bluuebunny/crossref_metadata_2025 huggingface dataset:
Using quantile regression to investigate racial disparities in medication non-adherence
Authors: Gebregziabher Mulugeta , Lynch Cheryl P , Mueller Martina , Gilbert Gregory E , Echols Carrae , Zhao Yumin , Egede Leonard E
Published: June 2011

Background

Many studies have investigated racial/ethnic disparities in medication non-adherence in patients with type 2 diabetes using common measures such as medication possession ratio (MPR) or gaps between refills. All these measures including MPR are quasi-continuous and bounded and their distribution is usually skewed. Analysis of such measures using traditional regression methods that model mean changes in the dependent variable may fail to provide a full picture about differential patterns in non-adherence between groups.

Methods

A retrospective cohort of 11,272 veterans with type 2 diabetes was assembled from Veterans Administration datasets from April 1996 to May 2006. The main outcome measure was MPR with quantile cutoffs Q1-Q4 taking values of 0.4, 0.6, 0.8 and 0.9. Quantile-regression (QReg) was used to model the association between MPR and race/ethnicity after adjusting for covariates. Comparison was made with commonly used ordinary-least-squares (OLS) and generalized linear mixed models (GLMM).

Results

Quantile-regression showed that Non-Hispanic-Black (NHB) had statistically significantly lower MPR compared to Non-Hispanic-White (NHW) holding all other variables constant across all quantiles with estimates and p-values given as -3.4% (p = 0.11), -5.4% (p = 0.01), -3.1% (p = 0.001), and -2.00% (p = 0.001) for Q1 to Q4, respectively. Other racial/ethnic groups had lower adherence than NHW only in the lowest quantile (Q1) of about -6.3% (p = 0.003). In contrast, OLS and GLMM only showed differences in mean MPR between NHB and NHW while the mean MPR difference between other racial groups and NHW was not significant.

Conclusion

Quantile regression is recommended for analysis of data that are heterogeneous such that the tails and the central location of the conditional distributions vary differently with the covariates. QReg provides a comprehensive view of the relationships between independent and dependent variables (i.e. not just centrally but also in the tails of the conditional distribution of the dependent variable). Indeed, without performing QReg at different quantiles, an investigator would have no way of assessing whether a difference in these relationships might exist.
Cognitive performance in relapsing remitting multiple sclerosis: A longitudinal study in daily practice using a brief computerized cognitive battery
Authors: Edgar Chris , Jongen Peter J , Sanders Evert , Sindic Christian , Goffette Sophie , Dupuis Michel , Jacquerye Philippe , Guillaume Daniel , Reznik Regine , Wesnes Keith
Published: June 2011

Background

There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally assessed cognition in patients with relapsing remitting (RR) MS.

Methods

Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores derived from the CDR computerized cognitive test system (CDR System): Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) measured disability.

Results

The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory]), when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and episodic memory (Quality of Episodic Memory) were unimpaired.

Conclusions

Preliminary validation of the CDR System indicated that for most, but not all measures psychometric properties were adequate and the measures were related to disability (EDSS and MSFC) and other measures of cognition.
T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor
Authors: Lee Yong-Soo , Kim Tae-Sik , Kim Dong-Ku
Published: June 2011

Background

Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.

Methods

We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells.

Results

We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.

Conclusions

Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.
Acupuncture for the treatment of severe acute pain in Herpes Zoster: results of a nested, open-label, randomized trial in the VZV Pain Study
Authors: Ursini Tamara , Tontodonati Monica , Manzoli Lamberto , Polilli Ennio , Rebuzzi Cristina , Congedo Gabriele , Di Profio Sonia , Toro Patrizia Marani , Consorte Augusta , Placido Giuseppina , Laganà Stefano , D'Amario Claudio , Granchelli Carla , Parruti Giustino , Pippa Lucio ,   the VZV Pain Study Group
Published: June 2011

Background

Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design.

Methods

Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated.

Results

One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/- 136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.

Conclusions

This controlled and randomized trial provides the first evidence of a potential role of AC for the treatment of acute herpetic pain.

Trial registration

ChiCTR-TRC-10001146.
Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress
Authors: Triantafyllou Angelike , Bikineyeva Alfiya , Dikalova Anna , Nazarewicz Rafal , Lerakis Stamatios , Dikalov Sergey
Published: June 2011

Background

Gum of Chios mastic (Pistacia lentiscus var. chia) is a natural antimicrobial agent that has found extensive use in pharmaceutical products and as a nutritional supplement. The molecular mechanisms of its anti-inflammatory activity, however, are not clear. In this work, the potential role of antioxidant activity of Chios mastic gum has been evaluated.

Methods

Scavenging of superoxide radical was investigated by electron spin resonance and spin trapping technique using EMPO spin trap in xanthine oxidase system. Superoxide production in endothelial and smooth muscle cells stimulated with TNF-α or angiotensin II and treated with vehicle (DMSO) or mastic gum (0.1-10 μg/ml) was measured by DHE and HPLC. Cellular H2O2 was measured by Amplex Red. Inhibition of protein kinase C (PKC) with mastic gum was determined by the decrease of purified PKC activity, by inhibition of PKC activity in cellular homogenate and by attenuation of superoxide production in cells treated with PKC activator phorbol 12-myristate 13-acetate (PMA).

Results

Spin trapping study did not show significant scavenging of superoxide by mastic gum itself. However, mastic gum inhibited cellular production of superoxide and H2O2 in dose dependent manner in TNF-α treated rat aortic smooth muscle cells but did not affect unstimulated cells. TNF-α significantly increased the cellular superoxide production by NADPH oxidase, while mastic gum completely abolished this stimulation. Mastic gum inhibited the activity of purified PKC, decreased PKC activity in cell homogenate, and attenuated superoxide production in cells stimulated with PKC activator PMA and PKC-dependent angiotensin II in endothelial cells.

Conclusion

We suggest that mastic gum inhibits PKC which attenuates production of superoxide and H2O2 by NADPH oxidases. This antioxidant property may have direct implication to the anti-inflammatory activity of the Chios mastic gum.
Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice
Authors: Pulavendran Sivasami , Rose Chellan , Mandal Asit Baran
Published: June 2011

Background

Short half-life and low levels of growth factors in the niche of injured microenvironment necessitates the exogenous and sustainable delivery of growth factors along with stem cells to augment the regeneration of injured tissues.

Methods

Here, recombinant human hepatocyte growth factor (HGF) was incorporated into chitosan nanoparticles (CNP) by ionic gelation method and studied for its morphological and physiological characteristics. Cirrhotic mice received either hematopoietic stem cells (HSC) or mesenchymal stemcells (MSC) with or without HGF incorporated chitosan nanoparticles (HGF-CNP) and saline as control. Biochemical, histological, immunostaining and gene expression assays were carried out using serum and liver tissue samples. One way analysis of variance was used for statics application

Results

Serum levels of selected liver protein and enzymes were significantly increased in the combination of MSC and HGF-CNP (MSC+HGF-CNP) treated group. Immunopositive staining for albumin (Alb) and cytokeratin 18 (CK18), and reverse transcription-polymerase chain reaction (RT-PCR) for Alb, alpha fetoprotein (AFP), CK18, cytokeratin 19 (CK19) ascertained that MSC-HGF-CNP treatment could be an effective combination to repopulate liver parenchymal cells in the liver cirrhosis. Zymogram and western blotting for matrix metalloproteinases 2 and 9 (MMP2 and MMP9) revealed that MMP2 actively involved in the fibrolysis of cirrhotic tissue. Immunostaining for alpha smooth muscle actin (αSMA) and type I collagen showed decreased expression in the MSC+HGF-CNP treatment. These results indicated that HGF-CNP enhanced the differentiation of stem cells into hepatocytes and supported the reversal of fibrolysis of extracellular matrix (ECM).

Conclusion

Bone marrow stem cells were isolated, characterized and transplanted in mice model. Biodegradable biopolymeric nanoparticles were prepared with the pleotrophic protein molecule and it worked well for the differentiation of stem cells, especially mesenchymal phenotypic cells. Transplantation of bone marrow MSC in combination with HGF-CNP could be an ideal approach for the treatment of liver cirrhosis.
Family association study between INSR gene polymorphisms and PCOS in Han Chinese
Authors: Xu Xinghua , Zhao Han , Shi Yuhua , You Li , Bian Yuehong , Zhao Yueran , Chen Zi-Jiang
Published: June 2011

Background

Polycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components. Candidate genes with insulin metabolism have been hypothesized to be involved in the etiology of this syndrome. In the present study, we investigated the genetic association between polymorphisms in the insulin receptor (INSR) gene and PCOS.

Methods

A total of 260 family trios were recruited and performed a family-based analysis to assess linkage and association between four single nucleotide polymorphisms (SNPs) (rs1799817, rs2059807, rs8108622 and rs10500204) of INSR gene and PCOS.

Results

Using the transmission disequilibrium test (TDT), we failed to find that rs1799817 (p = 0.486), rs2059807 (p = 0.195), rs8108622 (p = 0.866) and rs10500204 (p = 1.0) were significantly overtransmitted to PCOS offspring from their parents.

Conclusion

No significant evidence of association or linkage was found in the four tested markers, indicating that our family samples did not support susceptibility of the INSR gene to PCOS.
Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice
Authors: Zanini Graziela M , Cabrales Pedro , Barkho Wisam , Frangos John A , Carvalho Leonardo JM
Published: June 2011

Background

Cerebral malaria (CM) is a lethal complication of Plasmodium falciparum infections. In the Plasmodium berghei ANKA (PbA) murine model, CM is associated with marked brain inflammation, increased expression of endothelial cell adhesion molecules and leukocyte and platelet accumulation in brain vessels, causing vascular occlusion and decreased blood flow, damaging the endothelium and leading to blood-brain barrier breakdown, leakage and hemorrhages. Exogenous nitric oxide (NO) administration largely prevents the syndrome. Here we evaluated whether the mechanism of action of NO in preventing murine CM is related to its anti-inflammatory properties and to protection of the endothelium.

Methods

C57Bl/6 mice infected with PbA were treated twice a day with saline or dipropylenetriamineNONOate (DPTA-NO). Endothelial cell adhesion molecule (ICAM-1, VCAM, E- and P-selectin) expression in brain tissue on day 6 of infection was assessed in both groups by western blot. For intravital microscopy studies, DPTA-NO-treated and saline-treated mice with a previously implanted closed cranial window were injected with albumin-FITC, anti-CD45-TxR and anti-CD41-FITC antibodies on day 6 of infection for quantification of albumin leakage, leukocyte and platelet adherence in pial vessels.

Results

PbA-infected mice treated with the NO-donor DPTA-NO showed decreased expression of ICAM-1 and P-selectin, but not VCAM-1, in the brain, compared to saline-treated mice. DPTA-NO treatment also decreased the number of adherent leukocytes and platelets in pial vessels, particularly in venules 30-50 μm in diameter, decreased inflammatory vascular resistance and prevented the occurrence of arteriolar and venular albumin leakage observed in saline-treated PbA-infected mice, as assessed by intravital microscopy.

Conclusions

These results indicate that the protective effect of exogenous NO on murine CM is associated with decreased brain vascular expression of inflammatory markers resulting in attenuated endothelial junction damage and facilitating blood flow.
Alpha-1 antitrypsin is a potential biomarker for hepatitis B
Authors: Tan Xu-fei , Wu Shan-shan , Li Shu-ping , Chen Zhi , Chen Feng
Published: June 2011

Background

Function exertion of specific proteins are key factors in disease progression, thus the systematical identification of those specific proteins is a prerequisite to understand various diseases. Though many proteins have been verified to impact on hepatitis, no systematical protein screening has been documented to hepatitis B virus (HBV) induced hepatitis, hindering the comprehensive understanding to this severe disease.

Aim

To identify the major proteins in the progression of HBV infection from mild stage to severe stage.

Methods

We performed an integrated strategy by combining two-dimensional electrophoresis (2-DE), peptide mass fingerprinting (PMF) analysis, and tissue microarray techniques to screen the functional proteins and detect the localization of those proteins.

Results

Interestingly, MS/MS identification revealed the expression level of alpha-1 antitrypsin (AAT) was significantly elevated in serum samples from patients with severe chronic hepatitis. Immunoblotting with a specific AAT antibody confirmed that AAT is highly expressed in serum samples from patients with hepatic carcinoma and severe chronic hepatitis. Furthermore, we observed that AAT is with highest expression in normal tissue and cells, but lowest in hepatic carcinoma and severe chronic hepatitis tissues and cells, suggesting the specific secretion of AAT from tissues and cells to serum.

Conclusion

These results suggest the possibility of AAT as a potential biomarker for hepatitis B in diagnosis.
Characteristics and PD-1 expression of peripheral CD4+CD127loCD25hiFoxP3+ Treg cells in chronic HCV infected-patients
Authors: Shen Tao , Zheng Jiajia , Liang Hua , Xu Chunhui , Chen Xiangmei , Zhang Ting , Xu Qiang , Lu Fengmin
Published: June 2011

Background

Both regulatory T cells (Tregs) and PD-1/PD-L1 pathway were critically involved in HCV viral persistence. However, the association between them was not well investigated. Herein, we aimed to investigate the distributional profiles of Tregs subsets and association between PD-1 expression on these subsets and development of HCV long-term persistence.

Methods

CD45RA and CD27 were employed to separate peripheral Tregs as naïve/central memory/effector memory/effector subsets. The phenotypic characteristics and PD-1 expression of Tregs were studied by flow cytometry.

Results

In the present study, the majority of Tregs was identified as central memory phenotype in chronic hepatitis C patients compared with nearly equal contribution of naïve and central memory subsets in healthy individuals. PD-1 expression was elevated in all CD4+ T cell subset in chronic HCV infected patients, including Tregs. Of note, higher level of PD-1 expression was found on TEM- and effector-Treg than naïve- and TCM-Tregs subsets. The ratio of TEM-Tregs/naive-Tregs and TEM-Tregs/TCM-Tregs regarding to PD-1 MFI were significantly lower in CHC patients compared to controls.

Conclusions

Our study indicated that distinctive characteristics of PD-1 expression on Tregs in HCV infection suggests associated with impaired adaptive immunity as well as viral long-term persistence. The cross talk between Treg cells and PD-1 induced inhibition in chronic HCV infection deserved further exploration for HCV infection associated immune pathogenesis.
Prevalence of Hepatitis B virus genotypes in HBsAg positive individuals of Afghanistan
Authors: Attaullah Sobia , Rehman Saif ur , Khan Sanaullah , Ali Ijaz , Ali Sajid , Khan Shahid Niaz
Published: June 2011

Background

The structural and functional differences between hepatitis B virus (HBV) genotypes are the mainstay to severity, complications, treatment and possibly vaccination against the virus. This study was conducted to determine the HBV genotypes in HBsAg positive patients of Afghanistan as no such large scale data available previously.

Methods

Two hundred and fourteen HBsAg-positive patients were included in this study. All patients were anti-HCV and anti-HIV negative. All the samples were confirmed for HBV DNA with nested PCR while HBV DNA positive samples were subjected to type specific PCR for HBV genotyping (A-F).

Results

Of the total samples, 168 (78.5%) were males and 46 (21.49%) females, aged ranged between 18 to 71 years. This study demonstrated that genotype D (35.67%) is the predominant genotype circulating in Afghani's population. Genotype C was observed in 32.16% followed by genotype A (19.30%), and genotype B (7.02%) while 6.07% of the individuals were not typed.

Conclusion

This study has shown a heterogeneous distribution of HBV genotypes. Further more, extensive studies are required to investigate genetic and geographical divergence and characteristics of the virus in the country, as no such large sample sized study has been carried out so far in this country.
A comparison of two headless compression screws for operative treatment of scaphoid fractures
Authors: Grewal Ruby , Assini Joseph , Sauder David , Ferreira Louis , Johnson Jim , Faber Kenneth
Published: June 2011

Purpose

The purpose of this study was to compare the interfragmentary compression force across a simulated scaphoid fracture by two commonly used compression screw systems; the Acutrak 2 Standard and the 3.0 mm Synthes headless compression screw.

Methods

Sixteen (8 pairs; 6 female, 2 male) cadaver scaphoids were randomly assigned to receive either the Acutrak 2 or Synthes screw with the contralateral scaphoid designated to receive the opposite. Guide wires were inserted under fluoroscopic control. Following transverse osteotomy, the distal and proximal fragments were placed on either side of a custom load cell, to measure interfragmentary compression. Screws were placed under fluoroscopic control using the manufacturer's recommended surgical technique. Compressive forces were measured during screw insertion. Recording continued for an additional 60s in order to measure any loss of compression after installation was complete. The peak and final interfragmentary compression were recorded and paired t-tests performed.

Results

The mean peak compression generated by the Acutrak 2 Standard was greater than that produced by the Synthes compression screw (103.9 ± 33.2 N vs. 88.7 ± 38.6 N respectively, p = 0.13). The mean final interfragmentary compression generated by the Acutrak 2 screw (68.6 ± 36.4 N) was significantly greater (p = 0.04) than the Synthes screw (37.2 ± 26.8 N). Specimens typically reached a steady state of compression by 120-150s after final tightening.

Conclusion

Peak interfragmentary compression observed during screw installation was similar for both screw systems. However, the mean interfragmentary compression generated by the Acutrak 2 Standard was significantly greater. Our study demonstrates that the Synthes headless compression screw experienced a greater loss of interfragmentary compressive force from the time of installation to the final steady state compression level. The higher post-installation compression of the Acutrak 2 Standard may be attributable to the greater number of threads throughout the entire length of the screw. The clinical significance of these results, are, at this point uncertain. We do demonstrate that a fully threaded design offers a more reliable compression that may translate to more predictable bony union.
Generation of bivalent chromatin domains during cell fate decisions
Authors: De Gobbi Marco , Garrick David , Lynch Magnus , Vernimmen Douglas , Hughes Jim R , Goardon Nicolas , Luc Sidinh , Lower Karen M , Sloane-Stanley Jacqueline A , Pina Cristina , Soneji Shamit , Renella Raffaele , Enver Tariq , Taylor Stephen , Jacobsen Sten Eirik W , Vyas Paresh , Gibbons Richard J , Higgs Douglas R
Published: June 2011

Background

In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3) lineage control genes while 'poising' (H3K4me3) them for subsequent activation during differentiation, implying an important role for epigenetic modification in directing cell fate decisions. However, rather than representing an equivalently balanced epigenetic mark, the patterns and levels of histone modifications at bivalent genes can vary widely and the criteria for identifying this chromatin signature are poorly defined.

Results

Here, we initially show how chromatin status alters during lineage commitment and differentiation at a single well characterised bivalent locus. In addition we have determined how chromatin modifications at this locus change with gene expression in both ensemble and single cell analyses. We also show, on a global scale, how mRNA expression may be reflected in the ratio of H3K4me3/H3K27me3.

Conclusions

While truly 'poised' bivalently modified genes may exist, the original hypothesis that all bivalent genes are epigenetically premarked for subsequent expression might be oversimplistic. In fact, from the data presented in the present work, it is equally possible that many genes that appear to be bivalent in pluripotent and multipotent cells may simply be stochastically expressed at low levels in the process of multilineage priming. Although both situations could be considered to be forms of 'poising', the underlying mechanisms and the associated implications are clearly different.
In vitro and in vivo pre-clinical analysis of a F(ab')2 fragment of panitumumab for molecular imaging and therapy of HER1-positive cancers
Authors: Wong Karen J , Baidoo Kwamena E , Nayak Tapan K , Garmestani Kayhan , Brechbiel Martin W , Milenic Diane E
Published: June 2011

Background

The objective of this study was to characterize the in vitro and in vivo properties of the F(ab')2 fragment of panitumumab and to investigate its potential for imaging and radioimmunotherapy.

Methods

The panitumumab F(ab')2 was generated by enzymatic pepsin digestion. After the integrity and immunoreactivity of the F(ab')2 was evaluated, the fragment was radiolabeled. In vivo studies included direct quantitation of tumor targeting and normal organ distribution of the radiolabeled panitumumab F(ab')2 as well as planar γ-scintigraphy and PET imaging.

Results

The panitumumab F(ab')2 was successfully produced by peptic digest. The F(ab')2 was modified with the CHX-A"-DTPA chelate and efficiently radiolabeled with either 111In or 86Y. In vivo tumor targeting was achieved with acceptable uptake of radioactivity in the normal organs. The tumor targeting was validated by both imaging modalities with good visualization of the tumor at 24 h.

Conclusions

The panitumumab F(ab')2 fragment is a promising candidate for imaging of HER1-positive cancers.
Association between IL-32 genotypes and outcome in infection-associated acute lung injury
Authors: Arcaroli John J , Liu Nianjun , Yi Nengjun , Abraham Edward
Published: June 2011

Introduction

Our purpose was to investigate variation within the IL-32 promoter and gene, and susceptibility to and outcomes from infection associated acute lung injury (ALI).

Methods

Retrospective case-control study involving healthy individuals (controls) and patients (cases) with infection-associated ALI. Two hundred fifty-eight healthy normal controls and 251 patients with infection-associated ALI were used for comparison. The IL-32 promoter/gene was sequenced in 52 healthy Caucasian individuals to identify single nucleotide polymorphisms (SNPs). Allelic discrimination was performed on 11 SNPs to determine differences between cases and controls and outcomes in patients with infection associated ALI.

Results

Logistic and normal regression models were used to evaluate the associations with SNPs in cases and controls, and outcomes in patients with infection associated ALI. rs12934561, an intronic SNP, was found to be associated with risk for ALI in the case-control study and with more severe clinical course, as shown by increased time on the ventilator and the presence of fluid unresponsive hypotension. Further, it was found that rs12934561 has gender-specific effects and strongly interacts with other SNPs.

Conclusions

A common IL-32 genotype, rs12934561, is associated with the risk of ALI as well as the need for prolonged mechanical ventilatory support. This finding suggests that IL-32 is not only involved in the initiating inflammatory and cellular events that result in ALI, but also participates in determining the severity of pulmonary dysfunction associated with ALI.
Phase II Study of Single-Agent Arsenic Trioxide for the Front-Line Therapy of Acute Promyelocytic Leukemia
Authors: Ghavamzadeh Ardeshir , Alimoghaddam Kamran , Rostami Shahrbano , Ghaffari Seyed Hamidolah , Jahani Mohamad , Iravani Massoud , Mousavi Seyed Asadollah , Bahar Babak , Jalili Mahdi
Published: June 2011

Purpose

The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high efficacy of single-agent arsenic trioxide in newly diagnosed APL. However, long-term follow-up results are needed.

Patients and Methods

One hundred ninety-seven patients with newly diagnosed APL were treated with arsenic trioxide 0.15 mg/kg daily intravenous infusion until complete remission (CR). After achieving CR, the patients received one to four more courses of therapy with arsenic trioxide as consolidation and were observed with reverse-transcriptase polymerase chain reaction studies from peripheral blood (to detect of minimal residual disease) every 3 months or until relapse or death.

Results

The morphologic CR rate was 85.8%. The most common cause of remission failure was early death owing to APL differentiation syndrome (13.2%). The most important prognostic factor for early mortality was a high WBC count at presentation. The 5-year disease-free survival (DFS) rate was 66.7% ± 4% (SE). Relapse after 5 years in CR was rare. The 5-year overall survival (OS) rate by intention-to-treat analysis was 64.4% ± 4%. In patients who achieved CR, OS and DFS were identical.

Conclusion

The long-term follow-up of newly diagnosed patients with APL treated with single-agent arsenic trioxide shows high rates of DFS and OS.
Dynamic control of head mesoderm patterning
Authors: Bothe Ingo , Tenin Gennadiy , Oseni Adelola , Dietrich Susanne
Published: June 2011

The embryonic head mesoderm gives rise to cranial muscle and contributes to the skull and heart. Prior to differentiation, the tissue is regionalised by the means of molecular markers. We show that this pattern is established in three discrete phases, all depending on extrinsic cues. Assaying for direct and first-wave indirect responses, we found that the process is controlled by dynamic combinatorial as well as antagonistic action of retinoic acid (RA), Bmp and Fgf signalling. In phase 1, the initial anteroposterior (a-p) subdivision of the head mesoderm is laid down in response to falling RA levels and activation of Fgf signalling. In phase 2, Bmp and Fgf signalling reinforce the a-p boundary and refine anterior marker gene expression. In phase 3, spreading Fgf signalling drives the a-p expansion of MyoR and Tbx1 expression along the pharynx, with RA limiting the expansion of MyoR. This establishes the mature head mesoderm pattern with markers distinguishing between the prospective extra-ocular and jaw skeletal muscles, the branchiomeric muscles and the cells for the outflow tract of the heart.
A Dynamic Model of the Effect of Online Communications on Firm Sales
Authors: Sonnier Garrett P. , McAlister Leigh , Rutz Oliver J.
Published: June 2011

Interpersonal communications have long been recognized as an influential source of information for consumers. Internet-based media have facilitated information exchange among firms and consumers, as well as observability and measurement of such exchanges. However, much of the research addressing online communication focuses on ratings collected from online forums. In this paper, we look beyond ratings to a more comprehensive view of online communications. We consider the sales effect of the volume of positive, negative, and neutral online communications captured by Web crawler technology and classified by automated sentiment analysis. Our modeling approach captures two key features of our data, dynamics and endogeneity. In terms of dynamics, we model daily measures of online communications about a firm and its products as contributing to a latent demand-generating stock variable. To account for the endogeneity, we extend the latent instrumental variable technique to account for dynamic endogenous regressors. Our results demonstrate a significant effect of positive, negative, and neutral online communications on daily sales performance. Failure to account for endogeneity results in a severe attenuation of the estimated effects. From a managerial perspective, we demonstrate the importance of accounting for communication valence as well as the impact of shocks to positive, negative, and neutral online communications.
Queering Helga Crane: Black Nativism in Nella Larsen’s Quicksand
Authors: Macharia Keguro
Published: June 2011

Drawing from George Hutchinson’s recent revisionist biography of Nella Larsen and scholarship in the fields of immigration and queer studies, this article advances a new interpretation of Quicksand as a text that critiques racial and sexual normativity. I argue that Larsen identifies and critiques a distinct black nativism that, in the early decades of the twentieth century, sutured racial and sexual normativity, producing figures like Larsen as queer.
Periodizing the ‘80s: “The Differential of History” in Nicholson Baker’s The Mezzanine
Authors: Thompson Graham
Published: June 2011

This essay examines how Nicholson Baker’s The Mezzanine shifts engagement with the details of the material world consistently onto the axis of temporality. It also examines how, in so doing, Baker’s novel fashions a theory of periodization in which historical and social trends and events are relegated in importance. Asking how the detail or moment might both alter an understanding of the general and spread time to infinite proportions, The Mezzanine casts doubt on the process of periodizing by way of metonymy and synecdoche and offers instead a contingent and improvised version of the 1980s.
Pánicos racistas: reflexiones sobre la inmigración en Cataluña y España a partir de un texto de Najat El Hachmi
Authors: Celaya-Carrillo Beatriz
Published: June 2011

This essay reflects on the tensions and contradictions caused by the recent massive arrival of immigrants to Spain. This phenomenon reveals important failures in the process of receiving and integrating these new members into society. Thus, racist and/or xenophobic attitudes proliferate in different grades while the existence of such behaviors is being denied socially and institutionally. The analytical thread for this research is an autobiographic account by the Catalan writer Najat El Hachmi, Jo també sóc catalana (2004). There are three nationalisms in conflict in this text: Spanish, Catalan, and Moroccan. In particular, Catalan nationalism shows a more significant presence and influence; it confers identity to the author, although alternatively it excludes her from its shelter. In connection to nationalist definitions and the concrete uses El Hachmi grants them, I perceive the tensions between Catalan and Spanish culture (even though at points El Hachmi brings them together as "Western culture"), and Moroccan and Berber culture (which have their own particular conflicts). Between the culture left behind and the new one, two axes of conflict emerge from the receiving society in which Western culture opposes to Islam: religious differences and treatment of women.
Defining Usability: How Library Practice Differs from Published Research
Authors: Chen Yu-Hui , Germain Carol Anne , Rorissa Abebe
Published: June 2011

Library/information science professionals need a clearly articulated definition of usability/Web usability to implement intuitive websites. In this study, the authors analyzed usability definitions provided by the ARL library professionals and those found in the library/information science and computer science-information systems literature. Quantitative and qualitative methods were used to identify similarities and differences between the attributes emphasized by the two sets of definitions based on information behavior models and human-computer interaction (HCI) frameworks. Results indicated that both groups overlooked critical usability elements, such as environment and information objects/content/resources. Thus, the authors proposed a working, multi-faceted definition that presents a holistic view of usability.
Continuing Commentary: Shaking the Bedrock
Authors: Bortolotti Lisa
Published: June 2011

Abstract: In this paper, I articulate the thesis that most delusional beliefs are continuous with other irrational beliefs. Any interpreter with some knowledge about the cognitive and affective life of subjects with delusions can at least partially understand their reports, and explain and predict their behavior in intentional terms. I identify similarities and differences between this approach to the nature of delusions and the approach adopted by Rhodes and Gipps, who have recently defended the view that people with delusions do not share the same bedrock beliefs as people without (the Background Theory of Delusions).
Factors affecting success and constraints of introducing interconnected point-of-care glucose meters: findings and recommendations from the GLUMO-Study1
Authors: von Eiff Wilfried , Henke Viola
Published: June 2011

Innovative technologies play an important role within the health care sector. They not only improve the quality of treatment and enable life prolonging and life-supporting measures. Within an increasing efficiency and quality orientated competitive environment, they also support the provision of health services by medical service providers, for instance hospitals, and allow them to position themselves within the market and safeguard their competitive edge. Alongside the general financial viability is the actual adaption and acceptance of the innovation by the medical personnel essential for the success of a newly introduced medical device. Innovative technologies often impact the existing processes, making them obsolete which increases the necessity for revision and reorganisation.

A redesign of the processes concerned is generally only feasible through an active integration of all parties concerned. Change management can be seen as an essential requirement to coordinate the introduction of innovations as well as the redesign of processes within hospital wards to increase the clinical and economical success and to decrease possible failings, especially during the introduction phase of the innovation.

Within a study project, the Center for Hospital-Management conducted and analysed the introduction and utilisation of interconnected point-of-care meters in hospitals in Austria, Germany and Switzerland. Beside constrains also factors for success which advocate a fast introduction and adaption of the interconnected point-of-care meters could be identified.
Absoluter Aldosteronexzess, Bluthochdruck und koronare Herzerkrankung / Arterial hypertension and cardiovascular disease – absolute aldosterone excess is the tip of the iceberg
Authors: Tomaschitz Andreas , Pilz Stefan , März Winfried
Published: June 2011

Der arterielle Bluthochdruck ist weltweit einer der wichtigsten Risikofaktoren für vermeidbare Todesfälle. Rund 26% aller Todesfälle in Deutschland sind auf eine inadäquate Erhöhung des arteriellen Blutdrucks zurückzuführen. Für diese höhere Prävalenz dürfte zunehmend auch eine fehlende „awareness“ für kausal behandelbare Ursachen des arteriellen Bluthochdrucks verantwortlich sein.

Der primäre Hyperaldosteronismus (PHA) als absoluter Aldosteronüberschuss gilt heute als die häufigste behandelbare Ursache eines Hochdrucks. Der PHA ist mit einem deutlich erhöhten Risiko für die Entwicklung einer kardiovaskulären Herzerkrankung, Niereninsuffizienz und zerebrovaskulären Insult assoziiert. Die Prävelanz des PHA wird auf 5% bis 12% in hypertensiven und auf 17% bis 23% in therapieresistenten hypertensiven PatientInnen geschätzt. Damit dürften rund 1,2 Millionen Menschen in Deutschland von einem PHA betroffen sein.

Die American Endocrine Society empfiehlt das Screening nach einem PHA mittels Bestimmung des Aldosteron-Renin-Quotienten in bestimmten Risikogruppen. Ein standardisiertes Prozedere dieses Screenings soll falsch positive und falsch negative Ergebnisse vermindern. Rezente Untersuchungen zeigen, dass Aldosteron auch unabhängig von einem PHA ein gewichtiger Risikofaktor für eine erhöhte kardiovaskuläre Sterblichkeit bei Frauen und Männern ist. In Verbindung mit hohem Kochsalzkonsum, prä-existenten Organschäden, oxidativen Stress und eingeschränkter Nierenfunktion ist Aldosteron im Sinne eines relativen Überschusses mit einem erhöhten kardiovaskulären Risiko assoziiert. Eine Kochsalzrestriktion erscheint in diesem Zusammenhang als sinnvoll. Die positiven Effekte einer medikamentösen Aldosteronblockade sollten in weiteren interventionellen Untersuchungen evaluiert werden.
The effect of 17β-estradiol on cholesterol content in human macrophages is influenced by the lipoprotein milieu
Authors: Corcoran Michael P , Lichtenstein Alice H , Meydani Mohsen , Dillard Alice , Schaefer Ernst J , Lamon-Fava Stefania
Published: June 2011

Estrogen and testosterone are thought to modulate coronary heart disease (CHD) risk. To examine how these hormones affect human macrophage cholesterol transport, a key factor in atherogenesis, we obtained monocytes from healthy male and postmenopausal female donors (age 50–70 years). Cells were allowed to differentiate in autologous serum. Human monocyte-derived macrophages (HMDMs) were exposed to estrogen, testosterone, or vehicle, during differentiation. Cells were cholesterol enriched with oxidized low-density lipoprotein (oxLDL) in the presence of treatment. Cell cholesterol mass, efflux, and the expression of proteins involved in HMDM cholesterol transport were examined. Estrogen significantly reduced cholesteryl ester (CE) content in both female and male HMDMs while having no measurable effect on cholesterol efflux. Testosterone did not affect cholesterol content or efflux. Both hormones significantly but modestly affected the gene expression of several proteins involved in HMDM transport, yet these effects did not translate into significant changes in protein expression. In THP-1 macrophages, the effect of estrogen on CE content was more potent in unloaded macrophages and was estrogen receptor dependent. A trend for a reduction in non-oxLDL uptake by estrogen was observed and was also found to be dependent upon estrogen receptor activation. Our data indicate that estrogen, but not testosterone, reduces CE accumulation in HMDMs obtained from a CHD age relevant population, independent of changes in the expression of proteins important to macrophage cholesterol transport. In THP-1 cells, this effect is reduced in the presence of oxLDL, indicating that a pro-atherogenic lipoprotein milieu is an important variable in sex hormone modulation of CHD.
Hemophagocytic Lymphohistiocytosis With Munc13-4 Mutation: A Cause of Recurrent Fatal Hydrops Fetalis
Authors: Bechara Elie , Dijoud Frédérique , de Saint Basile Geneviève , Bertrand Yves , Pondarré Corinne
Published: June 2011

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder of immune regulation that leads to a hyperinflammatory syndrome responsible for fever, hepatosplenomegaly, cytopenia, and coagulopathy. Although presentation usually occurs in early infancy, antenatal presentation is extremely rare. To our knowledge, we are first to report genetically confirmed FHL in 2 consecutive siblings who presented with hydrops fetalis that led to spontaneous intrauterine death at 38 and 30 weeks of gestation. Because the diagnosis of FHL has important implications for genetic counseling, we suggest that FHL be considered in the differential diagnosis of nonimmune hydrops fetalis.
New Insights About Infant and Toddler Skin: Implications for Sun Protection
Authors: Paller Amy S. , Hawk John L. M. , Honig Paul , Giam Yoke Chin , Hoath Steven , Mack M. Catherine , Stamatas Georgios N.
Published: June 2011

The skin is increasingly recognized as a component of the innate immune response, in addition to its role as a physical barrier. Although the deleterious effects of solar ultraviolet radiation (UVR), including immunosuppression and cutaneous tumorigenesis, are widely acknowledged, most studies to date have concentrated on adult skin. Despite the more sensitive nature of infant and toddler skin, little is known about its responses to UVR exposure, whether acute or long-term. Accumulating evidence suggests not only that the skin's barrier protection remains immature throughout at least the first 2 years of life but also that accumulation of UVR-induced changes in the skin may begin as early as the first summer of life. Such evidence not only affirms the importance of sun protection during the infant and toddler years but underscores the need for more research to establish evidence-based standards of care in this area. In this article we review recent studies in which differences between the skin properties of infants and young children and those of adults were compared, and we discuss the implications of these differences for sun-protection practices.
Evaluation of Formation Damage from Transient Pressure Analysis: Unsteady State Skin Factor
Authors: El-Khatib Noaman
Published: June 2011

The damaged zone around the well is considered as the internal region of a composite system comprising two regions of different permeabilities. An analytical solution is obtained in Laplace space and is inverted using Stehfest Algorithm. The skin factor is obtained as the difference in dimensionless pressure at the well of the composite system and that of the homogeneous system at the same dimensionless time. The ratio of the skin factor to the steady state skin factor is estimated and correlated with the permeability ratio and the dimensionless depth of invasion.

The developed model and the correlation charts can be used to evaluate the formation damage from well test analysis around the well by estimating both the permability and depth of invasion in the damaged zone. This is an improvement in the conventional method that gives the steady state skin factor which is a combination of both permeability ratio and invasion radius.

Additional pressure drop due to damage is found to be time dependent and varies from zero at the start and approaches that obtained from steady state skin factor at very large dimensionless time. The unsteady state skin factor and skin factor ratio depends on both the permeability ratio and the dimensionless invasion radius and not uniquely on their combination.