. F. , Prior D. J.
Published: April 2009

A suite of experimentally deformed single-crystal pyrite samples has been investigated using electron backscatter diffraction (EBSD). Single crystals were loaded parallel to <100> or <110> and deformed at a strain rate of 10-5 s-1, confining pressure of 300 MPa and temperatures of 600°C and 700°C. Although geometrically (Schmid factor) the {001}<100> slip system should not be activated in <100> loaded samples, lattice rotation and boundary trace analyses of the distorted crystals indicate this slip system is easier to justify. Determination of 75 MPa as the critical resolved shear stress (CRSS) for {001}<100> activation, in the <110> loaded crystals, suggests a crystal misalignment of ~5—15° in the <100> loaded crystals would be sufficient to activate the {001}<100> slip system. Therefore, {001}<100> is considered the dominant slip system in all of the single-crystal pyrite samples studied. Slip-system analysis of the experimentally deformed polycrystalline pyrite aggregates is consistent with the single-crystal findings, with the exception that {001}<11̄> also appears to be important, although less common than the {001}<100> slip system. The lack of crystal preferred orientation (CPO) development in the polycrystalline pyrite aggregates can be accounted for by the presence of two independent symmetrically equivalent slip systems more than satisfying the von Mises criterion.
Participation of the urokinase receptor in neutrophil efferocytosis
Authors: Park Young-Jun , Liu Gang , Tsuruta Yuko , Lorne Emmanuel , Abraham Edward
Published: April 2009

The urokinase receptor (uPAR) plays an important role in regulation of fibronolysis, cell migration, and adhesion. In this study, we examined whether uPAR plays a role in modulating efferocytosis of neutrophils. Macrophages from uPAR−/− mice demonstrated enhanced ability to engulf viable wild-type (WT) neutrophils in vitro and in vivo in the lungs. The increased phagocytic activity of uPAR−/− macrophages was abrogated by incubation with soluble uPAR (suPAR), arginine-glycine-aspartic acid (RGD)–containing peptides, or anti-integrin antibodies. There was increased uptake of viable uPAR−/− neutrophils by WT macrophages. Incubation of uPAR−/− neutrophils with suPAR or anti-integrin antibodies diminished uptake by WT macrophages to baseline. Uptake of uPAR−/− neutrophils by uPAR−/− macrophages was not enhanced. However, incubation of uPAR−/− neutrophils or uPAR−/− macrophages, but not both, with suPAR enhanced the uptake of viable uPAR−/− neutrophils by uPAR−/− macrophages. The adhesion of WT neutrophils to uPAR−/− macrophages was higher than to WT macrophages. uPAR−/− neutrophils demonstrated increased adhesion to suPAR, which was abrogated by blocking of low-density lipoprotein related protein and integrins. Expression of uPAR on the surface of apoptotic neutrophils was reduced compared with levels on viable neutrophils. These results demonstrate a novel role for uPAR in modulating recognition and clearance of neutrophils.
MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2
Authors: Spaggiari Grazia Maria , Abdelrazik Heba , Becchetti Flavio , Moretta Lorenzo
Published: April 2009

Various studies analyzed the inhibitory effect exerted by mesenchymal stem cells (MSCs) on cells of the innate or acquired immunity. Myeloid dendritic cells (DCs) are also susceptible to such inhibition. In this study, we show that MSCs strongly inhibit DC generation from peripheral blood monocytes. In the presence of MSCs, monocytes supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) did not acquire the surface phenotype typical of immature (CD14−, CD1a+) or mature (CD80+, CD86+, CD83+) DCs, failed to produce IL-12, and did not induce T-cell activation or proliferation. Analysis of the molecular mechanism(s) responsible for the inhibitory effect revealed a major role of prostaglandin E2 (PGE2). Thus, addition of the PGE2 inhibitor NS-398 restored DC differentiation and function. Moreover, PGE2 directly added to cultures of monocytes blocked their differentiation toward DCs in a manner similar to MSCs. Although IL-6 has been proposed to play a role in MSC-mediated inhibition of DC differentiation, our data indicate that PGE2 and not IL-6 represents the key inhibitory mediator. Indeed, NS-398 inhibited PGE2 production and restored DC differentiation with no effect on IL-6 production. These data emphasize the role of MSCs in inhibiting early DC maturation and identifying the molecular mechanisms responsible for the inhibitory effect.
Identification of genes differentially expressed in dorsal and ventral chick midbrain during early Development
Authors: Chittka A , Volff JN , Wizenmann A
Published: April 2009

Background

During the development of the central nervous system (CNS), patterning processes along the dorsoventral (DV) axis of the neural tube generate different neuronal subtypes. As development progresses these neurons are arranged into functional units with varying cytoarchitecture, such as laminae or nuclei for efficient relaying of information. Early in development ventral and dorsal regions are similar in size and structure. Different proliferation rates and cell migration patterns are likely to result in the formation of laminae or nuclei, eventually. However, the underlying molecular mechanisms that establish these different structural arrangements are not well understood.

We undertook a differential display polymerase chain reaction (DD-PCR) screen to identify genes with distinct expression patterns between dorsal and ventral regions of the chick midbrain in order to identify genes which regulate the sculpturing of such divergent neuronal organisation. We focused on the DV axis of the early chick midbrain since mesencephalic alar plate and basal plate develop into laminae and nuclei, respectively.

Results

We identified 53 differentially expressed bands in our initial screen. Twenty-six of these could be assigned to specific genes and we could unambiguously show the differential expression of five of the isolated cDNAs in vivo by in situ mRNA expression analysis. Additionally, we verified differential levels of expression of a selected number of genes by using reverse transcriptase (RT) PCR method with gene-specific primers.

One of these genes, QR1, has been previously cloned and we present here a detailed study of its early developmental time course and pattern of expression providing some insights into its possible function. Our phylogenetic analysis of QR1 shows that it is the chick orthologue of Sparc-like 1/Hevin/Mast9 gene in mice, rats, dogs and humans, a protein involved in cell adhesion.

Conclusion

This study reveals some possible networks, which might be involved in directing the difference in neuronal specification and cytoarchitecture observed in the brain.
Parallel DNA pyrosequencing unveils new zebrafish microRNAs
Authors: Soares Ana R , Pereira Patrícia M , Santos Bruno , Egas Conceição , Gomes Ana C , Arrais Joel , Oliveira José L , Moura Gabriela R , Santos Manuel AS
Published: April 2009

Background

MicroRNAs (miRNAs) are a new class of small RNAs of approximately 22 nucleotides in length that control eukaryotic gene expression by fine tuning mRNA translation. They regulate a wide variety of biological processes, namely developmental timing, cell differentiation, cell proliferation, immune response and infection. For this reason, their identification is essential to understand eukaryotic biology. Their small size, low abundance and high instability complicated early identification, however cloning/Sanger sequencing and new generation genome sequencing approaches overcame most technical hurdles and are being used for rapid miRNA identification in many eukaryotes.

Results

We have applied 454 DNA pyrosequencing technology to miRNA discovery in zebrafish (Danio rerio). For this, a series of cDNA libraries were prepared from miRNAs isolated at different embryonic time points and from fully developed organs. Each cDNA library was tagged with specific sequences and was sequenced using the Roche FLX genome sequencer. This approach retrieved 90% of the 192 miRNAs previously identified by cloning/Sanger sequencing and bioinformatics. Twenty five novel miRNAs were predicted, 107 miRNA star sequences and also 41 candidate miRNA targets were identified. A miRNA expression profile built on the basis of pyrosequencing read numbers showed high expression of most miRNAs throughout zebrafish development and identified tissue specific miRNAs.

Conclusion

This study increases the number of zebrafish miRNAs from 192 to 217 and demonstrates that a single DNA mini-chip pyrosequencing run is effective in miRNA identification in zebrafish. This methodology also produced sufficient information to elucidate miRNA expression patterns during development and in differentiated organs. Moreover, some zebrafish miRNA star sequences were more abundant than their corresponding miRNAs, suggesting a functional role for the former in gene expression control in this vertebrate model organism.
Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma
Authors: Augello Claudia , Caruso Luca , Maggioni Marco , Donadon Matteo , Montorsi Marco , Santambrogio Roberto , Torzilli Guido , Vaira Valentina , Pellegrini Caterina , Roncalli Massimo , Coggi Guido , Bosari Silvano
Published: April 2009

Background

Similarly to other tumor types, an imbalance between unrestrained cell proliferation and impaired apoptosis appears to be a major unfavorable feature of hepatocellular carcinoma (HCC). The members of IAP family are key regulators of apoptosis, cytokinesis and signal transduction. IAP survival action is antagonized by specific binding of Smac/DIABLO and XAF1. This study aimed to investigate the gene and protein expression pattern of IAP family members and their antagonists in a series of human HCCs and to assess their clinical significance.

Methods

Relative quantification of IAPs and their antagonist genes was assessed by quantitative Real Time RT-PCR (qPCR) in 80 patients who underwent surgical resection for HCC. The expression ratios of XIAP/XAF1 and of XIAP/Smac were also evaluated. Survivin, XIAP and XAF1 protein expression were investigated by immunohistochemistry. Correlations between mRNA levels, protein expression and clinicopathological features were assessed. Follow-up data were available for 69 HCC patients. The overall survival analysis was estimated according to the Kaplan-Meier method.

Results

Survivin and Livin/ML-IAP mRNAs were significantly over-expressed in cancer tissues compared to non-neoplastic counterparts. Although Survivin immunoreactivity did not correlate with qPCR data, a significant relation was found between higher Survivin mRNA level and tumor stage, tumor grade and vascular invasion.

The mRNA ratio XIAP/XAF1 was significantly higher in HCCs than in cirrhotic tissues. Moreover, high XIAP/XAF1 ratio was an indicator of poor prognosis when overall survival was estimated and elevated XIAP immunoreactivity was significantly associated with shorter survival.

Conclusion

Our study demonstrates that alterations in the expression of IAP family members, including Survivin and Livin/ML-IAP, are frequent in HCCs. Of interest, we could determine that an imbalance in XIAP/XAF1 mRNA expression levels correlated to overall patient survival, and that high XIAP immunoreactivity was a poor prognostic factor.
Potentials of on-line repositioning based on implanted fiducial markers and electronic portal imaging in prostate cancer radiotherapy
Authors: Graf Reinhold , Wust Peter , Budach Volker , Boehmer Dirk
Published: April 2009

Background

To evaluate the benefit of an on-line correction protocol based on implanted markers and weekly portal imaging in external beam radiotherapy of prostate cancer. To compare the use of bony anatomy versus implanted markers for calculation of setup-error plus/minus prostate movement. To estimate the error reduction (and the corresponding margin reduction) by reducing the total error to 3 mm once a week, three times per week or every treatment day.

Methods

23 patients had three to five, 2.5 mm Ø spherical gold markers transrectally inserted into the prostate before radiotherapy. Verification and correction of treatment position by analysis of orthogonal portal images was performed on a weekly basis. We registered with respect to the bony contours (setup error) and to the marker position (prostate motion) and determined the total error. The systematic and random errors are specified. Positioning correction was applied with a threshold of 5 mm displacement.

Results

The systematic error (1 standard deviation [SD]) in left-right (LR), superior-inferior (SI) and anterior-posterior (AP) direction contributes for the setup 1.6 mm, 2.1 mm and 2.4 mm and for prostate motion 1.1 mm, 1.9 mm and 2.3 mm. The random error (1 SD) in LR, SI and AP direction amounts for the setup 2.3 mm, 2.7 mm and 2.7 mm and for motion 1.4 mm, 2.3 mm and 2.7 mm. The resulting total error suggests margins of 7.0 mm (LR), 9.5 mm (SI) and 9.5 mm (AP) between clinical target volume (CTV) and planning target volume (PTV). After correction once a week the margins were lowered to 6.7, 8.2 and 8.7 mm and furthermore down to 4.9, 5.1 and 4.8 mm after correcting every treatment day.

Conclusion

Prostate movement relative to adjacent bony anatomy is significant and contributes substantially to the target position variability. Performing on-line setup correction using implanted radioopaque markers and megavoltage radiography results in reduced treatment margins depending on the online imaging protocol (once a week or more frequently).
Comparing Adult and Pediatric Rhabdomyosarcoma in the Surveillance, Epidemiology and End Results Program, 1973 to 2005: An Analysis of 2,600 Patients
Authors: Sultan Iyad , Qaddoumi Ibrahim , Yaser Sameer , Rodriguez-Galindo Carlos , Ferrari Andrea
Published: April 2009

Purpose

To compare clinical features and outcomes of adults and children reported to have rhabdomyosarcoma.

Patients and Methods

We analyzed data from 1,071 adults (age > 19 years) and 1,529 children (age ≤ 19 years) reported in the public-access Surveillance, Epidemiology and End Results database as having rhabdomyosarcoma, diagnosed from 1973 to 2005. Survival estimates were determined using survival time with the end point being death from any cause.

Results

Adults with rhabdomyosarcoma had significantly worse outcome than children (5-year overall survival rates, 27% ± 1.4% and 61% ± 1.4%, respectively; P < .0001). Tumors in adults were more likely to be at an unfavorable site (65% v 55%; P < .0001) and to have histologies that are unusual during childhood, particularly the pleomorphic subtype (19%) and not otherwise specified (43%). Regional and distant spread was not more frequent in adults. Adults had significantly worse outcome than children with similar tumors. The most significant difference was in localized disease; 5-year survival estimates were 82% ± 2.0% for children and 47% ± 2.9% for adults (P < .0001). Multivariate analysis showed that age, histologic subtype, primary site location, stage, and local control with surgery and/or radiation were significant predictors of survival. However, alveolar subtype and unfavorable primary site lost significance when analysis was restricted to adults.

Conclusion

Adults reported to have rhabdomyosarcoma had worse survival than children with similar tumors. Predictors of poor outcome in children were valid in adults except for alveolar histology and unfavorable tumor site.
PTEN Expression and KRAS Mutations on Primary Tumors and Metastases in the Prediction of Benefit From Cetuximab Plus Irinotecan for Patients With Metastatic Colorectal Cancer
Authors: Loupakis Fotios , Pollina Luca , Stasi Irene , Ruzzo Annamaria , Scartozzi Mario , Santini Daniele , Masi Gianluca , Graziano Francesco , Cremolini Chiara , Rulli Eliana , Canestrari Emanuele , Funel Niccola , Schiavon Gaia , Petrini Iacopo , Magnani Mauro , Tonini Giuseppe , Campani Daniela , Floriani Irene , Cascinu Stefano , Falcone Alfredo
Published: April 2009

Purpose

PTEN, AKT, and KRAS are epidermal growth factor receptor (EGFR) downstream regulators. KRAS mutations confer resistance to cetuximab. This retrospective study investigated the role of PTEN loss, AKT phosphorylation, and KRAS mutations on the activity of cetuximab plus irinotecan in patients with metastatic colorectal cancer (mCRC).

Patients and Methods

A cohort of patients with irinotecan-refractory mCRC who were treated with cetuximab plus irinotecan was tested for PTEN immunoreactivity (ie, immunohistochemistry; IHC), pAKT IHC, and KRAS mutations. Analyses were performed both on primary tumors and on related metastases, and the association among IHC, mutational results, and treatment outcomes was investigated.

Results

One-hundred two patients were eligible. Ninety-six primary tumors, 59 metastases, and 53 paired samples were available. Forty-nine primary tumors (58% of assessable samples) had a preserved PTEN expression (PTEN-positive), whereas 35 (40% of assessable samples) were pAKT-positive. Levels of concordance between primary tumors and metastases were 60%, 68%, and 95% for PTEN, pAKT, and KRAS, respectively. PTEN status on primary tumors and pAKT status both on primary tumors and on metastases did not predict response or progression-free survival (PFS). On metastases, 12 (36%) of 33 patients with PTEN-positive tumors were responders compared with one (5%) of 22 who had PTEN-negative tumors (P = .007). The median PFS of patients with PTEN-positive metastases was 4.7 months compared with 3.3 months for those with PTEN-negative metastases (hazard ratio [HR], 0.49; P = .005). Patients with PTEN-positive metastases and KRAS wild type had longer PFS compared with other patients (5.5 months v 3.8 months; HR, 0.42; P = .001).

Conclusion

PTEN loss in metastases may be predictive of resistance to cetuximab plus irinotecan. The combination of PTEN IHC and KRAS mutational analyses could help to identify a subgroup of patients with mCRC who have higher chances of benefiting from EGFR inhibition.
Margin Clearance and Outcome in Resected Pancreatic Cancer
Authors: Chang David K. , Johns Amber L. , Merrett Neil D. , Gill Anthony J. , Colvin Emily K. , Scarlett Christopher J. , Nguyen Nam Q. , Leong Rupert W.L. , Cosman Peter H. , Kelly Mark I. , Sutherland Robert L. , Henshall Susan M. , Kench James G. , Biankin Andrew V.
Published: April 2009

Purpose

Current adjuvant therapies for pancreatic cancer (PC) are inconsistently used and only modestly effective. Because a high proportion of patients who undergo resection for PC likely harbor occult metastatic disease, any adjuvant trials assessing therapies such as radiotherapy directed at locoregional disease are significantly underpowered. Stratification based on the probability (and volume) of residual locoregional disease could play an important role in the design of future clinical trials assessing adjuvant radiotherapy.

Patients and Methods

We assessed the relationships between margin involvement, the proximity to operative resection margins and outcome in a cohort of 365 patients who underwent operative resection for PC.

Results

Microscopic involvement of a resection margin by tumor was associated with a poor prognosis. Stratifying the minimum clearance of resection margins by 0.5-mm increments demonstrated that although median survival was no different to clear margins based on these definitions, it was not until the resection margin was clear by more than 1.5 mm that optimal long-term survival was achieved.

Conclusion

These data demonstrate that a margin clearance of more than 1.5 mm is important for long-term survival in a subgroup of patients. More aggressive therapeutic approaches that target locoregional disease such as radiotherapy may be beneficial in patients with close surgical margins. Stratification of patients for entry onto future clinical trials based on this criterion may identify those patients who benefit from adjuvant radiotherapy.
Benchmarking nursing home performance at the state level
Authors: Lenard Melanie L , Shimshak Daniel G
Published: April 2009

This paper reports the results of a state-level comparison of the performance of nursing homes. The results were obtained by applying data envelopment analysis (DEA) to data (obtained from OSCAR, the online survey, certification and reporting database [2004]) for all the skilled nursing facilities in each of the 50 states and the District of Columbia. DEA produces an efficiency score for each state that can serve as a single comprehensive measure of its overall performance. However, two DEA models were used in the analysis reported here so that each state could be given two efficiency scores, one for each of the two aspects of their performance – quality efficiency and operating efficiency. Eleven states were identified as being 100% efficient for both quality and operating efficiency of their nursing homes. For the remaining states (i.e. those having lower scores for either quality efficiency or operating efficiency or both), DEA results include, in addition to the efficiency score, performance goals and a benchmark set of other states that could be used as models of ‘best practice’.
What motivated Dr David Livingstone (1813–73) in his work in Africa?
Authors: Beard John A S
Published: April 2009

Born of humble beginnings in a Scottish mill-town, David Livingstone would become one of the great explorers of the 19th century, traversing 30,000 miles of unknown Africa. His pioneering spirit and inquisitive mind brought knowledge and discoveries in the fields of tropical medicine, linguistics, botany, zoology, anthropology and geology. While it can be argued that Livingstone exhibited contradictions and shortcomings as a man, he nonetheless grasped the imagination of Victorian Britain and helped to change European attitudes towards Africa forever. His numerous endeavours were undertaken under the banner of divinely inspired missionary work – ‘If God has accepted my service, then my life is charmed till my work is done’ (Livingstone D. Livingstone's Private Journals, 1851–53. London: Chatto & Windus, 1960:108). Yet whether it was indeed religion that truly motivated Livingstone, or rather that he used it as a vehicle for his other passions, is less certain.
Samuel Alderman Lomas (1838–1901) the man with two gravestones, his brother MuscotAtkin Lomas (1840–1907) and their lives in Victorian asylums
Authors: Hilton Claire , Hilton Benjamin
Published: April 2009

Samuel Alderman Lomas died in the Hertfordshire County Asylum, Hill End, St Albans in 1901. He was buried in the asylum cemetery where two gravestones bear his name. This paper traces his life history and that of his brother Muscot Atkin Lomas. Both were classed as idiots in Victorian society and spent most of their lives – from childhood until death – in asylums.
Natan ‘Nikolai’ Abramovich Vigdorchik (1874-1954): social activism and public health in early 20th-century Russia
Authors: Sharp Dan S , Tanger Mark B
Published: April 2009

Virtually unknown in the West, the physician Nikolai Vigdorchik is recognized in Russian-Soviet history for his role in introducing social security into Russia. He rose from Jewish working-class origins to a career that combined activism in labour rights and public health with extensive and path-breaking publications in social security occupational safety and public health. He contributed more than 30 years of leadership to Soviet research and educational institutions devoted to occupational safety and health. Vigdorchik's 1935 publication on lead and hypertension is illustrative of his contribution to modern epidemiological methods, describing a statistical bias in the study of hospitalized patients. It predates by 11 years Joseph Berkson's paper, after whom the bias is named. Vigdorchik's life illustrates a modem-day conundrum: social activism comes with political cost - by virtue of its evidence-based orientation, public health science is safer but both are necessary to move a culture towards health and stability
George Higoumenakis (1895-1983): Greek dermatologist
Authors: Frangos Constantinos C , Frangos Christos C
Published: April 2009

This paper describes the Higoumenakis sign, enlargement of the sternal end of the clavicle in patients with late congenital syphilis and the dermatologist after whom it is named. Several professors and doctors from the Medical School of the University of Athens opposed his actions especially at the University in Greece. His persistence led him to productive scientific activity in syphilis, leishmaniasis and psoriasis. He became a member of the Greek Parliament from 1964 to 1967 and eventually Minister of Hygiene - even though this may have been an imprudent political choice, due to the unstable sociopolitical status of that period. He died on 27 December 1983 at the age of 88.
Dr Edward Wilson (1872-1912): Antarctic Hero
Authors: Williams Isobel
Published: April 2009

Edward Wilson was an artist, doctor, naturalist and explorer. He was on both Scott's Antarctic expeditions of the early 1900s, as Junior Surgeon and Zoologist on the Discovery expedition of 1901 and as Chief of Scientific Staff on the Terra Nova expedition of 1910. He reached the Pole with Scott in 1912 and died with him on their ill-fated return from the Pole.
Cold-inducible RNA binding protein (CIRP) expression is modulated by alternative mRNAs
Authors: Al-Fageeh Mohamed B. , Smales C. Mark
Published: April 2009

Cold-inducible RNA binding protein (CIRP) is a mammalian protein whose expression is up-regulated in response to mild hypothermia. Although the exact function of this protein is currently unknown, it is thought to function as an RNA chaperone, facilitating mRNA translation upon the perception of cold stress. In this study we have identified and characterized the major CIRP 5′-untranslated region (5′-UTR) transcripts in mouse embryonic fibroblast NIH-3T3 cells. We show that the 5′-UTR of CIRP, a protein highly homologous to the cold-shock protein Rbm3, is much shorter than the previously published 5′ leader sequence of Rbm3. In addition, three major CIRP transcripts with different transcription start sites are generated, with the levels of each of these transcripts being regulated in response to time and temperature. The major transcript generated at 37°C does not encode for the full-length CIRP open reading frame, while the two major transcripts at 32°C do. Further, the longest transcript detected at 32°C shows a discrete expression and stability profile under mild hypothermic conditions and exhibits internal ribosome entry segment (IRES)-like activity. The IRES-like activity is not responsive to conditions of mild hypothermia or hypoxia, but the levels and stability of the transcript harboring the putative IRES are increased at 32°C. We discuss the emerging transcriptional and translational mechanisms by which CIRP expression appears to be controlled and the role that the 5′-UTR plays in the modulation of CIRP expression.
Unpacking Organizational Ambidexterity: Dimensions, Contingencies, and Synergistic Effects
Authors: Cao Qing , Gedajlovic Eric , Zhang Hongping
Published: April 2009

Significant ambiguity remains in the literature regarding the conceptualization of organizational ambidexterity. We unpack this construct into one with two dimensions we term the balance dimension of ambidexterity (BD) and the combined dimension of ambidexterity (CD). BD corresponds to a firm's orientation to maintain a close relative balance between exploratory and exploitative activities, whereas CD corresponds to their combined magnitude. We reason that these dimensions are conceptually distinct, and rely on different causal mechanisms to enhance firm performance. We find that over and above their independent effects, concurrent high levels of BD and CD yield synergistic benefits. We also find that BD is more beneficial to resource-constrained firms, whereas CD is more beneficial to firms having greater access to internal and/or external resources. These results indicate that managers in resource-constrained contexts may benefit from a focus on managing trade-offs between exploration and exploitation demands, but for firms that have access to sufficient resources, the simultaneous pursuit of exploration and exploitation is both possible and desirable.
Social Reality, the Boundaries of Self-Fulfilling Prophecy, and Economics
Authors: Felin Teppo , Foss Nicolai J.
Published: April 2009

Organizational scholars have recently argued that economic theories and assumptions have adversely shaped management practice and human behavior, not only leading to the incorporation of trust-eroding market mechanisms into organizations, but also unnecessarily creating self-interested behavior. A number of highly influential papers have argued that the self-fulfilling nature of (even false) theories provides the underlying mechanism through which economics has adversely shaped not just social science but also management practice and individual behavior. We question these arguments and argue that there are important boundary conditions to theories falsely fulfilling themselves, boundary conditions that have hitherto been unexplored in organizational research, and boundary conditions that question the underlying premises used by organizational scholars and social scientists to attack economics. We specifically build on highly relevant findings from social psychology, philosophy, and organizational economics to show how (1) objective reality and (2) human nature provide two important boundary conditions for theories (falsely or otherwise) fulfilling themselves. We also defend organizational economics, specifically the use of high-powered incentives in organizations, and argue that self-interest (rightly understood) facilitates in creating beneficial individual and collective and societal outcomes.
How and Why Theories Matter: A Comment on Felin and Foss (2009)
Authors: Ferraro Fabrizio , Pfeffer Jeffrey , Sutton Robert I.
Published: April 2009

Theories matter because they affect behavior and can, under certain circumstances, become self-fulfilling. For a theory to become self-fulfilling, people must be aware of the theory and have the ability to make choices according to its dictates, social and physical arrangements are altered on the basis of the theory's prescriptions, and the proponents have the power to implement social arrangements consistent with the theory. Economics and other social science theories often fulfill these conditions, with implications not only for the work of scholars, but also for how we think about testing theories that can change the world they describe.